7,446 research outputs found
Improving GENCODE reference gene annotation using a high-stringency proteogenomics workflow.
Complete annotation of the human genome is indispensable for medical research. The GENCODE consortium strives to provide this, augmenting computational and experimental evidence with manual annotation. The rapidly developing field of proteogenomics provides evidence for the translation of genes into proteins and can be used to discover and refine gene models. However, for both the proteomics and annotation groups, there is a lack of guidelines for integrating this data. Here we report a stringent workflow for the interpretation of proteogenomic data that could be used by the annotation community to interpret novel proteogenomic evidence. Based on reprocessing of three large-scale publicly available human data sets, we show that a conservative approach, using stringent filtering is required to generate valid identifications. Evidence has been found supporting 16 novel protein-coding genes being added to GENCODE. Despite this many peptide identifications in pseudogenes cannot be annotated due to the absence of orthogonal supporting evidence
What two models may teach us about duality violations in QCD
Though the operator product expansion is applicable in the calculation of
current correlation functions in the Euclidean region, when approaching the
Minkowskian domain, violations of quark-hadron duality are expected to occur,
due to the presence of bound-state or resonance poles. In QCD finite-energy sum
rules, contour integrals in the complex energy plane down to the Minkowskian
axis have to be performed, and thus the question arises what the impact of
duality violations may be. The structure and possible relevance of duality
violations is investigated on the basis of two models: the Coulomb system and a
model for light-quark correlators which has already been studied previously. As
might yet be naively expected, duality violations are in some sense "maximal"
for zero-width bound states and they become weaker for broader resonances whose
poles lie further away from the physical axis. Furthermore, to a certain
extent, they can be suppressed by choosing appropriate weight functions in the
finite-energy sum rules. A simplified Ansatz for including effects of duality
violations in phenomenological QCD sum rule analyses is discussed as well.Comment: 17 pages, 6 figures; version to appear in JHE
Three-Dimensional Spectral-Domain Optical Coherence Tomography Data Analysis for Glaucoma Detection
Purpose: To develop a new three-dimensional (3D) spectral-domain optical coherence tomography (SD-OCT) data analysis method using a machine learning technique based on variable-size super pixel segmentation that efficiently utilizes full 3D dataset to improve the discrimination between early glaucomatous and healthy eyes. Methods: 192 eyes of 96 subjects (44 healthy, 59 glaucoma suspect and 89 glaucomatous eyes) were scanned with SD-OCT. Each SD-OCT cube dataset was first converted into 2D feature map based on retinal nerve fiber layer (RNFL) segmentation and then divided into various number of super pixels. Unlike the conventional super pixel having a fixed number of points, this newly developed variable-size super pixel is defined as a cluster of homogeneous adjacent pixels with variable size, shape and number. Features of super pixel map were extracted and used as inputs to machine classifier (LogitBoost adaptive boosting) to automatically identify diseased eyes. For discriminating performance assessment, area under the curve (AUC) of the receiver operating characteristics of the machine classifier outputs were compared with the conventional circumpapillary RNFL (cpRNFL) thickness measurements. Results: The super pixel analysis showed statistically significantly higher AUC than the cpRNFL (0.855 vs. 0.707, respectively, p = 0.031, Jackknife test) when glaucoma suspects were discriminated from healthy, while no significant difference was found when confirmed glaucoma eyes were discriminated from healthy eyes. Conclusions: A novel 3D OCT analysis technique performed at least as well as the cpRNFL in glaucoma discrimination and even better at glaucoma suspect discrimination. This new method has the potential to improve early detection of glaucomatous damage. © 2013 Xu et al
Accurate simultaneous quantification of liver steatosis and iron overload in diffuse liver diseases with MRI
Purpose: To evaluate the diagnostic performances of 3 Tesla multi-echo chemical shift-encoded gradient echo magnetic resonance (MECSE-MR) imaging to simultaneously quantify liver steatosis and iron overload in a wide spectrum of diffuse liver diseases having biopsy as reference standard.
Methods: MECSE-MR-acquired images were used to calculate fat fraction and iron content in a single breath-hold in 109 adult patients. Proton density fat fraction (PDFF) was prospectively estimated using complex-based data reconstruction with multipeak fat modeling. Water R2* was used to estimate iron content. Biopsy was obtained in all cases, grading liver steatosis, siderosis, inflammation, and fibrosis. Differences in PDFF and R2* values across histopathological grades were analyzed, and ROC curves analyses evaluated the MR diagnostic performance.
Results: Calculated fat fraction measurements showed significant differences (p < 0.001) among steatosis grades, being unaffected by the presence of inflammation or fibrosis (p ≥ 0.05). A strong correlation was found between fat fraction and steatosis grade (R S = 0.718, p < 0.001). Iron deposits did not affect fat fraction quantitation (p ≥ 0.05), except in cases with severe iron overload (grade 4). A strong positive correlation was also observed between R2* measurements and iron grades (R S = 0.704, p < 0.001). Calculated R2* values were not different across grades of steatosis, inflammation, and fibrosis (p ≥ 0.05).
Conclusion: A MECSE-MR sequence simultaneously quantifies liver steatosis and siderosis, regardless coexisting liver inflammation or fibrosis, with high accuracy in a wide spectrum of diffuse liver disorders. This sequence can be acquired within a single breath-hold and can be implemented in the routine MR evaluation of the liver.This work was partially funded by a research grant from the Teaching and Research Department of Centro Hospitalar do Porto (DEFI:309/12(213-DEFI/251-CES)) and from a Spanish Ministry of Health and Carlos III Health Institute funding grant (PI12/01262). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
The Complete Star Formation History of the Universe
The determination of the star-formation history of the Universe is a key goal
of modern cosmology, as it is crucial to our understanding of how structure in
the Universe forms and evolves. A picture has built up over recent years,
piece-by-piece, by observing young stars in distant galaxies at different times
in the past.
These studies indicated that the stellar birthrate peaked some 8 billion
years ago, and then declined by a factor of around ten to its present value.
Here we report on a new study which obtains the complete star formation history
by analysing the fossil record of the stellar populations of 96545 nearby
galaxies. Broadly, our results support those derived from high-redshift
galaxies elsewhere in the Universe. We find, however, that the peak of star
formation was more recent - around 5 billion years ago. Our study also shows
that the bigger the stellar mass of the galaxy, the earlier the stars were
formed. This striking result indicates a very different formation history for
high- and low-mass formation.Comment: Accepted by Nature. Press embargo until publishe
Large serological survey showing cocirculation of Ebola and Marburg viruses in Gabonese bat populations, and a high seroprevalence of both viruses in Rousettus aegyptiacus
<p>Abstract</p> <p>Background</p> <p>Ebola and Marburg viruses cause highly lethal hemorrhagic fevers in humans. Recently, bats of multiple species have been identified as possible natural hosts of <it>Zaire ebolavirus </it>(ZEBOV) in Gabon and Republic of Congo, and also of <it>marburgvirus </it>(MARV) in Gabon and Democratic Republic of Congo.</p> <p>Methods</p> <p>We tested 2147 bats belonging to at least nine species sampled between 2003 and 2008 in three regions of Gabon and in the Ebola epidemic region of north Congo for IgG antibodies specific for ZEBOV and MARV.</p> <p>Results</p> <p>Overall, IgG antibodies to ZEBOV and MARV were found in 4% and 1% of bats, respectively. ZEBOV-specific antibodies were found in six bat species (<it>Epomops franqueti, Hypsignathus monstrosus, Myonycteris torquata, Micropteropus pusillus, Mops condylurus </it>and <it>Rousettus aegyptiacus</it>), while MARV-specific antibodies were only found in <it>Rousettus aegyptiacus </it>and <it>Hypsignathus monstrosus</it>. The prevalence of MARV-specific IgG was significantly higher in <it>R. aegyptiacus </it>members captured inside caves than elsewhere. No significant difference in prevalence was found according to age or gender. A higher prevalence of ZEBOV-specific IgG was found in pregnant females than in non pregnant females.</p> <p>Conclusion</p> <p>These findings confirm that ZEBOV and MARV co-circulate in Gabon, the only country where bats infected by each virus have been found. IgG antibodies to both viruses were detected only in <it>Rousettus aegyptiacus</it>, suggesting that this bat species may be involved in the natural cycle of both Marburg and Ebola viruses. The presence of MARV in Gabon indicates a potential risk for a first human outbreak. Disease surveillance should be enhanced in areas near caves.</p
Electrophysiological Heterogeneity of Fast-Spiking Interneurons: Chandelier versus Basket Cells
In the prefrontal cortex, parvalbumin-positive inhibitory neurons play a prominent role in the neural circuitry that subserves working memory, and alterations in these neurons contribute to the pathophysiology of schizophrenia. Two morphologically distinct classes of parvalbumin neurons that target the perisomatic region of pyramidal neurons, chandelier cells (ChCs) and basket cells (BCs), are generally thought to have the same "fast-spiking" phenotype, which is characterized by a short action potential and high frequency firing without adaptation. However, findings from studies in different species suggest that certain electrophysiological membrane properties might differ between these two cell classes. In this study, we assessed the physiological heterogeneity of fast-spiking interneurons as a function of two factors: species (macaque monkey vs. rat) and morphology (chandelier vs. basket). We showed previously that electrophysiological membrane properties of BCs differ between these two species. Here, for the first time, we report differences in ChCs membrane properties between monkey and rat. We also found that a number of membrane properties differentiate ChCs from BCs. Some of these differences were species-independent (e.g., fast and medium afterhyperpolarization, firing frequency, and depolarizing sag), whereas the differences in the first spike latency between ChCs and BCs were species-specific. Our findings indicate that different combinations of electrophysiological membrane properties distinguish ChCs from BCs in rodents and primates. Such electrophysiological differences between ChCs and BCs likely contribute to their distinctive roles in cortical circuitry in each species. © 2013 Povysheva et al
Visual ecology of aphids – a critical review on the role of colours in host finding
We review the rich literature on behavioural responses of aphids (Hemiptera: Aphididae) to stimuli of different colours. Only in one species there are adequate physiological data on spectral sensitivity to explain behaviour crisply in mechanistic terms.
Because of the great interest in aphid responses to coloured targets from an evolutionary, ecological and applied perspective, there is a substantial need to expand these studies to more species of aphids, and to quantify spectral properties of stimuli rigorously. We show that aphid responses to colours, at least for some species, are likely based on a specific colour opponency mechanism, with positive input from the green domain of the spectrum and negative input from the blue and/or UV region.
We further demonstrate that the usual yellow preference of aphids encountered in field experiments is not a true colour preference but involves additional brightness effects. We discuss the implications for agriculture and sensory ecology, with special respect to the recent debate on autumn leaf colouration. We illustrate that recent evolutionary theories concerning aphid–tree interactions imply far-reaching assumptions on aphid responses to colours
that are not likely to hold. Finally we also discuss the
implications for developing and optimising strategies
of aphid control and monitoring
Structure of the trypanosome transferrin receptor reveals mechanisms of ligand recognition and immune evasion.
To maintain prolonged infection of mammals, African trypanosomes have evolved remarkable surface coats and a system of antigenic variation1. Within these coats are receptors for macromolecular nutrients such as transferrin2,3. These must be accessible to their ligands but must not confer susceptibility to immunoglobulin-mediated attack. Trypanosomes have a wide host range and their receptors must also bind ligands from diverse species. To understand how these requirements are achieved, in the context of transferrin uptake, we determined the structure of a Trypanosoma brucei transferrin receptor in complex with human transferrin, showing how this heterodimeric receptor presents a large asymmetric ligand-binding platform. The trypanosome genome contains a family of around 14 transferrin receptors4, which has been proposed to allow binding to transferrin from different mammalian hosts5,6. However, we find that a single receptor can bind transferrin from a broad range of mammals, indicating that receptor variation is unlikely to be necessary for promiscuity of host infection. In contrast, polymorphic sites and N-linked glycans are preferentially found in exposed positions on the receptor surface, not contacting transferrin, suggesting that transferrin receptor diversification is driven by a need for antigenic variation in the receptor to prolong survival in a host
Social interaction, noise and antibiotic-mediated switches in the intestinal microbiota
The intestinal microbiota plays important roles in digestion and resistance
against entero-pathogens. As with other ecosystems, its species composition is
resilient against small disturbances but strong perturbations such as
antibiotics can affect the consortium dramatically. Antibiotic cessation does
not necessarily restore pre-treatment conditions and disturbed microbiota are
often susceptible to pathogen invasion. Here we propose a mathematical model to
explain how antibiotic-mediated switches in the microbiota composition can
result from simple social interactions between antibiotic-tolerant and
antibiotic-sensitive bacterial groups. We build a two-species (e.g. two
functional-groups) model and identify regions of domination by
antibiotic-sensitive or antibiotic-tolerant bacteria, as well as a region of
multistability where domination by either group is possible. Using a new
framework that we derived from statistical physics, we calculate the duration
of each microbiota composition state. This is shown to depend on the balance
between random fluctuations in the bacterial densities and the strength of
microbial interactions. The singular value decomposition of recent metagenomic
data confirms our assumption of grouping microbes as antibiotic-tolerant or
antibiotic-sensitive in response to a single antibiotic. Our methodology can be
extended to multiple bacterial groups and thus it provides an ecological
formalism to help interpret the present surge in microbiome data.Comment: 20 pages, 5 figures accepted for publication in Plos Comp Bio.
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