Vesicular glutamatergic transmission in noise-induced loss and repair of cochlear ribbon synapses

Noise-induced excitotoxicity is thought to depend on glutamate. However, the excitotoxic mechanisms are unknown, and the necessity of glutamate for synapse loss or regeneration is unclear. Despite absence of glutamatergic transmission from cochlear inner hair cells in mice lacking the vesicular glutamate transporter-3

Genome-scale hypomethylation in the cord blood DNAs associated with early onset preeclampsia

Background: Preeclampsia is one of the leading causes of fetal and maternal morbidity and mortality worldwide. Preterm babies of mothers with early onset preeclampsia (EOPE) are at higher risks for various diseases later on in life, including cardiovascular diseases. We hypothesized that genome-wide epigenetic alterations occur in cord blood DNAs in association with EOPE and conducted a case control study to compare the genome-scale methylome differences in cord blood DNAs between 12 EOPE-associated and 8 normal births. Results: Bioinformatics analysis of methylation data from the Infinium HumanMethylation450 BeadChip shows a genome-scale hypomethylation pattern in EOPE, with 51,486 hypomethylated CpG sites and 12,563 hypermethylated sites (adjusted P <0.05). A similar trend also exists in the proximal promoters (TSS200) associated with protein-coding genes. Using summary statistics on the CpG sites in TSS200 regions, promoters of 643 and 389 genes are hypomethylated and hypermethylated, respectively. Promoter-based differential methylation (DM) analysis reveals that genes in the farnesoid X receptor and liver X receptor (FXR/LXR) pathway are enriched, indicating dysfunction of lipid metabolism in cord blood cells. Additional biological functional alterations involve inflammation, cell growth, and hematological system development. A two-way ANOVA analysis among coupled cord blood and amniotic membrane samples shows that a group of genes involved in inflammation, lipid metabolism, and proliferation are persistently differentially methylated in both tissues, including IL12B, FAS, PIK31, and IGF1. Conclusions: These findings provide, for the first time, evidence of prominent genome-scale DNA methylation modifications in cord blood DNAs associated with EOPE. They may suggest a connection between inflammation and lipid dysregulation in EOPE-associated newborns and a higher risk of cardiovascular diseases later in adulthood

Evidence for Exciton Crystals in a 2D Semiconductor Heterotrilayer

Two-dimensional (2D) transition metal dichalcogenides (TMDC) and their moire interfaces have been demonstrated for correlated electron states, including Mott insulators and electron/hole crystals commensurate with moire superlattices. Here we present spectroscopic evidences for ordered bosons - interlayer exciton crystals in a WSe2/MoSe2/WSe2 trilayer, where the enhanced Coulomb interactions over those in heterobilayers have been predicted to result in exciton ordering. While the dipolar interlayer excitons in the heterobilayer may be ordered by the periodic moire traps, their mutual repulsion results in de-trapping at exciton density larger than 10^11 cm^-2 to form mobile exciton gases and further to electron-hole plasmas, both accompanied by broadening in photoluminescence (PL) peaks and large increases in mobility. In contrast, ordered interlayer excitons in the trilayer are characterized by negligible mobility and by sharper PL peaks persisting to nex larger than 10^12 cm^-2. We find that an optically dark state attributed to the predicted quadrupolar exciton crystal transitions to the bright dipolar excitons either with increasing nex or by an applied electric field. These ordered interlayer excitons may serve as models for the exploration of quantum phase transitions and quantum coherent phenomena.Comment: 16 pages, 4 figures, S

LCrowdV: Generating Labeled Videos for Simulation-based Crowd Behavior Learning

We present a novel procedural framework to generate an arbitrary number of labeled crowd videos (LCrowdV). The resulting crowd video datasets are used to design accurate algorithms or training models for crowded scene understanding. Our overall approach is composed of two components: a procedural simulation framework for generating crowd movements and behaviors, and a procedural rendering framework to generate different videos or images. Each video or image is automatically labeled based on the environment, number of pedestrians, density, behavior, flow, lighting conditions, viewpoint, noise, etc. Furthermore, we can increase the realism by combining synthetically-generated behaviors with real-world background videos. We demonstrate the benefits of LCrowdV over prior lableled crowd datasets by improving the accuracy of pedestrian detection and crowd behavior classification algorithms. LCrowdV would be released on the WWW

Rhesus TRIM5α disrupts the HIV-1 capsid at the inter-hexamer interfaces

TRIM proteins play important roles in the innate immune defense against retroviral infection, including human immunodeficiency virus type-1 (HIV-1). Rhesus macaque TRIM5α (TRIM5αrh) targets the HIV-1 capsid and blocks infection at an early post-entry stage, prior to reverse transcription. Studies have shown that binding of TRIM5α to the assembled capsid is essential for restriction and requires the coiled-coil and B30.2/SPRY domains, but the molecular mechanism of restriction is not fully understood. In this study, we investigated, by cryoEM combined with mutagenesis and chemical cross-linking, the direct interactions between HIV-1 capsid protein (CA) assemblies and purified TRIM5αrh containing coiled-coil and SPRY domains (CC-SPRYrh). Concentration-dependent binding of CC-SPRYrh to CA assemblies was observed, while under equivalent conditions the human protein did not bind. Importantly, CC-SPRYrh, but not its human counterpart, disrupted CA tubes in a non-random fashion, releasing fragments of protofilaments consisting of CA hexamers without dissociation into monomers. Furthermore, such structural destruction was prevented by inter-hexamer crosslinking using P207C/T216C mutant CA with disulfide bonds at the CTD-CTD trimer interface of capsid assemblies, but not by intra-hexamer crosslinking via A14C/E45C at the NTD-NTD interface. The same disruption effect by TRIM5αrh on the inter-hexamer interfaces also occurred with purified intact HIV-1 cores. These results provide insights concerning how TRIM5α disrupts the virion core and demonstrate that structural damage of the viral capsid by TRIM5α is likely one of the important components of the mechanism of TRIM5α-mediated HIV-1 restriction. © 2011 Zhao et al

New directions in cellular therapy of cancer: a summary of the summit on cellular therapy for cancer

A summit on cellular therapy for cancer discussed and presented advances related to the use of adoptive cellular therapy for melanoma and other cancers. The summit revealed that this field is advancing rapidly. Conventional cellular therapies, such as tumor infiltrating lymphocytes (TIL), are becoming more effective and more available. Gene therapy is becoming an important tool in adoptive cell therapy. Lymphocytes are being engineered to express high affinity T cell receptors (TCRs), chimeric antibody-T cell receptors (CARs) and cytokines. T cell subsets with more naïve and stem cell-like characteristics have been shown in pre-clinical models to be more effective than unselected populations and it is now possible to reprogram T cells and to produce T cells with stem cell characteristics. In the future, combinations of adoptive transfer of T cells and specific vaccination against the cognate antigen can be envisaged to further enhance the effectiveness of these therapies

Synchronization modulation increases transepithelial potentials in MDCK monolayers through Na/K pumps

Peer reviewedPublisher PD

Evolutionary relationships among barley and <i>Arabidopsis</i> core circadian clock and clock-associated genes

The circadian clock regulates a multitude of plant developmental and metabolic processes. In crop species, it contributes significantly to plant performance and productivity and to the adaptation and geographical range over which crops can be grown. To understand the clock in barley and how it relates to the components in the Arabidopsis thaliana clock, we have performed a systematic analysis of core circadian clock and clock-associated genes in barley, Arabidopsis and another eight species including tomato, potato, a range of monocotyledonous species and the moss, Physcomitrella patens. We have identified orthologues and paralogues of Arabidopsis genes which are conserved in all species, monocot/dicot differences, species-specific differences and variation in gene copy number (e.g. gene duplications among the various species). We propose that the common ancestor of barley and Arabidopsis had two-thirds of the key clock components identified in Arabidopsis prior to the separation of the monocot/dicot groups. After this separation, multiple independent gene duplication events took place in both monocot and dicot ancestors. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00239-015-9665-0) contains supplementary material, which is available to authorized users

Pyrolysis of wastewater sludge and composted organic fines from municipal solid waste: laboratory reactor characterisation and product distribution

peer-reviewedSludge from municipal wastewater treatment plants and organic fines from mechanical sorting of municipal solid waste (MSW) are two common widespread waste streams that are becoming increasingly difficult to utilise. Changing perceptions of risk in food production has limited the appeal of sludge use on agricultural land, and outlets via landfilling are diminishing rapidly. These factors have led to interest in thermal conversion technologies whose aim is to recover energy and nutrients from waste while reducing health and environmental risks associated with material re-use. Pyrolysis yields three output products: solid char, liquid oils and gas. Their relative distribution depends on process parameters which can be somewhat optimised depending on the end use of product. The potential of pyrolysis for the conversion of wastewater sludge (SS) and organic fines of MSW(OF) to a combustion gas and a carbon-rich char has been investigated. Pyrolysis of SS and OF was done using a laboratory fixed-bed reactor. Herein, the physical characterisation of the reactor is described, and results on pyrolysis yields are presented. Feedstock and chars have been characterised using standard laboratory methods, and the composition of pyrolysis gases was analysed using micro gas chromatography. Product distribution (char/liquid/gas) from the pyrolysis of sewage sludge and compostedMSWfines at 700°C for 10 min were 45/26/29 and 53/14/33%, respectively. The combustible fractions of pyrolysis gases range from 36 to 54% for SS feedstock and 62 to 72% from OF. The corresponding lower heating value range of sampled gases were 11.8–19.1 and 18.2–21.0 MJ m-3, respectively

Defending the genome from the enemy within:mechanisms of retrotransposon suppression in the mouse germline

The viability of any species requires that the genome is kept stable as it is transmitted from generation to generation by the germ cells. One of the challenges to transgenerational genome stability is the potential mutagenic activity of transposable genetic elements, particularly retrotransposons. There are many different types of retrotransposon in mammalian genomes, and these target different points in germline development to amplify and integrate into new genomic locations. Germ cells, and their pluripotent developmental precursors, have evolved a variety of genome defence mechanisms that suppress retrotransposon activity and maintain genome stability across the generations. Here, we review recent advances in understanding how retrotransposon activity is suppressed in the mammalian germline, how genes involved in germline genome defence mechanisms are regulated, and the consequences of mutating these genome defence genes for the developing germline