This week in PLOS Biology

Berman Synopsis Figure FINAL

The antifungal drug fluconazole induces Candida albicans to form a novel cell
type—a ‘‘trimera’’—that contains two simultaneously dividing nuclei. Mitotic
spindles (green) are shown segregating sister nucleoli (red). Image by Benjamin D. Harrison.

In PLOS Biology this week you can read about neurons involved in circadian rhythms, decision-making in rats, modulation of a key cancer cell pathway, glucocorticoid receptor function and anti-fungal drug-resistance.

  • Yeast infections can be at best annoying, and at worst life-threatening. Unlike bacterial infections, there are relatively few drugs available to treat them. One of the most commonly used is Fluconazole, but resistance to this drug is increasing. In a research article this week (with accompanying synopsis), Benjamin Harrison, Judith Berman, and colleagues showed that Fluconazole may actually unwittingly collude in the steps leading to resistance. When Fluconazole was used to treat yeast (Candida albicans) infections in the ears of mice, some yeast cells showed abnormal growth, forming ‘trimeras’ of three-lobed cells. The progeny of these trimeras (yeasts reproduce by budding) had abnormal numbers of chromosomes, increasing the odds of some cells containing large numbers of drug-resistance genes.

 

  • The glucocorticoid receptor (GR) is a transcription factor expressed in almost every cell in the vertebrate body. It binds steroid hormones from the glucocorticoid family, which are often used in a therapeutic capacity. After binding these molecules, GR has two different modes of action – transactivation and transrepression. In an article in this week’s PLOS Biology Gordon L. Hager and colleagues (with an accompanying synopsis) attempt to clarify GR’s different activites. Their results challenge the prevailing view that GR’s dimerization state (whether the receptor exists as a single molecule or two tightly bound ones) determines whether it initiates transactivation or transrepression. As transactivation is linked to many of the side effects that GCs cause when used therapeutically, a deeper understanding of these mechanisms could have clinical relevance.

 

pbio.1001809

journal.pbio.1001809

  • The RAS/MAPK pathway was the focus of research by Dariel Ashton-Beaucage, Marc Therrien and colleagues. This pathway has a notable involvement in cancer as mutations in the components of the pathway are associated with uncontrolled cell proliferation. A global screen in Drosophila cells using RNAi to systematically knock down genes identifies a large group of transcription and splicing factors that modulate RAS/MAPK signalling by altering the expression of MAPK.

 

  • How do you prioritise decisions? Irene Avila & Shih-Chieh Lin looked at neurons in the brains of rats that determine responses to motivationally salient stimuli (those which are related to important outcomes). Their study shows that neurons in a region of the brain called the basal forebrain (BF) play a major role in determining the speed of decisions. When a stimulus (white noise or clicking) preceded a reward, decision-making speeds were increased. This research has implications for the potential role of BF neurons in neurological conditions characterised by slow reaction times, such as dementia and schizophrenia. More information is available in an accompanying synopsis.

 

  • The circadian clock runs as an intricate molecular oscillator in many separate cells, but these need to be synchronised in order to provide a consensus signal to control behaviour and other circadian traits. This syncing job is known to be done by the Pigment Dispersing Factor (PDF) neuropeptide signalling pathway. A study of Drosophila circadian neurons, by Adam Seluzicki, Ravi Allada and colleagues reveals that the PDF pathway splits in two, independently using cyclic AMP to sync circadian clocks via protein kinase A and to acutely control neuronal excitability, possibly via a cyclic nucleotide-gated channel.

 

Category: Biology, Cancer, Cell biology, Cell signalling, Infectious disease, Molecular biology, Neuroscience, PLOS Biology | Leave a comment

Collective behaviour, RAS and DNA repair, Semaphorin’s role in reproduction: this week in PLOS Biology

DOI:10.1371/journal.pbio.0020324

DOI:10.1371/journal.pbio.0020324

  • Systems biology looks at the big picture of complex interactions within biological systems; one example is collective behaviour, where a system comprising multiple entities operates with no centralised control. Examples of this can be seen from the cellular level (groups of patrolling immune cells on the prowl for pathogens) to groups of animals (birds flying in flocks that turn in the sky in perfect synchrony). In an Essay this week Deborah Gordon describes how environmental constraints (such as operating costs) may have shaped the evolution of collective behaviour. She argues that similar evolutionary pressures have produced similar collective behaviour in groups from molecules to cells to whole animals. Ants are used here as an example, as a large, diverse and extremely successful taxon that is well known for its collective behaviour.

 

  • A mark of a cancerous tumour is unregulated cell growth, potentially involving damage to the DNA of the cancer cells. However, in order to be successful and proliferate, cancer cells need to avoid the resulting senescence. In a Research Article this week, Alain Nepveu and colleagues identify a alternative workaround -  the presence of an oncogenic ‘RAS’ gene heightens the ability of cells to repair damage to their DNA (specifically targeting the type of damage caused by oxidative stress).

 

  • The semaphorins are a group of proteins present in cell membranes and responsible for diverse signalling functions. During the development of an embryo, they guide the development of blood vessels and neurons. However, whether these proteins continue to have any effects in the adult brain has been unclear. A new study by Paolo Giacobini, Vincent Prevot and colleagues suggests they do have a role: in mice they seem to be involved the essential regulation of reproduction – semaphorin molecules secreted by endothelial cells control axon growth and promote the timely release of a key hormone called Gonadotropin-releasing hormone (GnRH).

 

Category: Biology, Cancer, Cell biology, Cell signalling, PLOS Biology, Systems biology | Leave a comment

Welcoming three new Deputy Editors-in-Chief at PLOS Computational Biology

We’re thrilled to announce the appointment of three new Deputy Editors-in-Chief (DEICs) for PLOS Computational Biology: Sebastian Bonhoeffer, Jason Papin and Olaf Sporns.

As well-respected and committed Deputy Editors, Sebastian, Jason and Olaf have been key members of the editorial board for a number of years, and we’re delighted to welcome them to their new roles. Their areas of expertise represent PLOS Computational Biology’s broad scope, and as DEICs they will help Editor-in-Chief Ruth Nussinov shape the journal’s Editorial Board, scope and policies.

Here’s a bit more about each of our new DEICs.

Sebastian Bonhoeffer

Image credit: Sebastian Bonhoeffer

Sebastian Bonhoeffer is Full Professor of Theoretical Biology at the ETH Zurich. Following studies in music in Basel, and physics in Munich and Vienna, he then moved to Oxford to do a PhD with Martin Nowak and Robert May at the Department of Zoology. His research focuses on using population biological models to understand fundamental biological processes. He has worked extensively on mathematical models describing the population dynamics of virus infections within infected individuals.

BioMedical Engineering, UVa.

Image credit: Jason Papin

Jason Papin is on the faculty of the Department of Biomedical Engineering at the University of Virginia.  He received his BS, MS, and PhD in Bioengineering at the University of California, San Diego. His research group develops methods to integrate high-throughput data and generate predictive computational models to address challenges in metabolic engineering, infectious disease, and cancer.

Olaf1

Image credit: Olaf Sporns

After receiving an undergraduate degree in biochemistry, Olaf Sporns earned a PhD in neuroscience at Rockefeller University and then conducted postdoctoral work at The Neurosciences Institute in New York and San Diego. Currently he is a Distinguished Professor in the Department of Psychological and Brain Sciences at Indiana University in Bloomington. His main research area is theoretical and computational neuroscience, with a focus on complex brain networks.

We’d like to thank Sebastian, Jason and Olaf for their hard work for the journal over the past few years. Please join us in congratulating them on their new roles!

As a community journal, PLOS Computational Biology is your journal, and we want to hear from you. Please send your thoughts on the journal to ploscompbiol[at]plos.org or add them as comments to this blog post. We’re always happy to receive them.

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Understanding allostery, constructing structural pathways and exploring a new trend in data integration: the PLOS Comp Biol February issue

Here’s our pick of the best PLOS Computational Biology content for February.

The capacity of biological molecular data acquisition is growing faster than our ability to understand the relationships between molecules in a cell. There are multiple databases that store and organize these molecular data, yet emerging fundamental questions about the functions of these molecules in hierarchical cellular networks are poorly addressed. In a Perspective, Boris Kholodenko and colleagues explore recent advances in the development of publically available databases that help us analyze signal integration and processing by reconstructing multilayered networks that specify biological responses in both model organisms and human cells.

The Speed Boat activity: using interactive games to inspire creativity and explore challenges in computational biology. Image Credit: Jennifer A. Cham and the EMBL-EBI Industry Programme Agri-Food Workshop participants.

The February issue image depicts the Speed Boat activity: using interactive games to inspire creativity and explore challenges in computational biology. From Pavelin et al. Image Credit: Jennifer A. Cham and the EMBL-EBI Industry Programme Agri-Food Workshop participants.

Structural pathways are important because they provide insight into signaling mechanisms, help understand the mechanism of disease-related mutations, and assist in drug discovery. Ozbabacan et al. construct the IL-1 structural pathway and map oncogenic mutations and SNPs. They show that modeling of protein-protein interactions on a large scale can provide accurate, structural atom-level detail of signaling pathways in the human cell and help delineate the mechanism through which a mutation leads to disease.

Numerous approaches have been undertaken over the last 50 years in an effort to explain allostery. Chung-Jung Tsai and Ruth Nussinov survey points of view on allostery in a Perspective, synthesizing them via a mathematical model in order to obtain a coherent understanding of the question of how allostery works. They address this question from three standpoints: thermodynamics, free energy landscape of population shift, and structure; all with exactly the same allosteric descriptors.

 

Category: Biology, Cell signalling, Computational biology, Data, Education, Molecular biology, PLOS Computational Biology, Uncategorized | Tagged | Leave a comment

Call for blogs!

Is there a book that motivated you to become a scientist, or to research a certain aspect of genetics? Or perhaps your perception of science has been altered through something you’ve read? How far do you think the lives of researchers today have been influenced by learning about the lives of those in the past? We want to hear from you!

Jane Gitschier’s bookshelf

Inspired by the new Deep Reads series, kicked off in December with the article “Recommendations from Jane Gitschier’s Bookshelf”, PLOS Genetics would like to hear about the books that have inspired you as a scientist and your views of science in literature. We hope to discover how science, more specifically within the fields of genetics and genomics, is portrayed and its relationship to the wider community. To do this, we invite you to select your favourite genetics-themed book  (fiction or non-fiction) and write a short review, relating the piece back to your own experiences as a scientist, whether you are studying or embarking on a career in science.

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

PLOS Biologue publishes under the Open Access Creative Commons Attribution license. Please ensure that the image(s) you use, especially if taken from other sources, fall under this license or are in the public domain.

Please send entries to plosgenetics@plos.org by 14th March, 2014 and we’ll be in touch if yours is chosen.

We look forward to reading about the books that have motivated you!

Category: Announcement, Blog, Books, Genetics, Outreach, PLOS Genetics, Review | Tagged , , | Leave a comment

“Fish Fins and Fingers” Feeding Frenzy

DOI: 10.1371/journal.pbio.1001773

DOI: 10.1371/journal.pbio.1001773

How did we first acquire the limbs that allowed us to crawl onto dry land? Could the fins of our fishy ancestors hold previously undiscovered clues? A recent research article by Denis Duboule and colleagues published in PLOS Biology (and an accompanying Synopsis), attempted to shed more light on this fascinating topic.

The authors found that the genes and regulatory architecture necessary for digit patterning are present in fish (and therefore presumably in our last common ancestor); however some essential elements for actually forming digits are missing, and this functionality has been subsequently “retrofitted” in land-dwellers. The article has received over 7000 views since it was first published on January 21st, so here we take a look at some of the accompanying media interest.

 

Los Angeles Times

LA Times science writer Geoffrey Mohan gave some background to the debate of how fish could have evolved to walk on land, mentioning previous discoveries which have provided some pieces to the puzzle. “There have been tantalizing finds, including Tiktaalik, a prehistoric fish with shoulder and pelvis characteristics of a tetrapod, or four-legged animal. Modern genetics since has added evidence to supplement the fossil record.”

 

BBC News

BBC science reporter Melissa Hogenboom provided a detailed summary of the study, but also sought some expert opinions on whether the model organism used in the study (the zebrafish) is really the right fish for the job. Professor Jenny Clack, of the University of Cambridge explained “We know that this animal, and by inference its relatives… lack some of the developmental stages that make digits in tetrapods”. Prof. Clack suggests that zebrafish were not the best choice for this experiment, calling into question what can really be inferred from the study.

 

Phys.org

Phys.org discussed the Hox genes which are necessary for both fins and limbs to form, but which Duboule and colleagues found behave differently in fish and land animals.  “When inserted into transgenic mouse embryos, the fish Hox genes were only active in the mouse arm but not in the digits, showing that the fish DNA lacks essential genetic elements for digit formation”.

 

 

Category: Biology, Developmental biology, Epigenetics, Evolution, News, PLOS Biology, Publishing, Research | Leave a comment

Dynamics of leadership in dog packs, communication in the cerebral cortex and modelling anti-tumour immunity: the PLOS Comp Biol January issue

Here is our selection of highlights for PLOS Computational Biology’s January issue.

PLOS Comp Biol Featured Image for January. Image Credit: Zsuzsa Ákos & Máté Nagy

PLOS Comp Biol Featured Image for January. Image Credit: Zsuzsa Ákos & Máté Nagy

The movement of a pack of Hungarian Vizslas was tracked by researchers from Oxford University and the Hungarian Academy of Sciences using high-resolution GPS harnesses in order to determine the dynamics of leadership roles, individual social ranks and personality traits. The authors found that the dogs’ movements were measurably influenced by underlying social hierarchies. Dogs that consistently took the lead were more responsive to training, more controllable, older and more aggressive than the dogs that tended to follow.

A fundamental question in systems neuroscience is how the structural connectivity of the cerebral cortex shapes global communication. More specifically Bratislav Mišić et al. found that much of global communication was mediated by a “rich club” of hub regions, which are areas of the brain comprised of densely interconnected nodes. The paper describes how these regions attract the most signal traffic and have more connections than non-rich club regions. Furthermore, a number of these regions were significantly under-congested, which suggests how connectivity can actively shape information flow. Overall, the results reveal a dynamic aspect of the global information processing architecture and the critical role played by the so-called “rich club” of hub nodes.

Recent advances in cancer immunotherapy stem from increasing the number of tumour-infiltrating immune cells, which is accomplished by inhibiting immune checkpoints or adoptive T cell therapy. David J. Klinke used computational methods to identify potential mechanisms present within the tumour microenvironment that limit the efficacy of anti-tumour immunity. The results will help identify design constraints for engineering better pre-clinical models of breast cancer.

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Opening Up Data Access, Not Just Articles

journal.pbio.1001779.g001

Illustration credit: Ainsley Seago.
doi:10.1371/journal.pbio.1001779.g001

For those who’ve been paying attention, you’ll have noticed that we just published an interesting Perspective in PLOS Biology from Dominique Roche and colleagues that provides some practical hints on how to improve public data archiving for scientific research.

And if you’ve been even more on the ball, you’ll also have seen the recent announcement of PLOS’ new Data Policy and subsequent Update on the PLOS website.

The new Data Policy will be implemented for manuscripts submitted on, or after, March 1st. The main change is that all PLOS journals will require that all manuscripts have an accompanying data availability statement for the data used in that piece of research. We’re well aware that this may prove to be a challenge, but we think that this thorny issue needs to be tackled head-on. Ultimately, an Open Access paper for which the underlying data are not available doesn’t make a whole lot of sense.

Roche and colleagues raise some important and interesting points in their perspective and do a fine job of detailing the benefits to the scientific community of making data available. But for the eagle-eyed you’ll note an incongruity between their suggestion that a longer embargo period might be necessary before data need to be made available for some subjects, while the PLOS policy won’t make that distinction.

We don’t all have to agree here, and for the short term this may mean that some choose to send their research somewhere that permits them to keep their data under wraps. But funding agencies are also moving more towards our viewpoint, implementing requirements that data be made available. Whether researchers like it or not, this is something that needs to be addressed; it’s time to start ensuring there are better lab, university and institution practices for the storage and archiving of pertinent data.

If what we really want to see is optimal advancement of science, then open access to research means open access to as much as possible associated with the paper and not just the paper itself.  What should such openness include?  Well – probably everything – from methods to code to materials to equipment.  But without a doubt a key component of openness is access to the data behind a study.  Access to data facilitates reproducibility and testing of a papers conclusions and methods and also enables new discoveries to be made without the expense of redoing the experiments.   We believe that the more open we all are about open data, the more we discuss the benefits and challenges,  and the more we shift the bar towards openness, the better off all of science will be.

 

Roche DG, Lanfear R, Binning SA, Haff TM, Schwanz LE, et al. (2014). Troubleshooting Public Data Archiving: Suggestions to Increase Participation. PLoS Biology, 12 (1): e1001779. DOI: 10.1371/journal.pbio.1001779

 

More posts on PLOS Biologue about data:

“Dude, where’s my data?” by Roli Roberts

“Improving data access at PLOS” By John Chodacki

“Dealing with data” by Theo Bloom

 

Category: Biology, Data, PLOS Biology | Tagged , , , | 18 Comments

Reviewing software and code: an update

On June 14th 2013 Mozilla Science Lab announced their collaboration with PLOS Computational Biology. The collaboration was a trial series of software reviews conducted by Mozilla engineers for small pieces of code from articles already published with PLOS Computational Biology. The project began amidst discussion about the presentation of scientific code, such as this piece by Carl Boettiger, who stated: “We are not really taught to review software, any more than we are taught to write it in the first place.”

The project was spearheaded by Kaitlin Thaney from Mozilla Science Labs and Greg Wilson from Software Carpentry and announced by posts on Kaitlin’s blog and on PLOS Biologue. The full results have now been released on arXiv and summarised on the Mozilla Science blog, which explains that many of the scientists had never had their code reviewed before. Kaitlin states that while “the scientists aimed to produce readable, re-usable code, the reviewers felt their software was less reusable by others”. However, she also concludes that “the authors still found the comments useful, particularly feedback on usability, ease of re-use, organization of README files, code structure, performance questions and optimization”.

Since the first results were revealed, Mozilla Science Labs have announced that they are embarking on a second round of code reviews. In this version of the project, mentors from Mozilla will work with small groups of scientists, at first performing code reviews but also training the scientists to do the reviews themselves. Anyone who is interested in taking part as either a mentor or part of a team should use this email to get in touch.

It should be noted that this was a small-scale experiment and so much of the evidence provided is anecdotal. However, we believe that scientific research could benefit from an increase of these kinds of interactions. Overall we at PLOS Computational Biology are thrilled to have been a part of this project and hope that the results contribute to the growing world of scientific software.

Category: Bioinformatics, Computational biology, Open access, PLOS Computational Biology | Tagged , , , | Leave a comment

A huge thanks to our reviewers in 2013

thanks

Image credit ‘Todd’ on flickr

As 2014 begins we’d like to take the time to thank those who made it possible, including our fantastic peer reviewers.  In 2013 1199 people reviewed for PLOS Biology, 3780 in PLOS Genetics, and 2445 for PLOS Computational Biology. These generous individuals donated their time to assessing and improving our authors’ submissions. Their combined efforts have helped the PLOS biological journals (PLOS Biology, PLOS Genetics and PLOS Computational Biology) publish a fantastic and varied array of papers in 2013, amassing  6379364 online views and 673691 pdf downloads of articles so far!

We thank our reviewers for contributing their knowledge to the Open Access corpus. We here at PLOS would like to raise a toast to these amazing individuals. Without their critical insight, support, and hard work we couldn’t do what we do.

We’d also like to draw attention to the folks who have reviewed for the other PLOS journals:

PLOS ONE reviewers: http://blogs.plos.org/everyone/2014/01/06/thanking-peer-reviewers/

PLOS Medicine, PLOS Pathogens and PLOS Neglected Tropical Diseases reviewers: http://blogs.plos.org/speakingofmedicine/?p=16159

Thanks again!

 

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