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Archive for the ‘Molecular Genetics’ Category

EPA’s ‘transparency rule’ is bad for science and the environment – STAT

Sunday, December 15th, 2019

A proposed rule by the Environmental Protection Agency (EPA) that allegedly aims to strengthen transparency in regulatory science suggests that science is broken. It isnt.

We know it works because we can see the life-saving transplant technologies, hurricane forecasts, new medications, pest-resistant crops, and countless other breakthroughs that exist because of science. This discipline isnt perfect, but it is the best tool available to safeguard the planet and its people.

Last year, the EPA proposed a rule requiring that scientists disclose all raw data before any study conclusions would be considered. The rule, titled Strengthening Transparency in Regulatory Science, would apply retroactively to regulations already in place. It would make it harder to enact new regulations, because many studies from the past rely on personal medical information that was collected under confidentiality agreements and include consensus from reports that may not have shared all of the data according in ways compliant with the proposed rule.

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The EPA has received nearly 600,000 comments on the proposed rule.

The House Committee on Space, Science, and Technology recently held hearings on the transparency rule and, in a bipartisan show of support, advanced out of committee the Scientific Integrity Act. This legislation would require all federal agencies that conduct or use science to set up systems to address and better yet, prevent attacks on science, like the EPAs proposed rule. Please contact your representatives in Congress to support the Scientific Integrity Act.

Scientists like us have been raising our voices in opposition to a rule rooted in the misconception that science leaps to conclusions based on weak evidence in single papers. In reality, science works because it produces ideas that are continually tested under tremendous critical scrutiny over long periods of time.

We are writing not just for ourselves but on behalf of other leaders in open and reproducible science practices: Todd Vision, professor and founder of the Dryad Digital Repository; Laurie Goodman, editor-in-chief of the open-access journal GigaScience; Elizabeth Iorns, CEO of Science Exchange and the codirector of the Reproducibility Initiative; Carly Strasser, director of alliances and data strategy at the Fred Hutchinson Cancer Research Center; and Mark Johnston, editor-in-chief of the journal Genetics and former chair of the department of biochemistry and molecular genetics at the University of Colorado.

We are a group of scientists dedicated to accelerating discovery and improving the rigor, transparency, and reproducibility of research. So it may be surprising that we are writing in opposition, as others have done, to a rule whose title would lead one to think its good for science. We oppose it because it wont do what it alleges to do: increase transparency or improve the health and safety of people or the environment.

Various stakeholders in science including researchers, funders, publishers, private organizations, and various public groups are constantly working to maintain and improve the integrity of scientific research. The proposed EPA rule may seem on the surface to support that goal. But it is instead a misguided proposal that undercuts the ongoing efforts of the scientific community in favor of dangerous vetting by a regulatory agency that will not have access to the best information.

Moreover, the Office of Management and Budget estimated that complying with the transparency rule would initially cost $250 million, and then between $1 million and $100 million a year, making it an expensive boondoggle that reduces the quality of information available to EPA policymakers.

Independent validation and replication of the research on which significant regulatory actions are based is a worthwhile goal. But that wouldnt happen under the EPAs rule. Research journals are increasingly implementing data availability policies that, unlike this rule, dont impose onerous burdens on researchers and EPA administrators and that respect the need to protect the privacy of human subjects when sensitive public health data are involved.

In an editorial in PLOS Medicine, Stanfords John Ioannidis writes, If the proposed rule is approved, science will be practically eliminated from all [EPA] decision-making processes. Regulation would then depend uniquely on opinion and whim. This would be devastating to the EPA and would harm Americans.

The EPA was established in the Nixon administration after the Love Canal environmental disaster, and was strengthened in the Reagan era. This supposedly non-partisan organization must rely on the best available research and minimal political interference to devise regulations that balance safety with vigorous commercial growth. When the EPA comes under political pressure, the consequences are severe, as when former EPA head Christie Whitman incorrectly testified about post-9/11 air quality in lower Manhattan. With the EPA responsible for regulations such as the Food Quality Protection Act, which in 1999 finally removed dangerous organophosphate pesticides from our food, political interference can cost lives.

The attention given lately to the challenges in repeating and extending results of research reported in individual published papers has given rise to new tools and practices to further strengthen the scientific endeavor. Over time, given the self-correcting nature of research, science uncovers the truth. While any single result may be difficult to reproduce, with evidence and consensus, novel claims are verified or refuted, and theories are confirmed or modified.

To be sure, there are countless ways to improve the research enterprise and to strengthen the rigor of individual research studies. Government agencies are in a position to play an effective role in encouraging these changes, but the EPAs proposed transparency rule does nothing of the sort.

Reducing the EPAs reliance on scientific knowledge will undermine science and have a catastrophic impact on the health of the country and its citizens.

Lenny Teytelman, Ph.D., is CEO of protocols.io in Berkeley, California. William Gunn, Ph.D., is director of scholarly communications at Elsevier. Joanne Kamens, Ph.D., is executive director of Addgene in Cambridge, Massachusetts.

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EPA's 'transparency rule' is bad for science and the environment - STAT

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Myriads Polygenic Risk Score Personalizes Risk of Breast Cancer for Woman with a Genetic Mutation in Important Breast Cancer Genes – Yahoo Finance

Sunday, December 15th, 2019

New Clinical Validation Study Presented at 2019 San Antonio Breast Cancer Symposium

SALT LAKE CITY, Dec. 14, 2019 (GLOBE NEWSWIRE) -- Myriad Genetics, Inc. (MYGN), a leader in molecular diagnostics and precision medicine, announced that results of a new validation study of the companys polygenic risk score (PRS) for breast cancer were presented at the 2019 San Antonio Breast Cancer Symposium (SABCS) in San Antonio, Tx. The key finding is that the PRS significantly improves the precision and accuracy of breast cancer risk estimates for women of European ancestry who have pathogenic variants (PV) in high- and moderate-penetrance breast cancer genes.

Our goal is to help women understand their risk of breast cancer so that they can take steps to live longer, healthier lives. Women who have a family history of breast cancer should consider hereditary cancer testing with the myRisk Hereditary Cancer test, said Jerry Lanchbury, Ph.D., chief scientific officer of Myriad Genetics. In this landmark study, we demonstrated that for women who test positive for a mutation in one of the five most common breast cancer genes, there are additional genetic factors called single nucleotide polymorphisms (SNPs) that can further influence their lifetime risk of breast cancer.

A summary of the study follows below. Follow Myriad on Twitter via @myriadgenetics and keep up to date with SABCS meeting news and updates by using the #SACBS19 hashtag.

Myriad Poster Presentation Title: Polygenic Breast Cancer Risk Modification in Carriers of High and Intermediate Risk Gene Mutations.Presenter: Elisha Hughes, Ph.D.Date: Saturday, Dec. 14, 2019, 7:009:00 a.m. Location: Poster P6-08-07

This validation study evaluated the 86-SNP PRS as a breast cancer risk factor for women who carry PV in the BRCA1, BRCA2, CHEK2, ATM and PALB2 genes and for PV-free women. The analysis included data from 152,012 women of European ancestry who received a myRisk Hereditary Cancer test as part of their clinical hereditary cancer risk assessment. The results demonstrated that the 86-SNP PRS significantly modified the breast cancer risk for women with pathogenic mutations in the five tested breast cancer genes (p-value <10-4). For some women, the PRS significantly increased the gene-based risk of breast cancer, while in others the gene-based risk was reduced (see Graph 1). Importantly, the greatest PRS risk-modification was observed in carriers of CHEK2, ATM and PALB2 mutations with some women reaching the risk levels associated with BRCA1 and BRCA2 mutations.

To viewGraph 1: PRS Significantly Modifies Lifetime Breast Cancer Risk in Mutation Carriers , please visit the following link:https://www.globenewswire.com/NewsRoom/AttachmentNg/d56c93ca-e00f-452d-b051-6325a578454c

These findings mean that we have the potential to significantly improve the precision of hereditary cancer risk assessment for women who test positive for mutations in the high and intermediate risk breast cancer genes, said Elisha Hughes, Ph.D., lead investigator and director of Bioinformatics at Myriad Genetics. We are optimistic that this additional genetic information can help clinicians more accurately predict the risk of breast cancer and provide the best care for their patients in the future.

Next StepsThe company plans to publish these new data in a peer reviewed medical journal and make the PRS available for U.S. women of European ancestry who test positive for mutations in breast cancer genes. The PRS currently is available as part of myRisk Hereditary Cancer enhanced with riskScore for women of European ancestry who test negative for pathogenic mutations in the breast cancer genes. Specifically, the riskScore test combines the PRS with the Tyrer-Cuzick model to estimate a womans 5-year and lifetime risk for developing breast cancer. The company is committed to making myRisk Hereditary Cancer enhanced with riskScore available to all ethnicities and is developing the test for women of Hispanic and African-American ancestry who test negative. The company is currently conducting the largest ever PRS study in African Americans and will present the data at a future meeting.

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Please visit Myriad at booth #113 to learn more about our portfolio of genetic tests for breast cancer. Follow Myriad on Twitter via @myriadgenetics and keep up to date with Symposium news by using the hashtag #SABCS19.

AboutriskScoreriskScore is a new clinically validated personalized medicine tool that enhances Myriads myRisk Hereditary Cancer test. riskScore helps to further predict a womens lifetime risk of developing breast cancer using clinical risk factors and genetic-markers throughout the genome. The test incorporates data from more than 80 single nucleotide polymorphisms identified through 20 years of genome wide association studies in breast cancer and was validated in our laboratory to predict breast cancer risk in women of European descent. This data is then combined with a best-in-class family and personal history algorithm, the Tyrer-Cuzick model, to provide every patient with individualized breast cancer risk.

About Myriad myRisk Hereditary CancerThe Myriad myRisk Hereditary Cancer test uses an extensive number of sophisticated technologies and proprietary algorithms to evaluate 35 clinically significant genes associated with eight hereditary cancer sites including: breast, colon, ovarian, endometrial, pancreatic, prostate and gastric cancers and melanoma.

About Myriad GeneticsMyriad Genetics Inc. is a leading precision medicine company dedicated to being a trusted advisor transforming patient lives worldwide with pioneering molecular diagnostics. Myriad discovers and commercializes molecular diagnostic tests that: determine the risk of developing disease, accurately diagnose disease, assess the risk of disease progression, and guide treatment decisions across six major medical specialties where molecular diagnostics can significantly improve patient care and lower healthcare costs. Myriad is focused on five critical success factors: building upon a solid hereditary cancer foundation, growing new product volume, expanding reimbursement coverage for new products, increasing RNA kit revenue internationally and improving profitability with Elevate 2020. For more information on how Myriad is making a difference, please visit the Company's website: http://www.myriad.com.

Myriad, the Myriad logo, BART, BRACAnalysis, Colaris, Colaris AP, myPath, myRisk, Myriad myRisk, myRisk Hereditary Cancer, myChoice, myPlan, BRACAnalysis CDx, Tumor BRACAnalysis CDx, myChoice CDx, EndoPredict, Vectra, GeneSight, riskScore, Prolaris, Foresight and Prequel are trademarks or registered trademarks of Myriad Genetics, Inc. or its wholly owned subsidiaries in the United States and foreign countries. MYGN-F, MYGN-G.

Safe Harbor StatementThis press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including statements related to the Companys polygenic risk score and data being featured at the 2019 San Antonio Breast Cancer Symposium being held Dec. 10-14, 2019 in San Antonio, Tx.; the potential to significantly improve the precision of hereditary cancer risk assessment for women who test positive for mutations in the high and intermediate risk breast cancer genes; this additional genetic information helping clinicians more accurately predict the risk of breast cancer and provide the best care for their patients in the future; publishing these new data in a peer reviewed medical journal and making the PRS available for U.S. women of European ancestry who test positive for mutations in breast cancer genes; making myRisk Hereditary Cancer enhanced with riskScore available to all ethnicities and developing the test for women of Hispanic and African-American ancestry who test negative; conducting the largest ever PRS study in African Americans and presenting the data at a future meeting; and the Company's strategic directives under the caption "About Myriad Genetics." These "forward-looking statements" are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by forward-looking statements. These risks and uncertainties include, but are not limited to: the risk that sales and profit margins of our molecular diagnostic tests and pharmaceutical and clinical services may decline; risks related to our ability to transition from our existing product portfolio to our new tests, including unexpected costs and delays; risks related to decisions or changes in governmental or private insurers reimbursement levels for our tests or our ability to obtain reimbursement for our new tests at comparable levels to our existing tests; risks related to increased competition and the development of new competing tests and services; the risk that we may be unable to develop or achieve commercial success for additional molecular diagnostic tests and pharmaceutical and clinical services in a timely manner, or at all; the risk that we may not successfully develop new markets for our molecular diagnostic tests and pharmaceutical and clinical services, including our ability to successfully generate revenue outside the United States; the risk that licenses to the technology underlying our molecular diagnostic tests and pharmaceutical and clinical services and any future tests and services are terminated or cannot be maintained on satisfactory terms; risks related to delays or other problems with operating our laboratory testing facilities and our healthcare clinic; risks related to public concern over genetic testing in general or our tests in particular; risks related to regulatory requirements or enforcement in the United States and foreign countries and changes in the structure of the healthcare system or healthcare payment systems; risks related to our ability to obtain new corporate collaborations or licenses and acquire new technologies or businesses on satisfactory terms, if at all; risks related to our ability to successfully integrate and derive benefits from any technologies or businesses that we license or acquire; risks related to our projections about our business, results of operations and financial condition; risks related to the potential market opportunity for our products and services; the risk that we or our licensors may be unable to protect or that third parties will infringe the proprietary technologies underlying our tests; the risk of patent-infringement claims or challenges to the validity of our patents or other intellectual property; risks related to changes in intellectual property laws covering our molecular diagnostic tests and pharmaceutical and clinical services and patents or enforcement in the United States and foreign countries, such as the Supreme Court decision in the lawsuit brought against us by the Association for Molecular Pathology et al; risks of new, changing and competitive technologies and regulations in the United States and internationally; the risk that we may be unable to comply with financial operating covenants under our credit or lending agreements; the risk that we will be unable to pay, when due, amounts due under our credit or lending agreements; and other factors discussed under the heading "Risk Factors" contained in Item 1A of our most recent Annual Report on Form 10-K for the fiscal year ended June 30, 2019, which has been filed with the Securities and Exchange Commission, as well as any updates to those risk factors filed from time to time in our Quarterly Reports on Form 10-Q or Current Reports on Form 8-K. All information in this press release is as of the date of the release, and Myriad undertakes no duty to update this information unless required by law.

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Myriads Polygenic Risk Score Personalizes Risk of Breast Cancer for Woman with a Genetic Mutation in Important Breast Cancer Genes - Yahoo Finance

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Here’s why many CRISPR/Cas9 experiments could be wrong and how to fix them – Massive Science

Sunday, December 15th, 2019

Every living cell on Earth has proteins. Typically thousands of them, that serve as molecular machines to digest food, sense the environment, or anything else a cell must do. However, many genes, and the proteins they code for, have unknown functions. In humans, the function of about 1 out of 5 of genes is unknown. To explore these dark corners of the genome, scientists can break up DNA to disable a gene, making their encoded proteins nonfunctional, and watch what happens to cells as a result, inferring the lost function from what goes wrong.

When CRISPR/Cas9 came online in 2012, it offered scientists a tool to do exactly this cut genes. The Cas9 enzyme searches through DNA, using a "guide RNA" to look for a specific sequence, and makes a cut when it finds a match. The gene, split in two, is repaired by the cell, but often with a large chunk missing. Many scientists assume that if a chunk of a gene is missing then the protein that it encodes will not function, or even be produced.

Researchers at the European Molecular Biology Laboratory in Heidelberg, Germany used CRISPR to make cuts in 136 different genes. In about a third of cases, proteins were still produced from these "damaged" genes and, furthermore, many of the proteins remained partially functional. This strange phenomenon, of damaged DNA producing functional protein, does more than punctuate lifes remarkable adaptability and resilience.

It means that dozens, or hundreds, of studies that used CRISPR/Cas9 to knock out genes, but failed to validate that the encoded protein was fully removed, could be incorrect or misleading.

While many labs that use CRISPR to knock out genes dovalidate that the encoded protein is no longer produced, other labs fail to check. Searching for one protein in a cell is time-consuming and technically challenging; testing for protein function takes even longer. There are some methodsavailableto look for specific proteins, but many CRISPR/Cas9 studies fail to run these experiments or scientific journals dont ask for the data.

While many labs that use CRISPR to knock out genes do validate that the encoded protein is no longer produced, other labs fail to check.

Nature Methods, the same journal that published the paper from the Heidelberg laboratory, recognized shortcomings in CRISPR validation early on. In 2017, they highlighted agenome-editing consortium, in collaboration with theUS National Institute of Standards and Technology, that aims to develop standardized procedures for CRISPR research, including publishing guidelines that include which guide RNAs were tested, how they were designed, and which controls were used in experiments.

The problem with major scientific developments, especially CRISPR/Cas9, is that experimental tools often explode in popularity before scientists and editors can implement standard procedures. When DNA sequencing was developed in the 1970s, for instance, there was little need for standards because it was so challenging to decipher the sequence of even a short piece of DNA. A decade later, however, GenBank, a DNA sequence repository, came online and journals began to mandate that researchers deposit their sequences. This requirement, together with reporting standards issued by journals likeNature, have ensured that a rapidly growing collection of DNA sequences can be vetted and independently analyzed by the scientific community. The same is true for methods like x-ray crystallography, with journalsrequiring that protein structures be independently validated and uploaded to publicly-accessible databases.

But while some scientists were shocked by the new study, others took a laissez-faire approach to the findings. On Twitter, many vented their rage at what they felt was a lack of careful controls by the scientific community. Raphael Ferreira, a postdoctoral fellow at Harvard Medical School, was inspired, perceiving this study as a game changer for the CRISPR community.

I was surprised by the results in a really positive way, as this paper rings the wake-up call for every scientist using CRISPR/Cas9, Ferreira said.

Despite the enthusiasm, however, Ferreira will not change how he performs his own experiments. The few times I have [used CRISPR/Cas9] in mammalian cells, I have always confirmed them with a Western blot, referring to an experimental method to detect specific proteins.

Victor de Lorenzo, a research professor at the National Center for Biotechnology in Madrid, agreed, claiming that, the only way to ensure that a protein is altogether removed is by making a Western blot.

Down the hall or across the street from my office, dozens of scientists use CRISPR/Cas9 to uncover protein functions. One of these researchers is Shashank Gandhi, a PhD student at the California Institute of Technology (CalTech) that has published CRISPR/Cas9 methods to delete genes in chicken embryos. Though he agrees with Ferreira and de Lorenzo, Gandhi asserts that validations could be taken a step further, and believes that journal editors should take action.

I think that journal editors should encourage authors to present supplemental data on how the knockouts were validated, insists Gandhi. I know that Nature requires that information as part of a "research summary" document that is submitted to the journal with each paper submission.

CRISPR/Cas9 validations could be taken a step further, and this is where journal editors can take action.

If Nature, which is widely considered the premier academic research journal, takes action to ensure that CRISPR knockouts are validated, then perhaps other publishers will take notice. In the meantime, Gandhi and others are not taking any chances.

I use several approaches to validate my CRISPR knockouts. For starters, I design and test multiple [guide RNAs] targeting the same gene for all my knockout experiments. Secondly, wherever applicable, I try to perform rescue experiments to establish loss of function phenotypes, says Gandhi, referring to an experiment in which a deleted gene is restored to test whether that proteins phenotype returns, confirming a link between a gene and the function that was lost when the gene was broken.

While all of the scientists that I spoke with agreed that researchers could do more to double check their experiments, it is unclear what actionable steps could be taken. Perhaps a combination of scientific, academic, and institutional changes could alleviate the potential for misleading studies. Faster experimental methods to detect proteins, standardized publishing procedures, and an academic database that describes which guide RNAs have been tested in each organism, would all serve to enhance the rigor of current studies.

Unfortunately, academic institutions and scientific publishers are hulking bureaucracies with slow-moving policy changes. Ensuring that CRISPR/Cas9 produces repeatable experiments rather than blemishes on the scientific record will require the collective action of scientists. It will demand self-governance.

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Here's why many CRISPR/Cas9 experiments could be wrong and how to fix them - Massive Science

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U. professors Conley and Tilghman recognized as AAAS Fellows – The Daily Princetonian

Sunday, December 15th, 2019

Professors Dalton Conley (left) and Shirley Tilghman (right), who were named AAAS fellows

Dalton Conley and Shirley Tilghman have been named 2019 fellows of the American Association for the Advancement of Science (AAAS) for their scholarship in the fields of sociology and molecular biology, respectively.

AAAS is a non-profit organization that seeks to promote scientific cooperation, integrity, education, and policy. Founded in 1848, it is now the worlds largest general scientific society with over 120,000 members. The association is also responsible for publishing the well-established journal Science.

AAAS Fellows, elected annually, are chosen based on their achievements in a variety of aspects of science. Sections include, but are not limited to, Chemistry, Agriculture, Food, and Renewable Resources, Anthropology, Education, History and Philosophy of Science, Linguistic and Language Sciences, and Biological Sciences. The position is honorific, inducting scholars into the community but not requiring active participation.

The fellowship is a lifetime honor. Last year, University professors Rebecca Burdine and Elke Weber were appointed to the position. 37 members of Princetons faculty currently hold AAAS fellowships.

Conley, the Henry Putnam University Professor of Sociology, is recognized by AAAS in the Section on Social, Economic, and Political Sciences. At the University, he is also a faculty affiliate at the Office of Population Research and the Center for Health and Wellbeing. He currently teaches a year-long class on how to conduct quantitative research studies to answer sociological questions, as well as a biosociology class. His research focuses on the intersection between genetics and social science.

What are the relative contributions of nature and nurture to who we become, and how do the biologically hardwired aspects of ourselves play out in the world and depend on the world? Conley stated as the broad questions that drive his research.

With degrees in both sociology and biology, Conley uses empirical studies which rely on naturally produced factors, or natural experiments, combined with new genomic tools to answer sociological questions. His recent work concerns genetic differences between siblings and their impact on social relationships within families.

Tilghman is the President of the University, Emeritus, and professor of molecular biology and public affairs. Her research focus is mammalian developmental biology and science policy. After serving as President from 20012013, she returned to the faculty and now advises juniors and seniors on independent work. The AAAS fellowship recognizes her distinguished contributions in molecular biology as well as her esteemed leadership of the University.

Probably the most exciting aspect of this is to be selected along with [Tilghman], who I and so many others at Princeton have so much admiration for for her research, teaching, and leadership, Conley said. That was the coolest part, to be grouped in with her.

Conley and Tilghman will be honored in Seattle on Feb. 15 during the AAAS annual meeting, and in the Nov. 28 issue of Science.

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U. professors Conley and Tilghman recognized as AAAS Fellows - The Daily Princetonian

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GCRC postdoc recognized nationally and globally – McGill Reporter

Sunday, December 15th, 2019

Elena Kuzmin

A postdoctoral fellow in the lab of Prof. Morag Park at the Goodman Cancer Research Centre (GCRC), Elena Kuzmins work has been garnering a fair amount of recognition recently. After having received a Banting Postdoctoral Fellowship from the Canadian Institutes of Health Research back in May, Kuzmin was selected to be a Fellow of the Global Future Council on Biotechnology, World Economic Forum.

Most recently, on November 25, she was honoured with the Women in Science Research Excellence Fellowship, LOral Canada with the support of the Canadian Commission for UNESCO.

It is an honour to be the recipient of these fellowships in recognition of my work, says Kuzmin. This funding enables me to build networks by supporting my attendance to national and international conferences, where I can present my research and discuss the findings with peers and leaders in the field. Most importantly, it has enabled me to receive an unmatched training opportunity at McGill, to make a significant contribution to our understanding of cancer biology and hopefully to establish a well-rounded research program of my own studying complex genetic interaction networks in yeast and human cells.

The LOral Canada fellowships are meant to enhance the role of women in devising scientific solutions to problems confronting humankind in the 21st century. The purpose of this program is to support major research projects undertaken by Canadian scientists at the post-doctoral level in Canada.

The Global Future Council on Biotechnology is the worlds foremost knowledge network dedicated to promoting innovative thinking on the future and aims to launch initiatives capable of accelerating new medical biotechnological discoveries, diagnostics and therapeutics. The council consists of 20-25 members, including industry leaders, government officials and academic researchers, such as postdoctoral fellowsand faculty members from around the world.

Elena is at the forefront of applying complex genetic approaches to understand breast cancer interaction and progression, notes Park, who is also the Director of the GCRC. She is a role model for young women in science.

Kuzmin completed her Honours BSc with High Distinction in Human Biology and Zoology and her MSc in the Department of Laboratory Medicine and Pathobiology at the SickKids Research Institute, University of Toronto. She then went on to do her PhD in the Department of Molecular Genetics at the University of Toronto with Profs. Charles Boone and Brenda Andrews, where she studied complex genetic interaction networks in the budding yeast.

In her current work, Kuzmin is applying the principles of complex genetic interactions to address a current challenge in human disease the onset and progression of triple negative breast cancer. This subset of breast cancer has no targeted therapies, since it lacks 3 common biomarkers such as estrogen and progesterone receptors and Her2, and has the worst survival rates. The aim of her project is to use single-cell genomic and transcriptomic sequencing technologies combined with genetic screens to gain insight into the evolution of large copy number variants, which are characteristic of this cancer type. Ultimately, this research is expected to reveal genetic events that modulate triple negative breast cancer, enhancing our understanding of the disease and offering possible avenues for personalized interventions to affected individuals.

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GCRC postdoc recognized nationally and globally - McGill Reporter

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UCLA’s university housing projects are unlikely to reduce rent rates in Westwood – Daily Bruin

Sunday, December 15th, 2019

Several university housing projects set to be completed in the next few years are unlikely to lower rent costs in Westwood, experts say.

Westwood Village has been rated the most expensive place to rent in California. The high cost of rent can be burdensome for students, especially those who must live off campus. At the same time, a growing percentage of students on the Hill are expected to live in triple-occupancy dorms.

UCLA Housing previously announced its goal to guarantee four years of university housing for first-year students and two years for transfer students as part of its 2016-2026 master plan, which states its primary goals for housing development over the next 10 years.

To reach this target, UCLA Housing has begun construction on three new projects expected to create over 5,000 beds for undergraduate and graduate students. However, experts said these projects will do little to reduce rent costs for private housing in Westwood.

The first of these housing projects is the Lot 15 Residence Hall, which will include two eight-level mid-rise structures that will provide on-campus housing for first- and second-year undergraduates, according to the UCLA Housing website.

The second housing project is the Southwest Campus Apartments, three 8-to-10 story buildings that will provide 321 graduate beds and 1,958 upper-division undergraduate beds. The last of these housing projects is the 10995 Le Conte Avenue Apartments, which will provide 1,167 beds for upper-division undergraduate students.

UCLA Housing & Hospitality Services said in a statement that the rates for its housing units are not determined by the private rental market. University housing rates are determined to ensure that UCLA Housing & Hospitality remains self-financing, meaning they aim to secure funding to maintain current buildings while also gathering enough funds for future projects.

The current rates for UCLA Housing units range from $7,715.52 per academic year for a hall-style dorm to $16,872 per academic year for a university apartment. These rates do not include meal plans or social fees.

Dana Cuff, an architecture, urban design and urban planning professor at UCLA, said she does not believe that the new housing projects will have any effect on rent in Westwood. Cuff, who is also the director of cityLAB UCLA, said this is because the demand for housing in Westwood is disproportionately higher than the supply, which creates pent-up demand. However, she added that these projects could slow down the increase in rent.

Theres such a housing crisis and such pent-up demand, particularly among students to live near campus, that as soon as these new apartments come, they will be snapped up. It is not likely to pressure rents downwards, she said. If I were to predict, Id say rent might not continue to go up at the same rate, it would slow down rent increases that would be a good result.

Michael Lens, an urban planning and public policy associate professor at UCLA, said the effect of these new housing projects will be minimal.

I think that the impact will be very, very small, and close to nothing on the private market, he said. You are trying to play catch to very slow construction activity over recent years and decades even in this part of town. It is not a very big change in supply, he added.

North Westwood Neighborhood Council President Michael Skiles said UCLA remains an attractive option for students because UCLA typically charges around 30% below the market rate for housing. He added that these new buildings could slow down the increase in rent prices, but said he was unsure if rent would decrease in Westwood.

They are either going to result in lower rent or at least slow the rate at which rents in Westwood increase, Skiles said. What remains to be seen is whether it will slow (the price) so much just to actually reverse (increasing rent) and bring costs down a bit, or if it will instead just stop it from increasing.

Skiles said this uncertainty is due to the fact that UCLA does not guarantee housing for fourth-year undergraduate students and has historically offered limited housing for graduate students.

When the students get kicked out of housing, they have to compete for very few spots in Westwood all of them competing for scarce housing drives up the cost, he said.

The record-high rent in Westwood has prompted growing concerns among some UCLA students.

Chew Tin Zar Aung, a third-year microbiology, immunology and molecular genetics student, shared her concerns about the financial burden that high rent places on UCLA students.

While Westwood is a high-income neighborhood, it is still mainly populated by college students, and if we fail to protect (against) the rise in prices, this could be troublesome for students, she said. From my experience, it seems as if the rent in Westwood is getting worse every year.

Arvind Swaminathan, a third-year materials engineering student, said the high rent can still be significant burden for students with enough financial aid to cover tuition.

I think many students are in agreement that rent is important to them, Swaminathan said. While a lot of students already receive financial aid from the school for things like tuition, some still have trouble finding ways to pay for things like housing.

Piyapan Chaiprasit, a third-year business economics student, said she did not feel satisfied with the lack of affordable housing options in Westwood.

I think the situation is getting worse in Westwood because landlords keep trying to increase rent prices every year. Housing management companies will try to take advantage of the high demand and keep raising their prices, knowing that students will have no choice but to pay for these prices this is very burdensome on the students who have to bear these financial costs, Chaiprasit said.

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UCLA's university housing projects are unlikely to reduce rent rates in Westwood - Daily Bruin

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New Device Permits a Closer Look at Previously Inaccessible Areas of the Genome – Technology Networks

Sunday, December 1st, 2019

Expansions of DNA repeats are very hard to analyze. A method developed by researchers at the Max Planck Institute for Molecular Genetics in Berlin allows for a detailed look at these previously inaccessible regions of the genome. It combines nanopore sequencing, stem cell, and CRISPR-Cas technologies. The method could improve the diagnosis of various congenital diseases and cancers in the future.

Large parts of the genome consist of monotonous regions where short sections of the genome repeat hundreds or thousands of times. But expansions of these "DNA repeats" in the wrong places can have dramatic consequences, like in patients with Fragile X syndrome, one of the most commonly identifiable hereditary causes of cognitive disability in humans. However, these repetitive regions are still regarded as an unknown territory that cannot be examined appropriately, even with modern methods.

A research team led by Franz-Josef Mller at the Max Planck Institute for Molecular Genetics in Berlin and the University Hospital of Schleswig-Holstein in Kiel recently shed light on this inaccessible region of the genome. Mller's team was the first to successfully determine the length of genomic tandem repeats in patient-derived stem cell cultures. The researchers additionally obtained data on the epigenetic state of the repeats by scanning individual DNA molecules. The method, which is based on nanopore sequencing and CRISPR-Cas technologies, opens the door for research into repetitive genomic regions, and the rapid and accurate diagnosis of a range of diseases.A gene defect on the X chromosomeIn Fragile X syndrome, a repeat sequence has expanded in a gene called FMR1 on the X chromosome. "The cell recognizes the repetitive region and switches it off by attaching methyl groups to the DNA," says Mller. These small chemical changes have an epigenetic effect because they leave the underlying genetic information intact. "Unfortunately, the epigenetic marks spread over to the entire gene, which is then completely shut down," explains Mller. The gene is known to be essential for normal brain development. He states: "Without the FMR1 gene, we see severe delays in development leading to varying degrees of intellectual disability or autism."

Female individuals are, in most cases, less affected by the disease, since the repeat region is usually located on only one of the two X chromosomes. Since the unchanged second copy of the gene is not epigenetically altered, it is able to compensate for the genetic defect. In contrast, males have only one X chromosome and one copy of the affected gene and display the full range of clinical symptoms. The syndrome is one of about 30 diseases that are caused by expanding short tandem repeats.

First precise mapping of short tandem repeats

In this study, Mller and his team investigated the genome of stem cells that were derived from patient tissue. They were able to determine the length of the repeat regions and their epigenetic signature, a feat that had not been possible with conventional sequencing methods. The researchers also discovered that the length of the repetitive region could vary to a large degree, even among the cells of a single patient.

The researchers also tested their process with cells derived from patients that contained an expanded repeat in one of the two copies of the C9orf72 gene. This mutation leads to one of the most common monogenic causes of frontotemporal dementia and amyotrophic lateral sclerosis. "We were the first to map the entire epigenetics of extended and unchanged repeat regions in a single experiment," says Mller. Furthermore, the region of interest on the DNA molecule remained physically wholly unaltered. "We developed a unique method for the analysis of single molecules and for the darkest regions of our genome - that's what makes this so exciting for me."

Tiny pores scan single molecules

"Conventional methods are limited when it comes to highly repetitive DNA sequences. Not to mention the inability to simultaneously detect the epigenetic properties of repeats," says Bjrn Brndl, one of the first authors of the publication. That's why the scientists used Nanopore sequencing technology, which is capable of analyzing these regions. The DNA is fragmented, and each strand is threaded through one of a hundred tiny holes ("nanopores") on a silicon chip. At the same time, electrically charged particles flow through the pores and generate a current. When a DNA molecule moves through one of these pores, the current varies depending on the chemical properties of the DNA. These fluctuations of the electrical signal are enough for the computer to reconstruct the genetic sequence and the epigenetic chemical labels. This process takes place at each pore and, thus, each strand of DNA.

Genome editing tools and bioinformatics illuminate "dark matter"Conventional sequencing methods analyze the entire genome of a patient. Now, the scientists designed a process to look at specific regions selectively. Brndl used the CRISPR-Cas system to cut DNA segments from the genome that contained the repeat region. These segments went through a few intermediate processing steps and were then funneled into the pores on the sequencing chip.

"If we had not pre-sorted the molecules in this way, their signal would have been drowned in the noise of the rest of the genome," says bioinformatician Pay Giesselmann. He had to develop an algorithm specifically for the interpretation of the electrical signals generated by the repeats: "Most algorithms fail because they do not expect the regular patterns of repetitive sequences." While Giesselmann's program "STRique" does not determine the genetic sequence itself, it counts the number of sequence repetitions with high precision. The program is freely available on the internet.

Numerous potential applications in research and the clinic"With the CRISPR-Cas system and our algorithms, we can scrutinize any section of the genome - especially those regions that are particularly difficult to examine using conventional methods," says Mller, who is heading the project. "We created the tools that enable every researcher to explore the dark matter of the genome," says Mller. He sees great potential for basic research. "There is evidence that the repeats grow during the development of the nervous system, and we would like to take a closer look at this."

The physician also envisions numerous applications in clinical diagnostics. After all, repetitive regions are involved in the development of cancer, and the new method is relatively inexpensive and fast. Mller is determined to take the procedure to the next level: "We are very close to clinical application."

Reference: Giesselmann et al. 2019.Analysis of short tandem repeat expansions and their methylation state with nanopore sequencing. Nature Biotechnology.DOI: https://doi.org/10.1038/s41587-019-0293-x.

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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The nature of salmonella is changing and it’s meaner – MSUToday

Sunday, December 1st, 2019

Salmonella is acting up in Michigan, and it could be a model for whats happening in other states, according to a new Michigan State University study.

The study, appearing in Frontiers in Medicine, documents a substantial uptick in antibiotic resistant strains, and consequently, longer hospital stays as doctors work to treat the increasing virulent pathogens.

If you get a salmonella infection that is resistant to antibiotics today, you are more likely to be hospitalized longer, and it will take you longer to recover, said Shannon Manning, MSU Foundation professor in theDepartment of Microbiology and Molecular Genetics and senior author of the study. We need better detection methods at the clinical level to identify resistant pathogens earlier so we can treat them with the right drugs the first time.

Losing a day or more to misdiagnosis or improper treatment allows symptoms to get worse. Doctors might kill off a subpopulation of bacteria that are susceptible, but the ones that are resistant grow stronger, she added.

Salmonella is a diverse group of bacterial pathogens that causes foodborne infections. Infected patients often develop diarrhea, nausea, vomiting and abdominal pain, though some infections are more severe and can be life threatening.

When it comes to treatments, each strain reacts differently to the range of antibiotics available for prescription by doctors. So getting it right the first time is crucial.

Specifically in Michigan, doctors are seeing more strains that are resistant to ampicillin, a common antibiotic prescribed to treat salmonella. Multidrug resistance, or resistance to more than three classes of antibiotics, has also increased in Michigan and could further complicate patient treatment plans.

Were still uncertain as to why this is happening; it could be that these antibiotics have been overprescribed in human and veterinary medicine and that possessing genes for resistance has allowed these bacteria to grow and thrive in the presence of antibiotics, Manning said. Each state has its own antibiotic-resistance issues. Its important that the medical profession remains vigilant to ever-changing patterns of resistance in salmonella and other foodborne pathogens, rather than look for a blanket national solution.

Historically, salmonella has affected young children and the elderly, but now theres been a rise in adult cases, suggesting that the epidemiology of the infections has changed in Michigan.

Diving into individual strains of salmonella, the team of scientists found that patients with Typhimurium were more likely to have resistant infections as were patients infected during the fall, winter or spring months.

Another distinction was revealed between the strains affecting people living in rural and urban areas. Enteritis infections tend to be higher in rural areas. This may be attributed to rural residents exposure to farm animals or untreated sources of water.

Each states salmonella population has its own personality; so every states approach to identifying disease drivers and effective treatments should be modified to reflect these traits.

Our results show the importance of surveillance, monitoring resistance frequencies and identifying risk factors specific to each state and region, Manning said. The trends that are revealed can lead to new prevention strategies.

Additional MSU researchers contributing to the study include Sanjana Mukherjee, the lead author, Chase Anderson and Rebekah Mosci. Scientists from Wayne State, Sparrow Hospitals and the Michigan Department of Health and Human Services also contributed to this research.

(Note for media: Please include a link to the original paper in online coverage: https://www.frontiersin.org/articles/10.3389/fmed.2019.00250/full)

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52 UC San Diego Researchers Are Most Highly Cited in Their Fields – UC San Diego Health

Sunday, December 1st, 2019

Fifty-two faculty members and researchers at the University of California San Diego are among the worlds most influential in their fields. The Web of Science Group, an information and technology provider for the global scientific research community, compiled its2019 Highly Cited Researcherslist of more than 6,000 scientists from around the world whose studies were among the top 1% of most-cited publications in their field over the past 11 years.

The number of highly cited researchers from UC San Diego increased by 13% over last years number of forty-six. The listing covers 21 fields of study as well as a cross-field category for researchers who are widely cited across multiple fields. UC San Diego had researchers listed in 14 fields, with the most cited in cross-field (23), followed by molecular biology and genetics (5), clinical medicine (4) and social sciences (4).

UC San Diego has some of the most dedicated, brilliant and hard-working faculty and researchers in the world. Their inclusion on the list of highly cited researchers is a measure of their impact in their respective fields of study as they continue to advance the frontiers of knowledge, said Chancellor Pradeep K. Khosla.

Of particular note is Director for the Center of Microbiome Innovation Rob Knights inclusion in three separate areas of study (biology and biochemistry, environment and ecology, microbiology). Out of 6,216 highly cited researchers, only 11 were cited in three fields, making Knight part of a super elite 0.3% of those listed.

There were also 23 Nobel laureates on the list, one of whom, Roger Tsien, was a distinguished professor of both Pharmacology in the School of Medicine and of Chemistry and Biochemistry at UC San Diego until his death in 2016. He shared the Nobel Prize in Chemistry with two others in 2008 for discovering and developing green fluorescent protein.

David Pendlebury, Senior Citation Analyst at the Web of Science Groups Institute for Scientific Information said that the highly cited researchers create gains for society, innovation and knowledge that make the world healthier, richer, more sustainable and more secure.

It is especially encouraging to see not only the number of highly cited researchers at the university, but the broad range of fields in which they are cited. It really speaks to the fact that UC San Diego conducts groundbreaking research across a wide range of disciplines, said Vice Chancellor for Research Sandra A. Brown. I congratulate everyone on their excellent research and contributions.

The 52 UC San Diego faculty members named by Web of Science and the fields of study in which they were cited are:

Gregory Aarons,social sciences

Ludmil Alexandrov, molecular biology and genetics

David Brenner,cross-field

Kristin Cadenhead,psychiatry/psychology

Kelli Cain, social sciences

Shu Chien, cross-field

Don Cleveland,neuroscience and behavior

Seth Cohen,chemistry

Pieter Dorrestein,cross-field

Mark Ellisman, cross-field

Mark Estelle,plant and animal science

Michael Folger, cross-field

Anthony Gamst, cross-field

Christopher Glass,molecular biology and genetics

Uri Gneezy,economics and business

Antonio Gonzalez, microbiology

Kun-Liang Guan,molecular biology and genetics

Trey Ideker,cross-field

Michael Karin,molecular biology and genetics

Arthur Kavanaugh,clinical medicine

Dusan Keres, space science

Rob Knight,(listed in 3 fields) biology and biochemistry, environment and ecology, microbiology

Razelle Kurzrock, clinical medicine

Lisa Levin, cross-field

Irene Litvan, neuroscience and behavior

Rohit Loomba, clinical medicine

Prashant Mali, biology and biochemistry

Eliezer Masliah, cross-field

Victor Nizet, cross-field

Jerrold Olefsky,cross-field

Bernhard Palsson,biology and biochemistry

Veerabhadran Ramanathan,cross-field

Bing Ren,molecular biology and genetics

Jeremy Rich, cross-field

Douglas Richman,cross-field

Michael Sailor,cross-field

James Sallis,social sciences

William Sandborn,clinical medicine

Bernd Schnabl, cross-field

Julian Schroeder,plant and animal science

Terrence Sejnowski, cross-field

Claude Sirlin, cross-field

Murray Stein,psychiatry/psychology

Steffanie Strathdee, cross-field

Roger Tsien, cross-field

Ming Tsuang,psychiatry/psychology

Joseph Wang,chemistry

Shang-Ping Xie,geosciences

Gene Yeo, cross-field

Kun Zhang, cross-field

Liangfang Zhang,cross-field

Yunde Zhao, plant and animal science

Shu-Hong Zhu, social sciences

You can read about Web of Sciences methodology on their website.

UC San Diegos Studio Ten 300 offers radio and television connections for media interviews with our faculty. For more information, email .(JavaScript must be enabled to view this email address).

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Experts Barry Byrne, Jerry Mendell Lead NORD Webinar on Gene Therapy – Muscular Dystrophy News

Sunday, December 1st, 2019

A glance around the walls of Barry J. Byrnes office reveals a lot about the pediatric cardiologist who runs thePowell Gene Therapy Center at University of Florida (UF).

In one corner is an unusual painting by 9-year-old Will Barkowsky of Jacksonville, Fla. Will, the first boy with Duchenne muscular dystrophy to takeSarepta Therapeutics exon-skipping medication Exondys 51 (eteplirsen), put together his oil-on-canvas masterpiece using the tire tracks of his wheelchair, making sure the colors didnt mix.

Nearby is a movie poster for The Ataxian an award-winning 2015 documentary by Kevin Schlanser and Zack Bennett about 17-year-old Kyle Bryant, who despite having Friedreichs ataxia embarks on a cross-country bicycle trip with three buddies.

Another movie poster advertises Extraordinary Measures, the 2010 tearjerker starring Brendan Fraser as John Crowley the father of two kids with Pompe disease and later, the founder of Amicus Therapeutics and Harrison Ford as fictional researcher Robert Stonehill, who discovers a treatment for the genetic disorder that eventually saves the lives of Crowleys children.

Theres also a model of a Blalock-Taussig shunt frequently used in congenital heart surgery, as well as one of an adeno-associated virus (AAV) vector, along with a prominent photo of Byrne with Ron Bartek, co-founder and director of the Friedreichs Ataxia Research Alliance (FARA).

Friedreichs ataxia is where were putting most of our efforts now, said Byrne, who spoke to BioNews Services publisher of this website at length during a recent visit to his lab in Gainesville, Fla.

Byrne, along with Jerry Mendell, MD, a neurologist with Nationwide Childrens Hospital in Columbus, Ohio, hosted a Nov. 20 webinar on gene therapy organized by the National Organization for Rare Disorders (NORD) and the American Society for Gene & Cell Therapy.

The two experts were introduced by Katie Kowalski, senior program manager for NORDs Educational Initiatives. The webinar, Understanding the Gene Therapy Process and Aftercare, was the fourth in a five-part series underwritten by Amicus and Sarepta, as well as two other companies, Avrobio and Bluebird Bio.

The final webinar in the series, Life After Gene Therapy, is scheduled for Dec. 18.

Mendell, who heads Nationwides Center for Gene Therapy, specializes in gene therapy research for Duchenne as well as limb-girdle muscular dystrophy, spinal muscular atrophy (SMA) and X-linked myotubular myopathy. He was a principal investigator for the Novartis therapy Zolgensma, which uses an AAV vector to carry a working version of SMN1, the mutated gene in people with SMA.

Zolgensma won approval from the U.S. Food and Drug Administration (FDA) in May 2019 as the first gene therapy to treat SMA in infants up to 2 years of age.

At $2.125 million per patient, the hour-long Zolgensma infusion is the most expensive medicine in history. The cost easily eclipses that of the only other FDA-approved treatment for SMA, BiogensSpinraza(nusinersen), which retails for $750,000 the first year and $375,000 every year after.

Many of my colleagues have been trying to make inroads for years, Mendell said. When we first got into the gene therapy domain, we were limited by technology. We could not make enough virus for the kind of impact were having now. But technology has improved, and we can now deliver genes through circulation to reach all muscles.

Regardless of the disease, he said, its extremely important to confirm the patients specific mutation before anything else.

This is critical, because you dont want to deliver the wrong kind of gene in a disease like Friedreichs ataxia. That goes for all gene therapy trials, he said. Next, we want to check for pre-existing antibodies, whether theyre acquired from the environment or from close contact. They bind to the AAV and block entry to the target organ.

Checking for those antibodies requires a blood test. It generally takes 4-7 days to return lab results a nailbiting time for patients and families, Mendell said, because theyre waiting to be approved for enrollment in the trial.

Byrne estimated that 50-60% of all individuals may have been exposed to AAV.

Prior exposure at any level to any AAV infection is an exclusion in most studies, he said, noting that people who travel frequently or who have respiratory or gastrointestinal conditions are particularly susceptible. We are learning a lot about what thresholds are effective. Its about 10% of newborns and about 50% of those of school age and adulthood.

Patients must also be in general good health except, of course, for the genetic disease being treated. MRI and blood tests are done to rule out diabetes or any evidence of heart, liver, or kidney problems.

We put the patient to sleep so theres really no pain involved, Mendell said. We also use local numbing medicine, even though the patient is asleep, so theres no pain or discomfort.

The Powell Gene Therapy Center was established in 1996 the year before Byrne joined UF by Nicholas Muzyczka, PhD, who performed groundbreaking work on AAVs in the 1980s. The center has a dozen individual labs working in neuroscience and molecular genetics.

Byrne said that because gene therapy fundamentally changes many of the bodys cells, screening is crucial.

This is often a one-way street, in that since the effects are long-lasting, other experimental studies may not accept patients who have received gene therapy of any kind in the past, Byrne said. One must have the clinical features required of the study and meet certain functional and age criteria.

To prepare for screening, patients or their parents must read the informed consent and understand what the risks and benefits are. Genetic counseling also may be required to determine whether a given mutation is amenable to gene therapy.

Baseline evaluations are done when its a muscular skeletal disease timed function tests as well as lab tests and a study schedule is established, he said. In many of our studies, we see the patients very frequently, almost every day for the first two weeks. They stay in the area for up to a month. Because were often dealing with rare populations, that makes it convenient for us to evaluate these patients.

Byrne noted that gene therapy is not necessarily durable for the lifespan of the patient. Because the delivered gene does not integrate into the cells own DNA, it is not passed down to newly formed cells.

Some cells, particularly in the liver and muscle, continue to grow throughout childhood and AAV doesnt integrate, so its progressively less effective unless the cells being targeted, as in SMA, are not dividing, he said. Thats an example where newborn screening is critically important to better outcomes.

Mendell said he generally starts patients on prednisone one day before receiving gene therapy in order to suppress liver inflammation, and keeps them on it for 60 days after.

When were in the room, the first thing that happens is the gene is delivered. You push a button and get started, he said. Obviously it must be the correct gene. Its in there, but you cant see it.

The actual gene is delivered by intravenous (IV) infusion with a pump over a 90-minute period, Mendell said; anything faster than that could potentially cause harmful side effects.

We put IVs in both arms for continuous delivery in case one side gets clogged up. We dont want anything to stop gene delivery, he said. Meanwhile, the patient is constantly monitored for vital signs. We invite the whole family to stay together, and thats reassuring. Theres anxiety about gene therapy, but the potential benefits generally outweigh any risks involved.

Some patients may develop nausea and vomiting in the first one-to-three weeks following treatment. For this reason, blood is taken every two weeks for three months to check for side effects.

Mendell said he knows patients are responding to gene therapy by doing testing. In the case of Duchenne, he uses the North Star Ambulatory Assessment, which includes 17 timed tests such as climbing stairs, rising from a sitting position, and walking or running 100 meters. In addition, neck control is a very good indicator of efficacy among Duchenne boys, he said.

The FDA anticipates that within the next 10 years, it will approve up to 40 gene therapies for rare conditions. Mendell said the benefits of gene therapy for one condition in particular, SMA, are undeniable.

This is an absolutely devastating disease. In type 1 SMA, patients usually dont survive past age 2, and about 50% are gone by age 1, he said. Initially there was concern about giving this to infants, but we told the FDA we needed to test infants in order to save lives.

Continuing results from Mendells pivotal Phase 1 trial (NCT02122952) in 15 type 1 infants and along-term extension study (NCT03421977) have changed the way people view gene therapys potential in general.

After four years, he said, every patient in our trial went from being unable to sit to being able to, and several are able to walk. One patient was treated 28 days after birth, and now four years later, hes off to school. What Barry and I do is very gratifying, and we thank our patients and their families for this opportunity.

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Emerging science gives Norcod a path to further expansion – The Fish Site

Sunday, December 1st, 2019

While robust market fundamentals point to a bright future for responsible aquaculture generally, in Norway massively improved biological material is paving the way for a rebound in cod farming in particular.

There has been very limited activity in cod production globally in recent years but that is about to change as pioneering aquaculture venture Norcod's plans to establish cod farming on an industrial scale gather momentum. Led by personnel with deep industry experience, Norcod is convinced that cod has the potential to be a significant contributor to the Norwegian economy. Quality biomass is the critical input factor.

Stemfish with poor biology and first-generation fry of inconsistent quality were partly to blame for the biomass loss seen during the last foray into cod farming between 2004 and 2012. Since then quantum leaps in biology have radically changed the landscape, with an estimated half-a-billion Norwegian kroner invested in two cod breeding programs that have been working quietly in the background in the belief that the tide would again turn.

Aquaculture-focused national research institute Nofima's breeding programme kicked off in 2002 with the goal to evolve economically important characteristics and disease resistance. Commercial hatchery player Havlandet Marin Yngel AS followed suit a year later. Their far-sighted commitment has seen the biological challenges of stagnant growth, susceptibility to infection and high escape figures systematically overcome.

Dramatically increased survival rate and quality of fry has been achieved through careful selection of eggs post fertilisation. The development of stemfish feed with minimal contamination has also boosted egg quality. Detailed comparative studies also showed that using eggs from four-year-old fish produce the best outcomes, according to Nofima.

Fish have been selected and developed for faster growth, higher harvest yield and higher resistance, while new feeds have been developed that support optimal growth and intestinal health. Farmed cod now grows up to 35 percent to 40 percent faster than fish in the wild.

Faster growth has always been the highest priority and has been the focus of the cod breeding programme. Breeding has led to a growth increase of 9 percent to 10 percent per generation, or around 3 percent per year about the same as for farmed salmon, says Atle Mortensen, senior scientist at Nofima.

Data from the stemfish produced for Norcod shows a dramatic 40 percent increase in survival rate for fish below 5 grams, up from 10 percent a decade ago. Successfully selecting for smaller heads has also been a game changer in boosting yield. In wild cod the much larger head can account for 40 percent of body weight.

Today's sixth generation of stem fish is a highly stable product and a completely different fish to 15 years ago, says Norcod managing director Rune Eriksen. Havlandet is now at capacity to deliver around three million fry, at 2-3 grams each, per annum. A kick-off batch of 260,000 fry from Nofima is already in production for Norcod and slated to go into the sea at the company's two facilities northwest of Trondheim imminently.

While growth was the holy grail, selecting specifically for other characteristics typically reduced the growth rate. Targeted breeding for disease resistance was unavoidable until the arrival of new and effective vaccines on the market. With these now available, the bacterial infections vibrosis and atypical furunculosis no longer pose a threat to farmed cod.

As per today there are no virus diseases that create problems for farmed cod. Both cod lice and sea lice affect cod but do not harm the fish like salmon lice do. Intestinal obstruction has very occasionally caused mortality in the sea phase. Compared to farmed salmon the health status of farmed cod is extremely good, says Mortensen.

The fish now show significant domestication, especially calm behaviour in the sea phase, swimming as a school in rings around the net much like salmon. That is astonishing given that selection was not made based on behaviour characteristics, says Mortensen. Not surprisingly, healthy, happy fish adapted to confinement grow faster. The high level of escape in the past was caused by the cod chewing holes in the nets. Today's tame fish display little desire to escape, while new standards and net technologies have also mitigated this tendency. Norcod's facilities are state of the art, optimising technical developments in equipment and feeding systems achieved in salmon farming in recent years.

Cannibalism is a peculiar trait of cod under stress but this problem has been virtually eradicated in the sixth generation of tame fish by means of improved feed and better feed distribution, allowing even growth across the population. Better growth, improved feed and optimal utilisation of feed also make it much easier to satisfy year-round demand.

Breeding has traditionally featured a combination of individual and family-based selection, with family selection ensuring diversity in the broodstock. The advent of molecular genetics, where information from the entire genome can be used for much greater precision in selecting for positive characteristics, promises even faster progress in the future.

Norcod stands to reap the rewards of these biological breakthroughs as a first mover. The quality of its cod is unmatched and unique globally. Initiating such a breeding project from scratch that could guarantee such strong characteristics would require a huge investment of time and money. But consumers want cod right now. Wild stocks are under pressure with limitations in capture quotas squeezing supply. Demand can only be met with cost-effective farming. Norcod's timing is on target to satisfy a market hungry for stable deliveries of fresh cod 12 months of the year.

Ensuring the welfare of the cod themselves throughout the production cycle also remains top priority. We should always remember that these are living creatures that should be handled with care and respect. No question, Eriksen says.

The production process from fry to plate takes between 23 to 26 months. Norcod has its sights set on sales of 9,000 tonnes of cod in 2021, rising to a total of 10 facilities with an output of 25,000 tonnes in 2025. We believe we have a very solid business case, says Eriksen. The market is waiting.

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A better way to convert dog years to human years – EarthSky

Sunday, December 1st, 2019

On the left, a young dog (Jack), and on the right, an old dog (Snoop). Photo by Deborah Byrd.

What does it mean for us humans to age, and what does it mean for your dog to age? Turns out these two processes can be compared, some scientists are now saying, and we dont mean in the sense of the old adage that one dog year equals seven human years. That old saying has been recognized for some time as being, quite clearly, imprecise. If it were true, then like dogs humans should be able to reproduce at age 7. Many of us should live to be 150. Now, however, the tools of science have been applied to the question of true length of dog years. Biologist Tina Wang led new research at Ideker Lab at the UC San Diego School of Medicine. The work has resulted in a better formula for calculating your dogs age in human years. It stems from data on the effects of aging on dogs DNA. It takes breed size into account. The new formula suggests that a 1-year-old dog is closer to age 30 than age 7.

We humans and our dogs (and all other living things) have DNA within our cells, coded with the genetic information, inherited from generations of those who came before us. But aging isnt just about genetics. Its also about a healthy or unhealthy lifestyle, for example, and about whether you contract a disease. Scientists who study aging are now speaking of the effects of these environmental factors in terms of chemical markers on our DNA. These markers specifically methyl groups tag our DNA. According to a emerging theory of aging, its the changing pattern of these tags throughout our lives that determines whether you look and seem young for your age or instead age prematurely. This process the chemical modification of a persons DNA over a lifetime creates what aging researchers call an epigenetic clock

The researchers looked at DNA samples from 104 Labrador retrievers spanning a 16-year age range. They compared changes in their DNA samples against DNA previously collected from 320 humans between the ages of 1 and 103. They specifically looked for similarities in the methylation process between the two sets. Writing in the Washington Post on November 28, 2019, Christopher Ingraham explained that the researchers:

found that the DNA profiles evolved in similar ways across the life span of both [dogs and humans].

UCSDs Trey Ideker, leader of the lab that ran the study, told The Post:

If you look at the methylomes of 2-year-old Labs and you ask what are the closest human methylomes? The answer is that the best matches are in humans about 40 years old. That is just what the data show, no more, no less.

An example of the new dog aging chart using, for the sake of comparison, movie star Tom Hanks is below.

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EarthSky 2020 lunar calendars are available! They make great gifts. Order now. Going fast!

Wang, Ideker and colleagues illustrated their findings using 2 beloved icons: a Labrador and Tom Hanks. Heres the Washington Posts explanation of this chart: According to the DNA analysis, a 1-year-old Lab is equivalent to a Big-era Hanks, while a 4-year-old mirrors the actors star turn in The Da Vinci Code. By age 9, a Lab has obtained the approximate gravitas of Hanks starring as Ben Bradlee in The Post. Chart via Wang et al. and the Washington Post.

Want the actual formula for adjusting dogs ages to human years? You have to multiply the natural logarithm of the dogs age by 16 and add 31. Thus the formula is:

(human_age = 16ln(dog_age) + 31)

That looks like a complicated formula for most of us. Its the natural logarithm of the dogs real age, multiplied by 16, with 31 added to the total. This natural logarithm calculator might help.

Plus, youll find an easy-to-use dog age calculator in this article by Virginia Morell in Science on November 15, 2019.

Why study dog aging at all? As Morell points out in her article, its not just dogs and humans that undergo DNA methylation as they age. Mice, chimps and wolves have also been shown to have epigenetic clocks. Using dogs to study aging makes sense because dogs live in our homes, and many like their human owners receive once-a-year medical checkups and sometimes hospital treatments. Thus studying aging in dogs is another way of understanding how humans age.

Morell also spoke to Matt Kaeberlein, a biogerontologist at the University of Washington in Seattle, who was not involved with this research but whose lab is conducting a Dog Aging Project (open to all breeds) that includes epigenetic profiles of its canine subjects. He hopes to find out why some dogs develop disease at younger ages or die earlier than normal, whereas others live long, disease-free lives. Kaeberlein told Morell:

We already knew that dogs get the same diseases and functional declines of aging that humans do, and this work provides evidence that similar molecular changes are also occurring during aging.

Its a beautiful demonstration of the conserved features of the epigenetic age clocks shared by dogs and humans.

Read more via Science

Heres Jack again when he was 6 or 7 months old. He grew fast! According to the new formula devised by UC San Diego aging researchers, he would have been in his late teens or early 20s when this photo was taken.

Bottom line: A team of researchers on aging at the University of California San Diego performed a genetic analysis of dogs and humans and discovered that compared with humans dogs age faster at first. They reach the equivalent of human middle age after only a few years.

Source: Quantitative translation of dog-to-human aging by conserved remodeling of epigenetic networks

Via the Washington Post

Via Science

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Student life through the screen – The Gateway Online

Sunday, December 1st, 2019

Most of us on the University of Alberta campus have grown up intertwined with the internet. We are digital natives; social interaction on the web is just as natural as in-person communication to us. An essential part of our self-understanding as U of A students, then, comes not just from us interacting in physical space taking classes, participating in extracurriculars, and partying with our pals but also in the digital space of social media.

While the U of A has a plethora of social media pages dedicated to official campus organizations and events, there are a few private U of A pages that serve several purposes: asking questions about registration; sharing unique campus experiences; and even laughing at the U of A itself. How do all these pages operate differently, and how do they create a sense of identity on campus?

A block away from the Enbridge Centre, Im grabbing coffee with Ross Lockwood, the man who started one of the biggest U of A social media pages out there. Sitting at a table on a patio enclosed by office buildings, we sip coffee and talk about the origins of Overheard at the University of Alberta.

Overheard was started by Lockwood and a few friends back in 2007, back when Lockwood was in his third year of a physics degree and before Facebook allowed photo posts. Inspired by the blog Overheard in New York and the quote wall tradition in Lister, Lockwood says that the group mostly just wanted a fun space for U of A students to talk about the weird and wacky stuff theyd heard on campus.

[Overheard] was initially a small group, so maybe like five people had access to it, he says. But we made it public and more people found it useful its a good platform for discussions and things like that.

Due to its public status, the group began to grow very quickly. Overheard now has over 20,000 members, with posts being made daily. Overheard posts are supposed to tackle interesting, odd, or hilarious things overheard or seen on campus. Often this takes the form of text posts recalling snippets of conversation heard in a library; other times its bizarre photos of campus happenings.

If Overheard didnt exist, where would these people be expressing themselves, and where would that expression be appreciated?

Lockwood says that one of the reasons the group is great for U of A students is because it allows people to make connections that they may not have the chance to make in person. He cites Ray Dagg, a custodian at the University Station LRT stop, as one of the prime examples. Dagg, who has become a beloved figure in the group, often posts nature photos from around campus, which get a sizable amount of attention.

I think for a lot of people, being able to develop a community without face-to-face interaction is really good, he says. My question is, if Overheard didnt exist, where would these people be expressing themselves, and where would that expression be appreciated?

With the expansion of the group and Facebook adding new features over the years, the strictness of this doctrine has changed a bit. But its core philosophy has remained the same: make posts that are relevant to the U of A community.

Overheard has always [been about] whats relevant to the university community, Lockwood says. Memes might be funny for a subset of people, they might be annoying for another subset, but we really go for, does this contribute anything of value to the community at large?

This value is not just humorous or light-hearted anymore; at times, Overheard has been at the centre of more serious campus going-ons. One such event happened on October 21 2016, when multiple Overheard members began posting anecdotes about a man contemplating jumping off the sixth floor of CCIS (the man was later taken to hospital without injury). The incident, which was still ongoing when the first posts were made, sparked rampant discussion around the mans motivations, if he was safe, and how mental health is dealt with on campus. For Lockwood and the admin team at Overheard, this was a moment when they realized they needed to step up. They decided to include several campus and Edmonton mental health and distress line services on their page.

We were like, if its something that happens on campus and this person didnt have access to resources, we need to be the place where those resources exist, Lockwood says. Where else would somebody look for help? One of the first places that people get introduced to digitally [at] university, is Overheard.

A year before the CCIS incident, an Overheard post was made about Evan Tran, a U of A student who died by suicide. Tran was well-known on campus; he was a moderator on the Facebook page University of Alberta Compliments, volunteered with the Dean of Students office for their mental health initiatives, was a member of Students Council and General Faculties Council, and volunteered for various student groups. The post mentioning Tran has over 1,900 likes. Commenters are gave their condolences, offered solidarity with Trans family and other students on campus, and shared links to campus resources.

For Overheard admin and recent U of A engineering graduate Subhashis Chikoritaborty, this is one of his favorite moments hes seen on the page.

The amount of support I saw from faculty, [Trans] friends, and everyone who was close was absolutely incredible, he tells me.

Posts like these, and the reactions theyve garnered, seem to represent the other side of the discussion space that Overheard is attempting to foster: one thats not just about funny happenings, but also about vulnerable campus moments and the issues that affect all U of A students.

We want to create a discussion space where people should feel free to discuss [serious] things, [and] I think Overheard can provide that kind of space because its high-traffic, Chikoritaborty says. If you can share something like that [or] something vulnerable, we try to create a space where people can share those thoughts and feel a bit of comfort.

Moving on from Facebook, we come to reddit. More specifically, we come to r/uAlberta, the de-facto subreddit for the U of A community. Founded in 2011 and just over 13,500 members strong, the subreddit is a place for students to ask questions about anything related to their degree, including the quality of certain profs, how to register in certain courses, and what program is best to enroll in. Users have created lengthy guides for various programs and have told varied stories about their U of A experiences; some incredible successes, and some failures as well.

u/firesofpompeii, one of the admins of the subreddit and recent graduate from molecular genetics, says that the subreddit is set apart from other social media sites due to two things: its emphasis on anonymity, and its focus on user engagement.

With reddit in general, anyone can post at any time, [and] although there are users who are more well-known, its not like there are popular users who a lot of people follow, he says. [Everyone is] at an equal playing field, which you dont always get with other social media platforms.

The subreddit is not just a place to ask questions. Much like Overheard, r/ualberta has become a locus for campus discussion; unlike Overheard, however, the subreddits user anonymity has led to the rise and fall of several trollish characters.

If you were to sort of say something in a kind of normal way, often it doesnt get much traction on those sites, but if you say it in a more extreme way, you might get more of a reaction.

Theres been a few notorious users on the subreddit who have drawn the ire of many of the subreddits frequenters. The most notorious of them all, however, was u/unsunghero. They initially drew the ire of the subreddit by starting a thread called Am I too Competitive?. In the thread, they detailed how they would scout out classes considered GPA boosters and ask the professors to curve the class average down, all because they [wanted] to protect the sanctity of the A grade.

u/unsunghero would continue to troll the subreddit and share many controversial opinions, and soon the moderators of r/uAlberta were getting complaints. They couldnt do much, however, because u/unsunghero technically wasnt violating the rules of the subreddit. As long as a user is being civil in expressing their opinion, even if it is one that many people disagree with, the moderators let their posts stand.

Weve had a lot of users complain about them, thats why weve had to tell them that until theyre attacking other subscribers then theres nothing we can really do about it, u/firesofpompeii says. We definitely dont want to censor people.

To anyone whos spent anytime online, this kind of behaviour isnt unusual. Johnathan Cohn, an assistant professor in the department of English at the U of A whose research focuses on critical internet studies and digital culture, says that digital spaces often lend themselves to this kind of behaviour. This is both because theyre a relatively safe space to perform different identities and figure out who you are, and because these sites encourage more extreme modes of behaviour.

If you were to sort of say something in a kind of normal way, often it doesnt get much traction on those sites, but if you say it in a more extreme way, you might get more of a reaction, Cohn says. So it also sort of encourages people who are more extreme, in one way or another, to interact more, and it discourages people who maybe dont like that kind of interaction.

Trolls arent the only thing that the subreddit occasionally fosters. It has broken out into meme territory as well, creating lore that has arguably given the community its own identity and history beyond being a forum for student questions.

The most recent example of such territory is the Ghoul Wars, a saga that began on January 24 2019 with a post by u/lividnaynay that spoke of an experience they had with a particularly unhygienic student. Three days later, u/RogerMooreIsMyDad made a post stating I swear im (sic) going to buy a costco pack of deodorant and hand it out to all the little engg ghouls running around DICE.

That was enough to set off a dramatized war between the Ghouls and the Resistance. Posts were made detailing battle plans for the war, casualty reports, and the development of ghoul-repellant technology. Dozens upon dozens of these posts sprung up; it felt like an augmented reality game had suddenly began on the subreddit.

When I ask u/firesofpompeii about the Ghoul War, he simply laughs; I can practically hear his head shake over the phone.

That kinda made me feel really old, cause I had no idea what was going on, he says. I was just kind of a bystander to that.

In his five years as admin, this isnt the first time u/firesofpompeii has seen events like the Ghoul War arise. Back in 2016, r/uAlberta and r/UCalgary had a meme war, flaming each other in various memes over a period of a few months. Events like this are apparently cyclical on the subreddit; they come and go, cementing themselves as defining moments in the development of the rhetoric and identity of the subreddit.

With each of these cycles, r/uAlberta slowly becomes its own community apart from the physical U of A.

The term meme was first coined by Richard Dawkins in his book The Selfish Gene. For Dawkins, memes are like genes of culture; they are ideas and concepts that spread in communities and get passed down over time. A memes fidelity how well it can retain its original idea as it spreads varies depending on the specificity of the idea. Oftentimes memes with community-specific ideas dont travel very far, whiles memes with more generalizable ideas do.

This can be seen in the different content U of A-related Instagram meme pages put out. Some pages like @ualberta_memes stick very close to U of A material, with past topics including Konz (a short-lived and universally hated pizza place in the Students Union Building), the UASU, and other U of A happenings. Other pages, like @uofaenggmemes seem to take general engineering student memes and put a U of A label on them.

[More generalized memes] translate very broadly but are very weak in their transmission, Cohn says. They can be rethought and reused in a lot of ways, but the original meaning or community [from whence the meme came] gets lost very quickly.

@ualberta_memes is the biggest U of A Instagram meme page, having gained over 6,600 followers since its start on February 4 2019. The admin of the page a third-year kinesiology student who wishes to remain anonymous tells me over the phone that he started the page as a way to kill boredom. He posted a few memes on that fateful day, and the response he received encouraged him to continue.

We can either come to school and just clock-in clock-out, or you can look at everything around you and kind of care a little more than you usually do.

@ualberta_memes sources his content from a variety of places. Typically he makes the memes himself and posts them directly to his page, but he also will post submissions and take ideas for memes. The core of his content, in typical internet meme fashion, pokes fun at a group; namely, the various faculties on campus.

A lot of it is just to show that we all have faults and we can all kind of make fun of ourselves to a certain level, he says.

@ualberta_memes feels personally that the U of A lacks a strong sense of culture, given how large the school is and that people from all over the world attend it. Through making posts that highlight universal U of A experiences like the disaster that was Konz or Listers dodgeball culture @ualberta_memes hopes to help students feel more connected to their campus.

You get people [starting] to care a little more about the small things that you see on campus, he says. Thats kind of important because we can either come to school and just clock-in clock-out, or you can look at everything around you and kind of care a little more than you usually do.

In this way, students are able to feel more attached to their campus and to each other in more tangible ways; instead of simply proclaiming Im a U of A student because I go to the U of A, students can begin to point out the multitude of small, specific details that make up their campus experience.

Another account, @ualbertameme, started just a month after @ualberta_memes. The main admin of the page a third-year science student who also wished to remain anonymous was inspired to start his page in a similar way to @ualberta_memes.

When sourcing posts for the page, @ualbertameme looks for universal U of A experiences that are easily translatable into memes. The page is run by a small team of about five people, all of whom work on different aspects of the page; some post content, others check analytics, and others handle responding to DMs and comments from followers.

Some of the feedback that @ualbertameme has gotten from his followers is that his pages memes help boost student morale, especially during exam season. In a way, being able to laugh about the experience of being a U of A student helps to bring people together and make student life a little easier.

University is supposed to be a relatively fun experience, although it can get really difficult at times, he says. I guess seeing things like memes kind of helps alleviate the pressure or the anxiety that comes with university.

What makes an Instagram meme page different from hanging out on Overheard or r/uAlberta? Both page admins have different answers. For @ualberta_memes, its having an anonymous admin post all the memes. He can post memes on behalf of people who are afraid of judgement, and can also act as a scapegoat in case someone gets upset about their faculty being made fun of.

The whole anonymous aspect of me posting, I think, gives people more comfort to comment what they want, he says. It doesnt have to feel like whoever is posting it might be made fun of or might be judged by their friends or something.

Its easy on these sites to feel like you have nothing to contribute and that therefore youre not part of the community, but thats the normal situation.

For @ualbertameme, its the relaxed nature of Instagram pages, which dont have to have as strict of accountability measures as other platforms.

Certain pages like Overheard, they have to appear [to have] a certain level of responsibility and accountability, he says. On meme pages, people can post whatever they want and there wouldnt really be any repercussions unless its a very serious thing.

***

If theres one thing all of these pages try to do, its capture fragments of the U of A student experience and provide a space for them to be disseminated and discussed. With their varying degrees of anonymity, subject matter, and unique rhetoric and rules, each page fills a different niche.

Many of us may feel out of place on these pages; we may lurk instead of post, feeling out of place or feeling like we lack something to contribute. But as Cohn said before, most people who post on these pages are on the hyper end of extroverted, and they likely only make up a small percentage of the group.

If youre someone in these groups who doesnt post much and you feel sort of marginal, you are actually the norm, he says. Its easy on these sites to feel like you have nothing to contribute and that therefore youre not part of the community, but thats the normal situation.

Lurker or poster, we all can feel more connected to our campus through these pages. They bring us together in times of need, alleviate exam pain, foster discussion about issues on campus, and help us begin to love the little things about being a U of A student.

These pages, arguably, are just as integral to being a U of A student as going to class.

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Humans Co-Evolved with Immune-Related Diseasesand It’s Still Happening – Lab Manager Magazine

Sunday, December 1st, 2019

Credit: iStock

Some of the same mutations allowing humans to fend off deadly infections also make us more prone to certain inflammatory and autoimmune diseases, such as Crohn's disease. In a review published November 27 in the journalTrends in Immunology, researchers describe how ancestral origins impact the likelihood that people of African or Eurasian descent might develop immune-related diseases. The authors also share evidence that the human immune system is still evolving depending on a person's location or lifestyle.

"In the past, people's lifespans were much shorter, so some of these inflammatory and autoimmune diseases that can appear in the second half of life were not so relevant," says first author Jorge Dominguez-Andres (@dominjor), a postdoctoral researcher at Radboud Institute for Molecular Life Science in the Netherlands. "Now that we live so much longer, we can see the consequences of infections that happened to our ancestors."

One of the body's best defenses against infectious diseases is inflammation. Dominguez-Andres and senior author Mihai Netea, a Radboud University immunologist and evolutionary biologist, compiled data from genetics, immunology, microbiology, and virology studies and identified how the DNA from people within different communities commonly infected with bacterial or viral diseases was altered, subsequently allowing for inflammation. While these changes made it more difficult for certain pathogens to infect these communities, they were also associated with the emergenceover timeof new inflammatory diseases such as Crohn's disease, Lupus, and inflammatory bowel disease.

"There seems to be a balance. Humans evolve to build defenses against diseases, but we are not able to stop disease from happening, so the benefit we obtain on one hand also makes us more sensitive to new diseases on the other hand," says Dominguez-Andres. "Today, we are suffering or benefiting from defenses built into our DNA by our ancestors' immune systems fighting off infections or growing accustomed to new lifestyles."

For example, the malaria parasite Plasmodium sp. has infected African populations for millions of years. Because of this, evolutionary processes have selected people with DNA that favors resistance to infections by causing more inflammation in the body. In doing so, this has also contributed to making modern Africans prone to developing cardiovascular diseases, such as atherosclerosis, later in life.

Dominguez-Andres and Netea also write about how the early-human ancestors of Eurasians lived in regions still inhabited by Neanderthals and interbred. Today, people with remainders of Neanderthal DNA can be more resistant against HIV-1 and 'staph' infections, but are also more likely to develop allergies, asthma, and hay fever.

The negative side effects of changes in each population's immune systems are a relatively recent finding. "We know a few things about what is happening at the genetic level in our ancestry, but we need more powerful technology. So, next generation sequencing is bursting now and allowing us to study the interplay between DNA and host responses at much deeper levels," says Dominguez-Andres. "So, we are obtaining a much more comprehensive point of view."

These technologies are also revealing how our immune systems are evolving in real time because of modern lifestyle changes. African tribes that still engage in hunting have greater bacterial gut diversity than urbanized African-Americans that eat store-bought foods. Also, changes in hygiene patterns seen in the last two centuries have improved sanitation, drinking water, and garbage collection, and have led to reduced exposure to infectious pathogens relative to previous times. As humans move toward processed foods and stricter hygiene standards, their bodies adapt by developing what researchers call "diseases of civilization," such as type 2 diabetes.

Moving forward, Dominguez-Andres and Netea will expand their research to communities that fall outside African and Eurasian populations. "So far, all of the studies we went through are focused on populations with European and African descent, but they must also be extended to indigenous and other populations to improve the representation of human genetic diversity," says Dominguez-Andres. "Lifestyles and ecologic natures can really differ and influence immune responses. So, more work needs to be done."

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Molecular Forensics World Markets to 2029 – Massive Scope for Adoption of NGS & Capillary Electrophoresis in Emerging Nations – P&T Community

Sunday, November 24th, 2019

DUBLIN, Nov. 21, 2019 /PRNewswire/ -- The "Global Molecular Forensics Market: Focus on Product, Technology Application, End User, Country Data (16 Countries), and Competitive Landscape - Analysis and Forecast, 2019-2029" report has been added to ResearchAndMarkets.com's offering.

This analysis projects the market to grow at a significant CAGR of 9.09% during the forecast period, 2019-2029. The molecular forensics market generated $996.9 million in revenue in 2018, in terms of value.

With the completion of the Human Genome Project (HGP), a new wave of technologies, called next-generation sequencing (NGS) was introduced in the healthcare industry. PCR, and NGS have fundamentally changed genomics research and enabled the scientists to research extensively on the gene variants to specific molecular diagnostics and aided the development of targeted therapeutics depending on the genetic profile of an individual. The completion of the project, subsequently, created platform for the development of precision medicines.

One of the revolutionary breakthroughs which NGS has resulted in is molecular forensics. Molecular forensics involves a detailed study of individual information to identify and characterize the molecular sequences, resulting in target-based identification. This method approach based on biomarker study is perceived to be promising in driving a paradigm shift in the molecular forensics industry, facilitating the elimination of uncertainty pertaining to the trial-and-error method of medications, and certainly eliminating unnecessary healthcare spending. With sequencing being the primitive pivotal step involved in biomarker study and in the field of genetics, the development of the sequencing technologies played a crucial role in the evolution of molecular forensics.

Further remarkable advancements in the field of genomics, proteomics, molecular biology, data analytics, and technical engineering have paved the way for the development of advanced NGS-based technologies, such as SNP and STR sequencing. The impressive research on molecular technologies and biomarkers using NGS has unlocked pathways for the development of momentous various procedures such as mtDNA sequencing.

The growing demand for non-invasive diagnostic procedures enabling genetic profiling has further enhanced the requirement of NGS technologies. Acknowledging the future potential for massive growth in demand for non-invasive diagnostic procedures, several biotechnology companies such as Illumina, Inc., Thermo Fisher Scientific, and Agilent Technologies, Inc. have invested substantially to aid further developments in forensics technologies.

Key Companies in the Molecular Forensics Market

The key manufacturers who have been contributing significantly to the molecular forensics market include Agilent Technologies, Inc., Illumina, Inc., QIAGEN N.V., Bio-Rad Laboratories, Inc., Promega Corporation, Eurofins Scientific SE, General Electric Company, Merck KGaA, LGC Limited, and Thermo Fisher Scientific Inc. among others.

Key Questions Answered in this Report

Key Topics Covered

Executive Summary

1 Research Scope and Methodology1.1 Scope of the Study1.2 Research Methodology1.3 Data Sources1.4 Assumptions and Limitations1.5 Data and Prediction Modeling

2 Market Overview2.1 Introduction2.2 Molecular Forensics Technologies and Applications2.3 Market Available for Molecular Forensics2.4 Molecular Forensics Technology Trends2.5 Regulations and Compliances

3 Competitive Landscape3.1 Mergers and Acquisitions3.2 Product Launches and Product Updates3.3 Synergistic Activities3.4 Business Expansion Activities and Others

4 Market Dynamics4.1 Overview4.2 Impact Analysis4.3 Market Drivers4.3.1 Augmentation in the Incidences of Crime4.3.2 Growth in the Biomarker Identification Market and Advancements in Molecular Forensics Techniques4.3.3 Technological Advancements in the Field of Computational Biology4.3.4 Significant External Funding for Executing Research and Development Exercises4.4 Market Restraints4.4.1 Lack of High Complexity Testing Centers4.4.2 Expensive Sequencing Procedures and Their Applications in Medical Treatments4.4.3 High Capital Requirement Hampering the Expansion of Global Reach4.5 Market Opportunities4.5.1 Massive Scope for Adoption of NGS and Capillary Electrophoresis in Emerging Nations4.5.2 Technological Advancements in Molecular Techniques and Diagnostic Tests4.5.3 Hybridization of Technologies

5 Global Molecular Forensics Market (By Product)5.1 Overview5.2 Kits and Consumables5.3 Instruments5.4 Software and Other Products

6 Global Molecular Forensics Market (By Technology)6.1 Overview6.2 Polymerase Chain Reaction (PCR)6.2.1 Real-time PCR (q-PCR)6.2.2 Digital PCR (d-PCR)6.3 Capillary Electrophoresis6.4 NGS6.4.1 SNP and STR Sequencing6.4.2 mtDNA Sequencing6.5 Mass Spectrometry6.5.1 MS6.5.2 Tandem MS6.5.3 MS-FTIR6.6 Other Technologies

7 Global Molecular Forensics Market (By Application)7.1 Overview7.2 Radioactive Toxicology7.3 Nucleic Acid Analysis7.4 Forensic Databasing7.5 Microbial Forensics7.6 Other Applications

8 Global Molecular Forensics Market, By End User8.1 Overview8.2 Law Enforcement8.3 Disaster Management8.4 Hospitals and Healthcare Providers8.5 Other End Users

9 Global Molecular Forensics Market, By Region9.1 Overview9.2 North America9.3 Europe9.4 Asia-Pacific9.5 Latin America9.6 Rest-of-the-World

10 Company Profiles10.1 Overview10.2 Agilent Technologies, Inc.10.3 Analytik Jena AG10.4 AS ONE International, Inc.10.5 BioChain Institute Inc.10.6 Bio-Rad Laboratories, Inc.10.7 Eurofins Scientific SE10.8 General Electric Company10.9 Illumina, Inc.10.10 LGC Limited10.11 MACHEREY-NAGEL GmbH & Co KG10.12 Merck KGaA10.13 Promega Corporation10.14 QIAGEN N.V.10.15 Thermo Fisher Scientific Inc.10.16 Verogen, Inc.

For more information about this report visit https://www.researchandmarkets.com/r/gfz227

Research and Markets also offers Custom Research services providing focused, comprehensive and tailored research.

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Co-creator of CRISPR lectures about future applications of genome editing technology – Daily Bruin

Sunday, November 24th, 2019

This post was updated Nov. 20 at 7:47 p.m.

A University of California professor and co-originator of genome editing technology Clustered Regularly Interspaced Short Palindromic Repeats said researchers plan to expand the technology in order to increase human applications at a campus lecture series Thursday.

Jennifer Doudna, a UC Berkeley biochemistry professor, engaged students and the greater UCLA science community during the quarterly Donald J. Cram Distinguished Lecture series.

The Cram lecture series, a quarterly departmental event, invites prominent academics in the field of chemistry to speak about their research. The series is dedicated to Donald J. Cram, who was a Nobel laureate and a chemistry professor at UCLA for over 50 years.

This fall, the series was hosted by UCLA chemistry professor and Cram Chair Patrick Harran.

Scientists use CRISPR technology, formally known as CRISPR-Cas9, to modify DNA sequences and gene functions. Cas9 is a protein that can act like molecular scissor to cut the strands of DNA.

CRISPR is studied and used by students, scientists and researchers to advance progress in the field of gene editing, in medicine and the life sciences.

The UC holds the largest CRISPR patent portfolio in the nation with 16 total patents, according to a UC Berkeley press release.

The United States Patent and Trademark Office granted the UC, along with the University of Vienna and Emmanuelle Charpentier, the director of the Max Planck Institute for Infection Biology, its 16th patent in October.

Doudnas involvement in CRISPR technology began around 2005, when a professor at UC Berkeley, Jill Banfield, invited Doudna to help her with research into the mechanism. From there, Doudna teamed up with Charpentier, who was working with a CRISPR system and its associated protein, Cas9, in 2011.

Doudna is one of the creators of the CRISPR utility for the permanent excision of harmful genes. Doudna said that she developed the idea for the CRISPR technology in 2011 in collaboration with Charpentier.

During the lecture, Doudna detailed how scientists regulate CRISPR enzymes to modify DNA.

CRISPR is a portion of the bacterial genomic sequence that acts as an adaptive immune system, Doudna said.

Bacteria encode the CRISPR system through viral infections, which allows its genome to recognize foreign DNA insertions. These DNA sequences incorporate themselves into the bacterial genome at the CRISPR locus, a genetic database of past infections.

Doudna said this locus was of unique interest to her.

Those sequences, called CRISPR, are transcribed in RNA molecules that provide the zip codes for Cas proteins, allowing them to recognize foreign DNA and cut it up, Doudna said.

Doudna and Charpentier, with the assistance of their team, were able to realize that CRISPR RNA is a 20-nucleotide sequence, which interacts with DNA in a complementary fashion.

This complementarity allows the protein to form a double-stranded break in DNA, necessitating a second RNA tracrRNA to form this functional unit, Doudna said.

And it was (biochemist) Martin Jinek in our lab who figured out that you could combine these two RNAs into a single guide RNA, Doudna said.

From this experiment, Jinek found that single guide RNAs were used by Cas9 to excise DNA at specific sites in a plasmid, a circular piece of bacterial DNA. The revelation from this was that, upon excision, DNA would repair itself in animals and plants, Doudna said.

Doudna said at the end of her talk that the system is becoming increasingly important in the field of medicine, and is currently being used at UCLA, by Donald Kohn, a professor of microbiology, immunology and molecular genetics.

Were within about five years, maybe less, from being able to make, essentially, any change to any genome in any type of cell, Doudna said.

Doudna stressed that this ability to make changes in the genome comes with bioethical responsibility for genome editing in humans.

Fourth-year biochemistry student Jeremy Shek, who attended the event, said although he had done a project that was an offshoot of CRISPR, he had not heard of the progress Doudna discussed.

It is important to be informed on advancements and progress in the field, he added.

Fourth-year bioengineering student Timothy Yu said he came to the lecture to see Doudna in person and get a more solid grasp on the methodology of CRISPR.

Lexi Omholt, a fourth-year microbiology, immunology and molecular genetics student, said that she came to the talk to understand the basis of CRISPR technology.

Jennifer Doudna was one of the reasons I chose my major, Omholt said. At that time, CRISPR came into popular knowledge, and the knockout tool was just coming into use. I am involved in a cancer lab, the Soragni Lab, that uses CRISPR-Cas9 on a regular basis.

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Omega-3 fatty acids health benefit linked to stem cell… – ScienceBlog.com

Sunday, November 24th, 2019

For years, researchers have known that defects in an ancient cellular antenna called the primary cilium are linked with obesity and insulin resistance. Now, researchers at the Stanford University School of Medicine have discovered that the strange little cellular appendage is sensing omega-3 fatty acids in the diet, and that this signal is directly affecting how stem cells in fat tissue divide and turn into fat cells.

The finding represents a missing link between two worlds that of dietary science, and that of molecular and cellular biology. Dietary studies have long found that the consumption of omega-3 fatty acids, essential fatty acids common in fish and nuts, is associated with lower risk of heart disease, stroke, arthritis and even depression.

A paper describing the research was published online Nov. 21 in Cell. The senior author is Peter Jackson, PhD, professor of microbiology and immunology and of pathology. The lead author is postdoctoral scholar Keren Hilgendorf, PhD.

Researchers in Jacksons laboratory werent looking for omega-3s when they started their research. They were only looking for the signaling molecule that fat stem cells were sensing. The molecule could have been anything: signaling pathways in cellular biology often involve esoteric molecules few people have heard of. They only knew that in rare diseases involving a defect in the primary cilium, people are always hungry, cannot stop eating and become obese and insulin resistant. So they were surprised when the signal turned out to be omega-3 fatty acids.

When we saw that the cell was responding to omega-3 fatty acids, we realized that this had changed from just a molecular biology story to a story showing the molecular biology of how diet controls stem cells , Jackson said.

The cells sense the presence of omega-3 fatty acids through a tiny, hair-like appendage called the primary cilium, an ancient structure derived from the many flagella that algae cells first used almost 1 billion years ago to move through the oceans and sense their surroundings. Over time, as single-celled organisms evolved into multicellular creatures that first swam the oceans and then crawled onto land, cells ditched most of their flagella. But most cells kept a single flagellum, the primary cilium, to use as a highly sensitive antenna; it can pick up extremely subtle signals about the world outside the cell, helping to regulate the cells function and fate.

Jackson and his colleagues found that when omega-3 fatty acids bind to a receptor called FFAR4 on the cilia of fat stem cells, it prompts the fat stem cells to divide, leading to the creation of more fat cells. This provides the body with more fat cells with which to store energy, something that is healthier than storing too much fat in existing fat cells. What you want is more, small fat cells rather than fewer, large fat cells, Jackson said. A large fat cell is not a healthy fat cell. The center is farther away from an oxygen supply, it sends out bad signals and it can burst and release toxic contents. Large fat cells are associated with insulin resistance, diabetes and inflammation, he added.

Furthermore, the researchers found that the presence of saturated fats or the blockage of ciliary signaling of the FFAR4 receptor does not lead to an increase in the creation of new fat cells from stem cells, but rather the addition of fat to existing cells. Rather than looking how diet correlates with health, we have gone from molecule to receptor to cell to document why healthy fats are beneficial and unhealthy fats contribute to disease, Hilgendorf said. We have provided a mechanism explaining why omega-3 fatty acids are critical for maintaining healthy fat balance and saturated fats should be limited.

The research also may change scientific understanding of how the body manages fat storage in a healthy person. Researchers often talk about the movement of fat in and out of cells, but what we are showing is the importance of stem cell activity in creating new fat cells as being critical for the bodys energy management, said Carl Johnson, a graduate student in the stem cell biology and regenerative medicine program and a co-author of the paper.

Other Stanford co-authors are associate professor of genetics Will Greenleaf, PhD; postdoctoral scholar Anja Mezger, PhD; research engineer Janos Demeter, PhD; and technician Selena Rice.

The research was supported by the National Institutes of Health (grants 5R01GM114276, 5U01CA199216, 5UL1TR00108502, R01 AR054396, DK106404, GM095941. TG2-01159), the Damon Runyon Cancer Research Foundation, the Swedish Research Council, and the Chan-Zuckerberg Biohub.

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Biology: Insect populations plummeting, and we should worry – Stock Daily Dish

Sunday, November 24th, 2019

Steve Rissing

Jan13,2019at4:00AM Jan13,2019at10:44AM

Theres an old joke about what goes through a flys mind as it hits your windshield.

Problem is, not many insects hit windshields anymore, and we might be the butt of that joke.

Biologists have slowly realized our windshields are cleaner these days, even after long highway trips. (I first drove to Death Valley from Indiana to study ant colonies in 1974. I stopped as often for visibility as I did for fuel.)

But the windshield phenomenon, as it is known, suggests something much larger and potentially ominous is underway at the interface of modern humanity and insects. Simply put, there are fewer insects.

Join the conversation at Facebook/columbusdispatch and connect with us on Twitter

Insects are the most ubiquitous group of organisms in the world. They are the largest group of arthropods, and arthropods are 80 percent of all described animal species. Insects play dominant roles in most land-based ecosystems. They pollinate most agricultural crops, cycle nutrients and provide structural complexity and stability to natural food webs.

For some time, studies of single species have suggested that populations of iconic species such as monarch butterflies are crashing. Annual surveys of monarchs wintering in Mexico reveal population declines exceeding 80 percent over the past two decades.

Rusty patched bumblebees once thrived throughout the Midwest, including Ohio. The U.S. Fish & Wildlife Service reports that they have declined 87 percent over the past two decades. They likely live in one-tenth of 1 percent of their former range.

Detecting possible steep declines in insect populations requires long-term, broad-scale studies. Those require funding and professional expertise.

Fortunately, several long-term surveys exist. Publications based on them support what biologists are seeing through their windshields. A New York Times magazine cover story two months ago declared it the Insect Apocalypse.

A 2017 paper in the journal PLOS One reports total insect biomass in German nature reserves declined 76 percent in 27 years. A 2018 paper in the Proceedings of the National Academy of Sciences reports a 63-fold (not percent) reduction in insects captured on sticky traps on the floor of the U.S. El Yunque National Forest in Puerto Rico over the past 40 years. The authors also observed decreases in forest insect-eating birds, frogs and lizards.

Global climate change might account for the demise of insects in tropical areas such as Puerto Rico. The apparent drivers in temperate areas such as Germany are likely more complex. Those drivers include ongoing intensification of agricultural practices and pesticide use.

Making the apparent insect collapse even worse, a recent American Entomologist paper documents the disappearance of insects from college introductory biology textbooks. The authors found that a century ago, textbooks devoted 8.8 percent of their pages to insects and their interactions with humans. Textbooks published since 2000 devote less than 0.6 percent of their pages to insects, with even less emphasis on human-insect interactions.

Topics such as modern molecular genetics, exciting to instructors who adopt textbooks, crowd out topics possibly more relevant to students, especially in general education courses.

As humanity disrupts and reduces our planets natural systems, responsible citizens and the policymakers they elect eventually will need to develop policies that mitigate and respond to changes such as massive losses of insects.

This is no time to drive blindly into that future, even if our windshields are eerily clean.

Steve Rissingis a biology professor at Ohio State University.

steverissing

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115 more arazi centres to be set up – The News International

Sunday, November 24th, 2019

115 more arazi centres to be set up

LAHORE :The Punjab government will set up 115 arazi centres in different districts of the province by the end of the current year to facilitate the general public at their doorstep.

The arazi centres will provide revenue related facilities to the general public in an efficient and transparent manner.

This was stated by Provincial Minister for Revenue Malik Muhammad Anwar while talking to different delegations at his office on Friday.

The minister said that 153 arazi record centres were already providing different facilities to the people in 36 districts of the province.

He said the Board of Revenue was going to procure 20 state-of-the-art mobile vans so that revenue-related facilities could be provided to the people close to their residence.

The BOR has also taken steps to facilitate the rural population and computer technology has been utilised to facilitate the people.

The PTI led government has given special attention to ensuring complete transparency in revenue matters to save public properties from land grabbers, the minister concluded.

Magistrates: A spokesman for the Provincial Industries and Trade Department has the price control magistrates are conducing raids to check the price of essential commodities across the province.

The spokesman stated the price control magistrates conducted raids on 10,350 shops.

As many as 1,952 complaints relating to price-hike were lodged and 189 cases were registered in which 179 persons were arrested and fines amounting to more than Rs3.5 million were also imposed.

PhDs awarded: Punjab University (PU) has awarded PhD degrees to five scholars.

Ambreen Gul, daughter of Mirza Sultan Ahmed, has been awarded PhD in Molecular Biology after approval of her thesis entitled Overexpression of Aspartic Acid in Cotton Against Insects, Ammara Ahad, d/o Abdul Ahad Khan, in Molecular Biology after approval of her thesis entitled Expression of Flavonoid Pigment Related Genes in Cotton (Gossypium hirsutum), Khadija Aaliya, d/o Asif Hussain, Molecular Biology after approval of her thesis entitled Transformation and Expression Studies of Multiple Frost Tolerant Genes in Solanum Tuberosum L, Mehvish Ajaz, d/o Soofi Ajaz Ahmed, in Microbiology and Molecular Genetics after approval of her thesis entitled Azo Dyes Removal by Bacteria Isolated from Industrial Wastewater and Naveed Ahmad Noor, son of Muhammad Nawaz, in the subject of High Energy Physics after approval of his thesis entitled Under Pressure Study of Fundamental Properties of Perovskite Oxides Using Density Functional Theory (DFT).

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Medical News Today: How do genetic differences affect the risk of bipolar disorder? – Stock Daily Dish

Sunday, November 24th, 2019

Fresh insights from a recent study of the genetics and biology of bipolar disorder could improve the diagnosis and treatment of the debilitating condition. A new study shows how specific genetic differences affect neural circuits and raise the risk of bipolar disorder as a result.

So concluded the scientists at the Picower Institute for Learning and Memory at Massachusetts Institute of Technology (MIT) in Cambridge who carried out the novel research.

In previous work, they had already shown that a protein called candidate plasticity gene 2 (CPG2) helps to regulate the strength of synapses in brain circuits. Synapses are the connectors through which nerve cells, or neurons, relay chemical signals to each other.

In the more recent research, the investigators found that the brains of people with contained unusually low levels of CPG2.

They also linked specific variants in the gene for CPG2 to dysfunction in synapses. These same genetic differences happen to occur in people with bipolar disorder.

The team reports the findings in a that now features in the journal Molecular Psychiatry.

Its a rare situation, says senior study author Elly Nedivi, who is a professor in the Biology and Brain and Cognitive Sciences departments at MIT, where people have been able to link mutations genetically associated with increased risk of a disorder to the underlying cellular dysfunction.

For bipolar disorder this might be the one and only, she adds.

She and her colleagues are not suggesting that the gene variants that they uncovered actually cause bipolar disorder.

What they are proposing, however, is that having those particular genetic differences could make people more susceptible to bipolar disorder.

In laboratory models, for instance, they sometimes observed synapse dysfunction with combined rather than single variants.

According to the National Institute of Mental Health, around in the United States will have bipolar disorder at some point in their lives.

People with bipolar disorder experience episodes of mania and that bring on extreme shifts in mood, activity levels, and energy.

The episodes are much more severe than the ups and downs that affect most people. They can make it very difficult to carry out daily tasks, get along with people, study, and pursue a career.

Bipolar disorder is a and high rates of death by suicide. Drugs do not always work and not everyone with bipolar will experience complete recovery between episodes.

Prof. Nedivi and her team have been studying synapses for many years.

They discovered that CPG2 influences synaptic strength by helping to regulate the number of receptors for the chemical signals that pass between neurons.

The gene that holds the instructions for making CPG2 is Spectrin Repeat Containing Nuclear Envelope Protein 1 (SYNE1).

On learning that studies had linked variants in SYNE1 to raised risk of bipolar disorder, the team decided to investigate the underlying biology in the light of their own findings about CPG2.

The researchers began by examining postmortem brain tissue from various brain banks.

The samples came from people who had received a diagnosis of bipolar disorder, or other psychiatric conditions that share some of its symptoms, such as or major depression. They also examined samples from individuals who did not have any of these conditions.

The examinations revealed that only brain tissue from people with bipolar disorder contained significantly less CPG2.

The bipolar samples did not show lower levels of other proteins known to play a role in synaptic functions: only CPG2 was lower.

Our findings, the authors write, show a specific correlation between low CPG2 levels and incidence of [bipolar disorder] that is not shared with schizophrenia or major depression patients.

The researchers then used deep-sequencing tools to search for SYNE1 variants in the bipolar brain tissue samples that had shown reduced levels of CPG2.

They focused their efforts on the regions of the gene that control CPG2 expression and therefore the amount that cells produce.

In a separate exercise, they also searched genomic archives to identify variants in CPG2-encoding regions of SYNE1. Differences in this coding can affect the structure and function of the protein.

In experiments with cultured neurons, the team then examined the cellular effects of both types of variants: those in the CPG2 expression-altering region of SYNE1 and those in the coding region for the protein.

The results showed that some expression-altering gene variants had no effect on CPG2 level, while others altered it significantly.

The team also found two examples of paired variants that reduced CPG2 expression but that had no effect as single variants.

There was also a range of results in the experiments with protein-coding variants. These identified SYNE1 differences that altered the structure or function of CPG2 in specific ways.

For instance, one SYNE1 variant reduced the ability of CPG2 to attach to the spines that contain excitatory synapses, while another impaired the cycling of receptors in the synapses.

The findings reveal how specific SYNE1 differences that occur in people with bipolar disorder can upset the function of a protein that plays a key role in the connections in brain circuits.

Further research is now needed to determine how bipolar disorder might develop from such cellular disruptions.

Prof. Nedivi and her team are planning to examine the effect of some of the variants on behavior in animals. They also want to look more closely at some of the disrupted cell processes and how they might fix them.

Alongside these studies, they will continue to investigate human samples to find out more about the specific gene variants and their links to the risk and development of bipolar disorder.

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