Effects of acidosis on ventricular myocyte shortening and intracellular Ca2+ in streptozotocin-induced diabetic rats

We have investigated the effects of acute acidosis on ventricular myocyte shortening and intracellular Ca²⁺ in streptozotocin (STZ)-induced diabetic rat. Shortening and intracellular Ca²⁺ were measured in electrically stimulated myocytes superfused with either normal Tyrode solution pH adjusted to either 7.4 (control solution) or 6.4 (acid solution). Experiments were performed at 35–36°C. At 8–12 weeks after treatment, the rats that received STZ had lower body and heart weights compared to controls, and blood glucose was characteristically increased. Contractile defects in myocytes from diabetic rat were characterized by prolonged time to peak shortening. Superfusion of myocytes from control and diabetic rats with acid solution caused a significant reduction in the amplitude of shortening; however, the magnitude of the response was not altered by STZ treatment. Acid solution also caused significant and quantitatively similar reductions in the amplitude of Ca²⁺ transients in myocytes from control and diabetic rats. Effects of acute acidosis on amplitude of myocyte contraction and Ca²⁺ transient were not significantly altered by STZ treatment. Altered myofilament sensitivity to Ca²⁺ and altered mechanisms of sarcoplasmic reticulum Ca²⁺ transport might partly underlie the acidosis-evoked reduction in amplitude of shortening in myocytes from control and STZ-induced diabetic rat. (Mol Cell Biochem 261: 227–233, 2004)     

Gliotoxin penetrates and impairs the integrity of the human blood-brain barrier in vitro

Cerebral fungal infections represent an important public health concern, where a key element of pathophysiology is the ability of the fungi to cross the blood-brain barrier (BBB). Yet the mechanism used by micro-organisms to cross such a barrier and invade the brain parenchyma remains unclear. This study investigated the effects of gliotoxin (GTX), a mycotoxin secreted by Aspergillus fumigatus, on the BBB using brain microvascular endothelial cells (BMECs) derived from induced pluripotent stem cells (iPSCs). We observed that both acute (2 h) and prolonged (24 h) exposure to GTX at the level of 1 μM or higher compromised BMECs monolayer integrity. Notably, acute exposure was sufficient to disrupt the barrier function in iPSC-derived BMECs, resulting in decreased transendothelial electrical resistance (TEER) and increased fluorescein permeability. Further, our data suggest that such disruption occurred without affecting tight junction complexes, via alteration of cell-matrix interactions, alterations in F-actin distribution, through a protein kinase C-independent signaling. In addition to its effect on the barrier function, we have observed a low permeability of GTX across the BBB. This fact can be partially explained by possible interactions of GTX with membrane proteins. Taken together, this study suggests that GTX may contribute in cerebral invasion processes of Aspergillus fumigatus by altering the blood-brain barrier integrity without disrupting tight junction complexes.     

Sodium Acetate,Sodium Acid Pyrophosphate,and Citric Acid Impacts on Isolated Peripheral Lymphocyte Viability,Proliferation, and DNA Damage

The present study examined the impacts of sodium acetate (SA), sodium acid pyrophosphate (SAPP), and citric acid (CA) on the viability, proliferation, and DNA damage of isolated lymphocytes in vitro. 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) release assays were adopted to evaluate cell viability, while comet assay was employed to assess the genotoxic effects. The cells were incubated with different levels of SA (50, 100, and 200 mM), SAPP (25, 50, and 100 mM/L), or CA (100, 200, and 300 μg/mL). The lymphocytes treated with the tested food additives showed concentration‐dependent decreases in both cell viability and proliferation. A concentration‐dependent increase in LDH release was also observed. The comet assay results indicated that SA, SAPP, and CA increased DNA damage percentage, tail DNA percentage, tail length, and tail moment in a concentration‐dependent manner. The current results showed that SA, SAPP, and CA are cytotoxic and genotoxic to isolated lymphocytes in vitro.     

A nuclease‐toxin and immunity system for kin discrimination in Myxococcus xanthus

The use of toxin to attack neighbours and immunity proteins to protect against toxin has been observed in bacterial conflicts, including kin discrimination. Here, we report a novel nuclease‐toxin and its immunity protein function in the colony‐merger incompatibility, a kind of bacterial kin discrimination, in Myxococcus xanthus DK1622. The MXAN_0049 gene was determined to be a genetic determinant for colony‐merger incompatibility, and the incompatibility could be eliminated by deletion of the upstream co‐transcribed MXAN_0050 gene. We demonstrated that the MXAN_0050 protein was a nuclease, and MXAN_0049 protein was able to bind to MXAN_0050 to block nuclease activity in vitro. Expression of MXAN_0050 in Escherichia coli inhibited cellular growth, and the inhibition effect could be recovered by co‐expression of MXAN_0049. We found that deletion of the PAAR‐encoding gene (MXAN_0044) or the type VI secretion system led to the colony‐merger and co‐existence with the ΔMXAN_0049 mutant, suggesting that they were associated with colony‐merger incompatibility. Homologues of the nuclease‐toxin and cognate immunity pair are widely distributed in bacteria. We propose a simplified model to explain the kin discrimination mechanism mediated by the nuclease‐toxin and immunity protein.© 2018 Society for Applied Microbiology and John Wiley & Sons Ltd     

Association analysis between four vitamin D receptor gene polymorphisms and developmental dysplasia of the hip

Developmental dysplasia of the hip (DDH) is a congenital condition characterized by abnormality in acetabulum size and/or shape. The incidence rate of DDH differs between different populations with risk factors including positive family history, breech presentation, sex, firstborn status, side of the hip, mode of delivery and oligohydramnios. It is recognized that DDH has a genetic component that exhibit autosomal dominant patterns. Many candidate genes have been studied and found to be associated with the disease; most of them are normally involved in cartilage development and joint metabolism. In this study, the association of four single-nucleotide polymorphisms (SNPs) (rs731236, rs1544410, rs7975232 and rs2228570) in the vitamin D receptor (VDR) gene was studied by a case–control analysis. The study sample involves 50 cases with confirmed DDH presentation and 50 nonDDH controls. SNPs were genotyped using conventional polymerase chain reaction (PCR) and restriction fragment-length polymorphism (RFLP) techniques. Genotype and allele frequencies were analysed using SPSS software. No significant associations were found between the VDR polymorphisms analysed and DDH. Further work need to be performed using genomewide analysis to elucidate the genetic basis of DDH.     

Short-term and long-term effects of food supply on parasite burdens in Tawny Owls, Strix aluco

1. The relationships among food supply (Field Voles, Microtus agrestis ), reproduction and blood parasites was investigated in Tawny Owls, Strix aluco , in Kielder Forest, Northumberland, in 1994 and 1995. Vole populations were significantly lower in 1995 than in 1994.
2. Birds did not lose parasites after initial infection, and the level at which infections were maintained was characteristic of individual birds.
3. In 1994, the number and intensity of parasites was higher in adult owls that had experienced low food supply when they themselves were reared. This indicated that food supplied to chicks in the nest has a long-term effect on the parasite burden of adults.
4. In addition, there was evidence that parasite burdens of adults were influenced by their current food supply. Birds that suffered a decline in food abundance on their territories between 1994 and 1995 showed an increase in parasite load over the same period. In 1995, there was also a significant negative correlation between the parasite loads of owls and vole abundance on their territories.
5. The best predictor of parasite number of chicks reared in 1995 was the parasite load of their fathers. The parasites chicks developed were not the parasites with which their fathers were heavily infested. This result could be due to inherited immunity.
6. Our results indicated that food resources should be measured when investigating interactions between parasites and their hosts, and that offspring quality as well as quantity might suffer when food abundance is low.     

农田周围生态保留带中普通田鼠的种群生态学：种群数量动态及结构

于2003年5月~2004年11月,采用标志重捕法对栖息在生态保留带的普通田鼠种群结构和数量动态进行了跟踪研究。结果表明,两年中种群密度夏季最大分别达到410个体/hm2和641个体/hm2,春季最少分别达到166个体/hm2和153个体/hm2,种群数量从7月份开始增长,8月份种群密度减少并于11月份开始重新增长。种群中雌性个体数量比较多,雌性在种群中的居留时间较长,同时存活率比雄性高,这导致种群数量的季节变化。种群周转率比较高,在两个捕鼠期间种群中的80%个体被更新,这表明普通田鼠在生态保留带中的活动非常频繁,不断与周围的其他种群进行交流,提高了种群对环境的适应能力。种群中雌雄个体的巢区之间没有年间变化,活动巢区比较小,巢区长度2003年平均为11 m,最长为37.5 m,2004年平均为13 m,最长为52 m。Pearson相关指数表明种群数量和生态保留带年龄、覆盖率和高度之间没有相关性。