No abstract

Background The prevalence of mental illness, particularly depression and dementia, is increased by obesity. Here we test the hypothesis that obesity-associated changes in gut microbiota are intrinsically able to impair neurocognitive behavior in mice. Methods Conventionally housed, non-obese, adult male C57BL/6 mice maintained on a normal chow diet were subjected to a microbiome depletion/transplantation paradigm using microbiota isolated from donors (given) on either high-fat (HFD) or control diet (CD). Following recolonization, mice were subjected to comprehensive behavioral and biochemical analyses. Results The mice given HFD microbiota had significant and selective disruptions in exploratory, cognitive, and stereotypical behavior compared to mice with CD microbiota in the absence of significant differences in body weight. Sequencing-based phylogenetic analysis confirmed the presence of distinct core microbiota between groups, with alterations in α- and β- diversity, modulation in taxonomic distribution, and statistically significant alterations to metabolically active taxa. HFD microbiota also disrupted markers of intestinal barrier function, increased circulating endotoxin, and increased lymphocyte expression of Iba1, TLR2, and TLR4. Finally, evaluation of brain homogenates revealed that HFD-shaped microbiota increased neuroinflammation and disrupted cerebrovascular homeostasis. Conclusions Collectively, these data reinforce the link between gut dysbiosis and neurologic dysfunction and suggest that dietary and/or pharmacological manipulation of gut microbiota could attenuate the neurologic complications of obesity.

DNA replication in metazoans initiates from multiple chromosomal loci called origins. This study identifies 150 new origins of replication that were confirmed by two methods of nascent strand purification. We discern the role of transcription initiation and regulation, as well as chromatin signatures in determining origin selection in human genome.

Bacterial vaginosis (BV) is the most common cause of vaginal discharge. It is associated with an increased risk of preterm delivery, pelvic inflammatory disease, and an increased risk of acquisition of sexually transmitted infections including human immunodeficiency virus (HIV). The epidemiology of BV supports sexual transmission. However, its etiology remains unknown. At the center of the debate is whether BV is caused by a primary pathogen or a polymicrobial consortium of microorganisms that are sexually transmitted. We previously published a conceptual model hypothesizing that BV is initiated by sexual transmission of Gardnerella vaginalis. Critics of this model have iterated that G. vaginalis is found in virginal women and in sexually active women with a normal vaginal microbiota. In addition, colonization does not always lead to BV. However, recent advances in BV pathogenesis research have determined the existence of 13 different species within the genus Gardnerella. It may be that healthy women are colonized by nonpathogenic Gardnerella species, whereas virulent strains are involved in BV development. Based on our results from a recent prospective study, in addition to an extensive literature review, we present an updated conceptual model for the pathogenesis of BV that centers on the roles of virulent strains of G. vaginalis, as well as Prevotella bivia and Atopobium vaginae.

The objective of this study was to map quantitative trait loci (QTL) for the vernalization response in perennial ryegrass (Lolium perenne L.). The mapping population consisted of 184 F2 genotypes produced from a cross between one genotype of a synthetic perennial ryegrass variety "Veyo" and one genotype from the perennial ryegrass ecotype "Falster". Veyo and Falster were chosen among four different populations because of their contrasting vernalization requirements. In total, five QTL for the vernalization response, measured as days to heading, were identified and mapped to linkage groups (LG) LG2, LG4, LG6 and LG7. Individually, these QTL explained between 5.4 and 28.0% of the total phenotypic variation. The overall contribution of these five QTL was 80% of the total phenotypic variation. A putative orthologue of Triticum monococcum VRN1 was amplified from genomic DNA from perennial ryegrass. PCR fragments covering the proximal part of the promoter and the 5' end of the orthologue were subsequently PCR-amplified from both parents of the mapping population and shown to possess 95% DNA sequence identity to VRN1. Several polymorphisms were identified between Veyo and Falster in this fragment of the putative VRN1 orthologue. A CAPS marker, vrn-1, was developed and found to co-segregate with a major QTL on LG4 for the vernalization response. This indicates that the CAPS marker vrn-1 could be located in an orthologous gene of the wheat VRN1.