Molecular analysis of the diversity of vaginal microbiota associated with bacterial vaginosis

<p>Abstract</p> <p>Background</p> <p>Bacterial vaginosis (BV) is an ecological disorder of the vaginal microbiota that affects millions of women annually, and is associated with numerous adverse health outcomes including pre-term birth and the acquisition of sexually transmitted infections. However, little is known about the overall structure and composition of vaginal microbial communities; most of the earlier studies focused on predominant vaginal bacteria in the process of BV. In the present study, the diversity and richness of vaginal microbiota in 50 BV positive and 50 healthy women from China were investigated using culture-independent PCR-denaturing gradient gel electrophoresis (DGGE) and barcoded 454 pyrosequencing methods, and validated by quantitative PCR.</p> <p>Results</p> <p>Our data demonstrated that there was a profound shift in the absolute and relative abundances of bacterial species present in the vagina when comparing populations associated with healthy and diseased conditions. In spite of significant interpersonal variations, the diversity of vaginal microbiota in the two groups could be clearly divided into two clusters. A total of 246,359 high quality pyrosequencing reads was obtained for evaluating bacterial diversity and 24,298 unique sequences represented all phylotypes. The most predominant phyla of bacteria identified in the vagina belonged to <it>Firmicutes</it>, <it>Bacteroidetes</it>, <it>Actinobacteria </it>and <it>Fusobacteria</it>. The higher number of phylotypes in BV positive women over healthy is consistent with the results of previous studies and a large number of low-abundance taxa which were missed in previous studies were revealed. Although no single bacterium could be identified as a specific marker for healthy over diseased conditions, three phyla - <it>Bacteroidetes</it>, <it>Actinobacteria </it>and <it>Fusobacteria</it>, and eight genera including <it>Gardnerella</it>, <it>Atopobium</it>, <it>Megasphaera</it>, <it>Eggerthella</it>, <it>Aerococcus</it>, <it>Leptotrichia</it>/<it>Sneathia</it>, <it>Prevotella </it>and <it>Papillibacter </it>were strongly associated with BV (<it>p </it>< 0.05). These genera are potentially excellent markers and could be used as targets for clinical BV diagnosis by molecular approaches.</p> <p>Conclusions</p> <p>The data presented here have clearly profiled the overall structure of vaginal communities and clearly demonstrated that BV is associated with a dramatic increase in the taxonomic richness and diversity of vaginal microbiota. The study also provides the most comprehensive picture of the vaginal community structure and the bacterial ecosystem, and significantly contributes to the current understanding of the etiology of BV.</p

Antiviral therapy effectively improves liver hemodynamics as evidenced by serum biomarker and contrast-enhanced ultrasound examinations in patients with hepatitis B cirrhosis

Background and Aims To prospectively evaluate the effects of antiviral therapy on liver hemodynamics in patients with hepatitis B cirrhosis. Methods Seventy consecutive eligible HBV-related cirrhotic inpatients were enrolled in the prospective study. Fifty-two received different nucleoside analogs monotherapy and 18 denied antiviral therapy. Their liver biochemistry profiles and HBV-DNA were measured at the baseline and every 3 months. Peripheral blood vWF and sCD163, as well as liver ultrasound Doppler parameters including portal vein diameter (PVD), portal vein velocity (PVV), portal vein congestion index (PV-CI), hepatic vein damping index (HV-DI), hepatic arterial arrival time (HAAT), hepatic vein arrival time (HVAT) and intrahepatic cycle time (HV-HA), were measured at the baseline and the follow-up periods. Results In the antiviral group, all patients achieved complete virologic and liver biochemical responses after 3-month antiviral treatment. Furthermore, the response states were maintained till the follow-up endpoint. However, in the non-antiviral group, HBV DNA replication resulted in higher levels of ALT and AST compared to the baseline values (P < 0.05). In the antiviral group, PVD, PV-CI, HV-DI, vWF-Ag and sCD163 were all significantly reduced than the baseline values (P < 0.05), and PVV was significantly increased than the baseline value (P < 0.05). Conclusions Antiviral therapy could effectively suppress hepatocyte inflammation and alleviate the dysfunction of intrahepatic vascular endothelial and hepatic macrophages, which might improve hepatic hemodynamic function in HBV-related cirrhosis

Dense Feature Aggregation and Pruning for RGBT Tracking

How to perform effective information fusion of different modalities is a core factor in boosting the performance of RGBT tracking. This paper presents a novel deep fusion algorithm based on the representations from an end-to-end trained convolutional neural network. To deploy the complementarity of features of all layers, we propose a recursive strategy to densely aggregate these features that yield robust representations of target objects in each modality. In different modalities, we propose to prune the densely aggregated features of all modalities in a collaborative way. In a specific, we employ the operations of global average pooling and weighted random selection to perform channel scoring and selection, which could remove redundant and noisy features to achieve more robust feature representation. Experimental results on two RGBT tracking benchmark datasets suggest that our tracker achieves clear state-of-the-art against other RGB and RGBT tracking methods.Comment: arXiv admin note: text overlap with arXiv:1811.0985

The asparagus genome sheds light on the origin and evolution of a young Y chromosome

Several models have been proposed to explain the emergence of sex chromosomes. Here, through comparative genomics and mutant analysis, Harkess et al. show that linked but separate genes on the Y chromosome are responsible for sex determination in Asparagus, supporting a two-gene model for sex chromosome evolution

Discovery of [11C]MK-6884: a positron emission tomography (PET) imaging agent for the study of M4 muscarinic receptor positive allosteric modulators (PAMs) in neurodegenerative diseases

The measurement of receptor occupancy (RO) using positron emission tomography (PET) has been instrumental in guiding discovery and development of CNS directed therapeutics. We and others have investigated muscarinic acetylcholine receptor 4 (M4) positive allosteric modulators (PAMs) for the treatment of symptoms associated with neuropsychiatric disorders. In this article, we describe the synthesis, in vitro, and in vivo characterization of a series of central pyridine-related M4 PAMs that can be conveniently radiolabeled with carbon-11 as PET tracers for the in vivo imaging of an allosteric binding site of the M4 receptor. We first demonstrated its feasibility by mapping the receptor distribution in mouse brain and confirming that a lead molecule 1 binds selectively to the receptor only in the presence of the orthosteric agonist carbachol. Through a competitive binding affinity assay and a number of physiochemical properties filters, several related compounds were identified as candidates for in vivo evaluation. These candidates were then radiolabeled with 11C and studied in vivo in rhesus monkeys. This research eventually led to the discovery of the clinical radiotracer candidate [11C]MK-6884