药（毒）物对尸食性蝇类生长发育影响的研究进展

药（毒）物对尸食性蝇类生长发育影响是法医昆虫毒理学领域里一个十分重要的研究方向,其研究结果可对与药（毒）物相关死亡案件的死亡时间作出修正。随着近年来全球毒品及药物滥用情况的日趋严重,其所导致的死亡案件也越来越多。这类案件常常需要应用尸食性蝇类生长发育历期来推算死后经历时间（postmortem interval, PMI）。为了阐明该领域的研究进展以及未来研究的焦点和难点,本文在阐述法医昆虫毒理学概念和特点的基础上,按照不同的药（毒）物分类,对近年来药（毒）物对尸食性蝇类生长发育影响在国内外的研究进展进行了综述。研究表明,某些药（毒）物对尸食性蝇类生长发育具有一定的影响,且这种影响存在种属差异。目前,该领域的研究尚限于宏观现象观察阶段,其研究范围在不断拓宽,既有的研究也在进一步深化,但还有许多问题有待进一步探讨。     

Fire Severity in Conifer Forests of the Sierra Nevada, California

Natural disturbances are an important source of environmental heterogeneity that have been linked to species diversity in ecosystems. However, spatial and temporal patterns of disturbances are often evaluated separately. Consequently, rates and scales of existing disturbance processes and their effects on biodiversity are often uncertain. We have studied both spatial and temporal patterns of contemporary fires in the Sierra Nevada Mountains, California, USA. Patterns of fire severity were analyzed for conifer forests in the three largest fires since 1999. These fires account for most cumulative area that has burned in recent years. They burned relatively remote areas where there was little timber management. To better characterize high-severity fire, we analyzed its effect on the survival of pines. We evaluated temporal patterns of fire since 1950 in the larger landscapes in which the three fires occurred. Finally, we evaluated the utility of a metric for the effects of fire suppression. Known as Condition Class it is now being used throughout the United States to predict where fire will be uncharacteristically severe. Contrary to the assumptions of fire management, we found that high-severity fire was uncommon. Moreover, pines were remarkably tolerant of it. The wildfires helped to restore landscape structure and heterogeneity, as well as producing fire effects associated with natural diversity. However, even with large recent fires, rates of burning are relatively low due to modern fire management. Condition Class was not able to predict patterns of high-severity fire. Our findings underscore the need to conduct more comprehensive assessments of existing disturbance regimes and to determine whether natural disturbances are occurring at rates and scales compatible with the maintenance of biodiversity.     

Development changes of cuticular hydrocarbons in Chrysomya rufifacies larvae: potential for determining larval age

Age determination is the basis of determining the postmortem interval using necrophagous fly larvae. To explore the potential of using cuticular hydrocarbons for determining the ages of fly larvae, changes of cuticular hydrocarbons in developing larvae of Chrysomya rufifacies (Macquart) (Diptera: Calliphoridae) were investigated using gas chromatography with flame-ionization detection and gas chromatography-mass spectrometry. This study showed that the larvae produced cuticular hydrocarbons typical of insects. Most of the hydrocarbons identified were alkanes with the carbon chain length of 21-31, plus six kinds of alkenes. The hydrocarbon composition of the larvae correlated with age. The statistical results showed that simple peak ratios of n-C29 divided by another eight selected peaks increased significantly with age; their relationships with age could be modelled using exponential or power functions with R(2) close to or > 0.80. These results suggest that cuticular hydrocarbon composition is a useful indicator for determining the age of larval C. rufifacies, especially for post-feeding larvae, which are difficult to differentiate by morphology.     

hERG K+ channel blockade by the antipsychotic drug thioridazine: An obligatory role for the S6 helix residue F656

The phenothiazine antipsychotic agent thioridazine has been linked with prolongation of the QT interval on the electrocardiogram, ventricular arrhythmias, and sudden death. Although thioridazine is known to inhibit cardiac hERG K(+) channels there is little mechanistic information on this action. We have investigated in detail hERG K(+) channel current (I(hERG)) blockade by thioridazine and identified a key molecular determinant of blockade. Whole-cell I(hERG) measurements were made at 37 degrees C from human embryonic kidney (HEK-293) cells expressing wild-type and mutant hERG channels. Thioridazine inhibited I(hERG) tails at -40mV following a 2s depolarization to +20mV with an IC(50) value of 80nM. Comparable levels of I(hERG) inhibition were seen with physiological command waveforms (ventricular and Purkinje fibre action potentials). Thioridazine block of I(hERG) was only weakly voltage-dependent, though the time dependence of I(hERG) inhibition indicated contingency of blockade upon channel gating. The S6 helix point mutation F656A almost completely abolished, and the Y652A mutation partially attenuated, I(hERG) inhibition by thioridazine. In summary, thioridazine is one of the most potent hERG K(+) channel blockers amongst antipsychotics, exhibiting characteristics of a preferential open/activated channel blocker and binding at a high affinity site in the hERG channel pore.     

ACE inhibitors reduce fecundity in the mosquito,Anopheles stephensi

Angiotensin-converting enzyme (ACE) is a dipeptidyl carboxypeptidase, which cleaves dipeptides and, in some instances, dipeptide or tripeptide amides from the C-terminus of regulatory peptides (e.g. angiotensin I, bradykinin and substance P). The expression of ACE is highly regulated in insects, where it is thought to have a role in the metabolism of peptide hormones involved in regulating reproduction. After a blood meal, ACE activity in the female mosquito Anopheles stephensi, increases four-fold with much of the enzyme finally accumulating in the ovary. In the present study, we have studied the effect on reproduction of adding two selective inhibitors of ACE, captopril and lisinopril, to the blood meal. Both ACE inhibitors reduced the size of the batch of eggs laid by females in a dose-dependent manner, with no observable effects on the behaviour of the adult insect. The almost total failure to lay eggs after feeding on either 1 mM captopril or 1 mM lisinopril, did not result from interference with the development of the primary follicle, but was due to the inhibition of egg-laying. Since very similar effects on the size of the egg-batch were observed with two selective ACE inhibitors, belonging to different chemical classes, we suggest that these effects are mediated by the selective inhibition of the induced mosquito ACE, a peptidase probably involved in the activation/inactivation of a peptide regulating egg-laying activity in A. stephensi.     

The R453Q and D151A polymorphisms of hexose-6-phosphate dehydrogenase gene (H6PD) influence the polycystic ovary syndrome (PCOS) and obesity

Hexose-6-phosphate dehydrogenase (H6PDH) influences 11β-hydroxysteroid dehydrogenase activity, a key enzyme in the peripheral metabolism of cortisol that modulates insulin sensitivity in adipose tissue. To study the associations of R453Q and D151A polymorphisms in the H6PDH gene (H6PD) with polycystic ovary syndrome (PCOS) and their influence on clinical and metabolic variables, we genotyped 237 patients with PCOS and 135 control women for the R453Q (rs6688832) and D151A (rs34603401) variants in H6PD. The R453Q genotypes were distributed differently in patients and controls (χ(2)=9.55, P=0.002). Genotypes of D151A were distributed evenly in women with PCOS and controls, but showed a different distribution in non-obese and obese women (χ(2)=3.95, P=0.047), especially within the PCOS subgroup (χ(2)=4.65, P=0.031). A backward stepwise likelihood ratio logistic regression model (Nagelkerke's R(2)=0.490; χ(2)=164; P<0.0001) retained free testosterone (OR=1.13; 95% CI: 1.10-1.17) and H6PD Q453 alleles (OR=0.46; 95% CI: 0.27-0.79) as statistically significant predictors for PCOS, whereas homeostasis model assessment of insulin resistance and the H6PD D151A variant were excluded by the model. Both H6PD variants were associated with several phenotypic variables, including fasting insulin, homeostasis model assessment of insulin resistance and androstenedione levels. In summary, the R453Q and D151A variants of the H6PD gene are associated with PCOS and obesity, respectively, and may contribute to the PCOS phenotype by influencing obesity, insulin resistance and hyperandrogenism.     

Hsa-miR-499 polymorphism (rs3746444) and cancer risk: A meta-analysis of 17 case–control studies

Introduction

MicroRNAs (miRNAs) are a family of endogenous, small and noncoding RNAs that negatively regulate gene expression by suppressing translation or degrading mRNAs. Recently, many studies investigated the association between hsa-miR-499 rs3746444 polymorphism and cancer risk, which showed inconclusive results.

Methodology/main results

We conducted a meta-analysis of 17 studies that included 7842 cancer cases and 8989 case-free controls and assessed the strength of the association, using odds ratios (ORs) with 95% confidence intervals (CIs). Overall, hsa-miR-499 rs3746444 polymorphism was associated with higher cancer risk in heterozygote model (AG vs AA, OR = 1.15, 95%CI = 1.01–1.30, P_{heterogeneity} < 0.001), dominant genetic model (GG/AG vs AA, OR = 1.18, 95% CI = 1.04–1.33, P_{heterogeneity} < 0.001) and allele contrast (G vs A, OR = 1.09, 95% CI = 1.01–1.18, P_{heterogeneity} = 0.021). In the stratified analyses, we observed that the GG/AG genotype might modulate breast cancer risk (OR = 1.13, 95% CI = 1.01–1.26, P_{heterogeneity} = 0.111) comparing with the AA genotype. Moreover, a significantly increased risk was found among Asian populations in heterozygote model (AG vs AA, OR = 1.23, 95% CI = 1.06–1.43, P_{heterogeneity} < 0.001), homozygote model (GG vs AA, OR = 1.22, 95% CI = 1.02–1.46, P_{heterogeneity} = 0.319), dominant model (GG/AG vs AA, OR = 1.25, 95% CI = 1.06–1.39, P_{heterogeneity} < 0.001) and allele contrast (G vs A, OR = 1.14, 95% CI = 1.04–1.25, P_{heterogeneity} = 0.021).

Conclusions

These findings supported that hsa-miR-499 rs3746444 polymorphism contributes to the susceptibility of cancers.     

Association of interleukin-13 SNP rs1800925 with allergic rhinitis risk: A meta-analysis based on 1,411 cases and 3169 controls

Studies investigating the association between interleukin-13 (IL-13) single nucleotide polymorphism (SNP) rs1800925 and allergic rhinitis risk have reported conflicting results. The aim of the present study was to conduct a meta-analysis assessing the possible association of IL-13 SNP rs1800925 with allergic rhinitis risk. The relevant studies were identified through a search of PubMed, Embase, ISI Web of Knowledge and Chinese National Knowledge Infrastructure until December 2011 and selected on the basis of the established inclusion criteria for publications. Five studies were included in the present meta-analysis (1411 cases and 3169 controls). The combined results based on all studies showed that IL-13 SNP rs1800925 was not associated with increased allergic rhinitis risk (T versus C: odds ratio (OR)=1.06, 95% confidence interval (CI)=0.94-1.20; C/T versus C/C: OR=1.12, 95% CI=0.97-1.29; T/T versus C/C: OR=1.00, 95% CI=0.69-1.44; C/T+T/T versus CC: OR=1.10, 95% CI=0.96-1.27; T/T versus C/C+C/T: OR=0.91, 95% CI=0.64-1.31). This meta-analysis supported that IL-13 SNP rs1800925 was not associated with allergic rhinitis.     

Novel antimicrobial peptides isolated from the skin secretions of Hainan odorous frog, Odorrana hainanensis

Intraperitoneal (i.p.) administration of the synthetic agonist of the glucagon like peptide-1 (GLP-1) receptor exenatide reduces food intake. Here, we evaluated possible peripheral pathways for this reduction. Exenatide (0.5 μg/kg, i.p.) was given to three, overnight food-deprived, groups of rats: total subdiaphragmatic vagotomy (VGX, severs the vagus nerve), celiaco-mesenteric ganglionectomy (CMGX, severs the splanchnic nerve) and combined VGX/CMGX. Following the injection, meal sizes (MSs) and intermeal intervals (IMIs) were determined for a total of 120 min. We found that exenatide reduced the sizes of the first two meals but failed to prolong the IMI between them, that VGX attenuated the reduction of the first MS, and that VGX, CMGX and combined VGX/CMGX attenuated the reduction of the second MS by exenatide. Therefore, the vagus nerve appears necessary for the reduction of the first MS by exenatide, whereas both nerves appear necessary for the reduction of the second MS by this peptide.