Damaged axons promote OPC differentiation

Oligodendrocyte progenitor cell (OPC) differentiation is an important therapeutic target to promote remyelination in multiple sclerosis (MS). We previously reported hyperphosphorylated and aggregated microtubule-associated protein tau in MS lesions, suggesting its involvement in axonal degeneration. However, the influence of pathological tau-induced axonal damage on the potential for remyelination is unknown. Therefore, we investigated OPC differentiation in human P301S tau (P301S-htau) transgenic mice, both in vitro and in vivo following focal demyelination. In 2-month-old P301S-htau mice, which show hyperphosphorylated tau in neurons, we found atrophic axons in the spinal cord in the absence of prominent axonal degeneration. These signs of early axonal damage were associated with microgliosis and an upregulation of IL-1β and TNFα. Following in vivo focal white matter demyelination we found that OPCs differentiated more efficiently in P301S-htau mice than wild type (Wt) mice. We also found an increased level of myelin basic protein within the lesions, which however did not translate into increased remyelination due to higher susceptibility of P301S-htau axons to demyelination-induced degeneration compared to Wt axons. In vitro experiments confirmed higher differentiation capacity of OPCs from P301S-htau mice compared with Wt mice-derived OPCs. Because the OPCs from P301S-htau mice do not ectopically express the transgene, and when isolated from newborn mice behave like Wt mice-derived OPCs, we infer that their enhanced differentiation capacity must have been acquired through microenvironmental priming. Our data suggest the intriguing concept that damaged axons may signal to OPCs and promote their differentiation in the attempt at rescue by remyelination. GLIA 2016;64:457-471.This project was funded by the Multiple Sclerosis Society UK via the Cambridge Centre for Myelin Repair consortium, and core support grant from the Wellcome Trust and MRC to the Wellcome Trust – Medical Research Council Cambridge Stem Cell Institute

Multiple imputation for IPD meta-analysis: allowing for heterogeneity and studies with missing covariates.

Recently, multiple imputation has been proposed as a tool for individual patient data meta-analysis with sporadically missing observations, and it has been suggested that within-study imputation is usually preferable. However, such within study imputation cannot handle variables that are completely missing within studies. Further, if some of the contributing studies are relatively small, it may be appropriate to share information across studies when imputing. In this paper, we develop and evaluate a joint modelling approach to multiple imputation of individual patient data in meta-analysis, with an across-study probability distribution for the study specific covariance matrices. This retains the flexibility to allow for between-study heterogeneity when imputing while allowing (i) sharing information on the covariance matrix across studies when this is appropriate, and (ii) imputing variables that are wholly missing from studies. Simulation results show both equivalent performance to the within-study imputation approach where this is valid, and good results in more general, practically relevant, scenarios with studies of very different sizes, non-negligible between-study heterogeneity and wholly missing variables. We illustrate our approach using data from an individual patient data meta-analysis of hypertension trials. © 2015 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd

Vertex importance extension of betweenness centrality algorithm

Variety of real-life structures can be simplified by a graph. Such simplification emphasizes the structure represented by vertices connected via edges. A common method for the analysis of the vertices importance in a network is betweenness centrality. The centrality is computed using the information about the shortest paths that exist in a graph. This approach puts the importance on the edges that connect the vertices. However, not all vertices are equal. Some of them might be more important than others or have more significant influence on the behavior of the network. Therefore, we introduce the modification of the betweenness centrality algorithm that takes into account the vertex importance. This approach allows the further refinement of the betweenness centrality score to fulfill the needs of the network better. We show this idea on an example of the real traffic network. We test the performance of the algorithm on the traffic network data from the city of Bratislava, Slovakia to prove that the inclusion of the modification does not hinder the original algorithm much. We also provide a visualization of the traffic network of the city of Ostrava, the Czech Republic to show the effect of the vertex importance adjustment. The algorithm was parallelized by MPI (http://www.mpi-forum.org/) and was tested on the supercomputer Salomon (https://docs.it4i.cz/) at IT4Innovations National Supercomputing Center, the Czech Republic.808726

Intrinsic paramagnetic meissner effect due to s-wave odd-frequency superconductivity

In 1933, Meissner and Ochsenfeld reported the expulsion of magnetic flux, the diamagnetic Meissner effect, from the interior of superconducting lead. This discovery was crucial in formulating the Bardeen-Cooper-Schrieffer (BCS) theory of superconductivity. In exotic superconducting systems BCS theory does not strictly apply. A classical example is a superconductor-magnet hybrid system where magnetic ordering breaks time-reversal symmetry of the superconducting condensate and results in the stabilisation of an odd-frequency superconducting state. It has been predicted that under appropriate conditions, odd-frequency superconductivity should manifest in the Meissner state as fluctuations in the sign of the magnetic susceptibility meaning that the superconductivity can either repel (diamagnetic) or attract (paramagnetic) external magnetic flux. Here we report local probe measurements of faint magnetic fields in a Au/Ho/Nb trilayer system using low energy muons, where antiferromagnetic Ho (4.5 nm) breaks time-reversal symmetry of the proximity induced pair correlations in Au. From depth-resolved measurements below the superconducting transition of Nb we observe a local enhancement of the magnetic field in Au that exceeds the externally applied field, thus proving the existence of an intrinsic paramagnetic Meissner effect arising from an odd-frequency superconducting state.J.W.A.R. acknowledges financial support from the Royal Society through a University Research Fellowship. J.W.A.R. and A.D.B. acknowledge financial support from the UK EPSRC through NanoDTC EP/G037221/1 and the Leverhulme Trust through an International Network Grant (IN-2013-033). A.D.B. also acknowledges additional financial support from the Schiff Foundation. X.L.W. and J.H.Z. acknowledge support from the MOST of China (2015CB921500). J.L. acknowledges support from the Outstanding Academic Fellows programme at NTNU, the Norwegian Research Council Grant (205591, FRINAT, 216700). J. L., J.W.A.R, and A.D.B. finally acknowledge support from the COST Action MP-1201 'Novel Functionalities through Optimized Confinement of Condensate and Fields.' S.L. and M.G.F. acknowledge the support of the EPSRC through Grant No. EP/J01060X. The muSR measurements were performed at the Swiss Muon Source (SµS), at the Paul Scherrer Institute in Villigen, Switzerland. The project has also received funding from the European Union’s Seventh Framework Programme for research, technological development and demonstration under the NMI3-II Grant number 283883.This is the final version of the article. It first appeared from APS via http://dx.doi.org/10.1103/PhysRevX.5.04102

Large-Scale Sleep Condition Analysis Using Selfies from Social Media

Sleep condition is closely related to an individual's health. Poor sleep conditions such as sleep disorder and sleep deprivation affect one's daily performance, and may also cause many chronic diseases. Many efforts have been devoted to monitoring people's sleep conditions. However, traditional methodologies require sophisticated equipment and consume a significant amount of time. In this paper, we attempt to develop a novel way to predict individual's sleep condition via scrutinizing facial cues as doctors would. Rather than measuring the sleep condition directly, we measure the sleep-deprived fatigue which indirectly reflects the sleep condition. Our method can predict a sleep-deprived fatigue rate based on a selfie provided by a subject. This rate is used to indicate the sleep condition. To gain deeper insights of human sleep conditions, we collected around 100,000 faces from selfies posted on Twitter and Instagram, and identified their age, gender, and race using automatic algorithms. Next, we investigated the sleep condition distributions with respect to age, gender, and race. Our study suggests among the age groups, fatigue percentage of the 0-20 youth and adolescent group is the highest, implying that poor sleep condition is more prevalent in this age group. For gender, the fatigue percentage of females is higher than that of males, implying that more females are suffering from sleep issues than males. Among ethnic groups, the fatigue percentage in Caucasian is the highest followed by Asian and African American.Comment: 2017 International Conference on Social Computing, Behavioral-Cultural Modeling, & Prediction and Behavior Representation in Modeling and Simulation (SBP-BRiMS'17

Phenotypic and functional modulation of porcine monocyte-derived dendritic cells for foot-and-mouth disease virus

Dendritic cells (DCs) play an important role in inducing primary antigen-specific immune responses to viral antigens. In this study, the peripheral blood monocyte-derived (PBMC) were cultured in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-4. After 6 days of culture, immature monocyte-derived dendritic cells (Mo-DCs) were generated. The addition of lipopolysaccharide (LPS) during differentiation of Mo-DCs enhanced their ability to stimulate allogeneic mixed lymphocyte reaction (MLR) and alter their ability to produce cytokines. Then, we investigated the interaction between foot-and-mouth disease virus (FMDV) and porcine Mo-DCs in vitro and confirmed that the immunological phenotype and function of porcine Mo-DCs were modulated during FMDV infection. A down-regulated expression of MHC II and CD1 were observed at 48 h post FMDV infection. In addition, the infected porcine Mo-DCs exhibited ultrastructural morphological changes, FMDV-infected porcine Mo-DCs failed to stimulate T cell proliferation in vitro. Moreover, infection of porcine Mo-DCs in vitro induced the secretion of IFN-γ and the suppressive cytokine IL-10 in porcine Mo-DCs. Results indicated that the down-regulation of MHC II and CD1 molecules and the increased secretion of the IFN-γ and IL-10 cytokines might be the mechanisms that FMDV uses to evade the host immune responses.Key words: Dendritic cells, foot-and-mouth disease virus, MHC II, modulation, cytokines

Liposome Co-sedimentation and Co-flotation Assays to Study Lipid-Protein Interactions

A large proportion of proteins are expected to interact with cellular membranes to carry out their physiological functions in processes such as membrane transport, morphogenesis, cytoskeletal organization, and signal transduction. The recruitment of proteins at the membrane-cytoplasm interface and their activities are precisely regulated by phosphoinositides, which are negatively charged phospholipids found on the cytoplasmic leaflet of cellular membranes and play critical roles in membrane homeostasis and cellular signaling. Thus, it is important to reveal which proteins interact with phosphoinositides and to elucidate the underlying mechanisms. Here, we present two standard in vitro methods, liposome co-sedimentation and co-flotation assays, to study lipid-protein interactions. Liposomes can mimic various biological membranes in these assays because their lipid compositions and concentrations can be varied. Thus, in addition to mechanisms of lipid-protein interactions, these methods provide information on the possible specificities of proteins toward certain lipids such as specific phosphoinositide species and can hence shed light on the roles of membrane interactions on the functions of membrane-associated proteins.Peer reviewe

Water Quality in Irrigated Paddy Systems

Irrigated paddy rice (Oryza sativa L.) is a staple food for roughly half of the world’s population. Concerns over water quality have arisen in recent decades, particularly in China, which is the largest rice-producing country in the world and has the most intensive use of nutrients and water in rice production. On the one hand, the poor water quality has constrained the use of water for irrigation to paddy systems in many areas of the world. On the other hand, nutrient losses from paddy production systems contribute to contamination and eutrophication of freshwater bodies. Here, we review rice production, water requirement, water quality issues, and management options to minimize nutrient losses from paddy systems. We conclude that management of nutrient source, rate, timing, and placement should be combined with the management of irrigation and drainage water to reduce nitrogen and phosphorus losses from paddies. More research is needed to identify cost-effective monitoring approaches and mitigation options, and relevant extension and policy should be enforced to achieve water quality goals. The review is preliminarily based on China’s scenario, but it would also provide valuable information for other rice-producing countries