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screening.

The present study describes an in vitro system in which O. volvulus L3 larvae can be maintained in culture leading to the development of adult stages. Thus, this in vitro system may provide a platform to investigate mating behaviour and early stage of nodulogenesis of O. volvulus adult worms that can be used as additional targets for macrofilaricidal drug screening.

Whether consumption of egg and cholesterol is detrimental to cardiovascular health and longevity is highly debated. Data from large-scale cohort studies are scarce. This study aimed to examine the associations of egg and cholesterol intakes with mortality from all causes, cardiovascular disease (CVD), and other causes in a US population.

Overall, 521,120 participants (aged 50-71 years, mean age = 62.2 years, 41.2% women, and 91.8% non-Hispanic white) were recruited from 6 states and 2 additional cities in the US between 1995 and 1996 and prospectively followed up until the end of 2011. Intakes of whole eggs, egg whites/substitutes, and cholesterol were assessed by a validated food frequency questionnaire. Cause-specific hazard models considering competing risks were used, with the lowest quintile of energy-adjusted intake (per 2,000 kcal per day) as the reference. There were 129,328 deaths including 38,747 deaths from CVD during a median follow-up of 16 years. Whole egg and cholesterol intakes were both pish, dairy products, or nuts/legumes was related to lower all-cause, CVD, cancer, and respiratory disease mortality. Study limitations include its observational nature, reliance on participant self-report, and residual confounding despite extensive adjustment for acknowledged dietary and lifestyle risk factors.

In this study, intakes of eggs and cholesterol were associated with higher all-cause, CVD, and cancer mortality. The increased mortality associated with egg consumption was largely influenced by cholesterol intake. Our findings suggest limiting cholesterol intake and replacing whole eggs with egg whites/substitutes or other alternative protein sources for facilitating cardiovascular health and long-term survival.

ClinicalTrials.gov NCT00340015.

ClinicalTrials.gov NCT00340015.Hepatocellular carcinoma (HCC) is a significant health problem worldwide with poor prognosis. Drug repositioning represents a profitable strategy to accelerate drug discovery in the treatment of HCC. In this study, we developed a new approach for predicting therapeutic drugs for HCC based on tissue-specific pathways and identified three newly predicted drugs that are likely to be therapeutic drugs for the treatment of HCC. We validated these predicted drugs by analyzing their overlapping drug indications reported in PubMed literature. By using the cancer cell line data in the database, we constructed a Connectivity Map (CMap) profile similarity analysis and KEGG enrichment analysis on their related genes. By experimental validation, we found securinine and ajmaline significantly inhibited cell viability of HCC cells and induced apoptosis. Among them, securinine has lower toxicity to normal liver cell line, which is worthy of further research. Our results suggested that the proposed approach was effective and accurate for discovering novel therapeutic options for HCC. This method also could be used to indicate unmarked drug-disease associations in the Comparative Toxicogenomics Database. Meanwhile, our method could also be applied to predict the potential drugs for other types of tumors by changing the database.Several intracellular trafficking pathways contribute to the regulation of AMPA receptor (AMPAR) levels at synapses and the control of synaptic strength. While much has been learned about these intracellular trafficking pathways, a major challenge is to understand how extracellular factors, such as growth factors, neuropeptides and hormones, impinge on specific AMPAR trafficking pathways to alter synaptic function and behavior. Here, we identify the secreted ligand PVF-1 and its cognate VEGF receptor homologs, VER-1 and VER-4, as regulators of glutamate signaling in C. elegans. Loss of function mutations in ver-1, ver-4, or pvf-1, result in decreased cell surface levels of the AMPAR GLR-1 and defects in glutamatergic behavior. Rescue experiments indicate that PVF-1 is expressed and released from muscle, whereas the VERs function in GLR-1-expressing neurons to regulate surface levels of GLR-1 and glutamatergic behavior. Additionally, ver-4 is unable to rescue glutamatergic behavior in the absence of pvf-1, suggesting that VER function requires endogenous PVF-1. Inducible expression of a pvf-1 rescuing transgene suggests that PVF-1 can function in the mature nervous system to regulate GLR-1 signaling. Genetic double mutant analysis suggests that the VERs act together with the VPS-35/retromer recycling complex to promote cell surface levels of GLR-1. Our data support a genetic model whereby PVF-1/VER signaling acts with retromer to promote recycling and cell surface levels of GLR-1 to control behavior.Domestic ducks are of paramount importance as a cheap source of protein in rural India. Andaman local duck (ALD) is an indigenous avian genetic resource of Andaman and Nicobar islands (ANI) and is mainly distributed in Middle and Northern parts of these islands. check details Negligence has brought this breed on the edge of extinction necessitating immediate conservation efforts. Here, we report the genetic diversity, population structure and matrilineal genetic root of ALD. Partial mtDNA D-loop sequences were analyzed in 71 ALD samples and analysis revealed 19 polymorphic sites and 13 haplotypes. Estimated haplotype (Hd ± SD) and nucleotide diversity (π ± SD) were 0.881 ± 0.017 and 0.00897 ± 0.00078 respectively. The high genetic diversity of ALD indicates introgression of genetic material from other local duck breeds. In addition, it can be postulated that ALD bearing high genetic diversity has strong ability to adapt to environmental changes and can withstand impending climate change. Phylogenetic and network analysis indicate that ALD falls under Eurasian clade of mallard and ALD forms three clusters; one cluster is phylogenetically close to Southeast Asian countries, one close to Southern part of mainland India and the third one forms an independent cluster. Therefore, ALD might have migrated either from Southeast Asian countries which enjoy a close cultural bondage with ANI from time immemorial or from Southern part of India. The independent cluster may have evolved locally in these islands and natural selection pressure imposed by environmental conditions might be the driving force for evaluation of these duck haplotypes; which mimics Darwin's theory of natural selection. The results of the study will be beneficial for formulating future breeding programme and conservation strategy towards sustainable development of the duck breed.

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