Expression of new loci associated with obesity in diet-induced obese rats: from genetics to physiology

Genome-wide association studies (GWAS) are a powerful tool for revealing genes associated with common human obesity. New loci associated with obesity have recently been reported, but their function and metabolic implications remain to be elucidated. In order to begin identifying the role of some of these obesity-related loci, the closest genes to the polymorphism of each locus were selected and their expression was compared in the hypothalamus, adipose tissue, liver, soleus muscle, and extensor digitorum longus muscle (EDL) of Long-Evans rats maintained on chow or a high-fat diet (HFD) for 6 weeks. From a total of 19 genes analyzed, seven genes (ETV5, FTO, GNPDA2, KCTD15, TMEM18, MC4R, and SH2B1) were down-regulated in the hypothalamus of HFD compared to chow-fed rats. In adipose tissue of rats fed on HFD, the mRNA levels of BCDIN3, KCTD15, and SULT1A1 were down-regulated, whereas those of MTCH2, PTER, and TUFM were up-regulated. In the liver, three genes were up-regulated (PTER, SULT1A1, and TUFM) in HFD relative to chow-fed rats, and TMEM18 was down-regulated. Finally, in soleus muscle of HFD-fed rats, BCDIN3, BDNF, and TMEM18 were down-regulated, and in the EDL muscle SH2B1 and TUFM were up-regulated. mRNA levels in the hypothalamus were compared between fed and fasted states, and only KCTD15 was down-regulated during fasting when fed a chow diet. In conclusion, novel genes found to be associated with obesity are regulated by a HFD and the mRNA levels of KCTD15 is dependent on the nutritional status. These results suggest a potential role of these genes in the regulation of energy balance.     

Inflection points in sepsis biology: from local defense to systemic organ injury

Sepsis and septic shock lead to considerable morbidity and mortality in developed and developing countries. Despite advances in understanding the innate immune events that lead to septic shock, molecular therapies based on these advances have failed to improve sepsis mortality. The clinical failure of laboratory-derived therapies may be, in part, due to the pleiotropic consequences of the acute inflammatory response, which is the focus of this review. A brisk response to infecting organism is essential for pathogen containment and eradication. However, systemic spread of inflammation beyond a single focus leads to organ injury and higher mortality. The primary goal of this article is to discuss recent animal- and human-based scientific advances in understanding the host response to infection and to highlight how these defense mechanisms can be locally beneficial but systemically detrimental. There are other factors that determine the severity of sepsis that are beyond the scope of this review, including the virulence of the pathogen and regulation by Toll-like receptors. Specifically, this review focuses on how the effector mechanisms of platelets, mast cells, neutrophil extracellular traps (NETs), and the endothelium participate in combating local infections yet can induce organ injury during systemic infection.     

Alterations in evertor/invertor muscle activation and center of pressure trajectory in participants with functional ankle instability

Participants with ankle instability demonstrate more foot inversion during the stance phase of gait than able-bodied subjects. Invertor excitation, coupled with evertor inhibition may contribute to this potentially injurious position. The purpose of this experiment was to examine evertor/invertor muscle activation and foot COP trajectory during walking in participants with functional ankle instability (FI). Twelve subjects were identified with FI and matched to healthy controls. Tibialis anterior (TA) and peroneus longus (PL) electromyography (EMG), as well as COP, were recorded during walking. Functional analyses were used to detect differences between FI and control subjects with respect to normalized EMG and COP trajectory during walking. Relative to matched controls, COP trajectory was more laterally deviated in the FI group from 20% to 90% of the stance phase. TA activation was greater in the FI group from 15% to 30% and 45% to 70% of stance. PL activation was greater in the FI group at initial heel contact and toe off and trended lower from 20% to 40% of stance in the FI group. Altered motor strategies appear to contribute to COP deviations in FI participants and may increase the susceptibility to repeated ankle inversion injury.     

Sexually different actions of leptin in proopiomelanocortin neurons to regulate glucose homeostasis

Leptin regulates energy balance and glucose homeostasis, at least in part, via activation of receptors in the arcuate nucleus of the hypothalamus located in proopiomelanocortin (POMC) neurons. Females have greater sensitivity to central leptin than males, suggested by a greater anorectic effect of central leptin administration in females. We hypothesized that the regulation of energy balance and peripheral glucose homeostasis of female rodents would be affected to a greater extent than in males if the action of leptin in POMC neurons were disturbed. Male and female mice lacking leptin receptors only in POMC neurons gained significantly more body weight and accumulated more body fat. However, female mice gained disproportionately more visceral adiposity than males, and this appeared to be largely the result of differences in energy expenditure. When maintained on a high-fat diet (HFD), both male and female mutants had higher levels of insulin following exogenous glucose challenges. Chow- and HFD-fed males but not females had abnormal glucose disappearance curves following insulin administrations. Collectively, these data indicate that the action of leptin in POMC neurons is sexually different to influence the regulation of energy balance, fat distribution, and glucose homeostasis.     

苯肼对红细胞在体衰老过程中微观流变特性的影响

在Brunara等人用苯肼使动物造成急性溶血性贫血的方法基础上,建立一种由急性溶血性贫血后,而诱发家兔幼红细胞增多的非正常生理状态的红细胞在体衰老模型,继而研究新生红细胞从产生到死亡死亡过程,即衰老过程的流变学特性的变化规律。通过对新生红细胞的压积、变形、取向及与之相应的全血的粘度、血沉等指标的连续60多天的监测,发现红细胞在衰老过程中的微观流变学特性确实有明显改变。红细胞在体衰老过程中微观流变特性逐渐变差。     

Quantitative characterization of domes in primary mouse mammary epithelial tumor cell cultures

Summary Dome populations from primary cultures of mouse mammary tumor cells were quantitatively studied in regard to size, distribution, density and the area occupied by light-diffusion photography and image analysis. The effects of fetal bovine serum, insulin and hydrocortisone were analyzed. Quantitative characterization documented dome diameter (mode diameter 0.26 to 0.52 mm), dome area occupied (average 23%, maximum 38.7%), and density (average 78 domes per cm², maximum 117 domes per cm²) for standard culture conditions. Insulin and hydrocortisone had a primary effect on dome density whereas 15% fetal bovine serum had a minimal effect. However, insulin and hydrocortisone had a synergistic optimal effect on dome population. Time-lapse cinematography revealed that the dome population is not static, but a very dynamic one. Domes underwent irregular pulsations of expansion and contraction. Dome enlargement was either by a series of expansions and contractions, by lateral involvement of other cells, or by coalescence of two or more domes. Domes have been considered to be the in vitro counterpart of the in vivo acinus of the mouse mammary gland. However, quantitative dome population characterization has not been available. Dome analysis by light-diffraction photography and image analysis lends itself towards correlative studies of domes and their differentiative products. Supported in part by Public Health Service Contract NO1-CP 61013 within the Virus Cancer Program of the National Cancer Institute and by Public Health Service Training Grant CA05245 from the National Cancer Institute.     

Effects of citronella oil (Cymbopogon winterianus Jowitt ex Bor) on Spodoptera frugiperda (J. E. Smith) midgut and fat body

The armyworm, Spodoptera frugiperda, is the principal pest of corn in Brazil. Control is achieved primarily by synthetic insecticides, which cause problems for the agro-ecosystem. Alternative methods of control are under investigation and citronella (Cymbopogon winterianus) essential oil appears to be a promising agent. We investigated the effects of citronella oil using histological, histochemical and immunohistochemical methods. The midgut of larvae treated with citronella exhibited altered epithelium including cytoplasmic protrusions, columnar cell extrusion, pyknotic nuclei, and increased periodic acid-Schiff positive granules. Regenerative cells in the epithelium of the midgut increased in number, which facilitated subsequent regeneration of this tissue. After exposure to citronella, trophocytes, the principal cell type of the fat body, possessed enlarged vacuoles and mitotic bodies, and contained reduced amounts of glycogen, lipid, and protein. Citronella oil caused morphological changes of the midgut and reduction of stored resources in the fat body, which may adversely affect insect reproduction and survival.     

Total sleep deprivation does not significantly degrade semantic encoding

ABSTRACT

Sleep deprivation impairs performance on cognitive tasks, but it is unclear which cognitive processes it degrades. We administered a semantic matching task with variable stimulus onset asynchrony (SOA) and both speeded and self-paced trial blocks. The task was administered at the baseline and 24 hours later after 30.8 hours of total sleep deprivation (TSD) or matching well-rested control. After sleep deprivation, the 20% slowest response times (RTs) were significantly increased. However, the semantic encoding time component of the RTs remained at baseline level. Thus, the performance impairment induced by sleep deprivation on this task occurred in cognitive processes downstream of semantic encoding.     

DNA barcoding of South Africa’s ornamental freshwater fish – are the names reliable?

Trade in freshwater ornamental fish in South Africa is currently regulated by a ‘blacklist’ to prevent potentially invasive taxa from establishing in the country. Because its effective implementation requires accurate identification, the aim of the present study was to test whether DNA barcoding is a useful tool to identify freshwater fishes in the South African pet trade. A total of 351 aquarium fish specimens, representing 185 traded taxa, were sequenced for the mitochondrial COI barcoding marker in 2011 and 2012. Lake Malawi cichlids were treated as a single group due to a lack of resolution in their COI marker, resulting in a data set of 137 successfully sequenced taxa. The Barcode Of Life Database (BOLD) and GenBank were used for taxonomic assignment comparisons. The genetic identification matched the scientific name inferred from the trade name for 60 taxa (43.8%) using BOLD, and for 67 taxa (48.9%) using GenBank. A genetic ID could not be assigned in 47 (34.3%) cases using BOLD and in 37 cases (27%) using GenBank. Whereas DNA barcoding can be a useful tool to help identify imported freshwater fishes, it requires further development of publicly available databases to become a reliable means of identification.