Spinal Cord Injury, Gut Microbiome, and White-Plague Coral Disease: the PLOS Comp Biol June Issue

Here are some highlights from June’s PLOS Computational Biology

 

Inference of Network Dynamics and Metabolic Interactions in the Gut Microbiome

June Issue Image: Handmade painting representing FAAH bound to the membrane. Image Credit: Painting by Giulia Palermo with digital manipulation by O'Reilly Science Art, LLC

June Issue Image: Handmade painting representing FAAH bound to the membrane. Credit: Painting by Giulia Palermo with digital manipulation by O’Reilly Science Art, LLC

The community of bacteria that live in our intestines (called the “gut microbiome”) is important to normal intestinal function, and the destruction of this community has a causative role in diseases including obesity, diabetes, and even neurological disorders. Reka Albert and colleagues use a mathematical model to identify how the normal bacterial community interacts and how this community changes with antibiotic treatment and C. difficile infection.

 

A Computational, Tissue-Realistic Model of Pressure Ulcer Formation in Individuals with Spinal Cord Injury

 

People with spinal cord injury are predisposed to pressure ulcers. These ulcers remain a significant burden in cost of care and quality of life, despite improved mechanistic understanding and advanced interventions. Yoram Vodovotz and colleagues create a virtual pressure ulcer as a platform to test therapies and determine the mechanisms most correlated with unfavourable outcomes. Their analysis reveals that inflammation is an important determinant of ulcer severity and overall tissue damage.

 

Coral colonies from the genus Favia infected with white-plague disease. Credit:  Zvuloni et al.

Coral colonies from the genus Favia infected with WPD. Credit: Zvuloni et al.

 

Modeling the Impact of White-Plague Coral Disease in Climate Change Scenarios

 

Coral reefs are deteriorating at alarming rates, with coral disease outbreaks increasing in prevalence and in special distribution. Anomalously high ocean temperatures are thought to significantly contribute to this problem. Yael Artzy-Randrup and colleagues have collected a unique dataset of a White Plague Disease (WPD) outbreak from the coral reef of Eilat (Israel, Red Sea). By fitting a novel epidemiological model to the data, they characterize the dynamics of WPD, and study the possible effects of future increasing sea-surface temperatures on disease dynamics.

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Calling All Bloggers for ISMB/ECCB 2015

ISMB/ECCB 2015 in Dublin, Ireland, is fast approaching and we invite you to be involved in the live coverage of the event.

 

In previous years, ISMB has been way ahead of the social media curve with microblogging in 2008, one year before the launch of Flickr, one year after the launch (in the USA) of the Apple original iPhone 1, and just two years after Twitter was founded. Now at the last count, Twitter has averaged at 236 million users, three million blogs come online each month, and Tumblr owners publish approximately 27,778 new blog posts every minute. We all know that, in like-fashion, social media is a growing aspect of conferences, — read more in our Ten Simple Rules for Live Tweeting at Scientific Conferences, –and we think ISMB is a great venue for progress.

Sean MacEntee/Flickr

Sean MacEntee/Flickr

How can you be involved?

We want you to take live blogging to ISMB/ECCB. If you are planning to attend the conference in Dublin and you blog or tweet, or even if you would like to try it for the first time, we want to hear from you – Everyone can get involved.

Our invitation extends to attendees from all backgrounds and experience who could contribute blog posts covering the conference. In addition we are looking for a number of ‘super bloggers’ who can commit to blogging two to three high-quality posts or who would be interested in interviewing certain speakers at the conference. If you are speaking at ISMB/ECCB and would like to be involved, please do also get in touch.

In acknowledgment of your time and effort, each contributor will receive a select PLOS Computational Biology 10th Anniversary t-shirt (only available at ISMB/ECCB 2015) and your work will be shared on the PLOS Medium.com page, making it easier for all to contribute and collaborate.

 

What are the next steps?

If you’re active on Twitter or the blogosphere and want to help us share the latest and greatest from ISMB/ECCB 2015 conference, please email us at ploscompbiol@plos.org with a bit about your background and how you’d like to contribute. See you in Dublin!

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ISMB/ECCB 2015

Heading to Dublin for ISMB/ECCB 2015? Swing by Booth 1 and say hello to PLOS!

Many of the journal’s academic editors will be in attendance, and PLOS Computational Biology staff Gary Beardmore and Bethany Coates will be manning the booth, alongside Catherine Nancarrow, Senior Managing Editor, and Mei-Yan Leung, Product Marketing Manager. They’re keen to answer your questions, talk about your research, and hear your thoughts on Open Access and the journal’s role in the community.

We will also be running a live blog, with guest bloggers relating their experiences of ISMB/ECCB 2015 and interviewing some of the speakers. If you are interested in taking part, please e-mail ploscompbiol@plos.org or drop by Booth 1.

PLOS/Kifayathullah Liakath-Ali

PLOS/Kifayathullah Liakath-Ali

We will have special PLOS Computational Biology 10th Anniversary t-shirts available from the booth, featuring a design by this year’s winner Kifayathullah Liakath-Ali. Numbers are limited however, so come early to snag one before they’re gone!

Keep an eye out for PLOS Computational Biology editors across the conference and follow us on Twitter for live updates on events in which they are involved. Here are some to get you started:

 

Friday 10th July

Sunday 12th July

  • Michael Levitt gives a keynote presentation on the Birth & Future of Multiscale Modeling of Macromolecules
  • Francis Oulette, Gabrielle Rustici, Annette McGrath, and Dave Clements host a workshop on Experience Exchange: Focus on NGS Course.

Monday 13th July

  • Donna Slonim presents her paper ‘Finding Novel Molecular Connections between Developmental Processes and Disease’.
  • Marc Marti-Renom presents a special session on ‘Assessing the limits of restraint-based 3D modelling of genomes and genomic domains’.
  • Later in the day Philip Bourne and Niklas Blomberg talk data with their special session on ‘Elixir – Towards unifying a computational biology ecosystem’.
  • Steven Brenner will lead one of ISMB’s theme presentations on ‘Widespread degradation of transcripts by splicing and nonsense-mediated mRNA decay (NMD) includes ultraconserved targets whose regulation by alternative splicing and NMD is conserved between kingdoms’.

Tuesday 14th July

  • David Searls will be giving a special presentation on ‘James Joyce’s Ulysses: A bioinformatics perspective.

 

There’s still time to register for ISMB/ECCB 2015 online if you’ve not yet done so. We look forward to seeing you in Dublin!

 

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PLOS Computational Biology’s 10th Anniversary

This post marks a very important date for PLOS Computational Biology and highlights how we are celebrating.

Image credit: Cade Buchana / Flickr

Ten years ago, on June 24th 2005, the inaugural issue of PLOS Computational Biology was published, making this our 10th anniversary!

To mark this momentous occasion, the journal is launching a special anniversary collection. The collection showcases some of the best of PLOS Computational Biology – high-quality research articles; the feature series, “Ten Simple Rules”; and an editorial by Founding Editor-in-Chief Philip E. Bourne and Founding Editors Steven E. Brenner and Michael B. Eisen, – Ten Years of PLOS Computational Biology: A Decade of Appreciation and Innovation – in which they reflect on the journal’s evolution and offer a few thoughts for the next ten years.

The first Issue Image.  Image credit:Image Credit: Drawn by Barker and Pagel using BioLayout software.

The first Issue Image.
Image credit:Image Credit: Drawn by Barker and Pagel using BioLayout software.

The collection also contains a PLOS Computational Biology “Taster”; here readers can sample a flavour of PLOS Computational Biology and the kinds of articles we publish. Covering Software, Education, About My Lab, Topic Pages and a Focus Feature, we’re sure you’ll find something to pique your interest.

Our tenth anniversary is the perfect time to reflect on the journal’s progress. The collaboration with ISCB – and the participation of its membership – has been critical to the success of the journal. In the collection, you can read the newly published Message from ISCB which describes the growth of computational biology as a discipline, reaching into every facet of scientific research from the viewpoints of experts in the field – Philip Bourne, Win Hide, Janet Kelso, Scott Markel, Ruth Nussinov and Janet Thornton.

PLOS Computational Biology is, by definition and at its heart, a community journal. The Editorial Board of academics, who are active members of the communities we serve, keeps PLOS Computational Biology at the cutting edge of research. The journal’s success is due in no small part to the rigour and quality of our editorial board, guest editors and reviewers. It was our pleasure to publicly thank our reviewers this year for their contribution, but we would also like to take this opportunity to thank everybody who submits, reads, and edits the articles we publish. Together, we have developed a journal that is by the community and for the community.

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Winning design of the 10th Anniversary T-shirt Competition. Image credit: Kifayathullah Liakath-Ali

The collection is joined in our celebrations by our PLOS Computational Biology 10th Anniversary T-shirt competition, through which the favourite T-shirt design of the past ten years was voted for by our readership. The T-shirts will be first available at ISMB in Dublin on July 11th-14th, so be sure to visit PLOS at Booth 1, say happy birthday and pick up a T-shirt from PLOS staff. You can keep up to date with all these celebrations and more @PLOSCompBiol via our anniversary hashtag #PLOSCB10.

 

As we close out this special year, we’ll be adding more 10th anniversary content, so watch this space…

 

 

 

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PLOS Genetics editors – David Kwiatkowski and Peter McKinnon

The first post in our PLOS Genetics’ editors series introduces David Kwiatkowski, Brigham and Women’s Hospital and Harvard Medical School, USA and Peter McKinnon, St Jude Children’s Research Hospital, USA, who are Section Editors for Cancer Genetics. David and Peter began their roles on PLOS Genetics in October 2014 and February 2014, respectively. Here they provide an introduction to their background and research, tell us about their positions on the PLOS Genetics Editorial Board, and explain how they feel their role fits into the mission of PLOS Genetics and PLOS as a whole.

 

David Kwiatkowski:

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David Kwiatkowski. Image credit: David Kwiatkowski.

I am an oncologist and geneticist, with some research specialisms; however, I maintain a broad range of interests across the field of cancer genetics. Growing up, I loved and was very good at mathematics which led me to undertake a BSc and PhD in Mathematics at Caltech and the Massachusetts Institute of Technology, respectively. Subsequently, I decided that I wanted to pursue something more practical and went to medical school. During medical training, I became interested in Medical Oncology, which appealed to me due to the possibility of treating and curing an otherwise fatal disease, and the intensity of the patient-doctor relationship.

Fellowship training introduced me to biomedical research, and I felt a natural affinity for genetics, which was an expanding field at the time. Mostly by chance my research led me to study Tuberous Sclerosis Complex (TSC) from a genetic perspective, and this disorder, which results in non-cancerous tumours, became my lifelong research interest. It has been gratifying in TSC research to see the progression from gene identification, to pathway definition, to therapeutic success, although there is still a long way to go. I have continued to practice as a thoracic oncologist at the Dana Farber Cancer Institute, USA.

About five years ago, I undertook a mini-sabbatical at the Broad Institute with Gad Getz and Matthew Meyerson.  The era of modern cancer genetics was just beginning and the sabbatical gave me the opportunity to learn computational and statistical methods, in addition to participating in several projects run by The Cancer Genome Atlas (TCGA).

I am one of two Senior Editors in the Cancer Genetics section of PLOS Genetics, along with Peter McKinnon. My favorite part of this role is the weekly calls, in which we review new submissions, typically about five new manuscripts. This review pushes me to stay current on all aspects of cancer genetics, and the interaction and discussion with Peter is always fun. It is also gratifying to attempt to accelerate the review process as much as I can, and it is always satisfying when a review has been completed and the letter sent to the author, especially when it is an acceptance!

The mission of PLOS is to advance Open Access scientific research, and I am pleased to play a role in advancing this objective. It is also worth noting that PLOS maintains very high standards of manuscript review and conflicts of interest, which means that Peter or I recuse ourselves from any role in the review of manuscripts in which we have any possible competing interests.

 

 

Peter McKinnon:

pmckinnon

Peter McKinnon. Image credit: The University of Tennessee Health Science Center

I grew up in a small town in Australia and wanted to become a research scientist focusing on chemistry. An early and important start for me was an after school job in an old-style English pharmacy (in Australia they are referred to as a Chemist shop; so what better start than to get a job doing ‘chemistry’). This Chemist shop was from the turn of the 20th century, and still had shelf upon shelf filled with large exotic glass bottles with chemical names gold-etched in Latin, making it feel that I was immersed in chemistry. The reality was that the job mostly entailed counting pills into bottles for prescriptions, and very occasionally watching the pharmacist formulating some old-style skin creams. Upon entering University, I maintained my interest and specialised in biological chemistry, and eventually molecular biology. For the last two decades, my scientific work has focussed on understanding the processes of DNA damage signalling, and its relationship to human disease, with an emphasis on the nervous system. These topics overlap broadly with DNA repair, neuroscience and cancer.

As an editor for PLOS Genetics, I see my role as helping to maintain the high quality content the journal publishes. This mainly involves acting as a co-Senior Editor with David Kwiatkowski for the Cancer Genetics section and we aim to identify exciting and topical papers that provide a range of new findings of broad relevance to genetics research and cancer. One of the great things about being an editor is the opportunity to see such a large amount of high-calibre science. David and I work by consensus when we are evaluating papers, and I believe that having the two of us discuss each manuscript is important to ensure balance and fairness as we decide which manuscripts should be sent out for review. We aim to continue to ensure that PLOS Genetics is a high-quality journal that researchers consider when deciding where to submit an exciting new story for publication.

Category: Cancer, PLOS Genetics, Uncategorized | Tagged , , , , | 2 Comments

Understanding images: microRNAs contribute to hair loss and follicle regression

In a piece reflecting on this month’s PLOS Genetics issue image, author Zhengquan Yu discusses the research behind Yuan et al.

Author: Zhengquan Yu, State Key Laboratories for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China

Competing interests: Zhengquan Yu is an author of the paper discussed in this blog.

Immunoflorscent staining of hair follicles. Image Credit: Yuan and colleagues

PLOS Genetics May Issue Image. Immunoflorscent staining of hair follicles. Image Credit: Yuan and colleagues

Up to 60% of men experience some degree of hair loss in their lifetime. However, despite its prevalence, efficient treatment for hair loss is lacking. One of the key distinguishing features of hair follicles in baldness-affected areas is premature  regression. This leads to shorter hairs and excessive hair fallout. This month’s cover image features actively growing hair follicles with prominent layers of the outer root sheath surrounding the hair shaft cortex. In this issue of PLOS Genetics, we describe an essential role for a highly conserved microRNA, miR-22, in regulating the regression of mouse hair follicles. New insights into the mechanism of premature hair growth regression in mice enrich our understanding of the pathogenesis of hair loss.

 

The basics of hair loss

Because hair loss results from the premature termination of the follicle’s growth phase, it is essential to understand in more detail the mechanism underlying normal hair regeneration. During the active phase of the hair growth cycle, stem cell activity sustains an actively dividing population of epithelial cells at the base of the follicle called matrix cells. As progeny of the matrix cells move upward from the follicle base (or bulb), they differentiate into a hardened hair shaft, which emerges above the skin surface. Fully differentiated hair shafts consist of dead, but mechanically sound and highly cross-linked, keratin-filled cells. After a period of active hair shaft production, follicles activate an involution program, during which a large portion of epithelial cells die, and the remaining stem cells are reduced to a tight cluster underneath the skin surface. These follicles then remain dormant for some time; however, they can undergo activation and restart active hair shaft production.

Image credit: Aida. CC BY 3.0.

Hair loss. Image credit: Aida. CC BY 3.0. Licence.

The growth, regression, and resting phases together constitute the hair growth cycle, and this cycling can be influenced by a variety of local and systemic signaling factors. Consequently defects in hair cycling can arise from changes in the normal signaling milieu due to disease, aging, or injury. Commonly, in humans, scalp hair follicles enter resting phase prematurely, and hairs shafts become shorter and fall out, resulting in visible baldness. Therefore, identifying new signaling regulators of hair follicle regression will provide a better understanding of the hair loss pathogenesis mechanism and will likely identify novel therapeutic targets.

 

miR-22 induction causes premature hair loss by promoting follicle involution

Immunoflorescence of hair follicle. Image credit: Yuan and colleagues.

Immunoflorescence of hair follicle. Image credit: Yuan and colleagues.

To test the function of miR-22, we generated a genetic tool to induce miR-22 overexpression in mouse hair follicles, and interestingly, found that increasing miR-22 results in hair loss in mice due to the premature regression of actively growing follicles. Surprisingly, our data reveal that the expression of over 50 distinct keratin genes are markedly reduced by miR-22 and that silencing of keratin-mediated hair shaft assembly by miR-22 is a prerequisite for follicle regression. At the molecular level, we found that miR-22 directly represses multiple transcription factors, including Dlx3 and Foxn1, which positively regulate the expression of keratin genes.

Hair loss in mice. Image credit: Yuan and colleagues.

Hair loss in mice. Image credit: Yuan and colleagues.

Indeed, deletion of Dlx3 or Foxn1 closely resembles the hair loss phenotype caused by miR-22 induction. Thus, by suppressing Dlx3- and Foxn1-dependent keratin expression, miR-22 is sufficient to terminate hair differentiation. In addition, miR-22 contributes to follicle regression by repressing proliferation of hair stem cells and promoting their death. Collectively, miR-22 emerges as a key regulator of follicle transition from the growth to regression phase. There are hundreds of microRNAs expressed in a hair follicle [2], but most of them are not well studied. Our findings of the essential role of miR-22 highlight the importance of determining the combinatorial effects of the microRNA regulatory network in hair cycling.

 

Implications of findings

In the future, our findings are likely to benefit human hair loss research efforts. Androgenic alopecia, where premature regression of scalp hair follicles is induced by increasing androgen levels, is the most common hair loss disorder in humans. Interestingly, it has been reported that miR-22 is strongly induced in the liver in response to testosterone treatment [3,4]. Our unpublished data show that two binding sites for an androgen receptor are located in the promoter of both human and mouse miR-22. These findings support the hypothesis that miR-22 functions in the pathogenesis of Androgenic Alopecia, warranting future studies of miR-22 inhibitors as potential anti-hair loss drugs.

 

  1. Lee J, Tumbar T (2012) Hairy tale of signaling in hair follicle development and cycling. Semin Cell Dev Biol 23: 906-916.
  2. Mardaryev AN, Ahmed MI, Vlahov NV, Fessing MY, Gill JH, et al. (2010) Micro-RNA-31 controls hair cycle-associated changes in gene expression programs of the skin and hair follicle. FASEB J 24: 3869-3881.
  3. Delic D, Grosser C, Dkhil M, Al-Quraishy S, Wunderlich F (2010) Testosterone-induced upregulation of miRNAs in the female mouse liver. Steroids 75: 998-1004.
  4. Wang WL, Chatterjee N, Chittur SV, Welsh J, Tenniswood MP (2011) Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer 10: 58.

 
ResearchBlogging.org

Yuan, S., Li, F., Meng, Q., Zhao, Y., Chen, L., Zhang, H., Xue, L., Zhang, X., Lengner, C., & Yu, Z. (2015). Post-transcriptional Regulation of Keratinocyte Progenitor Cell Expansion, Differentiation and Hair Follicle Regression by miR-22 PLOS Genetics, 11 (5) DOI: 10.1371/journal.pgen.1005253

Category: Biology, Blog, Genetics, Image, Molecular biology, PLOS Genetics, Uncategorized | Tagged , , , , , , , , | Leave a comment

New Charges of Climate Skeptic’s Undisclosed Ties to Energy Industry Highlight Journals’ Role as Gatekeeper

In theory, it shouldn’t matter where authors of scientific papers get their research funding, a longtime journal editor once told me. Papers should be judged on their own merits, not based on who funded the scientists who collected and analyzed the data. But in practice, as journals are increasingly recognizing, funding sources matter.

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Thanks to documents obtained from court settlements, whistleblowers and investigations by reporters and U.S. congressmen, we know that corporations hire scientists to write studies that help delay regulations, defend products worth billions and discredit research to protect their bottom line.

Reviews of studies in several high-stake fields, including pharmaceutical research, chemical toxicity and passive smoking, have found a “funding effect.” Researchers who receive funding from industry in these fields, the reviews show, are more likely than those who don’t take industry money to publish results in line with the company’s interests.

That’s why the watchdog group Climate Investigations Center (CIC) has been investigating the funding sources of Wei-Hock “Willie” Soon, a scientist at the Harvard-Smithsonian Center for Astrophysics known for disputing the role of rising greenhouse gas emissions in climate change, in contrast to the overwhelming majority of climate researchers and the U.N.’s Intergovernmental Panel on Climate Change.

And now, as a report released by CIC and Greenpeace on Wednesday details, the group has turned its attention to the journals who publish his papers.

As a result, five journals, including an Elsevier ethics committee, are investigating charges that Soon failed to disclose financial ties to the fossil fuel industry in papers published by the journals since 2008. Soon characterized these papers as “deliverables” in grant reports to his corporate sponsors, CIC charges, citing documents obtained through the Freedom of Information Act from the Harvard-Smithsonian Center for Astrophysics.

The Soon investigation is intended to underscore the need for greater transparency in science publishing about conflicts of interest, CIC Executive Director Kert Davies told me. “This is a strong case study of how corporate interests have intentionally used the scientific literature,” Davies says.

CIC is also asking PNAS and Nature Geoscience to reassess papers Soon published in the journals in the past two years, when he did not disclose grants he received from utility giant Southern Co. and Donors Trust, a foundation that encourages anonymous donations to support limited government. Donors Trust received nearly $5 million from a Koch family foundation in 2013 alone.

Three of the journals do not have identifiable conflict of interest policies, according to the report. PLOS considers the disclosure of competing interests – which can include non-financial, professional and personal conflicts — as essential to the transparent reporting of research. Manuscripts submitted by authors who fail to declare such conflicts may be rejected immediately after a conflict comes to light. If a conflict is revealed after publication, journal editors will follow guidelines from the Committee on Publication Ethics and notify the community.

CIC has been corresponding with the journals since February, when the nonprofit and Greenpeace released documents showing that Soon had received over $1.2 million from fossil fuel interests since 2001 that he failed to disclose in at least 11 papers. The documents show that Soon accepted money from ExxonMobil Corp., the American Petroleum Institute, the Charles G. Koch Foundation and Southern Co., one of the largest electric utility companies in the United States valued at $40 billion.

Soon rarely talks to media outlets but reportedly said that funding does not bias his findings.

Charles Koch and his brother, David, regularly give millions of dollars to foundations and think tanks like The Heartland Institute – which sponsors an annual conference for global warming deniers, where Soon is a regular speaker – that support the fossil fuel industry that made them billionaires. Southern Co. remains reliant on coal-fired plants, a major source of carbon dioxide emissions, and supports voluntary measures to mitigate climate change.

Conflicts of interest can violate scientific ethics and skew scientific results as much as fabricating or manipulating research results can, argues Sheldon Krimsky, an adjunct professor in public health and family medicine at Tufts University who has long studied the funding effect. He argues that lack of transparency about conflicts of interest to reviewers, journals and readers should be considered scientific misconduct.

The full extent of biased corporate influence on the scientific literature is difficult to measure. To guard against it, academic institutions and scientific journals must be more vigilant against dubious research crafted to serve a corporate agenda, Naomi Oreskes, a Harvard historian of science who documents industry strategies to bend science to their interests, told The New York Times.

Courtesy AAAS

Courtesy AAAS

The key point, as Oreskes argued in a 2004 paper in Environmental and Science Policy, is not that support from industry is intrinsically problematic. “Rather,” she wrote, “the issue is that the research is supported by a sponsor who wants a particular result…and the researchers know in advance what that outcome is, producing an explicit conflict of interest, which undermines the integrity of the research performed.”

Journals can uphold their duty as guardians of scientific integrity by doing a better job of enforcing their conflict of interest policies, perhaps by tailoring practices that ensure compliance with data and animal research policies to codes of scientific conduct. Failure to do so threatens not just the public’s trust in the results of the research they fund, but the integrity of science itself. With corporate funding of scientific research now outpacing government funding, the difference between theory and practice regarding the potential for biases from industry funding is too great – and the stakes too high – to be ignored.

Category: Advocacy, Editorial policy, Funding, PLOS Biology, Policy, Publishing, Research | 5 Comments

Suffering for Science: Balancing the Costs and Benefits of Animal Research

Think for a moment, if you will, of all the chemicals that you conscientiously and unconsciously are exposed to everyday. Banal, daily-life things like toothpaste, cosmetics, food additives, pharmaceuticals. They are composed of manufactured chemicals, synthesized and tested in a lab. You have probably never doubted the safety of your toothpaste or the efficacy of your pain reliever, but that comfort and assurance doesn’t come for free. The testing of safety and efficacy of the chemicals that we subject our bodies to depends on the use of animals that may suffer for our conveniences.

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Image credit: Flickr user Mycroyance http://tinyurl.com/noe58b9

How do we – as a society – balance the cost of animal research with the benefits? Who decides how many and how much animals suffer for the conveniences of our daily lives? Are there other alternatives? In PLOS Biology we have recently published two Perspectives that looks closely at these questions and propose meaningful ways to think of these moral dilemmas and possible steps forward.

 

In “The Challenging Road Towards a Unified Animal Research Network in Europe” Emma Martinez-Sanchez and Kirk Leech of The European Animal Research Association (EARA) advocate for scientists and research organizations to increase transparency and openness about the use of animals and the scientific research and developments gleaned from their work. By increasing communication, scientists can combat misinformation. Through advocacy and outreach that explains the unique benefits of animal research, as well as efforts to reduce the use of animals, the public can form an accurate picture of animal research. The authors encourage applying the 3R strategy (Replacement, Reduction and Refinement) during experimental design and the ARRIVE guidelines (Animal Research: Reporting in Vivo Experiments) when publishing animal studies.

 

One field that relies heavily on animal research is chemical safety assessment. Natalie Burden, Fiona Sewell, and Kathryn Chapman of the National Center for the Replacement, Refinement and Reduction of Animals in Research (NC3R) write in their Perspective “Testing chemical safety: What is needed to ensure the widespread application of non-animal approaches?” about the pressure to replace animal models. Currently animal models are considered the gold standard for determining if manufactured chemicals are safe for human use, exposure, or consumption. However, recent legislation in Europe that bans the testing of cosmetics on animals is propelling the development and use of non-animal techniques to assess chemical safety.

 

Burden and colleagues describe the challenges of moving away from animal models in the chemical safety field. The foremost challenge is in the development and acceptance of non-animal techniques that are able to accurately predict toxic effects. Replacing animal models will likely require a combination of techniques including in vitro methods, next generation sequencing and ‘omics’ technologies, and computational modeling. This will require not only the development of new techniques, but a standardization of the interpretation of results,and a cohesive regulatory process.

 

While our current scientific understanding and regulatory organizations require the use of animal testing to answer some key scientific questions, such as determining chemical safety, there are significant benefits to moving away from animal models. Scientists, research organizations, and regulatory bodies need to cooperate and work together to improve alternative techniques and their acceptance so that animal use can be reduced.

Category: Debate, PLOS Biology, Policy, Research | Tagged , , | 2 Comments

Convex Clustering and Synaptic Restructuring: the PLOS CB May Issue

Here are some highlights from May’s PLOS Computational Biology

 
Convex Clustering: An Attractive Alternative to Hierarchical Clustering

May Issue Image: Hi-C Chromatin Interaction Networks Predict Co-expression in the Mouse Cortex. Image Credit: Ms. Annelies te Selle

May Issue Image: Hi-C Chromatin Interaction Networks Predict Co-expression in the Mouse Cortex.
Image Credit: Ms. Annelies te Selle

The recently developed method of convex clustering preserves the visual appeal of hierarchical clustering while ameliorating its propensity to make false inferences in the presence of outliers and noise. Despite the advantages of convex clustering, there are still obstacles that stand in its way of becoming a practical tool in bioinformatics: current algorithms are computationally intensive, and there is minimal guidance available on how to choose penalty weights. To address these issues, Gary K. Chen and colleagues describe a fast new algorithm and a corresponding software implementation, CONVEXCLUSTER (freely available at http://www.genetics.ucla.edu/software/).

 

Modelling Circulating Tumour Cells for Personalised Survival Prediction in Metastatic Breast Cancer

Breast cancer survival is strongly correlated with genetic markers that are associated with increased resistance and invading skills of cancer cells, but it is poorly correlated with the amount of circulating tumour cells. To improve the understanding of the dynamic progression of the disease, Annalisa Occhipinti and colleagues develop a multi-compartment model which mimics the dynamics of tumoural cells in the mammary duct, in the circulatory system and in the bone.

 

Synaptic Restructuring Across the Sleep-Wake Cycle

Synaptic patterns are downscaled during sleep without LTP, but undergo restructuring after sleep-dependent LTP. Credit: Blanco et al.

Sleep is important for long-lasting memories. One existing theory posits that sleep weakens synapses, leading to the forgetting of all but the strongest memories. An alternative theory proposes that sleep promotes both weakening and strengthening of different connections, the latter through a process known as long-term potentiation (LTP). Sidarta Ribeiro and colleagues measure the levels of a protein related to LTP during the sleep cycle of rats, and use these data to build models of sleep-dependent synaptic plasticity. The results indicate that the current competing theories are not mutually exclusive; rather, each constitutes an important stage of memory consolidation.

 

 

Category: Cancer, Cell biology, Community, Computational biology, Neuroscience, PLOS Computational Biology, Uncategorized | Tagged , , , | 1 Comment

Deep Reads: John Bryant reflects on a book that inspired his research

The fourth of our Deep Reads blog posts is written by John Bryant,  a Professor Emeritus of Cell and Molecular Biology at the University of Exeter, UK. In addition to his deep interest in plant DNA, John has been involved actively in Bioethics for the past 20 years. He retains a passion for the natural world in general and is very active in communicating science and bioethics to a wider public.

A colleague and I were talking about the books we had kept since our undergraduate days. As we compared our lists, both of which were relatively short, we were delighted to find one book in common: Towards an Understanding of the Mechanism of Heredity by H.L.K. Whitehouse. My colleague and I were each fortunate enough, in our respective undergraduate years at Cambridge, to ‘sit at the feet’ of the author, Harold Whitehouse, or ‘Flash’ as we affectionately called him. Needless to say, Harold was not in any way ‘Flash Harry’, rather the opposite in fact. In my third year as a student, Whitehouse gave a series of lectures on genetics that really were inspirational! They were models of clarity and of organisation. Each lecture told a story; stories that dealt with classical views of inheritance, Mendelian genetics, chromosome theory, views on the nature of genes, the functioning of DNA and so on. Evidence was discussed and evaluated, and conclusions were reached. We were brought right up-to-date.

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DNA. Image from Pixabay CC BY.

In my time at university, we learnt that the lectures were based on a book (or was it the other way round?) that was soon to be published. Towards an Understanding of the Mechanism of Heredity was published after I graduated, but I can genuinely say that its contents and associated lectures pushed my career in a particular direction. I think especially of the chapters on DNA as genetic material, the genetic code, the nature of genes and operons and above all on the replication of DNA. I was, in addition to being thrilled by developments in molecular genetics, very interested in and committed to plant biochemistry. Indeed, I had already started to sound out Thomas ap Rees (who has been a major role model throughout my academic life) with a view to doing a PhD with him. But the combination of plant biochemistry and molecular genetics meant that for me, only one option was possible: I had to work with nucleic acids. Tom ap Rees was primarily known for his work on metabolic regulation which, without a doubt, would have been the direction I would have taken, had it not been for Harold Whitehouse’s lectures and book. As it happened, Tom allowed me to go where I wanted to go and I started a research career in which a major focus has been the biochemistry of plant DNA replication and its place in the cell division cycle.

But back to Towards an Understanding of the Mechanism of Heredity. As mentioned earlier, it was not published in time for me to read as an undergraduate, even though we had been exposed to its contents in lectures. PhD grants do not have much leeway for buying books and thus it was not until the second edition was published (just four years after the first) that I splashed out some of my postdoc salary to get my own copy. It is indeed a wonderful text. Look at the modesty and understatement of the title: Towards an Understanding … This contrasted greatly with the brashness and confidence of much of the molecular biology community. The book is highly readable, clear and well-organised, with each chapter devoted to a specific theme (or in Whitehouse’s terminology, theory) in genetics, dealing with the evidence and the conclusions with admirable clarity. It was a great help to me in my early years as a university teacher, with much of my teaching being at the interface between biochemistry and genetics. It is still a very good read, even though, inevitably in this field, much of it is now out-of-date.

Inspired by Towards an Understanding of the Mechanism of Heredity, my research interests led me to investigate plant DNA polymerases and other enzymes involved in plant DNA replication in my own research group. Indeed, for several years, mine was one of only four groups across the world working on these enzymes. This reinforced my interest in cell division and led me, together with Dr Dennis Francis, to set up the Cell Cycle group within the Society for Experimental Biology. The success of that group was celebrated in three days of good science at the 2013 Annual Main Meeting of the Society¹. In the meantime, working on DNA, the stuff of genes, eventually led me back to genes themselves, in looking at the regulation of genes encoding proteins involved in the initiation of DNA replication. And, just like Harold Whitehouse in his writings and lectures, I think we are approaching an understanding of these things².

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Image credit: Miki Yoshihito, Flickr CC BY

 

We at PLOS Genetics are looking for new submissions for our Deep Reads blog series and would love to find out more about the books that have inspired you as a scientist. Have any books introduced you to a captivating new scientific concept? Or made you think about something in a completely different way? Perhaps there’s a biography of a prominent scientist that you found particularly moving. If so, please get in touch.

Selected posts will be published on PLOS Biologue and should be no more than 800 words with one or two images. Entries should relate to a book (either fiction or non-fiction) with a genetics/genomics component.

Please send entries to plosgenetics@plos.org by 20th July, 2015 and we’ll be in touch if yours is chosen.

 

1 See, for example http://jxb.oxfordjournals.org/content/early/2014/02/02/jxb.ert469.full.pdf?keytype=ref&ijkey=lzrXOMWCzlazdzl

2 This understanding of science as ‘an approach to the truth’, verisimilitude, is one of the main ideas discussed by the science philosopher Michael Polyani whose work I have come to appreciate

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