AIGO: towards a unified framework for the analysis and the inter-comparison of GO functional annotations

BACKGROUND: In response to the rapid growth of available genome sequences, efforts have been made to develop automatic inference methods to functionally characterize them. Pipelines that infer functional annotation are now routinely used to produce new annotations at a genome scale and for a broad variety of species. These pipelines differ widely in their inference algorithms, confidence thresholds and data sources for reasoning. This heterogeneity makes a comparison of the relative merits of each approach extremely complex. The evaluation of the quality of the resultant annotations is also challenging given there is often no existing gold-standard against which to evaluate precision and recall. RESULTS: In this paper, we present a pragmatic approach to the study of functional annotations. An ensemble of 12 metrics, describing various aspects of functional annotations, is defined and implemented in a unified framework, which facilitates their systematic analysis and inter-comparison. The use of this framework is demonstrated on three illustrative examples: analysing the outputs of state-of-the-art inference pipelines, comparing electronic versus manual annotation methods, and monitoring the evolution of publicly available functional annotations. The framework is part of the AIGO library (http://code.google.com/p/aigo) for the Analysis and the Inter-comparison of the products of Gene Ontology (GO) annotation pipelines. The AIGO library also provides functionalities to easily load, analyse, manipulate and compare functional annotations and also to plot and export the results of the analysis in various formats. CONCLUSIONS: This work is a step toward developing a unified framework for the systematic study of GO functional annotations. This framework has been designed so that new metrics on GO functional annotations can be added in a very straightforward way

Tectonic and climatic controls on rift escarpments: Erosion and flexural rebound of the Dhofar passive margin (Gulf of Aden, Oman)

International audienceWe investigate the respective roles of climatic parameters and the flexural rigidity of the lithosphere in the erosion history and behavior of two adjacent rift escarpments along the northern coast of the Gulf of Aden, in Oman. At this 25 Myr old passive margin, we define a type 1 scarp, which is high, sharp-crested and has retreated 25-30 km inland from its master fault, and a type 2 scarp, which exhibits a more rounded profile, lower relief, and still coincides with its mapped normal fault trace. Since about 15 Ma, the margin has been seasonally affected by monsoon precipitation but with contrasting effects at the type 1 and type 2 escarpments depending on the position of the Intertropical Convergence Zone in the geologic past: during peak monsoon conditions, both scarps experienced heavy rainfall and runoff, whereas during monsoon-starved conditions (such as today), the type 2 scarp experienced a foggy, moist climate while the type 1 scarp remained much drier. In order to assess the relative effects of climate and flexural parameters on the present-day morphology of the Dhofar margin, we present onedimensional numerical models of erosion and flexure along two profiles representative of the type 1 and type 2 scarps. Unlike most surface process models previously published, where present-day topography is the only criterion by which to evaluate the quality of model outputs, model behavior here is additionally constrained by independent estimates of denudation provided by geological cross sections, well-defined fault traces, and other stratigraphic markers. The best fitting models indicate that the type 1 escarpment formed under relatively arid climatic conditions and was affected by significant erosion, recession and flexural uplift due to a low (7 km) effective elastic thickness. In contrast, the morphology of the type 2 fault scarp was smoothed by a more humid climate, but a high effective elastic thickness ( 15 km) prevented it from uplifting or receding. In addition, we show that the sedimentary load acting at the foot of the escarpments exerts significant influence on their morphological evolution, though this parameter is often neglected in other scarp evolution models

Accelerated development of cerebral small vessel disease in young stroke patients.

OBJECTIVE: To study the long-term prevalence of small vessel disease after young stroke and to compare this to healthy controls. METHODS: This prospective cohort study comprises 337 patients with an ischemic stroke or TIA, aged 18-50 years, without a history of TIA or stroke. In addition, 90 age- and sex-matched controls were included. At follow-up, lacunes, microbleeds, and white matter hyperintensity (WMH) volume were assessed using MRI. To investigate the relation between risk factors and small vessel disease, logistic and linear regression were used. RESULTS: After mean follow-up of 9.9 (SD 8.1) years, 337 patients were included (227 with an ischemic stroke and 110 with a TIA). Mean age of patients was 49.8 years (SD 10.3) and 45.4% were men; for controls, mean age was 49.4 years (SD 11.9) and 45.6% were men. Compared with controls, patients more often had at least 1 lacune (24.0% vs 4.5%, p < 0.0001). In addition, they had a higher WMH volume (median 1.5 mL [interquartile range (IQR) 0.5-3.7] vs 0.4 mL [IQR 0.0-1.0], p < 0.001). Compared with controls, patients had the same volume WMHs on average 10-20 years earlier. In the patient group, age at stroke (β = 0.03, 95% confidence interval [CI] 0.02-0.04) hypertension (β = 0.22, 95% CI 0.04-0.39), and smoking (β = 0.18, 95% CI 0.01-0.34) at baseline were associated with WMH volume. CONCLUSIONS: Patients with a young stroke have a higher burden of small vessel disease than controls adjusted for confounders. Cerebral aging seems accelerated by 10-20 years in these patients, which may suggest an increased vulnerability to vascular risk factors.This is the final version of the article. It first appeared from Wolters Kluwer via https://doi.org/10.​1212/​WNL.​0000000000003123

The word as a unit of meaning. The role of context in words meaning

A unit of meaning is a word plus all those words within its contextual context that are needed to disambiguate this word to make it monosemous. A lot of research were made to study the influence of the context. They testify that there is usually in each word a hard core of relatively stable meaning and can be modified by the context within certain limits

The glutathione biosynthetic pathway of Plasmodium is essential for mosquito transmission

1Infection of red blood cells (RBC) subjects the malaria parasite to oxidative stress. Therefore, efficient antioxidant and redox systems are required to prevent damage by reactive oxygen species. Plasmodium spp. have thioredoxin and glutathione (GSH) systems that are thought to play a major role as antioxidants during blood stage infection. In this report, we analyzed a critical component of the GSH biosynthesis pathway using reverse genetics. Plasmodium berghei parasites lacking expression of gamma-glutamylcysteine synthetase (γ-GCS), the rate limiting enzyme in de novo synthesis of GSH, were generated through targeted gene disruption thus demonstrating, quite unexpectedly, that γ-GCS is not essential for blood stage development. Despite a significant reduction in GSH levels, blood stage forms of pbggcs− parasites showed only a defect in growth as compared to wild type. In contrast, a dramatic effect on development of the parasites in the mosquito was observed. Infection of mosquitoes with pbggcs− parasites resulted in reduced numbers of stunted oocysts that did not produce sporozoites. These results have important implications for the design of drugs aiming at interfering with the GSH redox-system in blood stages and demonstrate that de novo synthesis of GSH is pivotal for development of Plasmodium in the mosquito

When Music and Long-Term Memory Interact: Effects of Musical Expertise on Functional and Structural Plasticity in the Hippocampus

The development of musical skills by musicians results in specific structural and functional modifications in the brain. Surprisingly, no functional magnetic resonance imaging (fMRI) study has investigated the impact of musical training on brain function during long-term memory retrieval, a faculty particularly important in music. Thus, using fMRI, we examined for the first time this process during a musical familiarity task (i.e., semantic memory for music). Musical expertise induced supplementary activations in the hippocampus, medial frontal gyrus, and superior temporal areas on both sides, suggesting a constant interaction between episodic and semantic memory during this task in musicians. In addition, a voxel-based morphometry (VBM) investigation was performed within these areas and revealed that gray matter density of the hippocampus was higher in musicians than in nonmusicians. Our data indicate that musical expertise critically modifies long-term memory processes and induces structural and functional plasticity in the hippocampus

Cortical Plasticity Induced by Short-Term Multimodal Musical Rhythm Training

Performing music is a multimodal experience involving the visual, auditory, and somatosensory modalities as well as the motor system. Therefore, musical training is an excellent model to study multimodal brain plasticity. Indeed, we have previously shown that short-term piano practice increase the magnetoencephalographic (MEG) response to melodic material in novice players. Here we investigate the impact of piano training using a rhythmic-focused exercise on responses to rhythmic musical material. Musical training with non musicians was conducted over a period of two weeks. One group (sensorimotor-auditory, SA) learned to play a piano sequence with a distinct musical rhythm, another group (auditory, A) listened to, and evaluated the rhythmic accuracy of the performances of the SA-group. Training-induced cortical plasticity was evaluated using MEG, comparing the mismatch negativity (MMN) in response to occasional rhythmic deviants in a repeating rhythm pattern before and after training. The SA-group showed a significantly greater enlargement of MMN and P2 to deviants after training compared to the A- group. The training-induced increase of the rhythm MMN was bilaterally expressed in contrast to our previous finding where the MMN for deviants in the pitch domain showed a larger right than left increase. The results indicate that when auditory experience is strictly controlled during training, involvement of the sensorimotor system and perhaps increased attentional recources that are needed in producing rhythms lead to more robust plastic changes in the auditory cortex compared to when rhythms are simply attended to in the auditory domain in the absence of motor production

Glucocorticoid Regulation of Astrocytic Fate and Function

Glial loss in the hippocampus has been suggested as a factor in the pathogenesis of stress-related brain disorders that are characterized by dysregulated glucocorticoid (GC) secretion. However, little is known about the regulation of astrocytic fate by GC. Here, we show that astrocytes derived from the rat hippocampus undergo growth inhibition and display moderate activation of caspase 3 after exposure to GC. Importantly, the latter event, observed both in situ and in primary astrocytic cultures is not followed by either early- or late-stage apoptosis, as monitored by stage I or stage II DNA fragmentation. Thus, unlike hippocampal granule neurons, astrocytes are resistant to GC-induced apoptosis; this resistance is due to lower production of reactive oxygen species (ROS) and a greater buffering capacity against the cytotoxic actions of ROS. We also show that GC influence hippocampal cell fate by inducing the expression of astrocyte-derived growth factors implicated in the control of neural precursor cell proliferation. Together, our results suggest that GC instigate a hitherto unknown dialog between astrocytes and neural progenitors, adding a new facet to understanding how GC influence the cytoarchitecture of the hippocampus

miR-132 Enhances Dendritic Morphogenesis, Spine Density, Synaptic Integration, and Survival of Newborn Olfactory Bulb Neurons

An array of signals regulating the early stages of postnatal subventricular zone (SVZ) neurogenesis has been identified, but much less is known regarding the molecules controlling late stages. Here, we investigated the function of the activity-dependent and morphogenic microRNA miR-132 on the synaptic integration and survival of olfactory bulb (OB) neurons born in the neonatal SVZ. In situ hybridization revealed that miR-132 expression occurs at the onset of synaptic integration in the OB. Using in vivo electroporation we found that sequestration of miR-132 using a sponge-based strategy led to a reduced dendritic complexity and spine density while overexpression had the opposite effects. These effects were mirrored with respective changes in the frequency of GABAergic and glutamatergic synaptic inputs reflecting altered synaptic integration. In addition, timely directed overexpression of miR-132 at the onset of synaptic integration using an inducible approach led to a significant increase in the survival of newborn neurons. These data suggest that miR-132 forms the basis of a structural plasticity program seen in SVZ-OB postnatal neurogenesis. miR-132 overexpression in transplanted neurons may thus hold promise for enhancing neuronal survival and improving the outcome of transplant therapies

Smart Moves: Effects of Relative Brain Size on Establishment Success of Invasive Amphibians and Reptiles

Brain size relative to body size varies considerably among animals, but the ecological consequences of that variation remain poorly understood. Plausibly, larger brains confer increased behavioural flexibility, and an ability to respond to novel challenges. In keeping with that hypothesis, successful invasive species of birds and mammals that flourish after translocation to a new area tend to have larger brains than do unsuccessful invaders. We found the same pattern in ectothermic terrestrial vertebrates. Brain size relative to body size was larger in species of amphibians and reptiles reported to be successful invaders, compared to species that failed to thrive after translocation to new sites. This pattern was found in six of seven global biogeographic realms; the exception (where relatively larger brains did not facilitate invasion success) was Australasia. Establishment success was also higher in amphibian and reptile families with larger relative brain sizes. Future work could usefully explore whether invasion success is differentially associated with enlargement of specific parts of the brain (as predicted by the functional role of the forebrain in promoting behavioural flexibility), or with a general size increase (suggesting that invasion success is facilitated by enhanced perceptual and motor skills, as well as cognitive ability)