The Effects of Ovarian Hormones on Memory Bias and Progesterone Receptors in Female Rats

Ovarian hormones can bias female rats to use one memory system over another when navigating a novel or familiar environment, resulting in a memory bias. High levels of estrogen (E) promotes places memory while low level of E promotes response memory. However, little is known about the effects of progesterone (P) on memory bias. Experiment 1 determined whether P affects memory bias. Ovariectomized (OVX) female rats were trained in a plus shaped maze, which assesses memory system bias, and received one of three hormonal treatments: Low 17β estradiol (E2), high E2 or high E2 + P. P did affect memory bias by reversing the effects of high E2 when rats receive P one hour prior to testing. To understand the mechanisms by which P affect memory bias in the hippocampus (HPC), antibodies directed at nPR, mPRβ and mPRδ were examined. The effects of low E2, high E2, and high E2+P were examined on immunoreactivity to these receptors in the HPC. All three receptor-types were found in the female rat HPC and were found to be insensitive to hormone administration. The presence of these receptors suggests that P can exert both genomic and non-genomic effects in the HPC. Other brain areas involved in memory bias remain to be examined further

The C-terminal tail of the yeast mitochondrial transcription factor Mtf1 coordinates template strand alignment, DNA scrunching and timely transition into elongation

Mitochondrial RNA polymerases depend on initiation factors, such as TFB2M in humans and Mtf1 in yeast Saccharomyces cerevisiae, for promoterspecific transcription. These factors drive the melting of promoter DNA, but how they support RNA priming and growth was not understood. We show that the flexible C-terminal tails of Mtf1 and TFB2M play a crucial role in RNA priming by aiding template strand alignment in the active site for high-affinity binding of the initiating nucleotides. Using single-molecule fluorescence approaches, we show that the Mtf1 C-tail promotes RNA growth during initiation by stabilizing the scrunched DNA conformation. Additionally, due to its location in the path of the nascent RNA, the C-tail of Mtf1 serves as a sensor of the RNA- DNA hybrid length. Initially, steric clashes of the Mtf1 C-tail with short RNA-DNA hybrids cause abortive synthesis but clashes with longer RNA-DNA trigger conformational changes for the timely release of the promoter DNA to commence the transition into elongation. The remarkable similarities in the functions of the C-tail and sigma 3.2 finger of the bacterial factor suggest mechanistic convergence of a flexible element in the transcription initiation factor that engages the DNA template for RNA priming and growth and disengages when needed to generate the elongation complex

Service Now: CMDB Research

The MAPFRE Capstone team has been tasked with reviewing and recommending roadmap on the existing CMDB configuration. Paper discusses the team’s overall research on ServiceNow CMDB, Client’s deliverables and introduction to the latest technological innovations. Based on given objectives and team’s analysis we have recommended key solutions for the client to better understand the IT environment areas of business service impact, asset management, compliance, and configuration management. In addition, our research has covered all the majority of the technical and functional areas to provide greater visibility and insight into existing CMDB and IT environment

Dietary supplementation with Bifidobacterium longum subsp. infantis (B. infantis) in healthy breastfed infants: study protocol for a randomised controlled trial.

BackgroundThe development of probiotics as therapies to cure or prevent disease lags far behind that of other investigational medications. Rigorously designed phase I clinical trials are nearly non-existent in the field of probiotic research, which is a contributing factor to this disparity. As a consequence, how to appropriately dose probiotics to study their efficacy is unknown. Herein we propose a novel phase I ascending dose trial of Bifidobacterium longum subsp. infantis (B. infantis) to identify the dose required to produce predominant gut colonisation in healthy breastfed infants at 6 weeks of age.Methods/designThis is a parallel-group, placebo-controlled, randomised, double-blind ascending dose phase I clinical trial of dietary supplementation with B. infantis in healthy breastfed infants. The objective is to determine the pharmacologically effective dose (ED) of B. infantis required to produce predominant (>50 %) gut colonisation in breastfed infants at 6 weeks of age. Successively enrolled infant groups will be randomised to receive two doses of either B. infantis or placebo on days 7 and 14 of life. Stool samples will be used to characterise the gut microbiota at increasing doses of B. infantis.DiscussionProbiotic supplementation has shown promising results for the treatment of a variety of ailments, but evidence-based dosing regimes are currently lacking. The ultimate goal of this trial is to establish a recommended starting dose of B. infantis for further efficacy-testing phase II trials designed to evaluate B. infantis for the prevention of atopic dermatitis and food allergies in at-risk children.Trial registrationClinicaltrials.gov # NCT02286999 , date of trial registration 23 October 2014

Anatomic Relationships Between the Coronary Venous System, Surrounding Structures, and the Site of Origin of Epicardial Ventricular Arrhythmias

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109967/1/jce12497.pd

Highly efficient 5\u27 capping of mitochondrial RNA with NAD+ and NADH by yeast and human mitochondrial RNA polymerase

Bacterial and eukaryotic nuclear RNA polymerases (RNAPs) cap RNA with the oxidized and reduced forms of the metabolic effector nicotinamide adenine dinucleotide, NAD+ and NADH, using NAD+ and NADH as non-canonical initiating nucleotides for transcription initiation. Here, we show that mitochondrial RNAPs (mtRNAPs) cap RNA with NAD+ and NADH, and do so more efficiently than nuclear RNAPs. Direct quantitation of NAD+- and NADH-capped RNA demonstrates remarkably high levels of capping in vivo: up to ~60% NAD+ and NADH capping of yeast mitochondrial transcripts, and up to ~15% NAD+ capping of human mitochondrial transcripts. The capping efficiency is determined by promoter sequence at, and upstream of, the transcription start site and, in yeast and human cells, by intracellular NAD+ and NADH levels. Our findings indicate mtRNAPs serve as both sensors and actuators in coupling cellular metabolism to mitochondrial transcriptional outputs, sensing NAD+ and NADH levels and adjusting transcriptional outputs accordingly. © 2018, Bird et al