Accurate Determination of Conformational Transitions in Oligomeric Membrane Proteins

The structural dynamics governing collective motions in oligomeric membrane proteins play key roles in vital biomolecular processes at cellular membranes. In this study, we present a structural refinement approach that combines solid-state NMR experiments and molecular simulations to accurately describe concerted conformational transitions identifying the overall structural, dynamical, and topological states of oligomeric membrane proteins. The accuracy of the structural ensembles generated with this method is shown to reach the statistical error limit, and is further demonstrated by correctly reproducing orthogonal NMR data. We demonstrate the accuracy of this approach by characterising the pentameric state of phospholamban, a key player in the regulation of calcium uptake in the sarcoplasmic reticulum, and by probing its dynamical activation upon phosphorylation. Our results underline the importance of using an ensemble approach to characterise the conformational transitions that are often responsible for the biological function of oligomeric membrane protein states

Myeloid cells in glioblastoma microenvironment

Glioblastoma (GBM) is the most aggressive, malignant primary brain tumor in adults. GBM is notoriously resistant to immunotherapy mainly due to its unique immune microenvironment. High dimensional data analysis reveals the extensive heterogeneity of immune components making up the GBM microenvironment. Myeloid cells are the most predominant contributors to the GBM microenvironment; these cells are critical regulators of immune and therapeutic responses to GBM. Here, we will review the most recent advances on the characteristics and functions of different populations of myeloid cells in GBM, including bone marrow-derived macrophages, microglia, myeloid-derived suppressor cells, dendritic cells, and neutrophils. Epigenetic, metabolic, and phenotypic peculiarities of microglia and bone marrow-derived macrophages will also be assessed. The final goal of this review will be to provide new insights into novel therapeutic approaches for specific targeting of myeloid cells to improve the efficacy of current treatments in GBM patients

Small for Gestational Age Babies After 37 Weeks: An Impact Study of a Risk Stratification Protocol.

OBJECTIVES: Although no clear evidence exists, many international guidelines advocate early term delivery of small for gestational age (SGA) fetuses. The aim of this study was to determine whether a protocol that included monitoring SGA fetuses beyond 37 weeks affected perinatal and maternal outcomes. METHODS: The impact of the introduction in 2014 of a protocol for management of SGA, which included risk stratification with surveillance and expectant management after 37 weeks for lower risk babies (Group 2), was compared with the previous strategy, which recommended delivery at around 37 weeks (Group 1). Data from all referred SGA babies over a 39 month period were analyzed. RESULTS: In group 1 there were 138 SGA babies; in group 2 there were 143. The mean gestation at delivery was 37 + 4 and 38 + 2 weeks respectively (p = 0.04). The incidence of neonatal composite adverse outcomes was lower in Group 2 (9% v 22% v; p < 0.01) as was neonatal NNU admission (13% v 42%; p < 0.01). Induction of labour and caesarean section rates were lower, and vaginal delivery (83% v 60%; p < 0.01) was higher in group 2. Most of the differences were due to delayed delivery of SGA babies that were stratified as low risk. CONCLUSIONS: This study suggests that protocol-based management of SGA babies may improve outcomes and that identification of moderate SGA should not alone prompt delivery. Larger numbers are required to assess any impact on perinatal mortality

Network Awareness of P2P Live Streaming Applications

Early P2P-TV systems have already attracted millions of users, and many new commercial solutions are entering this market. Little information is however available about how these systems work. In this paper we present large scale sets of experiments to compare three of the most successful P2P-TV systems, namely PPLive, SopCast and TVAnts. Our goal is to assess what level of "network awareness" has been embedded in the applications, i.e., what parameters mainly drive the peer selection and data exchange. By using a general framework that can be extended to other systems and metrics, we show that all applications largely base their choices on the peer bandwidth, i.e., they prefer high-bandwidth users, which is rather intuitive. Moreover, TVAnts and PPLive exhibits also a preference to exchange data among peers in the same autonomous system the peer belongs to. However, no evidence about preference versus peers in the same subnet or that are closer to the considered peer emerges. We believe that next-generation P2P live streaming applications definitively need to improve the level of network-awareness, so to better localize the traffic in the network and thus increase their network-friendliness as wel

Network Awareness of P2P Live Streaming Applications: A Measurement Study

Abstract: Early P2P-TV systems have already attracted millions of users, and many new commercial solutions are entering this market. Little information is however available about how these systems work, due to their closed and proprietary design. In this paper, we present large scale experiments to compare three of the most successful P2P-TV systems, namely PPLive, SopCast and TVAnts. Our goal is to assess what level of "network awareness" has been embedded in the applications. We first define a general framework to quantify which network layer parameters leverage application choices, i.e., what parameters mainly drive the peer selection and data exchange. We then apply the methodology to a large dataset, collected during a number of experiments where we deployed about 40 peers in several European countries. From analysis of the dataset, we observe that TVAnts and PPLive exhibit a mild preference to exchange data among peers in the same autonomous system the peer belongs to, while this clustering effect is less intense in SopCast. However, no preference versus country, subnet or hop count is shown. Therefore, we believe that next-generation P2P live streaming applications definitively need to improve the level of network-awareness, so to better localize the traffic in the network and thus increase their network-friendliness as well