H2A.Z: a molecular rheostat for transcriptional control

The replacement of nucleosomal H2A with the histone variant H2A.Z is critical for regulating DNA-mediated processes across eukaryotes and for early development of multicellular organisms. How this variant performs these seemingly diverse roles has remained largely enigmatic. Here, we discuss recent mechanistic insights that have begun to reveal how H2A.Z functions as a molecular rheostat for gene control. We focus on specific examples in metazoans as a model for understanding how H2A.Z integrates information from histone post-translational modifications, other histone variants, and transcription factors (TFs) to regulate proper induction of gene expression programs in response to cellular cues. Finally, we propose a general model of how H2A.Z incorporation regulates chromatin states in diverse processes

Assessment of body composition by air-displacement plethysmography: influence of body temperature and moisture

BACKGROUND: To investigate the effect of body temperature and moisture on body fat (%fat), volume and density by air-displacement plethysmography (BOD POD). METHODS: %fat, body volume and density by the BOD POD before (BOD POD(BH)) and immediately following hydrostatic weighing (BOD POD(FH)) were performed in 32 healthy females (age (yr) 33 ± 11, weight (kg) 64 ± 14, height (cm) 167 ± 7). Body temperature and moisture were measured prior to BOD POD(BH )and prior to BOD POD(FH )with body moisture defined as the difference in body weight (kg) between the BOD POD(BH )and BOD POD(FH )measurements. RESULTS: BOD POD(FH )%fat (27.1%) and body volume (61.5 L) were significantly lower (P ≤ 0.001) and body density (1.0379 g/cm(3)) significantly higher (P ≤ 0.001) than BOD POD(BH )%fat (28.9%), body volume (61.7 L), and body density (1.0341 g/cm(3)). A significant increase in body temperature (~0.6°C; P ≤ 0.001) and body moisture (0.08 kg; P ≤ 0.01) were observed between BOD POD(BH )and BOD POD(FH). Body surface area was positively associated with the difference in %fat independent of changes in body temperature and moisture, r = 0.30, P < 0.05. CONCLUSION: These data demonstrate for the first time that increases in body heat and moisture result in an underestimation of body fat when using the BOD POD, however, the precise mechanism remains unidentified

Kentucky Traffic Collision Facts 2019

KENTUCKY’S TRAFFIC COLLISION FACTS report is based on collision reports submitted to the Kentucky State Police Records Branch. As required by Kentucky Revised Statutes 189.635: “Every law enforcement agency whose officers investigate a vehicle accident of which a report must be made...shall file a report of the accident...within ten days after investigation of the accident upon forms supplied by the bureau.” The stated purpose of this requirement is to utilize data on traffic collisions for such purposes as will improve the traffic safety program in the Commonwealth

Analysis of Traffic Crash Data in Kentucky 2015-2019

Executive Summary and Introduction This report documents an analysis of traffic crash data in Kentucky. A primary objective of this study was to determine average crash statistics for Kentucky highways. Where used, rates were calculated for various types of highways and for counties and cities. Difference criteria were used for exposure. Average and critical numbers, SPFs, and rates of crashes were calculated for various types of highways in rural and urban areas. These use crashes identified on highways where Annual Average Daily Traffic (AADT) volumes were available. The data in this report may be used to help identify problem areas. The other primary objective of this study was to provide data that can be used in the preparation of the problem identification portion of Kentucky’s Annual Highway Safety Plan (HSP). Crash statistics were analyzed and a summary of results and recommendations in several problem identification areas is presented. These general areas include; alcohol involvement, occupant protection, speed, teenage drivers, pedestrians, bicycles, motorcycles, trucks, and vehicle defects. Other areas included in the analysis for which specific recommendations were not made include, school bus crashes and train crashes. The crash data are stored in the Collision Report Analysis for Safer Highways (CRASH) database. This database is updated daily so the number of crashes in a given calendar year will continue to change for a substantial time after the end of that year. KTC captures an extract annually for analysis. Annual reports have previously been prepared since 1978 dealing with the calculation of statewide traffic crash rates for Kentucky and preparation of the problem identification portion of Kentucky’s Annual Highway Safety Plan. Traffic crash data for a five-year period were used in the preparation of this report. Kentucky has a systematic procedure to identify locations that have had abnormal rates or numbers of traffic crashes. However, before that procedure may be utilized, average crash rates and numbers must be determined for appropriate highway categories and for rural and urban areas. A primary objective of this study was to determine average traffic crash statistics for Kentucky. Those statistics may then be used in the high-crash location identification program to identify locations that should be investigated to determine whether changes should be made. A highway safety program is prepared each year for Kentucky in order to comply with Section 402, Title 23 of the United States Code. This program includes the identification, programming, budgeting, and evaluation of safety projects with the objective of reducing the number and severity of traffic crashes. The second major objective of this report is to provide data that may be included as the problem identification portion of Kentucky’s Annual Highway Safety Plan. Results from this report are used to provide benchmark data for that process

Validity of new child-specific thoracic gas volume prediction equations for air-displacement plethysmography

BACKGROUND: To determine the validity of the recently developed child-specific thoracic gas volume (TGV) prediction equations for use in air-displacement plethysmography (ADP) in diverse pediatric populations. METHODS: Three distinct populations were studied: European American and African American children living in Birmingham, Alabama and European children living in Lisbon, Portugal. Each child completed a standard ADP testing protocol, including a measured TGV according to the manufactures software criteria. Measured TGV was compared to the predicted TGV from current adult-based ADP proprietary equations and to the recently developed child-specific TGV equations of Fields et al. Similarly, percent body fat, derived using the TGV prediction equations, was compared to percent body fat derived using measured TGV. RESULTS: Predicted TGV from adult-based equations was significantly different from measured TGV in girls from each of the three ethnic groups (P < 0.05), however child-specific TGV estimates did not significantly differ from measured TGV in any of the ethnic or gender groups. Percent body fat estimates using adult-derived and child-specific TGV estimates did not differ significantly from percent body fat measures using measured TGV in any of the groups. CONCLUSION: The child-specific TGV equations developed by Fields et al. provided a modest improvement over the adult-based TGV equations in an ethnically diverse group of children

Braveheart, a Long Noncoding RNA Required for Cardiovascular Lineage Commitment

Long noncoding RNAs (lncRNAs) are often expressed in a development-specific manner, yet little is known about their roles in lineage commitment. Here, we identified Braveheart (Bvht), a heart-associated lncRNA in mouse. Using multiple embryonic stem cell (ESC) differentiation strategies, we show that Bvht is required for progression of nascent mesoderm toward a cardiac fate. We find that Bvht is necessary for activation of a core cardiovascular gene network and functions upstream of mesoderm posterior 1 (MesP1), a master regulator of a common multipotent cardiovascular progenitor. We also show that Bvht interacts with SUZ12, a component of polycomb-repressive complex 2 (PRC2), during cardiomyocyte differentiation, suggesting that Bvht mediates epigenetic regulation of cardiac commitment. Finally, we demonstrate a role for Bvht in maintaining cardiac fate in neonatal cardiomyocytes. Together, our work provides evidence for a long noncoding RNA with critical roles in the establishment of the cardiovascular lineage during mammalian development.Damon Runyon Cancer Research Foundation (DRG 2032-09)Damon Runyon Cancer Research Foundation (DFS 04-12)European Molecular Biology Organization (Long-term Fellowship)National Heart, Lung, and Blood Institute. Bench to Bassinet Program (U01HL098179)National Heart, Lung, and Blood Institute. Bench to Bassinet Program (U01HL098188)Smith Family FoundationPew Charitable Trusts. Program in the Biomedical Science

Dynamic chromatin organization and regulatory interactions in human endothelial cell differentiation

Vascular endothelial cells are a mesoderm-derived lineage with many essential functions, including angiogenesis and coagulation. The gene-regulatory mechanisms underpinning endothelial specialization are largely unknown, as are the roles of chromatin organization in regulating endothelial cell transcription. To investigate the relationships between chromatin organization and gene expression, we induced endothelial cell differentiation from human pluripotent stem cells and performed Hi-C and RNA-sequencing assays at specific time points. Long-range intrachromosomal contacts increase over the course of differentiation, accompanied by widespread heteroeuchromatic compartment transitions that are tightly associated with transcription. Dynamic topologically associating domain boundaries strengthen and converge on an endothelial cell state, and function to regulate gene expression. Chromatin pairwise point interactions (DNA loops) increase in frequency during differentiation and are linked to the expression of genes essential to vascular biology. Chromatin dynamics guide transcription in endothelial cell development and promote the divergence of endothelial cells from cardiomyocytes