Synthesis and in vitro antiviral evaluation of 4-substituted 3,4-dihydropyrimidinones

A series of 4-substituted 3,4-dihydropyrimidine-2-ones (DHPM) was synthesized, characterized by IR, ¹H NMR, ¹³C NMR and HRMS spectra. The compounds were evaluated in vitro for their antiviral activity against a broad range of DNA and RNA viruses, along with assessment for potential cytotoxicity in diverse mammalian cell lines. Compound 4m, which possesses a long lipophilic side chain, was found to be a potent and selective inhibitor of Punta Toro virus, a member of the Bunyaviridae. For Rift Valley fever virus, which is another Bunyavirus, the activity of 4m was negligible. DHPMs with a C-4 aryl moiety bearing halogen substitution (4b, 4c and 4d) were found to be cytotoxic in MT4 cells.     

Arterial pulse wave velocity measurement: different techniques, similar results—implications for medical devices

Different characteristic points used for the evaluation of pulse wave velocity (PWV) give significantly different results. Hence, the accuracy of using these points is questionable. There is need for quantitative comparison of different techniques to determine PWV. Previous studies aimed at comparing different PWV measurement techniques have been noted, however, on a limited number of smaller animals (mice, dogs, etc.). This simulation-based study aims to compare different techniques for PWV measurement in a large representative human population. A computer model is developed for simulating the pressure wave propagation between the carotid and femoral arteries. Using relationships observed in clinical trials, the model input parameters for a statistically representative population are expressed in terms of a person’s age, gender and height. The model is used to calculate the carotid–femoral pressure ratio for different individuals, which is then parameterised into a number of features, and the equivalent propagation time is calculated using the phase-slope method. Using this time, the apparent phase velocity is determined and compared with PWV determined by the foot-to-foot technique. The two velocities compare well with a difference of 0.0059±0.0904 m/s. An averaging criterion for the calculation of apparent phase velocity has been tested and shown to give good estimates compared to the foot-to-foot technique. As it does not involve the identification of characteristic points on the measured pressure waves, the phase-slope method is more suitable for implementation in PWV monitors.     

A Novel Copper Chelate Modulates Tumor Associated Macrophages to Promote Anti-Tumor Response of T Cells

BackgroundAt the early stages of carcinogenesis, the induction of tumor specific T cell mediated immunity seems to block the tumor growth and give protective anti-tumor immune response. However, tumor associated macrophages (TAMs) might play an immunosuppressive role and subvert this anti tumor immunity leading to tumor progression and metastasis.Conclusion/SignificanceOur results show the potential usefulness of CuNG in immunotherapy of drug-resistant cancers through reprogramming of TAMs that in turn reprogram the T cells and reeducate the T helper function to elicit proper anti-tumorogenic Th1 response leading to effective reduction in tumor growth.     

Competitive interactions with dominant carnivores affect carrion acquisition of striped hyena in a semi-arid landscape of Rajasthan,India

Mammal Research - Scavenging of carrion is an important ecological process that influences ecological communities and food webs. The competitive inter- and intra-specific interactions in...     

Validation of molecular markers associated with perpetual flowering in Octoploid <Emphasis Type="Italic">Fragaria</Emphasis> germplasm

Perpetual-flowering (PF) is a highly desirable trait within cultivated strawberries (Fragaria ×ananassa) for the commercial and home garden markets. The most widely used source of the PF trait was originally introgressed from a wild F. virginiana subsp. glauca accession collected in the Wasatch Mountains near Salt Lake City, UT in 1955. This source is conferred by a single dominant QTL, FaPFRU, and was recently identified in multiple bi-parental populations. Multiple markers have been proposed as diagnostic tests for marker-assisted selection (MAS). These markers were proposed after looking at a relatively small sample of germplasm. To identify the best diagnostic testing procedure for MAS, the markers were evaluated individually and in combination on a training set of cultivars with known genotypes and the best test was used to determine the distribution of the FaPFRU source of PF within a large sample of octoploid Fragaria germplasm. Of the tests evaluated, the microsatellite marker Bx215 alone was found to have the best diagnostic ability for MAS with an accuracy of 93.1% in controlled conditions. When utilizing the test on 390 F. ×ananassa accessions, 164 accessions were identified to likely have the FaPFRU locus. Nine octoploid Fragaria accessions were PF and did not have this marker, indicating possible recombination events or potentially novel sources of the PF trait. Future work will be needed to dissect the PF trait in these nine individuals.     

The influence of abiotic and spatial variables on woody and herbaceous species abundances in a woodland–grassland system in the Eastern Terai of India

印度特莱东部林地-草地系统中非生物和空间变量对木本和草本物种丰度的影响 目前尚不清楚哪些环境因素决定了热带稀树草原特别是在潮湿地带的林地和草地镶嵌处的林地和草地的物种多度。基于此,本研究探究了非生物和空间变量对印度东北部的台拉河生态系统木本和草本物种分布的影响,评估了气候和非气候因素在整个景观中保持可变的树草比和空间连通性和分散性的相对重要性。在519 km²的受保护的特莱栖息地中随机建立了134个30 m × 30 m的抽样样方,并调查了每个样方的木本和草本植物的物种多度和气候,以及非气候环境因素。基于不同的地点空间连通性模型,通过构建变量检验气候和非气候环境因素对物种多度的影响。使用冗余分析和方差分解定量解析环境变量和空间结构对林地和草地物种多度的相对重要性。研究结果表明,降雨、火灾、水分胁迫、地形和土壤养分在内的环境变量对物种多度和林草比有显著的影响。空间结构显著,最佳空间模型为反距离加权模型(inverse distance-weighted model), 而且显示最大的空间扩散距离可以达到23.5 km,表明扩散限制较弱。约21%的物种多度变化能够被环境和空间因素解释。这些结果揭示了植物群落动态的决定因素,即环境因子的时空变化可能驱动物种分布和多度的随机性,并对植被镶嵌产生主导影响。     

Augmentation of cellular NAD+ by NQO1 enzymatic action improves age‐related hearing impairment

Age‐related hearing loss (ARHL) is a major neurodegenerative disorder and the leading cause of communication deficit in the elderly population, which remains largely untreated. The development of ARHL is a multifactorial event that includes both intrinsic and extrinsic factors. Recent studies suggest that NAD⁺/NADH ratio may play a critical role in cellular senescence by regulating sirtuins, PARP‐1, and PGC‐1α. Nonetheless, the beneficial effect of direct modulation of cellular NAD⁺ levels on aging and age‐related diseases has not been studied, and the underlying mechanisms remain obscure. Herein, we investigated the effect of β‐lapachone (β‐lap), a known plant‐derived metabolite that modulates cellular NAD⁺ by conversion of NADH to NAD⁺ via the enzymatic action of NADH: quinone oxidoreductase 1 (NQO1) on ARHL in C57BL/6 mice. We elucidated that the reduction of cellular NAD⁺ during the aging process was an important contributor for ARHL; it facilitated oxidative stress and pro‐inflammatory responses in the cochlear tissue through regulating sirtuins that alter various signaling pathways, such as NF‐κB, p53, and IDH2. However, augmentation of NAD⁺ by β‐lap effectively prevented ARHL and accompanying deleterious effects through reducing inflammation and oxidative stress, sustaining mitochondrial function, and promoting mitochondrial biogenesis in rodents. These results suggest that direct regulation of cellular NAD⁺ levels by pharmacological agents may be a tangible therapeutic option for treating various age‐related diseases, including ARHL.