This week in PLOS Biology

This week sees the launch of a new PLOS Biology CollectionThe Promise of Plant Translational Research, and a research article into a possible new drug target for rheumatoid arthritis.

 

Chun thumb1

Image credit: pbio.1001881

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation in the synovia of the joints. Its causes are still somewhat unclear, and there’s an urgent need for new and effective treatments. New research by Je-Hwang Ryu, Jang-Soo Chun and colleagues in PLOS Biology this week explored the role of HIF-2α, a transcription factor involved in the response to hypoxic conditions; hypoxia in the inflamed synovium is a known feature of RA. This new research showed that in mice, HIF-2α is markedly increased in the tissue lining the RA-affected joints. Interestingly, when it was overexpressed in normal mouse joint tissue, HIF-2α caused RA-like symptoms by itself. The authors conclude that HIF-2α could therefore be a therapeutic target for treatment of this disease.

 

Gates collection thumbnailWith the world’s population projected to rise from the current 7 billion to 9 billion by 2040, feeding these people from the same limited land and water resources will need considerable technology-driven advances in agricultural productivity. This week PLOS launches a new Collection, marked by 7 inaugural articles* in PLOS Biology, with the aim of encouraging submission of relevant research to Open Access venues like the PLOS journals, where they can be read by those who most need to. Read the Biologue blog post “How Will We Feed the World?” by Roli Roberts and our Editorial for more details.

 

*New articles in PLOS Biology published as part of “The Promise of Plant Translational Research”:

 

New Horizons for Plant Translational Research: Jeffrey Dangl, Sophien Kamoun, Susan McCouch and Jane Alfred present an overview of the Collection.

Moving beyond the GM debate: In this Perspective, Ottoline Leyser calls for the public to move on from the common logical fallacy that anything natural is good, and anything unnatural is bad, and addresses the misconception that GM, as a technique, is specifically and generically different from other crop genetic improvement techniques.

Genome Elimination: Translating Basic Research into a Future Tool for Plant Breeding: This Perspective by Luca Comai discusses the contribution of the late Simon Chan to the invention of genome elimination, and ponders the future of his approach as a way of streamlining the optimisation of plant genotype.

 

Finally, four Essays explore the technological basis and real-life application of genetic and genomic research, genome editing, whole-genome sequencing and metabolic engineering to the improvement of food crops:

 

Lab to Farm: Applying Research on Plant Genetics and Genomics to Crop Improvement by Pamela Ronald.

Precision Genome Engineering and Agriculture: Opportunities and Regulatory Challenges by Daniel Voytas and Caixia Gao.

Harvesting the Promising Fruits of Genomics: Applying Genome Sequencing Technologies to Crop Breeding: by Rajeev Varshney, Ryohei Terauchi and Susan McCouch.

Key Applications of Plant Metabolic Engineering by Warren Lau, Michael Fischbach, Anne Osbourn and Elizabeth Sattely.

 

 

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How Will We Feed the World?

Gates collection thumbnailPLOS has just launched a new Collection, “The Promise of Plant Translational Research”. Here’s why we did it, and what we hope to achieve.

 

The human race has a very serious problem; so serious that millions will die unless we solve it. It all started about 10,000 years ago. Up until then we’d lived as hunter-gatherers, and our humble lifestyle limited our numbers. But then we started to explore the benefits of exploiting the land more effectively, and agriculture was born. This technological suite of seed collection, sowing, irrigation, weeding and harvest allowed the same land to support many more of us.

 

Over the millennia we bred better crops (hexaploid wheat from emmer, maize from teosinte, paddy rice from Oryza rufipogon), systematically mechanised most aspects of the process (ox-drawn plough, seed drill, combine harvester), and artificially fertilised the soil (animal manure, the Haber process). And of course more food means more kids, and more kids need… You get the picture – a snowballing dependency on ever-improving the efficiency of our food production. All grown – by plants – using the solar energy that hits our finite planet.

 

Image Credit: Flickr user Frederic

Image Credit: Flickr user Frederic

The problem is that while population increases exponentially, food production increases only arithmetically. Seven billion souls – and counting – currently share our planet, with a projected population of nine billion by 2040. While the Green Revolution of the late 20th century went some way to keeping productivity in pace with demand, feeding these extra mouths will require a substantial increase in agricultural output while competing with the burgeoning population for valuable land and water resources. Furthermore, if a population is able to achieve food security, along with health care and education, people will tend to limit family size of their own accord, keeping population in check. So working to achieve food security for the world’s billions offers a constructive way out of the debacle.

 

PLOS recognises that many of these problems (and the need for attendant solutions) impinge directly on those people and countries least able to break through the pay-wall that many scientific journals use to guard their content. For translational plant research, more than most fields,  Open Access is crucial to maximise the availability and utility of research by those who need it most. We, and the rest of the scientific community, can facilitate information and knowledge exchange by promoting Open Access.

 

What our Collection aims to do is a) open up the debate about the urgent need for plant translational research, b) discuss the ways in which scientific research and technological advance can meet this need, and c) encourage the submission of such research to Open Access journals, like those of the PLOS family.

 

What can you do? Firstly, read the inaugural articles of the Collection that we’ve just published in PLOS Biology (see below). I’d recommend starting with the magnificently punchy Perspective by Ottoline Leyser, which lays out the scale of the problem and exhorts us to ignore red herrings and concentrate on the pressing task in hand. Secondly, submit your translational plant research to one of our journals (PLOS Biology, PLOS Pathogens, PLOS Genetics, PLOS Computational Biology and PLOS ONE are the most relevant) and make sure that the people who need to read it can!

 

We’re grateful to Jeffrey Dangl, Sophien Kamoun and Susan McCouch, who as academic editors of the Collection have provided us with advice and guidance throughout, including helpful comments on this blog post. We’d also like to thank the Bill and Melinda Gates Foundation for supporting the Collection.

 

 

New articles in PLOS Biology published as part of “The Promise of Plant Translational Research”:

 

New Horizons for Plant Translational Research: Jeffrey Dangl, Sophien Kamoun, Susan McCouch and Jane Alfred present an overview of the Collection.

Moving beyond the GM debate: In this Perspective, Ottoline Leyser calls for the public to move on from the common logical fallacy that anything natural is good, and anything unnatural is bad, and addresses the misconception that GM, as a technique, is specifically and generically different from other crop genetic improvement techniques.

Genome Elimination: Translating Basic Research into a Future Tool for Plant Breeding: This Perspective by Luca Comai discusses the contribution of the late Simon Chan to the invention of genome elimination, and ponders the future of his approach as a way of streamlining the optimisation of plant genotype.

 

Finally, four Essays explore the technological basis and real-life application of genetic and genomic research, genome editing, whole-genome sequencing and metabolic engineering to the improvement of food crops:

 

Lab to Farm: Applying Research on Plant Genetics and Genomics to Crop Improvement by Pamela Ronald.

Precision Genome Engineering and Agriculture: Opportunities and Regulatory Challenges by Daniel Voytas and Caixia Gao.

Harvesting the Promising Fruits of Genomics: Applying Genome Sequencing Technologies to Crop Breeding: by Rajeev Varshney, Ryohei Terauchi and Susan McCouch.

Key Applications of Plant Metabolic Engineering by Warren Lau, Michael Fischbach, Anne Osbourn and Elizabeth Sattely.

 

 

 

 

Category: Announcement, Biology, Climate, Community, Ecology, Environment, Genetics, Genomics, Open access, Plant biology, PLOS Biology, PLOS Computational Biology, PLOS Genetics, Research | 5 Comments

PLOS Comp Biol style for 2014: Nonconsensus binding

PLOS Computational Biology is delighted to reveal the winner of this year’s t-shirt design competition: Ariel Afek, from Ben-Gurion University! Ariel’s design “Nonconsensus Protein-DNA binding” will appear on t-shirts available from the PLOS booth at the ISMB 2014 conference in Boston. PLOS Computational Biology t-shirts have become a popular staple of the journals’ presence at ISMB over the past six years, so make sure you drop by the PLOS booth to grab one before they’re gone!

Image credit: PLOS

Image credit: PLOS

The winning design is based on the phenomenon of “Nonconsensus Protein-DNA binding”, where proteins bind to DNA in the absence of a binding site. Normally proteins require specific sequences (called motifs) to be present in an area of DNA before they can bind to it, but in the scenarios modelled by Ariel and his co-authors and depicted in the design, different proteins can bind to DNA in various genomic locations which lack motifs. The initial image appeared as a way for Ariel to help explain the process at a conference and, with feedback from friends, was developed into the final design.

Ariel and his co-authors have modelled this form of binding in the yeast genome, and will be presenting experimental results and bioinformatics analysis on this topic as a poster at ISMB, in the “Functional Genomics” category.

The PLOS booth will be open at ISMB 2014 from 12th July to 15th July. We’d love to hear your feedback and suggestions for the journal, so please come and say hello!

 By Arielle Bennett, Publications Assistant, PLOS Computational Biology 

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Modelling arterial hypertension, using the human genome in drug discovery and lessons from professional basketball: The PLOS Comp Biol May issue

Here is our selection of PLOS Computational Biology highlights for May.

Getting to know you: Innate immune sensing of fungal pathogen surfaces. Image Credit: Matthew S. Graus, Aaron K. Neumann

Getting to know you: Innate immune sensing of fungal pathogen surfaces. Image Credit: Matthew S. Graus, Aaron K. Neumann

No man ever steps into the same river twice, for it’s not the same river and he’s not the same man (Heraclitus of Ephesus, 535–475 BCE).  This is how Yonatan Lowenstien and Tal Neiman introduce their paper, “Spatial Generalization in Operant Learning”: Lessons from Professional Basketball”. The paper looks at operant learning and how behaviours are not reinforced or inhibited by the “same” actions, but instead by similar events, as in natural environments the “same” situation never occurs. While this is a familiar generalisation, the computational principles that underlie it are not fully understood, so the paper used statistics from professional basketball to study these principles. It was found that players are more likely to attempt a field goal from the vicinity of a previously made shot than they are from the vicinity of a missed shot. This result indicates that rather than using low-level features, operant learning in basketball is determined by high-level cognitive processes that incorporate the abstract rules of the game.

Genome-Wide Association Studies can provide great understanding for the etiologies of many complex diseases and have the potential to inform the discovery of safe and effective medicines. However, authors Lei Xie et al. write in their Review that these data have not been fully explored in order to improve the efficiency of drug discovery. The Review studies the dynamics of molecular interactions for the entirety of the human genome and shows that progress is being made towards the final goal of personalised medicines for the treatment of complex diseases.

Despite arterial hypertension, or high blood-pressure, being one of the most common age-related chronic disorders, its major cause remains enigmatic. Klas H. Pettersen et al. developed a computer model of the circulatory system; using this they demonstrate that arterial stiffening seems sufficient to explain age-related emergence of hypertension. The stiffening causes the blood-pressure sensors in the arterial wall to misinform the highly complex machinery responsible for blood pressure regulation.

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PLOS at OHBM – Be Part of the PLOS Neuroscience Community

Image credit: Goulas, A. et al., (2014). PLOS Comput. Biol. DOI: 10.1371/journal.pcbi.1003529

Image credit: Goulas, A. et al., (2014). PLOS Comput. Biol. DOI: 10.1371/journal.pcbi.1003529

Will you be attending the 20th Annual Meeting of the Organization for Human Brain Mapping in Hamburg (June 8-12)? We will be there and look forward to meeting you and hearing your thoughts about neuroscience at PLOS, open access, open data, and open science.

 

What’s happening at OHBM 2014:

 

  • Interested in hearing more about article-level metrics, open data, and our new Data Policy? Martin Fenner, technical lead for the PLoS Article Level Metrics project, will be available on Tuesday, June 10, 2-4pm, to answer your questions and hear your feedback.

 

  • Would you like to know more about neuroscience at PLOS, the editorial process, and how to get involved in the PLOS neuroscience community? Join us for afternoon refreshments on Wednesday, June 11, 12:45-2:45pm, and meet with myself, PLOS Academic Editors, authors, and reviewers.

 

You will find us at the PLOS table in the Exhibit Hall (Hall H) of the Congress Center Hamburg. Feel free to drop by any time.

 

PLOS LogoDid you know?

  • The top 25 PLOS neuroscience articles have received 1,265,514 views and 2,334 citations
  • The PLOS journals have collectively published more than 14,000 neuroscience articles. Here is a selection of recent brain mapping papers published across the PLOS journals:

 

Brain Systems for Probabilistic and Dynamic Prediction: Computational Specificity and Integration

Jill X. O’Reilly et al., PLOS Biology, 2013

 

A Toolbox for Representational Similarity Analysis

Hamed Nili et al., PLOS Computational Biology, 2014

 

Spatial Dependencies between Large-Scale Brain Networks

Robert Leech et al., PLOS ONE, 2014

 

Structurally-Constrained Relationships between Cognitive States in the Human Brain

Ann M. Hermundstad et al., PLOS Computational Biology, 2014

 

A Critical Role for the Hippocampus in the Valuation of Imagined Outcomes

Maël Lebreton et al., PLOS Biology, 2013

 

Revealing Time-Unlocked Brain Activity from MEG Measurements by Common Waveform Estimation

Yusuke Takeda et al., PLOS ONE, 2014

 

Comparative Analysis of the Macroscale Structural Connectivity in the Macaque and Human Brain

Alexandros Goulas et al., PLOS Computational Biology, 2014

 

Speech Rhythms and Multiplexed Oscillatory Sensory Coding in the Human Brain

Joachim Gross et al., PLOS Biology, 2013

 

Voluntary Enhancement of Neural Signatures of Affiliative Emotion Using fMRI Neurofeedback

Jorge Moll et al, PLOS ONE, 2014

 

Influence of Wiring Cost on the Large-Scale Architecture of Human Cortical Connectivity

David Samu et al., PLOS Computational Biology, 2014

 

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This week in PLOS Biology

In PLOS Biology this week, read about new research into the way our immune and nervous systems interact with each other in response to disease. Also find out more in the accompanying synopsis.

 

Image credit: pbio.1001874

Image credit: pbio.1001874

We know that the nervous and immune systems interact constantly in complex ways, but there is much we don’t know about the mechanisms of such signalling. In the context of inflammation, for example, the influence of the immune system on the brain is highly relevant for a number of diseases. In new research published this week, Kirsten Ridder, Stefan Momma and colleagues used a genetic tracing system in mice to show that white blood cells can transfer functional RNA directly to neurons in the brain using extracellular vesicles. Interestingly the activity of this pathway was very low in healthy individuals, but jumped by several orders of magnitude when an inflammatory response was triggered. The study reveals a previously unknown medium of information exchange between the immune and nervous system, and the authors predict a complex regulation of gene expression in neural cells in response to peripheral inflammation. Read more in the accompanying synopsis.

Category: Biology, Cell signalling, Disease, Immunology, Infectious disease, Neuroscience, PLOS Biology, Research | Leave a comment

Meiosis Gordon Conference: Gregory Copenhaver

As part of its mission to encourage engagement within the genetics community, PLOS Genetics is sponsoring a number of conferences and meetings this year. In order to raise awareness about these conferences and the researchers who attend them we are featuring a number of these conferences on Biologue, with posts written by the organizers or PLOS Genetics editors who are involved.

The third of these conferences is the Meiosis Gordon Research Conference, which takes place in New London between the 1st and 6th of June. We hear from Gregory Copenhaver, PLOS Genetics co-Editor-in-Chief, about organizing the conference and the areas of research that he finds exciting.

The image is from one of PLOS Genetic’s own Associate Editors, Kirsten Bomblies, who will be presenting at the meeting. Image credit: James Higgins

The image is from one of PLOS Genetic’s own Associate Editors, Kirsten Bomblies, who will be presenting at the meeting. Image credit: James Higgins

I’m Gregory P. Copenhaver, co-Editor-in-Chief of PLOS Genetics, and together with my vice-Chair, Neil Hunter, I’m organizing the Meiosis Gordon Research Conference (GRC) to be held at Colby-Sawyer College in New London, NH on June 1-6, 2014. The conference has been held biennially for 22 years with an over-arching goal of presenting the most cutting-edge, unpublished research on the fundamental mechanisms that ensure the stable inheritance of the genome during meiotic cell divisions.  The program comprises 9 plenary sessions that broadly address current issues in meiotic recombination, meiotic progression and cell cycle checkpoints, epigenetic control of meiotic processes, regulation of meiotic gene expression, chromosome pairing and synapsis, sister chromatid cohesion, chromosome interactions with the nuclear envelope, chromosome segregation, and the evolution and natural variation of meiotic processes. The meiosis GRC is paired with a sister meeting – the Meiosis Gordon Research Seminar – that is organized and attended by graduate students and postdocs.  This pair of conferences brings together scientists from around the world and at all career stages to push the leading edge of innovation and knowledge in this critical area fundamental biology.

Meiosis is the definitive set of processes for sexually reproducing organisms, and it is near and dear to my heart since it is the central focus of my lab.  The Meiosis Gordon Conference is the premier scholarly meeting in the field and this year promises to be packed with exciting, hot-off-the-press science. In addition, the meeting will continue a strong tradition of promoting diversity at all levels – career stage, gender, organismal system and geographic distribution.  It’s great that PLOS can support the dissemination of some of the newest research in genetics by being a sponsor of this meeting – it’s a wonderful dovetailing of two organizations (PLOS and the Gordon Conferences) that have both had a huge influence on promoting excellent science.

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PLOS Data Policy: Update

Two months after the implementation of the PLOS journals’ data policy, what have we learned from our authors, reviewers, editors, correspondents, and commenters in the blogosphere?

More than 16,000 manuscripts have been submitted with a data availability statement

In order to optimise the re-use of data by readers and by data miners, authors of all new manuscripts submitted since March 3, 2014 have included a statement about where the data underlying their description of research can be found. At the time of writing, more than 16,000 sets of authors have included information about data availability with their submission. We have had fewer than 10 enquiries per week to data@plos.org from authors who need advice about ‘edge cases’ of data handling and availability – fewer than 1% of authors – and these cases have helped us to further update our FAQ, contributing to a decline in such enquiries over time. We would like to say a huge thankyou to all the authors and editors who have worked with us in this period to iron out wrinkles in our submission processes and helped us make it as easy as possible to capture information about data availability. Special mention is due to the pioneering subset of authors who have already published articles in PLOS journals with a Data Availability Statement, whether all data are provided within the manuscript and its supplementary files or providing links to a domain-specific repository, a non-specific repository or more diverse resources (see Image).

 

Screen Shot 2014-05-28 at 11 20 28

 

Some groups of authors still have concerns about data sharing

From our period of increasing public consultation about the PLOS data policy, we knew that at launch we would encounter authors with specific issues in two main areas: firstly, big datasets that are too large for hosting in most repositories (although some, such as the journal GigaScience target precisely this domain), and secondly around patient confidentiality and the associated need to have oversight committees for instances in which access should be restricted to appropriate individuals. Since the launch we have heard these issues raised again, but we have also heard three main arguments used by bloggers and others to justify not sharing the data underlying research articles that we find it hard to agree with. They can be summarised as follows.

It’s mine, I collected it. Most funders and institutions have moved away from this idea, but it persists in the mind of many researchers.

It’s complicated and unique: no-one else could understand it properly This “data as a unique snowflake” argument supposes that no-one other than those who collected the data can understand it enough to re-use it. Taken to an extreme, this argument would tend to suggest that there is no point in peer-reviewing or publishing research at all. We would rather work with those (e.g. BioSharing) who are working to develop standards and approaches to describing data so that it can indeed be used by others.

I’d like to share, but my lab is little and/or under-funded and/or in a lower-income country, and once I share the big guys can jump on the data and do cool things with it before I can do them myself. We of course have sympathy with this perspective, and PLOS journals work specifically with authors in less-developed countries to help them publish their work. However, as noted by panellist Joe DeRisi in a discussion of data sharing at UCSF earlier this month, it would be perverse to suggest that we delay, for example, progress in malaria research in order to allow researchers in the most-affected countries to contribute optimally.

There is one additional argument that has been made, and we acknowledge this one reflects a genuine concern, namely that it takes work to make data sharing-ready. Previously we required all PLOS authors to share data “on request”, but some bloggers have noted that no-one ever requested much of their data, or that when it was requested they in fact refused, whereas now all data should be made ready for sharing, whether ultimately needed or not. We agree that this does require work, however it takes less work to prepare the data at the same time as the publication than was previously required when trying to dig into archives to find material some time later (humorously summarised in a video cartoon). And we would note that increasingly all funders require, as a condition of a grant, that a data-management plan be included, and that this is driving researchers and their institutions to have good systems in place that will meet the criteria of the PLOS policy.

We focused on where, when and how to share, but many are still concerned about what to share

The new PLOS data policy refers to sharing the data underlying a publication, just as our previous policy did. The new part of the policy is to ask for sharing ‘up front’, at the time a manuscript is submitted, rather than subsequently and on request. But an awful lot of the responses to the policy have focussed on the issue of which datasets need to be included. It was not quite as apparent from our prior consultation as it is now: researchers in many fields don’t know which data to archive and share and which should be considered ‘disposable’ moments en route to data worth preserving. Although funders such as NIH and community organisations such as MIBBI try to outline the requirements either generally or specifically, it seems it will be a sisyphean task to provide detailed guidance for every type of experiment in every domain within science. We are therefore currently considering the extent to which we at PLOS can or should aim to provide this type of guidance, and would welcome your input on this issue.

There can be real difficulties about ‘limited sharing’, whether during peer review or after publication. Most repositories, whether subject-specific or general, institutional or international, are set up to allow full open access. But there are two main circumstances in which more limited sharing is appropriate. The first is during peer review, when editors and reviewers need access to the data but the authors may not want it to be public; we are aware of only a few databases (e.g. Dryad) that routinely provide this facility. The second circumstance is when datasets contain sensitive information – whether about patients or, for example, endangered species’ locations -  such that it may be appropriate to share only a subset of the information more widely, and/or to share only with appropriately screened individuals. Several databases and repositories have plans to allow more limited access (e.g. Dataverse, figshare), which should help address concerns in this area, but this is a work in progress. For now, it remains a major challenge for clinical studies to both provide controlled access to the data and preserve patient confidentiality.

There is plenty still to do

The 2014 PLOS data policy deliberately set out to take just one step towards improved integration between the published literature and the data underlying it, by asking authors to say where there data can be found ( that somewhere being not on their own hard drives). We know that much more will be needed before we are dealing with data satisfactorily. For a small minority of commenters, we did not go far enough. For many more, we leave too many open questions, and we agree there are many, most of which are not unique to PLOS and need further community discussion. Among the most pressing, from our perspective:

  • When should an author choose Supplementary Files vs. a repository vs. figures and tables.
  • Should software/code be treated any differently from ‘data’? How should materials-sharing differ?
  • What does peer review of data mean, and should reviewers and editors be paying more attention to data than they did previously, now that they can do so?
  • And getting at the reason why we encourage data sharing: how much data, metadata, and explanation is necessary for replication?
  • A crucial issue that is much wider than PLOS is how to cite data and give academic credit for data reuse, to encourage researchers to make data sharing part of their everyday routine.
  • And for long-term preservation, we must ask who funds the costs of data sharing? What file formats should be acceptable and what will happen in the future with data in obsolete file formats? Is there likely to be universal agreement on how long researchers should store data, given the different current requirements of institutions and funders?

As we continue to work on these issues and others, we would once again welcome your feedback and input, here on the blog, via individual journals, or at data@plos.org.

Theo Bloom and Jennifer Lin, for the PLOS Data Policy group.

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This week in PLOS Biology

In PLOS Biology this week you can read about metabolome evolution, protein flexibility and interactions between proteases and their inhibitors.

Image Credit: journal.pone.0041044.g001

Image Credit: journal.pone.0041044.g001

In their new research paper, Katarzyna Bozek, Philipp Khaitovich and colleagues analysed thousands of metabolites from brain, kidney and muscle tissue of humans, chimps and monkeys. They found accelerated evolution of metabolites not only in the human brain – which might be expected – but also human muscle metabolomes. The physiological impact of the surprisingly rapid evolution of human muscle remains unclear, although the authors did do a follow up study testing strength in humans and non-human primates and found human strength was barely half that of primates. Read more in the accompanying synopsis.

 

pbio.1001870

Image credit: pbio.1001870

Proteins often interact with other proteins and assemble into complexes.  Joseph Marsh and Sarah Teichmann computationally assessed the structural flexibility of thousands of proteins in their research article, and found that the flexibility of individual proteins aids their evolutionary recruitment into complexes with increasing numbers of distinct subunits. This flexibility becomes increasingly important as a greater number of proteins are packed together within a single complex.

 

pbio.1001869

Image credit: pbio.1001869

Proteases (enzymes that break down other proteins) are an important target for drug development, as deregulated protease activity is a common characteristic of many diseases. However we have incomplete understanding of their biology due in part to their complex functions: some activate other proteases whereas some inactivate inhibitors. Network modelling of interactions between proteases and their inhibitors, carried out by Nikolaus Fortelny, Christopher Overall and colleagues reveals a network of new protein connections and cascades in the protease web. They also tested some of the predicted effects in mice.

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This week in PLOS Biology

In PLOS Biology this week you can read about new ways to approach preclinical trials, signaling in the vertebrate retina, how Leishmania adapts to its environment and a protein which can stop bacterial protein synthesis when nutrients are low.

In their Perspective this week, Jonathan Kimmelman, Jeffrey Mogil and Ulrich Dirnagl discuss the recent consternation over the way in which preclinical investigations of new drugs are performed and reported. They argue that we first need to distinguish between ‘exploratory’ investigation - generating robust pathophysiological theories of disease - and ‘translational’ or ‘confirmatory’ investigation, which seeks to demonstrate reproducible effects in animal models. Kimmelman and colleagues say that each type of research requires different study designs and suffers from different validity threats, and that this should be taken into account in research policy.

pbio.1001865

Image credit: pbio.1001865.

In the vertebrate retina, an interaction between the horizontal cells and photoreceptor cells allows us to remove redundant visual information in space and time, in order optimally see a scene. But how, physiologically, does this work? Rozan Vroman, Maarten Kamermans and colleagues measured current within goldfish cone-horizontal cell synapses to answer this question. They found that the horizontal cells feed back to photoreceptors via both a very fast mechanism and by a relatively slow mechanism. This slow mechanism requires ATP release from the tips of horizontal cell dendrites, followed by hydrolysis of ATP to products that acidify the synaptic cleft. Read more in the accompanying synopsis.

A research article by Jean-Michel Ubeda, Marc Ouellette and colleagues finds that the human parasite Leishmania uses gene rearrangements and repeat-mediated amplification on a genome-wide scale as a strategy to adapt to a changing environment. This means that upon selection with either drugs or culture conditions, a subpopulation can emerge where the amplicon copy number per cell increases and this clone of cells can then expand to dominate the population.

pbio.1001867

Image credit: pbio.1001866

Typical bacterial cells contain tens of thousands of ribosomes, which make the proteins needed for life. However, during hard times, when nutrients (and therefore amino acids) are low, the cell needs to slam on the brakes.  In their new paper, Boya Feng, Ning Gao and colleagues found that a protein called ObgE can bind to the large subunit of the ribosome, disrupting its association with the small subunit and stopping translation. They suggest that the presence of (p)ppGpp – a chemical made by bacteria in response to low levels of amino acids – causes ObgE to linger on the large subunit longer than it would in its normal role. Read more in the accompanying synopsis.

Category: Biology, Cell biology, Disease, Evolution, Genomics, Infectious disease, Microbiology, Molecular biology, Neuroscience, PLOS Biology, Policy, Research | Leave a comment