HIV-1 Virological Synapse: Live Imaging of Transmission

A relatively new aspect of HIV-1 biology is the ability of the virus to infect cells by direct cellular contacts across a specialized structure, the virological synapse. This process was recently described through live cell imaging. Together with the accumulated knowledge on cellular and molecular structures involved in cell-to-cell transmission of HIV-1, the visualization of the virological synapse in video-microscopy has brought exciting new hypotheses on its underlying mechanisms. This review will recapitulate current knowledge with a particular emphasis on the questions live microscopy has raised

Numerical approach of cyclic behavior of 316LN stainless steel based on a polycrystal modeling including strain gradients.

International audienceA non-local polycrystal approach, taking into account strain gradients, is proposed to simulate the 316LN stainless steel fatigue life curve in the hardening stage. Material parameters identification is performed on tensile curves corresponding to several 316LN polycrystals presenting different grain sizes. Applied to an actual 3D aggregate of 316LN stainless steel of 1,200 grains, this model leads to an accurate prediction of cyclic curves. Geometrical Necessary Dislocation densities related to the computed strain gradient are added to the micro-plasticity laws. Compared to standard models, this model predicts a decrease of the local stresses as well as a grain size effect

A New Role for the HTLV-1 p8 Protein: Increasing Intercellular Conduits and Viral Cell-to-Cell Transmission

Retroviruses like HIV-1 and HTLV-1 can be transmitted efficiently by direct contact between infected and target cells. For HIV-1, various modes of cell-to-cell transfer have been reported, including virological synapses, polysynapses, filopodial bridges, and nanotube-like structures. So far, only synapses and biofilms have been described for HTLV-1 transmission. Recently, Van Prooyen et al. [1] identified an additional mode of HTLV-1 transmission through cellular conduits induced by the viral accessory protein p8

Dual inhibitory effects of APOBEC family proteins on retrotransposition of mammalian endogenous retroviruses

We demonstrated previously that the cytosine deaminase APOBEC3G inhibits retrotransposition of two active murine endogenous retroviruses, namely intracisternal A-particles (IAP) and MusD, in an ex vivo assay where retrotransposition was monitored by selection of neo-marked elements. Sequencing of the transposed copies further disclosed extensive editing, resulting in a high load of G-to-A mutations. Here, we asked whether this G-to-A editing was associated with an impact of APOBEC3G on viral cDNA yields. To this end, we used a specially designed quantitative PCR method to selectively measure the copy number of transposed retroelements, in the absence of G418 selection. We show that human APOBEC3G severely reduces the number of MusD and IAP transposed cDNA copies, with no effect on the level of the intermediate RNA transcripts. The magnitude of the decrease closely parallels that observed when transposed copies are assayed by selection of G418-resistant cells. Moreover, sequencing of transposed elements recovered by PCR without prior selection of the cells reveals high-level editing. Using this direct method with a series of cytosine deaminases, we further demonstrate a similar dual effect of African green monkey APOBE3G, human APOBEC3F and murine APOBEC3 on MusD retrotransposition, with a distinct extent and site specificity for each editing activity. Altogether the data demonstrate that cytosine deaminases have a protective effect against endogenous retroviruses both by reducing viral cDNA levels and by introducing mutations in the transposed copies, thus inactivating them for subsequent rounds of retrotransposition. This dual, two-step effect likely participates in the efficient defense of the cell genome against invading endogenous retroelements

Loss of brain inter-frequency hubs in Alzheimer's disease

Alzheimer's disease (AD) causes alterations of brain network structure and function. The latter consists of connectivity changes between oscillatory processes at different frequency channels. We proposed a multi-layer network approach to analyze multiple-frequency brain networks inferred from magnetoencephalographic recordings during resting-states in AD subjects and age-matched controls. Main results showed that brain networks tend to facilitate information propagation across different frequencies, as measured by the multi-participation coefficient (MPC). However, regional connectivity in AD subjects was abnormally distributed across frequency bands as compared to controls, causing significant decreases of MPC. This effect was mainly localized in association areas and in the cingulate cortex, which acted, in the healthy group, as a true inter-frequency hub. MPC values significantly correlated with memory impairment of AD subjects, as measured by the total recall score. Most predictive regions belonged to components of the default-mode network that are typically affected by atrophy, metabolism disruption and amyloid-beta deposition. We evaluated the diagnostic power of the MPC and we showed that it led to increased classification accuracy (78.39%) and sensitivity (91.11%). These findings shed new light on the brain functional alterations underlying AD and provide analytical tools for identifying multi-frequency neural mechanisms of brain diseases.Comment: 27 pages, 6 figures, 3 tables, 3 supplementary figure

Diachronous evolution of the alpine continental subduction wedge: evidence from P-T estimates in the Briançonnais Zone houillère (France - Western Alps).

International audienceThe study of continental subduction processes requires detailed Pressure Temperature (P-T) paths to understand the kinematic of burial and exhumation of continental units. In the French Western Alps, the Briançonnais zone is a remnant of the continental subduction wedge. P-T conditions have been estimated in its most internal parts, but there is a lack of data in the western part, known as the "Zone houillère". This Briançonnais Zone houillère is classically divided into two sub-units: the upper and lower Houiller units. This study focuses on both of these in the Clarée valley, north of Briançon. In this low-grade metamorphic terrain, estimation of P-T history is complicated because there are few adapted methods and these rocks have a poor metamorphic mineralogical content, including detrital metamorphic minerals inherited from their hercynian history. Therefore, to acquire accurate P-T estimates a multi-method approach is required, involving qualitative and quantitative Raman study of Carbonaceous Material (RSCM), chemical analysis from quantified X-ray maps and thermodynamic modelling of chlorites and K-white micas. Such multi-approach P-T estimates on a sandstone sample allow distinguishing hercynian peak metamorphic conditions of 371 ± 26°C and 3.5 ± 1.4 kbar and alpine peak metamorphic conditions of 275 ± 23°C and 5.9 ± 1.7 kbar. These results are consistent with our RSCM and Tmax estimates. Raman study conducted on organic-rich schist samples shows an eastward increase of the alpine Tmax in the upper Houiller unit, from 280 to 300°C across the Briançonnais Zone houillère. In contrast, carbonaceous material included in detrital grains of muscovite in the sandstone exhibits higher temperatures. This hercynian Tmax is estimated using thermodynamic modelling at 376 ± 50°C. According to these results and previous work in more internal parts of the Briançonnais zone, a geodynamic reconstruction is proposed, which is characterized by a diachronous evolution of the Briançonnais zone involved in alpine continental subduction at different times. The geothermal gradient in the Briançonnais zone changes from 8°C/km during early continental subduction, to 40°C/km during the collisional event at about 35-30 Ma. The intermediate gradient of 15°C/km estimated in the Briançonnais Zone houillère suggests that this unit was buried later, than the more internal Briançonnais units, after 40 Ma

Molecular mechanisms of HIV-1 persistence in the monocyte-macrophage lineage

The introduction of the highly active antiretroviral therapy (HAART) has greatly improved survival. However, these treatments fail to definitively cure the patients and unveil the presence of quiescent HIV-1 reservoirs like cells from monocyte-macrophage lineage. A purge, or at least a significant reduction of these long lived HIV-1 reservoirs will be needed to raise the hope of the viral eradication. This review focuses on the molecular mechanisms responsible for viral persistence in cells of the monocyte-macrophage lineage. Controversy on latency and/or cryptic chronic replication will be specifically evoked. In addition, since HIV-1 infected monocyte-macrophage cells appear to be more resistant to apoptosis, this obstacle to the viral eradication will be discussed. Understanding the intimate mechanisms of HIV-1 persistence is a prerequisite to devise new and original therapies aiming to achieve viral eradication

Reproducing Biologically Realistic Regimes on a Highly-Accelerated Neuromorphic Hardware System

Analog implementations of neural networks have several advantages over computer simulations: they are usually faster, more energy efficient and fault-tolerant. However, compared to purely digital systems, analog hardware is subject to transistor size mis- matches. For neuromorphic systems, and in particular for neuron circuits, this means that there will be neuron-to-neuron variations on the chip, resulting in a different behav- ior for each hardware neuron. This is why a calibration step is necessary to compensate these variations, and guarantee a correct operation of all neuron circuits. This thesis presents a software framework to automatically convert the parameters of a neuron models written in a description language, PyNN, to parameters which will be used to configure the hardware system, while making sure that the hardware neurons behave in the same way that their theoretical counterparts. After a theoretical analysis, this framework is applied both on transistor-level level simulations of the hardware as well as on the hardware system itself. Finally, the software framework is used to emulate some simple neural networks on the neuromorphic hardware system