Synthesis and discovery of novel hexacyclic cage compounds as inhibitors of acetylcholinesterase

Hexacyclic derivatives share vital pharmacological properties, considered useful in Alzheimer’s disease. The aim of this study was synthesis and its evaluation for acetyl cholinesterase inhibitory activity of novel hexacyclic analogues. Compound 4f, showed potent inhibitory activity against acetyl cholinesterase enzyme with IC₅₀ 0.72 μmol/L.     

Influence of native ants on arthropod communities in a vineyard

• 1 Ants can have a range of effects on arthropods in crops, including suppressing herbivores such as caterpillars. However, ants can also increase hemipteran densities while reducing natural enemy numbers. In vineyard ecosystem, the effects of native ants and their interactions with other arthropods are poorly understood.
• 2 An ant‐exclusion experiment was designed to test the impact of native ants on both canopy and ground arthropods concurrently. The potential influence of ants on predation and parasitism of light brown apple moth (LBAM) eggs, a grape pest, was also examined. Adult grapevine scale insects and earwigs under bark were counted after a season of ant‐exclusion.
• 3 Among 23 ground ant species collected, six were found to forage in the canopy, with two Iridomyrmex species being the most commonly encountered.
• 4 There was no difference in the abundance of most arthropod orders and feeding groups between ant‐excluded and control vines, although ground spiders were more abundant under ant‐excluded vines, despite increased ground ant foraging pressure. LBAM egg parasitism and predation were low and probably affected by weather and other arthropods. Ant exclusion did not reduce survival of scale insects, although the distribution and abundance of scale insects were negatively associated with earwigs.
• 5 In conclusion, native ants did not consistently suppress arthropod assemblages, including natural enemies, and they did not promote the survival of scale insects. Interactions among native ant species within a vineyard might minimize their effects on other arthropods, although this needs further study.

     

Uncoupling protein 2 promoter polymorphism -866G/A, central adiposity, and metabolic syndrome in Asians

A polymorphism in the promoter region of uncoupling protein 2 gene -866G/A has been associated with its expression levels in adipose tissue, the risk of obesity, and metabolic abnormalities. Our purpose was to examine the associations of -866G/A with body fat and the risk of metabolic syndrome in a random sample of 4018 Asians (1858 men and 2160 women) from three ethnic groups (Chinese, Malay, and Indian). The minor allele frequency of -866G/A polymorphism in South Asians was similar to that in whites. After adjustment for covariates including age, cigarette smoking, and physical activity, the -866A/A genotype was associated with higher waist-to-hip ratio as compared with the wild-type genotype in Chinese and Indian men (p = 0.018 and p = 0.046, respectively). Moreover, Indian men with -866A/A genotype had a significantly increased risk of metabolic syndrome as compared with those homozygous for the wild-type (odds ratio, 2.66; 95% confidence interval, 1.21 to 5.88; p = 0.015). Such a risk was mainly caused by the excess presence of hypertriglyceridemia and central obesity. Our findings indicate that the uncoupling protein 2 gene -866G/A polymorphism may increase the risks of central obesity and metabolic syndrome, with greater effects on Asian men.     

Meta-analysis identified the TNFA -308G > A promoter polymorphism as a risk factor for disease severity in patients with rheumatoid arthritis

Introduction

The goal of this study is to investigate whether the -308G > A promoter polymorphism in the tumor necrosis factor alpha (TNFA) gene is associated with disease severity and radiologic joint damage in a large cohort of patients with rheumatoid arthritis (RA).

Methods

A long-term observational early RA inception cohort (n = 208) with detailed information about disease activity and radiologic damage after 3, 6 and 9 years of disease was genotyped for the TNFA -308G > A promoter polymorphism (rs1800629). A longitudinal regression analysis was performed to assess the effect of genotype on RA disease severity and joint damage. Subsequently, a meta-analysis, including all publically available data, was performed to further test the association between joint erosions and the TNFA polymorphism. To learn more about the mechanism behind the effect of the polymorphism, RNA isolated from peripheral blood from RA patients (n = 66) was used for TNFA gene expression analysis by quantitative PCR.

Results

Longitudinal regression analysis with correction for gender and disease activity showed a significant difference in total joint damage between GG and GA+AA genotype groups (P = 0.002), which was stable over time. The meta-analysis, which included 2,053 patients, confirmed an association of the genetic variant with the development of erosions (odds ratio 0.78, 95% CI 0.62, 0.98). No significant differences in TNFA gene expression were observed for the different genotypes, confirming earlier findings in healthy individuals.

Conclusions

Our data confirm that the TNFA -308G > A promoter polymorphism is associated with joint damage in patients with RA. This is not mediated by differences in TNFA gene expression between genotypes.     

Effect of temperature upon heart preservation for transplantation.

In this work we studied the effect of three different temperatures (7 °, 15 °, and 30 °C) on heart preservation. The best temperature for 24 hr pulsatile perfusion of canine hearts was 7 °C. Hearts perfused at this temperature showed no evidence of abnormal preservation changes nor of histological damage immediately upon transplantation. If the temperature was increased to 15 ° or 30 °C, moderate to severe preservation and histological damage were observed, and only three out of 10 dogs survived upon heart implantation.     

Endogenous pararetroviral sequences in tomato (<Emphasis Type="Italic">Solanum lycopersicum</Emphasis>) and related species

Background  

Endogenous pararetroviral sequences (EPRVs) are a recently discovered class of repetitive sequences that is broadly distributed in the plant kingdom. The potential contribution of EPRVs to plant pathogenicity or, conversely, to virus resistance is just beginning to be explored. Some members of the family Solanaceae are particularly rich in EPRVs. In previous work, EPRVs have been characterized molecularly in various species of Nicotiana including N.tabacum (tobacco) and Solanum tuberosum (potato). Here we describe a family of EPRVs in cultivated tomato (Solanum lycopersicum L.) and a wild relative (S.habrochaites).     

Oncogenic Pathway Combinations Predict Clinical Prognosis in Gastric Cancer

Many solid cancers are known to exhibit a high degree of heterogeneity in their deregulation of different oncogenic pathways. We sought to identify major oncogenic pathways in gastric cancer (GC) with significant relationships to patient survival. Using gene expression signatures, we devised an in silico strategy to map patterns of oncogenic pathway activation in 301 primary gastric cancers, the second highest cause of global cancer mortality. We identified three oncogenic pathways (proliferation/stem cell, NF-κB, and Wnt/β-catenin) deregulated in the majority (>70%) of gastric cancers. We functionally validated these pathway predictions in a panel of gastric cancer cell lines. Patient stratification by oncogenic pathway combinations showed reproducible and significant survival differences in multiple cohorts, suggesting that pathway interactions may play an important role in influencing disease behavior. Individual GCs can be successfully taxonomized by oncogenic pathway activity into biologically and clinically relevant subgroups. Predicting pathway activity by expression signatures thus permits the study of multiple cancer-related pathways interacting simultaneously in primary cancers, at a scale not currently achievable by other platforms.