Author: Claire Mclaughlan

This week in PLOS Biology

In PLOS Biology this week you can read about the development of a vital vessel in the eye, the structure of a protein involved in Vitamin K synthesis and how protein synthesis is maintained at both high accuracy and high speed.

 

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Image credit: pbio.1001913

Schlemm’s canal is a vital draining vessel which can be found in the eye, between the cornea and the lens. It collects aqueous humour and delivers it into the bloodstream:  it is therefore vital for preventing the build-up of pressure associated with ocular hypertension and glaucoma. Despite its importance, little is known about its development. New research by Krishnakumar Kizhatil, Simon John and colleagues characterised Schlemm’s canal development, and in doing so discovered a novel process of vascular development. The cells of the canal express proteins characteristic of both blood and lymphatic vessels. Understanding these processes may lead to better understanding of the workings of the canal and how it can be manipulated to control glaucoma. Read more in the accompanying synopsis.

 

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Hua Huang, Ming Zhou and colleagues have used x-ray crystallography to determine the structure of a member of the UbiA family of integral membrane proteins. The protein structures were for an archaeal homologue of UBIAD1 – an important enzyme that attaches prenyl groups during the synthesis of Vitamin K and Coenzyme Q in humans. Determining structure allows function to be predicted – in particular how the enzymatic mechanism works.

 

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When cells are growing at a rapid rate, protein synthesis via ribosomal translation needs to be both rapid and accurate to sustain growth. New research by Jian-Rong Yang, Xiaoshu Chen and Jianzhi Zhang analysed datasets on the budding yeast Saccharomyces cerevisae. They propose that secondary structure in mRNAs modulates the speed of protein synthesis, therefore improving accuracy at functionally important sites while ensuring high speed elsewhere. They argue that this demonstrates the power of natural selection in mitigating efficiency-accuracy conflicts, which are prevalent in biology.

Category: Bioinformatics, Biology, Computational biology, Developmental biology, Disease, Evolution, Molecular biology, PLOS Biology | Leave a comment

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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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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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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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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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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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

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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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.

 

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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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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.

 

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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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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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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.

 

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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.

 

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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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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.

 

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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.

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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.

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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.

 

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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.

 

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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.

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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.

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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.

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