Chromatin proteins and RNA are associated with DNA during all phases of mitosis.

Mitosis brings about major changes to chromosome and nuclear structure. We used recently developed proximity ligation assay-based techniques to investigate the association with DNA of chromatin-associated proteins and RNAs in Drosophila embryos during mitosis. All groups of tested proteins, histone-modifying and chromatin-remodeling proteins and methylated histones remained in close proximity to DNA during all phases of mitosis. We also found that RNA transcripts are associated with DNA during all stages of mitosis. Reduction of H3K27me3 levels or elimination of RNAs had no effect on the association of the components of PcG and TrxG complexes to DNA. Using a combination of proximity ligation assay-based techniques and super-resolution microscopy, we found that the number of protein-DNA and RNA-DNA foci undergoes significant reduction during mitosis, suggesting that mitosis may be accompanied by structural re-arrangement or compaction of specific chromatin domains

Effects of Mowing and Tebuthiuron on the Nutritional Quality of Wyoming Big Sagebrush

Wyoming big sagebrush (Artemisia tridentata Nutt. ssp. wyomingensis Beetle & Young) is the most abundant and widely distributed subspecies of big sagebrush and has been treated through chemical application, mechanical treatments, and prescribed burning in efforts thought to improve habitat conditions for species such as greater sage-grouse (Centrocercus urophasianus) and mule deer (Odocoileus hemionus). Although the response of structural attributes of sagebrush communities to treatments is well understood, there is a need to identify how treatments influence the quality of sagebrush as winter food for wildlife. Our purpose was to identify how mowing and tebuthiuron treatments influenced dietary quality of Wyoming big sagebrush in central Wyoming. Two study areas were mowed in January and February 2014 and tebuthiuron was applied in two study areas in May 2014. We constructed 6 exclosures in each of these four study areas (24 total), which encompassed 30 m x 30 m areas of treated and untreated sagebrush within each exclosure. Samples of current annual growth were collected from 18 sagebrush plants from treated and 12 plants from control portions of mowing exclosures during November 2013–2015 and tebuthiuron exclosures during November 2014–2015. Samples were analyzed for crude protein and plant secondary metabolites known to influence dietary selection of sagebrush by sage-grouse and other sagebrush occurring herbivores. Our results suggest mowing and tebuthiuron treatments may slightly increase crude protein concentrations directly after treatments without immediate changes in plant secondary metabolites. Slight increases in dietary quality of sagebrush following treatments coupled with potential trade-offs with loss of biomass associated with treatments corroborates previous research that treating Wyoming big sagebrush may have little benefit for sage-grouse and other sagebrush-dependent wildlife. Future work should evaluate not only how treatments influence sage-grouse habitat use and 2 reproductive success, but how treatments influence other wildlife species in fragile sagebrush ecosystems

An In Vitro Model of the Horse Gut Microbiome Enables Identification of Lactate-Utilizing Bacteria That Differentially Respond to Starch Induction

Laminitis is a chronic, crippling disease triggered by the sudden influx of dietary starch. Starch reaches the hindgut resulting in enrichment of lactic acid bacteria, lactate accumulation, and acidification of the gut contents. Bacterial products enter the bloodstream and precipitate systemic inflammation. Hindgut lactate levels are normally low because specific bacterial groups convert lactate to short chain fatty acids. Why this mechanism fails when lactate levels rapidly rise, and why some hindgut communities can recover is unknown. Fecal samples from three adult horses eating identical diets provided bacterial communities for this in vitro study. Triplicate microcosms of fecal slurries were enriched with lactate and/or starch. Metabolic products (short chain fatty acids, headspace gases, and hydrogen sulfide) were measured and microbial community compositions determined using Illumina 16S rRNA sequencing over 12-hour intervals. We report that patterns of change in short chain fatty acid levels and pH in our in vitro system are similar to those seen in in vivo laminitis induction models. Community differences between microcosms with disparate abilities to clear excess lactate suggest profiles conferring resistance of starch-induction conditions. Where lactate levels recover following starch induction conditions, propionate and acetate levels rise correspondingly and taxa related to Megasphaera elsdenii reach levels exceeding 70% relative abundance. In lactate and control cultures, taxa related to Veillonella montpellierensis are enriched as lactate levels fall. Understanding the microbial dynamics underlying lactic acidosis and laminitis will lead to better informed models of health and the development of a probiotic treatment to prevent acidosis

The Impact of Study Strategies on Knowledge Growth and Summative Exam Performance in the First Year of Medical School

Although the distinction between deep and surface processing strategies, their potential to differentially impact learning, and data supporting the superiority of deep processing strategies on summative exam scores are well supported by the literature, more work is needed to understand: (1) how medical students combine study strategies into learning practices, and (2) the effectiveness of these learning practices in facilitating knowledge gains as measured by standardized test scores

The Importance of Taking a Military History

The most important action a provider can take to ensure that a veteran receives optimal health care is perhaps the easiest and, ironically, the most neglected: asking if a patient has served in the military and taking a basic military history. In previously published articles, Jeffrey Brown1 and Ross Boyce,2 physicians with prior military service, reported that their own health care providers had rarely asked about their service. For Dr Brown, in the four decades since his combat service in Vietnam, he noted

Metabolic Changes Precede the Development of Pulmonary Hypertension in the Monocrotaline Exposed Rat Lung.

There is increasing interest in the potential for metabolic profiling to evaluate the progression of pulmonary hypertension (PH). However, a detailed analysis of the metabolic changes in lungs at the early stage of PH, characterized by increased pulmonary artery pressure but prior to the development of right ventricle hypertrophy and failure, is lacking in a preclinical animal model of PH. Thus, we undertook a study using rats 14 days after exposure to monocrotaline (MCT), to determine whether we could identify early stage metabolic changes prior to the manifestation of developed PH. We observed changes in multiple pathways associated with the development of PH, including activated glycolysis, increased markers of proliferation, disruptions in carnitine homeostasis, increased inflammatory and fibrosis biomarkers, and a reduction in glutathione biosynthesis. Further, our global metabolic profile data compare favorably with prior work carried out in humans with PH. We conclude that despite the MCT-model not recapitulating all the structural changes associated with humans with advanced PH, including endothelial cell proliferation and the formation of plexiform lesions, it is very similar at a metabolic level. Thus, we suggest that despite its limitations it can still serve as a useful preclinical model for the study of PH

Randomized, double-blind, parallel-group, 48-week study for efficacy and safety of a higher-dose rivastigmine patch (15 vs. 10 cm(2)) in Alzheimer’s disease

Aim: Determine whether patients with Alzheimer’s disease demonstrating functional and cognitive decline, following 24-48 weeks of open-label treatment with 9.5 mg/24 h (10 cm(2)) rivastigmine patch, benefit from a dose increase in a double-blind (DB) comparative trial of two patch doses. Methods: Patients meeting prespecified decline criteria were randomized to receive 9.5 or 13.3 mg/24 h (15 cm(2)) patch during a 48-week, DB phase. Coprimary outcomes were change from baseline to week 48 on the Instrumental Activities of Daily Living domain of the Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS-IADL) scale and the Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-cog). Safety and tolerability were assessed. Results: Of 1,584 patients enrolled, 567 met decline criteria and were randomized. At all timepoints, ADCS-IADL and ADAS-cog scores favoured the 13.3 mg/24 h patch. The 13.3 mg/24 h patch was statistically superior to the 9.5 mg/24 h patch on the ADCS-IADL scale from week 16 (p = 0.025) onwards including week 48 (p = 0.002), and ADAScog at week 24 (p = 0.027), but not at week 48 (p = 0.227). No unexpected safety concerns were observed. Conclusions: The 13.3 mg/24 h rivastigmine patch significantly reduced deterioration in IADL, compared with the 9.5 mg/24 h patch, and was well tolerated. Copyright © 2012 S. Karger AG, Base

3D CFD Analysis of Natural Ventilation in Reduced Scale Model of Compost Bedded Pack Barn for Dairy Cows

Compost bedded pack (CBP) barns have been receiving increased attention as an alternative housing system for dairy cattle. To create a satisfactory environment within CBP barns that promotes a good composting process, an adequate air movement and minimal temperature fluctuations throughout the building are required. Therefore, a study based on compost barn structure model employing techniques of dimensional analysis for naturally ventilated buildings was developed. Three-dimensional computational fluid dynamic (CFD) simulations of compost barns with different ridge designs and wind direction, along with the visual demonstration of the impact on airflow through structure were performed. The results showed that the barn ventilation CFD model and simulations were in good agreement with the experimental measurements, predicting the airflow through the CBP barns structure for alternative roof ridge types adequately. The results also indicate that the best roof configuration in the winter was the open ridge with chimney for a west to east wind direction

A Dual Inhibitory Mechanism Sufficient to Maintain Cell-Cycle-Restricted CENP-A Assembly

The deposited article is a post-print version and has peer review. The deposited article version contains attached the supplementary materials within the pdf. This publication hasn't any creative commons license associated.Chromatin featuring the H3 variant CENP-A at the centromere is critical for its mitotic function and epigenetic maintenance. Assembly of centromeric chromatin is restricted to G1 phase through inhibitory action of Cdk1/2 kinases in other phases of the cell cycle. Here, we identify the two key targets sufficient to maintain cell-cycle control of CENP-A assembly. We uncovered a single phosphorylation site in the licensing factor M18BP1 and a cyclin A binding site in the CENP-A chaperone, HJURP, that mediated specific inhibitory phosphorylation. Simultaneous expression of mutant proteins lacking these residues results in complete uncoupling from the cell cycle. Consequently, CENP-A assembly is fully recapitulated under high Cdk activities, indistinguishable from G1 assembly. We find that Cdk-mediated inhibition is exerted by sequestering active factors away from the centromere. Finally, we show that displacement of M18BP1 from the centromere is critical for the assembly mechanism of CENP-A.Fundação para a Ciência e a Tecnologia grants: (SFRH/BD/51878/2012, SFRH/BD/74284/2010, BIA-BCM/100557/2008); NIH/National Institute of General Medical Sciences grants: (R01-GM082989; T32-GM008275); NIH/NCI grant: (F30-CA186430); NIH grants (GM 037537, GM 110174); EMBO installation grant: (1818); ERC-consolidator grant: (ERC-2013-CoG-615638).info:eu-repo/semantics/publishedVersio