Differential roles of breakfast and supper in rats of a daily three-meal schedule upon circadian regulation and physiology

The timing of meals has been suggested to play an important role in circadian regulation and metabolic health. Three meals a day is a well-established human feeding habit, which in today's lifestyle may or may not be followed. The aim of this study was to test whether the absence of breakfast or supper significantly affects the circadian system and physiological function. The authors developed a rat model for their daily three meals study, whereby animals were divided into three groups (three meals, TM; no first meal, NF; no last meal, NL) all fed with the same amount of food every day. Rats in the NF group displayed significantly decreased levels of plasma triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and glucose in the activity phase, accompanied by delayed circadian phases of hepatic peripheral clock and downstream metabolic genes. Rats in the NL group showed lower concentration of plasma TC, HDL-C, and glucose in the rest phase, plus reduced adipose tissue accumulation and body weight gain. Real-time polymerase chain reaction (PCR) analysis indicated an attenuated rhythm in the food-entraining pathway, including down-regulated expression of the clock genes Per2, Bmal1, and Rev-erbα, which may further contribute to the delayed and decreased expression of FAS in lipogenesis in this group. Our findings are consistent with the conclusion that the daily first meal determines the circadian phasing of peripheral clocks, such as in the liver, whereas the daily last meal tightly couples to lipid metabolism and adipose tissue accumulation, which suggests differential physiological effects and function of the respective meal timings.     

Effects of the position and manner of hydration on the stability of solvated N-methylacetamides and the strength of binding between N-methylacetamide and water clusters: a computational study

This work mainly studies the effects of the position (there are two possible hydrated sites) and the manner (i.e., whether water acts as a proton donor or acceptor) of hydration by various numbers of water molecules on the stability of 14 solvated N-methylacetamide structures, NMA-(H₂O) _n (n = 1–3), as well as the binding strength between the NMA and the water cluster, using molecular dynamics (MD) and B3LYP methods. Natural bond orbital (NBO) analysis is used to explore the origin of these effects. Some novel observations are obtained from the work. Our results show that monohydration at the carbonyl site favors stability and binding strength compared to monohydration at the amino site. Similarly, the preferred hydration at the carbonyl site is observed for dihydrated NMAs when the second water is added as a proton donor to the C=O group or the first water is H-bonded to the C=O group. However, unfavorable hydration at the C=O site occurs if the second water acts as a proton acceptor. Trihydration by a ring cluster of three water molecules at either the carbonyl site or the amino one yields relatively stable complexes, but significantly disfavors binding strength. The other trihydrated NMAs show similar behavior to dihydrated NMAs. In addition, our results show that the C=O and N–H frequencies can still be utilized to examine the H-bond effects of the water cluster.     

Predicting the risk of soybean rust in Minnesota based on an integrated atmospheric model

To minimize crop loss by assisting in timely disease management and reducing fungicide use, an integrated atmospheric model was developed and tested for predicting the risk of occurrence of soybean rust in Minnesota. The model includes a long-range atmospheric spore transport and deposition module coupled to a leaf wetness module. The latter is required for spore germination and infection. Predictions are made on a daily basis for up to 7 days in advance using forecast data from the United States National Weather Service. Complementing the transport and leaf wetness modules, bulk (wet plus dry) atmospheric deposition samples from Minnesota were examined for soybean rust spores using a specific DNA test and sequence analysis. Overall, the risk prediction worked satisfactorily within the bounds of the uncertainty associated with the use of modeled 7-day weather forecasts, with more than 65% agreement between the model forecast and the DNA test results. The daily predictions are available as an advisory to the user community through the University of Minnesota Extension. However, users must take the actual decision to implement the disease management strategy.     

Deficient of LRRC8A attenuates hypoxia-induced necrosis in 3T3-L1 cells

ABSTRACT

Under acute hypoxia, multiple ion channels on the cell membrane are activated, causing cell swelling and eventually necrosis. LRRC8A is an indispensable protein of the volume-regulated anion channel (VRAC), which participates in swelling and the acceleration of cell necrosis. In this study, we revealed a dynamic change in the expression level of the LRRC8 family during hypoxia in 3T3-L1 cells. The disruption of LRRC8A in 3T3-L1 cells was also associated with a significant anti-necrotic phenotype upon hypoxia accompanied by the reduced expression of necrosis-related genes. In vivo, differential expression of LRRC8 family members was also identified between high-altitude pigs and their low-altitude relatives. Taken these findings together, this study demonstrates the involvement of LRRC8A in hypoxia-induced cell necrosis.     

Desmosomal cell adhesion in mammalian development

Defects in desmosome-mediated cell-cell adhesion can lead to tissue fragility syndromes. Both inherited and acquired diseases caused by desmosomal defects have been described. The two organs that appear most vulnerable to these defects are the skin with its appendages, and the heart. Furthermore, the analysis of genetically engineered mice has led to the discovery that desmosomal proteins are also required for normal embryonic development. Knockout mice for several desmosomal proteins die in utero. Depending on the protein studied, death occurs either around the time of implantation, at mid-gestation or shortly before birth. So far, it appears that structural defects leading to abnormal histo-architecture and tissue fragility are the main cause of death, i.e. there is no evidence that loss of a desmosomal protein would abort specific cell lineages or differentiation programs. Nevertheless, we are only beginning to understand the functions of individual desmosomal proteins during development. This review focuses on the role of desmosomes during mouse embryonic development.     

Predicting G-protein coupled receptors-G-protein coupling specificity based on autocross-covariance transform

Determining G-protein coupled receptors (GPCRs) coupling specificity is very important for further understanding the functions of receptors. A successful method in this area will benefit both basic research and drug discovery practice. Previously published methods rely on the transmembrane topology prediction at training step, even at prediction step. However, the transmembrane topology predicted by even the best algorithm is not of high accuracy. In this study, we developed a new method, autocross-covariance (ACC) transform based support vector machine (SVM), to predict coupling specificity between GPCRs and G-proteins. The primary amino acid sequences are translated into vectors based on the principal physicochemical properties of the amino acids and the data are transformed into a uniform matrix by applying ACC transform. SVMs for nonpromiscuous coupled GPCRs and promiscuous coupled GPCRs were trained and validated by jackknife test and the results thus obtained are very promising. All classifiers were also evaluated by the test datasets with good performance. Besides the high prediction accuracy, the most important feature of this method is that it does not require any transmembrane topology prediction at either training or prediction step but only the primary sequences of proteins. The results indicate that this relatively simple method is applicable. Academic users can freely download the prediction program at http://www.scucic.net/group/database/Service.asp.     

A genetic variant in 3'-untranslated region of cyclooxygenases-2 gene is associated with risk of gastric cancer in a Chinese population

Cyclooxygenase-2 (COX-2) involves in multiple processes in carcinogenesis, including inflammation, apoptosis inhibition, immune response suppression, tumor cell invasion, and angiogenesis. COX-2 is overexpressed in various cancers, including gastric cancer. COX-2 is encoded by prostaglandin endoperoxide synthase 2 (PTGS2) gene. We hypothesized that potentially functional polymorphisms in PTGS2 may contribute to gastric cancer risk. To assess this hypothesis, we conducted a case-control study with 1681 gastric cancer cases and 1916 control subjects in a Chinese population to evaluate the association between a polymorphism in 3'-untranslated region of PTGS2, rs5275, and the risk of gastric cancer. Logistic regression analysis revealed that variant allele (C) of rs5275 was significantly associated with an increased risk of gastric cancer (per allele odds ratio [OR] = 1.14, 95% confidence interval [CI] = 1.01-1.29, p = 0.030). This association was more prominent in females (per allele OR = 1.42, 95% CI = 1.11-1.81, p = 0.005) and nonsmokers (per allele OR = 1.35, 95% CI = 1.14-1.59, p = 0.001). Interestingly, we detected a negative interaction between rs5275 and smoking on the gastric cancer risk (p = 0.007). Our findings indicate that PTGS2 rs5275T/C may be a candidate genetic marker for gastric cancer susceptibility.