Histone exchange is associated with activator function at transcribed promoters and with repression at histone loci

Transcription in eukaryotes correlates with major chromatin changes, including the replacement of old nucleosomal histones by new histones at the promoters of genes. The role of these histone exchange events in transcription remains unclear. In particular, the causal relationship between histone exchange and activator binding, preinitiation complex (PIC) assembly, and/or subsequent transcription remains unclear. Here, we provide evidence that histone exchange at gene promoters is not simply a consequence of PIC assembly or transcription but instead is mediated by activators. We further show that not all activators up-regulate gene expression by inducing histone turnover. Thus, histone exchange does not simply correlate with transcriptional activity, but instead reflects the mode of action of the activator. Last, we show that histone turnover is not only associated with activator function but also plays a role in transcriptional repression at the histone loci

Proposal and multicentric validation of a laparoscopic Roux-en-Y gastric bypass surgery ontology.

BACKGROUND Phase and step annotation in surgical videos is a prerequisite for surgical scene understanding and for downstream tasks like intraoperative feedback or assistance. However, most ontologies are applied on small monocentric datasets and lack external validation. To overcome these limitations an ontology for phases and steps of laparoscopic Roux-en-Y gastric bypass (LRYGB) is proposed and validated on a multicentric dataset in terms of inter- and intra-rater reliability (inter-/intra-RR). METHODS The proposed LRYGB ontology consists of 12 phase and 46 step definitions that are hierarchically structured. Two board certified surgeons (raters) with > 10 years of clinical experience applied the proposed ontology on two datasets: (1) StraBypass40 consists of 40 LRYGB videos from Nouvel Hôpital Civil, Strasbourg, France and (2) BernBypass70 consists of 70 LRYGB videos from Inselspital, Bern University Hospital, Bern, Switzerland. To assess inter-RR the two raters' annotations of ten randomly chosen videos from StraBypass40 and BernBypass70 each, were compared. To assess intra-RR ten randomly chosen videos were annotated twice by the same rater and annotations were compared. Inter-RR was calculated using Cohen's kappa. Additionally, for inter- and intra-RR accuracy, precision, recall, F1-score, and application dependent metrics were applied. RESULTS The mean ± SD video duration was 108 ± 33 min and 75 ± 21 min in StraBypass40 and BernBypass70, respectively. The proposed ontology shows an inter-RR of 96.8 ± 2.7% for phases and 85.4 ± 6.0% for steps on StraBypass40 and 94.9 ± 5.8% for phases and 76.1 ± 13.9% for steps on BernBypass70. The overall Cohen's kappa of inter-RR was 95.9 ± 4.3% for phases and 80.8 ± 10.0% for steps. Intra-RR showed an accuracy of 98.4 ± 1.1% for phases and 88.1 ± 8.1% for steps. CONCLUSION The proposed ontology shows an excellent inter- and intra-RR and should therefore be implemented routinely in phase and step annotation of LRYGB

Storability of some apricot varieties as affected by storage period

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Artificial molecular motors

Motor proteins are nature's solution for directing movement at the molecular level. The field of artificial molecular motors takes inspiration from these tiny but powerful machines. Although directional motion on the nanoscale performed by synthetic molecular machines is a relatively new development, significant advances have been made. In this review an overview is given of the principal designs of artificial molecular motors and their modes of operation. Although synthetic molecular motors have also found widespread application as (multistate) switches, we focus on the control of directional movement, both at the molecular scale and at larger magnitudes. We identify some key challenges remaining in the field

Toxicity of Waterpipe Tobacco Smoking: the Role of Flavors, Sweeteners, Humectants, and Charcoal

Waterpipe tobacco (WPT) smoking is a public health concern, particularly among youth and young adults. The global spread of WPT use has surged since the introduction of pre-packaged flavored and sweetened WPT, which is widely marketed as a safer tobacco alternative. Besides flavorants and sugars, WPT additives include humectants, which enhance the moisture and sweetness of WPT, act as solvents for flavors, and impart smoothness to the smoke, thus increasing appeal to users. In the United States (U.S.), unlike cigarette tobacco flavoring (with the exception of menthol), there is no FDA product standard or policy in place prohibiting sales of flavored WPT. Research has shown that the numerous fruit, candy, and alcohol flavors added to WPT entice individuals to experience those flavors, putting them at an increased risk of exposure to WPT smoke-related toxicants. Additionally, burning charcoal briquettes-used as a heating source for WPT-contributes to the harmful health effects of WPT smoking. This review presents existing evidence on the potential toxicity resulting from humectants, sugars, and flavorants in WPT, and from the charcoal used to heat WPT. The review discusses relevant studies of inhalation toxicity in animal models and of biomarkers of exposure in humans. Current evidence suggests that more data are needed on toxicant emissions in WPT smoke to inform effective tobacco regulation to mitigate the adverse impact of WPT use on human health

Genetic Analysis of Root and Shoot Traits in the ‘Essex’ By ‘Forrest’ Recombinant Inbred Line (RIL) Population of Soybean [Glycine max (L.) Merr.]

Crop productivity is severely reduced by water deficit and drought in many plant species including soybean. Improved root and shoot traits can contribute to drought tolerance ability of the plant. This research was conducted to identify QTL that underlie several root and shoot traits in the ‘Essex’ by ‘Forrest’ (ExF RILs, n=94) recombinant inbred line (RIL) soybean population. Field collected samples were used for gathering phenotypic data of basal root thickness (BRT), lateral root number (LRN), maximum root length (MRL), root fresh weight (RFW), root dry weight (RDW), shoot fresh weight (SFW), shoot dry weight (SDW), and calculating RFW/SFW, and RDW/SDW ratios. All traits and ratios were compared against DNA markers using the composite interval mapping (CIM). A total of 12 QTL: 3 for MRL, 1 QTL for LRN, 1 QTL for BRT, 2 QTL for RFW, 2 QTL for RDW, 4 QTL for SFW, 3 QTL for SDW, and 3 QTL for SFW/SDW were identified and mapped on different linkage groups (LGs) A2, B2, C2, D1a, F, G, and N. The LOD scores of these QTL ranged from 2.5 to 6.0. No QTL were associated with RFW/RDW. The root and shoot trait QTL of this study may benefit breeding programs for producing cultivars tolerant to water deficit and high yield. Preliminary analyses of genes the QTL regions using GO annotation gave insight into genes that may underlie some of these QTLs

Finding Rare, Disease-Associated Variants in Isolated Groups: Potential Advantages of Mennonite Populations

Large-scale genotyping and next-generation sequencing techniques have allowed great advances in the field of molecular genetics. Numerous common variants of low impact have been associated with many complex human traits and diseases, such as bipolar disorder and schizophrenia. Although they may exert a greater impact on risk, few rare disease variants have been found, owing to the greatly increased sample sizes that are typically necessary to demonstrate association with rarer variants. One alternative strategy is to study isolated populations, where historical bottlenecks reduce genetic diversity and some otherwise rare variants may drift to higher frequencies. Here we describe the Mennonite population settlements, considering their history of multiple bottlenecks followed by demographic expansion and a currently widespread geographical distribution. We argue that Mennonite populations are valuable partners for studies seeking genetic variants that exert a high impact on risk for a variety of common disorders, including mental illnesses

Greater Weight Gain in Treatment-naive Persons Starting Dolutegravir-based Antiretroviral Therapy

Background Recent studies have reported weight gain in virologically suppressed persons living with human immunodeficiency virus (PLWH) switched from older antiretroviral therapy (ART) to newer integrase strand transfer inhibitor (INSTI)–based regimens. In this study, we investigated whether weight gain differs among treatment-naive PLWH starting INSTI-based regimens compared to other ART regimens. Methods Adult, treatment-naive PLWH in the Vanderbilt Comprehensive Care Clinic cohort initiating INSTI-, protease inhibitor (PI)–, and nonnucleoside reverse transcriptase inhibitor (NNRTI)–based ART between January 2007 and June 2016 were included. We used multivariable linear mixed-effects models to generate marginal predictions of weights over time, adjusting for baseline clinical and demographic characteristics. We used restricted cubic splines to relax linearity assumptions and bootstrapping to generate 95% confidence intervals. Results Among 1152 ART-naive PLWH, 351 initiated INSTI-based regimens (135 dolutegravir, 153 elvitegravir, and 63 raltegravir), 86% were male, and 49% were white. At ART initiation, median age was 35 years, body mass index was 25.1 kg/m2, and CD4+ T-cell count was 318 cells/μL. Virologic suppression at 18 months was similar between different ART classes. At all examined study time points, weight gain was highest among PLWH starting dolutegravir. At 18 months, PLWH on dolutegravir gained 6.0 kg, compared to 2.6 kg for NNRTIs (P < .05), and 0.5 kg for elvitegravir (P < .05). PLWH starting dolutegravir also gained more weight at 18 months compared to raltegravir (3.4 kg) and PIs (4.1 kg), though these differences were not statistically significant. Conclusions Treatment-naive PLWH starting dolutegravir-based regimens gained significantly more weight at 18 months than those starting NNRTI-based and elvitegravir-based regimens