This week in PLOS Biology

In PLOS Biology this week, you can read about new research on the making of the vertebrate neural tube and a chemical modification essential for the functioning of inhibitory synapses in the brain.

 

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Image credit: pbio.1001908

Efficient signal transmission at synapses is essential for higher brain functions. Inhibitory signalling in the brain mainly takes place at GABAergic synapses. Gephyrin is an intracellular component of the postsynaptic protein network in these inhibitory synapses (i.e. on the “receiving” side of the synapse), and importantly, is responsible for clustering GABA receptors at the synaptic membrane. Borislav Dejanovic, Guenter Schwarz and colleagues demonstrate that in order to perform its function, gephyrin needs to be modified by palmitoylation – the reversible posttranslational attachment of the fatty acid palmitate (commonly used to make soaps).

 

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Image credit: pbio.1001907

A relatively small number of signals are responsible for the variety and pattern of cell types generated in developing vertebrate embryos. The diversity in cell types depends, at least in part, on changes in the way cells respond to each signal. In new research Noriaki Sasai, Eva Kutejova and James Briscoe looked at neural cord development in chick and mouse embryos, and found that in order to specify two important cell types (Floor Plate and Neural Crest) FGF signalling needs to integrate with two perpendicular signalling pathways (Shh and BMP).

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This week in PLOS Biology

In PLOS Biology this week, you can read about tracking the evolution of cancer, sexual dimorphism, parasite tolerance in wild mammals and negative feedback mechanisms in cortical neurons.

A new Community Page by Miriam Jamal-Hanjani, Charles Swanton and colleagues highlights TRACERx, a prospective study of patients with primary non-small cell lung cancer. The idea is to follow cancer cases from diagnosis to relapse and conduct tumour sampling and genetic analysis. When paired with data on therapeutic interventions, the resulting information on the evolution of real tumours could help identify novel therapeutic targets.

 

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Image credit: pbio.1001905

Anisogamy – the phenomenon of the gametes of each mating type differing in form (e.g. small, mobile sperm and large, stationary eggs) – is common across the tree of life. A study by Sa Geng, Peter DeHoff and James Umen investigated sex determination in the multicellular green alga Volvox carteri. They found that a protein that controlled identical-looking mating types in an ancestral unicellular alga evolved to control the development of visibly different sexes in its multicellular descendant Volvox. This study seems to show that sexual dimorphism can arise from isogamy (sexual reproduction where gametes are of similar shape and size) largely via changes in the sex-determining gene itself.

 

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Image credit: Flickr user Peter Trimming

When faced with a parasite infection, the two options for animals are resistance (expelling the parasites) and tolerance (mitigating the damage caused by the parasites). New research by Joseph Jackson, Mike Begon and colleagues used field voles to investigate the switch between these two strategies. As the voles matured, they moved from resistance to tolerance of parasite infection. They identified the transcription factor Gata3 as an important marker of the shift to tolerance over time.

 

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Image Credit: 10.1371/journal.pcbi.1000877

In order for cortical neurons (brain cells responsible for memory) to work properly, the ratio of excitation and inhibition (E/I) has to remain constant. However, this locked relationship can constrain neuronal plasticity and learning. New research by Joana Lourenço, Alberto Bacci and colleagues finds that activation of cortical pyramidal neurons mobilizes nitric oxide, which then enhances release of the neurotransmitter GABA from nearby inhibitory interneurons, thereby transiently freeing specific pyramidal neurons from the tyranny of a fixed E/I.

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Lessons from the fruit fly, spatial transmission of influenza and the mechanism of tissue-specific hereditary diseases: The PLOS Comp Biol June issue

Here is a selection of PLOS Computational Biology highlights for June.

Stepping Up a Notch: An Expanded Mathematical Model for Notch-Delta Signaling. Image Credit: Jerry S. Chen and Robert W. Zeller

“Minimization of opportunity costs” is a commonly used phrase within economics; however, less commonly known is that the fruit fly Drosophila melanogaster also uses this theory. In “A Normative Theory of Forgetting: Lessons from the Fruit Fly”, Brea et al. note that fruit fly behaviour is compatible with the classical optimality criterion of choosing actions that maximize future rewards. A consequence of future reward maximization is that negative experiences that lead to timid behaviour should be quickly forgotten in order to not miss out on potentially rewarding opportunities. Recent experiments have revealed that the fruit fly has a dedicated mechanism for forgetting, which is consistent with the view that forgetting is adaptive, rather than a consequence of limitations of the memory system. The authors show that forgetting in Drosophila appears as an optimal adaptive behaviour in a changing environment.

The 2009 H1N1 influenza pandemic provides a unique opportunity for Gog et al. to provide a detailed examination of the spatial dynamics of an emerging pathogen. In “Spatial Transmission of 2009 Pandemic Influenza in the US” the authors apply statistical and mathematical models to disease data and find that the main fall wave of the 2009 pandemic in the US was remarkably spatially structured. The authors report that the protracted spread of pandemic influenza in fall 2009 in the US was dominated by short-distance spatial spread partially catalysed by school openings rather by than long-distance transmission events. The findings of the paper underline the critical role that school-age children play in facilitating the geographic spread of pandemic influenza and highlight the need for further information on the movement and mixing patterns of this age group.

An open question in human genetics is what underlies the tissue-specific manifestation of hereditary diseases, which are caused by genomic aberrations present in cells across the entire human body. In order to answer this question, Barshir et al. analyzed this phenomenon for over 300 hereditary diseases and created a resource of protein expression and interactions across 16 main human tissues. In “Comparative Analysis of Human Tissue Interactomes Reveals Factors Leading to Tissue-Specific Manifestation of Hereditary Diseases” the authors identify two distinct, statistically-significant factors that could lead to tissue-specific vulnerability in the face of this broad expression: (i) many disease-causing genes have elevated expression levels in their disease tissues, and (ii) disease-causing genes have a significantly higher tendency for tissue-specific interactions in their disease tissues. Together the two factors identified are relevant for as many as two thirds of the tissue-specific hereditary diseases.

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Stories from the road: Trials and tribulations of the ISCB Student Council

The Student Council for the International Society for Computational Biology was established in 2004 to promote the development of computational biology among young scientists. The group runs events and programmes, as well as supporting the creation of Regional Student Groups.

Image Credit: Vignesh GPAs an official journal of the ISCB, PLOS Computational Biology is delighted to be publishing ‘Stories from the road: ISCB Student Council Collection’, a series of articles documenting the various activities of the ISCB student community and providing guidance to future generations of ISCB Student Council members. From the importance of creating a culture where networking is possible, to tips for workshopping ideas and problems, the series captures the experiences of young scientists.

“Collaborating with authors and contributors from dozens of countries around the globe has been an extremely interesting, challenging and rewarding experience,” says Thomas Abeel, one of the authors of the series. “Putting this series together has brought back some great memories, reinforced friendships and has re-taught some of the lessons we highlighted in these articles all over again.”

The collection’s primary authors and organisers were Thomas Abeel, Geoff Macintyre and Magali Michaut. Their own account of the council and the creation of the collection can be read here.

It is the journal’s hope that this collection will help spread some of the wisdom that the council has acquired over the course of a decade.

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This week in PLOS Biology

In PLOS Biology this week, you can read about a molecule with the potential to treat malaria, the remarkable diversity in sex determination and regulation of synaptic homeostasis.

 

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Malaria-infected red blood cell. Image credit: NIAID

Malaria is a mosquito-borne infectious disease which in 2010 killed up to 1.2 million people. The parasites that cause malaria live inside red blood cells, and while there secrete many different proteins that mold the host cells to their own purposes. An enzyme called Plasmepsin V is known to be involved in the correct secretion of these proteins. In new research, Brad Sleebs, Justin Boddey and colleagues showed that Plasmepsin V is essential for malarial parasite survival, and were able to design a molecule which could inhibit its activity. Although this molecule was needed at too high a concentration for it to be useful clinically, future refinements could lead to a useful drug. Read more in the accompanying synopsis.

 

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Image credit: pbio.1001899

Sex determination – isn’t it mostly about X and Y? This is one of several commonly held myths debunked by Doris Bachtrog, Jana Vamosi and co-authors in a new addition to our ‘Unsolved Mystery’ series. The authors discuss the myriad different mechanisms by which sex has evolved to be determined in eukaryotes. They survey our current understanding of the topic and identify important knowledge gaps.

 

Negative feedback is an important mechanism across many systems. One example is in the dampening down of excessive activity in neurons. New research by Seonil Kim and Edward Ziff highlights the importance of the calcium-dependent phosphatase calcineurin. Calcineurin activity is decreased when inhibition of neuronal excitability reduces calcium influx. This leads in turn to increased levels of phosphorylation and resulting stabilisation of AMPA receptors – a type of glutamate receptor that’s permeable to calcium, thereby closing the feedback loop.

 

Category: Biology, Cell biology, Cell signalling, Developmental biology, Disease, Evolution, Genetics, Infectious disease, Molecular biology, Neuroscience, PLOS Biology | Leave a comment

Meet the “PLOSSE” at ISMB 2014

Heading to the ISCB’s annual conference, ISMB 2014, July 11– 15, in Boston this year?  Swing by Booth 409 and say hello to PLOS!

PLOS Computational Biology staff Clare Weaver and Chris Hall will be manning the booth, alongside PLOS ONE Associate Editor Renee Hoch and Mei Yan Leung, Product Marketing Manager. They’re keen to answer your questions and hear your thoughts on Open Access, the journals and exciting projects such as PLOS Computational Biology’sOutside the Box”.

Image credit: PLOS

Image credit: PLOS

We’ll also be hosting “Meet PLOS” drop-in sessions on the evenings of Sunday 13th and Monday 14th July. In the same vein as previous years’ “Meet the Editor” sessions, these drop-ins are your opportunity to chat to editors across PLOS ONE and PLOS Computational Biology. Visit Booth 409 for more information on these events and to snag a free PLOS Computational Biology t-shirt before they’re all gone. This year’s shirt was designed by Ariel Afek who will be at ISMB presenting the work featured in his design.

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

Friday 11th July

Sunday 13th July

  • Christine Orengo and Lonnie Welch host a special session on “Communities of Special Interest”, which includes contributions from Hilmar Lapp and Fran Lewitter
  • Celebrating Nobel prize winners Martin Karplus and Michael Levitt, and reflecting on their enormous impact on those they have mentored, Steven Brenner and Mark Gerstein take part in a Special Session, and Roland Dunbrack gives a Special Talk
  • Teresa Przytycka presents her paper “Dissecting Cancer Heterogeneity with network based approach”

Monday 14th July

Tuesday 15th July

There’s still time to register for ISMB 2014 online if you’ve not yet done so. We look forward to seeing you in Boston!

Category: Announcement, Community, Computational biology, Conference, News, Open access, Outreach, PLOS Computational Biology | Tagged , , , | Leave a comment

This week in PLOS Biology

In PLOS Biology this week, you can read about meeting biodiversity targets, sequencing microbial life, a new piece of the Nodal pathway, early problems in Huntington’s disease and how fly larvae choose to eat or crawl.

 

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Image credit: pbio.1001892

In a new research article this week, Oscar Venter, James Watson and colleagues argue that we need to approach protected areas expansion in a way that conserves the maximum number of endangered species. Currently much of the land protected is cheap but relatively species-poor. The authors analysed the number of threatened vertebrate species which would be covered by the implementation of the Aichi biodiversity target to protect 17% of the globe’s land surface by 2020. The results showed that only 249 more species would benefit compared to current reserves. They argue that as protecting more species-rich land brings a proportionately larger benefit in terms of biodiversity conservation, a ‘happy medium’ can be found to achieve these targets. Read more in the accompanying synopsis.

 

Bruce Anderson (University of Stellenbosch) dinoflagellates

Dinoflagellates glow blue after a chemical reaction is triggered by the wind. Image credit: Bruce Anderson (University of Stellenbosch)

Molecular sequence data are essential for making sense of the spectacular diversity of microbial life on our planet.  We’ve made a start, but there are significant taxonomic biases in the eukaryotic organisms chosen for sequencing so far, usually limited to those of medical or biotechnological significance. Resources are particularly scarce for marine organisms, and a new Community Page by Alexandra Worden, Patrick Keeling and members of the MMETSP Consortium highlights The Marine Microbial Eukaryotic Transcriptome Sequencing Project – a resource of 700 transcriptome sequences from marine microbial eukaryotes to help understand their role in the world’s oceans.

 

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Image credit: pbio.1001890

In mammalian developmental biology, the Nodal signalling protein is well-known for its importance in promotion of differentiation in extra-embryonic tissues (such as the placenta). Now new research by Costis Papanayotou, Jérôme Collignon and colleagues has found a novel enhancer within the Nodal gene which is involved in activating Nodal expression in early stages of development (in response to pluripotency factors and SMAD signalling) and orchestrating the activation of other Nodal enhancers later on.

 

Neurodegenerative diseases such as Huntington’s cause damage to neurons before symptoms even appear. In new research, Cendrine Tourette, Christian Neri and colleagues showed that the Wnt receptor Ryk is involved in the pathways of neuronal cell homeostasis. Levels of Ryk were increased in mouse models of Huntington’s disease, a finding that has clinical implications for potential early-stage restoration of neurons’ capacity to resist damage in patients with this and related diseases.

 

In the animal kingdom, two of the most essential behaviours are locomotion and feeding, but how is the choice between these two made? Andreas Schoofs, Michael J. Pankratz, and colleagues show that a single cluster of neurons in the fly central nervous system simultaneously suppresses feeding behaviour and induces food-seeking movements in larvae. These neurons, characterised by their expression of the neuropeptide ‘hugin’, transmit inputs from higher brain centres to motor centres. Read more in the accompanying synopsis.

 

Category: Biology, Cell biology, Cell signalling, Computational biology, Developmental biology, Disease, Ecology, Environment, Genomics, Microbiology, Molecular biology, Neuroscience, PLOS Biology, Research | Leave a comment

Evolution Conference: Bret Payseur

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 conference of the Society for the Study of Evolution started on the 20th of June, and is taking place in North Carolina. Bret Payseur, PLOS Genetics editor, says a few words about the conference and why he finds it exciting.

The Society for the Study of Evolution is meeting June 20-24 at the Raleigh Convention Center. This is a joint meeting with the Society of Systematic Biologists and the American Society of Naturalists. Participants include faculty, postdoctoral researchers, graduate students, and undergraduates from around the world. The meeting impeccably organized. I am delighted that PLOS Genetics is a sponsor of this exciting meeting.

Image credit: Kevin Dooley Flickr CC-BY

A unifying theme of the conference is biodiversity. Collectively, presenters provide portraits of evolution in organisms from across the tree of life. Both the patterns of biodiversity and the evolutionary processes that created them are of interest. Big, longstanding questions are discussed and debated through an impressive amalgamation of empirical and theoretical approaches. How are species related to one another? How do new species arise? What is the genetic basis of trait evolution? What are the evolutionary and ecological determinants of biodiversity? How do organisms adapt to their environments? More practical issues are also at the forefront of the meeting, including the prospects, challenges and limitations of genomic data for evolutionary biology. The smorgasbord of offerings is enough to inspire anyone interested in biological variation.

Of all the scientific meetings I attend, this is my favorite.

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PLOS Biology Paper Wins Omenn Prize for Viral Evasion Story

We talk to the authors of a PLOS Biology research article published last May that has just won the Omenn Prize for the best article published in 2013. The Omenn Prize is awarded annually by the Evolution, Medicine, & Public Health Foundation to authors of articles related to “evolution in the context of medicine and public health,” and the winner was picked from a tough long-list of 47 papers. Four other papers, including two from our sister journal PLOS Pathogens, were cited for “honorable mention” (Graves et al. Huijben et al.).

 

The PLOS Biology paper looks at how an essential mammalian protein – the transferrin receptor, TfR1 – evolves in the face of contrasting selective pressures. TfR1 is a protein that sits on the membrane of our cells and mediates the regulated uptake of iron. TfR1 is stuck in the horns of a dilemma. On the one hand, it has to be able to bind its functional partners – the iron-loaded plasma protein transferrin, and a negative regulator protein called HFE; this requirement constrains the sequence and structure of TfR1 through evolutionary time. On the other hand, it has to evade viruses that exploit its handy cell-surface location, such as arenaviruses and the rodent retrovirus MMTV.

 

TfR1 can carry on binding transferrin and HFE while dodging viruses. DOI: 10.1371/journal.pbio.1001571

TfR1 can carry on binding transferrin and HFE while dodging viruses. DOI: 10.1371/journal.pbio.1001571

The authors compared sequences of TfR1 from various mammalian hosts and then expressed them on the surface of cells to check a) their ability to confer vulnerability or resistance to MMTV and arenaviruses such as Machupo, Junin and Guanarito virus and b) their ability to bind to transferrin. This image from the paper summarises the central finding – how TfR1 (green) manages to square this circle by evolving rapidly (red) to change the outer surfaces that are hijacked by viruses while keeping constant the central surfaces that it uses to bind transferrin and HFE (purple, blue).

 

First author Ann Demogines and lead author Sara Sawyer – both from the University of Texas at Austin – told us how the study first arose and then evolved into the paper that you can now read on our website.

 

Sawyer recalls the exact point at which the project started: “In the first year of my faculty position, Welkin Johnson invited me to give a talk at the New England Primate Research Center.  While I was there, I had a 45 minute meeting with his colleague, Mike Farzan [also a co-author]. Mike had just discovered TfR1 as the cellular receptor for arenaviruses, and suggested to me that this might be a molecule that is engaged in an evolutionary arms race.  While ideas like this often arise out of conversations between scientists, I remember having a gut reaction that this was something worth pursuing.”

 

Amino acids marked in red track virus binding sites on TfR1 (blue, grey) DOI: 10.1371/journal.pbio.1001571

Positively selected amino acids (red) hit the virus binding sites on TfR1 (blue, grey) DOI: 10.1371/journal.pbio.1001571

Demogines, who received $5000 from the Foundation, describes how the spectacular arrangement of the evolutionarily selected sites emerged: “I am still amazed to this day by the results of the evolutionary analysis.  We were able to take DNA sequence from just 7 species and computationally predict six sites under selection.  These sites were scattered on the linear diagram of the protein, and didn’t make much sense to us. But, when we placed them onto the 3D crystal structure they formed a beautiful ridge going straight down the outer surface of the receptor.  That was a great day in the lab.  We knew this had to mean something!”

 

Demogines goes on to think about the implications of her paper and related studies: “This work really gets me excited about the future of evolutionary analysis applied in biomedical research.  As we collect the genome sequences from more and more species, especially rodents and bats which are major reservoirs for zoonotic and potentially zoonotic viruses, we should be able to do this type of analysis more and more.  This type of analysis has many applications: allowing us to identify critical cofactors involved in the viral lifecycle, viral binding sites, and potentially novel drug targets. It can also be used to study interactions with bacterial pathogens, although this has not yet been extensively explored.”

 

If you’d like to find out more about this elegant study, why not read the article itself, or the accompanying Primer written by John Coffin:

 

“Dual Host-Virus Arms Races Shape an Essential Housekeeping Protein” by Ann Demogines, Jonathan Abraham, Hyeryun Choe, Michael Farzan and Sara L. Sawyer. DOI: 10.1371/journal.pbio.1001571

“Virions at the Gates: Receptors and the Host–Virus Arms Race” by John M. Coffin. DOI: 10.1371/journal.pbio.1001574

 

 

Category: Biology, Computational biology, Evolution, Microbiology, News, PLOS Biology, Research | Leave a comment

This week in PLOS Biology

In PLOS Biology this week, you can read about interdisciplinary community building, how yeast cells deal with stress, 3D printing and conservation of the Antarctic.

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Image credit: pbio.1001885

During their lifetime, cells accumulate damage such as aggregated proteins, which is inherited by the daughter cells when the mother cell divides. In cells that normally divide symmetrically, such as the yeast Schizosaccharomyces pombe it has been shown that under stress conditions this can change and the cells switch to asymmetric division. Miguel Coelho, Iva Tolić and colleagues have shown in a new study how this adaptively valuable transition is achieved. Under stress, more and larger clumps of protein are created, which after one or two cell divisions end up in one huge cluster – this can only be passed onto one daughter cell, leaving the other pristine. Read more in the accompanying synopsis.

 

This week a Community Page by Holly BikDavid Coil and Jonathan Eisen highlights the Microbiology of the Built Environment Network (microBEnet), which was formed as an experiment in interdisciplinary community building. It aimed to bring together investigators and stakeholders in a new area of research: the microbiology of the built environment (MBE). This field was born of the observation that as modern humans we spend most of our time indoors, and yet we know little about the countless microorganisms that exist within buildings.

 

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3D printing, originally developed for plastic and metal manufacturing, now represents high hopes for applications to human tissue and organ engineering. In his Essay, Jordan Miller discusses the key challenges that remain in this endeavour, and the conceptual targets on the horizon. Examples of possible opportunities that are highlighted include building physiologically relevant models of disease and testing drugs on human tissues fabricated with 3D printers.

 

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Image credit: pbio.1001888

In their Perspective on the Antarctic, Steven Chown, Justine Shaw and colleagues argue that with a surge in visitors, Antarctica’s ice-free land needs better protection from human activities. Global comparisons show that Antarctica’s terrestrial biodiversity is poorly protected; only 1.5% of its ice-free regions were found to be protected formally. They highlight the fact that this means Antarctica currently falls well short of the Aichi Biodiversity Targets – an international biodiversity strategy that aims to reduce threats to biodiversity, and protect ecosystems, species and genetic diversity.

 

Category: Biology, Biotechnology, Cell biology, Climate, Community, Ecology, Environment, Microbiology, PLOS Biology, Research | 2 Comments