From adjacent activation in Escherichia coli and DNA cyclization to eukaryotic enhancers: the elements of a puzzle

Deoxyribonucleic acid cyclization, Escherichia coli lac repressor binding to two spaced lac operators and repression enhancement can be successfully used for a better understanding of the conditions required for interaction between eukaryotic enhancers and the machinery of transcription initiation. Chronologically, the DNA looping model has first accounted for the properties initially defining enhancers, i.e., independence of action with distance or orientation with respect to the start of transcription. It has also predicted enhancer activity or its disruption at short distance (site orientation, alignment between promoter and enhancer sites), with high-order complexes of protein, or with transcription factor concentrations close or different from the wild-type situation. In another step, histones have been introduced into the model to further adapt it to eukaryotes. They in fact favor DNA cyclization in vitro. The resulting DNA compaction might explain the difference counted in base pairs in the distance of action between eukaryotic transcription enhancers and prokaryotic repression enhancers. The lac looping system provides a potential tool for analysis of this discrepancy and of chromatin state directly in situ. Furthermore, as predicted by the model, the contribution of operators O2 and O3 to repression of the lac operon clearly depends on the lac repressor level in the cell and is prevented in strains overproducing lac repressor. By extension, gene regulation especially that linked to cell fate, should also depend on transcription factor levels, providing a potential tool for cellular therapy. In parallel, a new function of the O1–O3 loop completes the picture of lac repression. The O1–O3 loop would at the same time ensure high efficiency of repression, inducibility through the low-affinity sites and limitation of the level of repressor through self-repression of the lac repressor. Last, the DNA looping model can be successfully adapted to the enhancer auxiliary elements known as insulators

Rural Disparities in Lung Cancer Mortality: An Ecologic Study in Florida

Lung cancer is the leading cause of cancer death in the United States and worldwide. The higher mortality among patients with lung cancer is related to cases being diagnosed in late stage where treatment is limited. Urban and rural health outcomes are potentially influenced by differences in accessibility to health care services. We are unaware of existing research examining geographic differences in or factors related to lung cancer mortality in Florida. Therefore, this study aims to examine lung cancer mortality differences between urban and rural counties in Florida. We examined all 67 counties in Florida to investigate if a rural disparity exists in lung cancer mortality. We collected data from the National Cancer Institute (NCI) State Cancer Profile. We assigned urban and rural designation using the United States Census Bureau definition based on population density. We then used a t-test for unequal variances to compare the mean lung cancer mortality rate for the urban counties versus rural counties using Microsoft Excel. We used ArcGIS Pro software to create three maps: one showing urban and rural county designations, one showing lung cancer mortality, and a third bivariate map of urban and rural designations combined with age-adjusted lung cancer mortality rates together to examine the geographic distributions in Florida. We observed a mean age-adjusted lung cancer mortality of 62.7 per 100,000 for rural counties in Florida and a mean of 44.2 per 100,000 for urban counties which was significantly different using a t-test for unequal variances (p \u3c 0.0001). The counties with the highest lung cancer mortality were grouped geographically in Florida’s Big Bend area. Overall, rural counties had a significantly higher average lung cancer mortality than the urban counties in Florida. Future research should examine factors affecting higher lung cancer mortality in rural counties such as screening locations and access to care

Silver-Antimony-Telluride: From First-Principles Calculations to Thermoelectric Applications

Silver-antimony-telluride (AgSbTe2) based compounds have emerged as a promising class of materials for thermoelectric (TE) power generation at the mid-temperature range. This Chapter demonstrates utilization of first-principles calculations for predicting TE properties of AgSbTe2-based compounds and experimental validations. Predictive calculations of the effects of La-doping on vibrational and electronic properties of AgSbTe2 compounds are performed applying the density functional theory (DFT), and temperature-dependent TE transport coefficients are evaluated applying the Boltzmann transport theory (BTE). Experimentally, model ternary (AgSbTe2) and quaternary (3 at. % La-AgSbTe2) compounds were synthesized, for which TE transport coefficients were measured, indicating that thermal conductivity decreases due to La-alloying. The latter also reduces electrical conductivity and increases Seebeck coefficients. All trends correspond with those predicted from first-principles. Thermal stability issues are essential for TE device operation at service conditions, e.g. changes of matrix composition and second-phase precipitation, and are also addressed in this study on both computational and experimental aspects. It is shown that La-alloying affects TE figure-of-merit positively, e.g., improving from 0.35 up to 0.50 at 260 °C. We highlight the universal aspects of this approach that can be applied for other TE compounds. This enables us screening their performance prior to synthesis in laboratory

Differential Pre-mRNA Splicing Regulates Nnat Isoforms in the Hypothalamus after Gastric Bypass Surgery in Mice

Background Neuronatin (NNAT) is an endoplasmic reticulum proteolipid implicated in intracellular signalling. Nnat is highly-expressed in the hypothalamus, where it is acutely regulated by nutrients and leptin. Nnat pre-mRNA is differentially spliced to create Nnat-α and -β isoforms. Genetic variation of NNAT is associated with severe obesity. Currently, little is known about the long-term regulation of Nnat. Methods Expression of Nnat isoforms were examined in the hypothalamus of mice in response to acute fast/feed, chronic caloric restriction, diet-induced obesity and modified gastric bypass surgery. Nnat expression was assessed in the central nervous system and gastrointestinal tissues. RTqPCR was used to determine isoform-specific expression of Nnat mRNA. Results Hypothalamic expression of both Nnat isoforms was comparably decreased by overnight and 24-h fasting. Nnat expression was unaltered in diet-induced obesity, or subsequent switch to a calorie restricted diet. Nnat isoforms showed differential expression in the hypothalamus but not brainstem after bypass surgery. Hypothalamic Nnat-β expression was significantly reduced after bypass compared with sham surgery (P = 0.003), and was positively correlated with post-operative weight-loss (R2 = 0.38, P = 0.01). In contrast, Nnat-α expression was not suppressed after bypass surgery (P = 0.19), and expression did not correlate with reduction in weight after surgery (R2 = 0.06, P = 0.34). Hypothalamic expression of Nnat-β correlated weakly with circulating leptin, but neither isoform correlated with fasting gut hormone levels post- surgery. Nnat expression was detected in brainstem, brown-adipose tissue, stomach and small intestine. Conclusions Nnat expression in hypothalamus is regulated by short-term nutrient availability, but unaltered by diet-induced obesity or calorie restriction. While Nnat isoforms in the hypothalamus are co-ordinately regulated by acute nutrient supply, after modified gastric bypass surgery Nnat isoforms show differential expression. These results raise the possibility that in the radically altered nutrient and hormonal milieu created by bypass surgery, resultant differential splicing of Nnat pre-mRNA may contribute to weight-loss

Energy-Saving Periodic Flight at Transonic Speeds Abstract:

We examine possible energy saving by periodicchanges in speed and altitude relative to steady state cruise, inthe transonic regime. We develop a theoretical model of twophase periodic flight with altitude variation in the transonicregime and compare it with a steady horizontal flight at thesame average speed. The model predictions are verified by windtunnel experiments. For example, by periodically acceleratingfrom M=0.7 to M=1.1 while losing altitude, and then climbingback to the original height while decelerating, one can achievesavings of about 20% relative to steady flight at the sameaverage speed and constant altitude.

Spectrophotometric determination of the formation constants of calcium(II) complexes with 2,2'-bipyridyl and 1,10-phenanthroline in acetonitrile

AbstractThe oxygen-evolving complex (OEC), which consists of a calcium-manganese cluster, is the reaction center of the Photosystem II. At this catalytic site, the water-splitting reaction in dioxygen and hydronium ions occurs. In order to partially reproduce the water splitting process, several studies have reported the synthesis of functional model complexes. Nevertheless, there is a small amount of reports, concerning the spectral behavior of calcium complexes or the calcium role in the cluster. In this work, in order to explore the absorption spectrum of calcium species in acetonitrile, an equilibrium study of the calcium complexes with 2,2'-bipyridyl or 1,10-phenanthroline, was carried out. The formation constants and the calculated electronic spectrum of each complex was obtained by a modified method of continuous variations consisting in a correlation of the experimental spectrophotometric data with the HypSpec software. The values of the formation constants for the calcium(II) complexes with 2,2'-bipyridyl and 1,10-phenanthroline, are Log β110 = 4.39 ± 0.02 and Log β110 = 5.94 ± 0.05, respectively

Microstructural evolution of a delta containing nickel-base superalloy during heat treatment and isothermal forging

The next generation of aerospace gas turbine engines need to operate at higher temperatures and stresses to improve their efficiency and reduce emissions. These operating conditions are beyond the capability of existing nickel-base superalloys, requiring the development of new high temperature materials. Controlling the microstructures of these new materials is key to obtaining the required properties and, therefore, it is critical to understand how these alloys respond to processing and heat treatment. Here, the microstructural evolution of V207M, a new δ containing, nickel-base superalloy, has been investigated following heat treatment and forging. The solvus temperatures of the γ′ and δ phases, determined by differential scanning calorimetry and microscopy, were found to be ~985 and ~1060 °C respectively. Isothermal forging of the alloy was conducted at 1000, 1050 and 1100 °C, corresponding to different volume fractions of retained δ. Considerable softening was observed prior to steady state flow when forging at 1000 °C, whilst only steady state flow occurred at 1050 and 1100 °C. The steady state flow process was believed to be dominated by dynamic recovery in the γ phase, with an activation energy of 407 kJmol−1. Samples that exhibited flow softening also showed a significant change in the orientation of the δ precipitates, preferentially aligning normal to the forging axis, and this reorientation was thought to be the cause of the observed flow softening

Increasing GLP-1 Circulating Levels by Bariatric Surgery or by GLP-1 Receptor Agonists Therapy: Why Are the Clinical Consequences so Different?

The “incretin effect” is used to describe the observation that more insulin is secreted after the oral administration of glucose compared to that after the intravenous administration of the same amount of glucose. During the absorption of meals, the gut is thought to regulate insulin secretion by secreting a specific factor that targets pancreatic beta cells. Additional research confirmed this hypothesis with the discovery of two hormones called incretins: gastric inhibitory peptide (GIP) and glucagon-like peptide 1 (GLP-1). During meals, specific cells in the gut (L and K enteroendocrine cells) secrete incretins, causing an increase in the blood concentrations of, respectively, GLP-1 and GIP. Bariatric surgery is now proposed during the therapeutic management of type 2 diabetes in obese or overweight populations. It has been hypothesized that restoration of endogenous GLP-1 secretion after the surgery may contribute to the postsurgical resolution of diabetes. In 2005, the commercialization of GLP-1 receptor agonists gave the possibility to test this hypothesis. A few years later, it is now accepted that GLP-1 receptor agonists and bariatric surgery differently improve type 2 diabetes. These differences between endogenous and exogenous GLP-1 on glucose homeostasis emphasized the dual properties of GLP-1 as a peptide hormone and as a neurotransmitter