Regulation of TORC2 function and localization by Rab5 GTPases in Saccharomyces cerevisiae

The evolutionarily conserved Target of Rapamycin (TOR) complex-2 (TORC2) is an essential regulator of plasma membrane homeostasis in budding yeast (Saccharomyces cerevisiae). In this yeast, TORC2 phosphorylates and activates the effector protein kinase Ypk1 and its paralog Ypk2. These protein kinases, in turn, carry out all the crucial functions of TORC2 by phosphorylating and thereby controlling the activity of at least a dozen downstream substrates. A previously uncharacterized interplay between the Rab5 GTPases and TORC2 signaling was uncovered through analysis of a newly suspected Ypk1 target. Muk1, one of two guanine nucleotide exchange factors for the Rab5 GTPases, was found to be a physiologically relevant Ypk1 substrate; and, genetic analysis indicates that Ypk1-mediated phosphorylation activates the guanine nucleotide exchange activity of Muk1. Second, it was demonstrated both in vivo and in vitro that the GTP-bound state of the Rab5 GTPase Vps21/Ypt51 physically associates with TORC2 and acts as a direct positive effector required for full TORC2 activity. These interrelationships provide a self-reinforcing control circuit for sustained up-regulation of TORC2-Ypk1 signaling. In this overview, we summarize the experimental basis of these findings, their implications, and speculate as to the molecular basis for Rab5-mediated TORC2 activation.     

SAR optimization studies on a novel series of 2-anilinopyrimidines as selective inhibitors against triple-negative breast cancer cell line MDA-MB-468

Triple-negative breast cancers (TNBCs) account for approximately 15% of breast cancer cases and exhibit an aggressive clinical behavior. In this study, we designed and synthesized two series of 2-anilinopyrimidines based on the structure of our previously reported compound 1 that act as a selective inhibitor of the basal-like TNBC cell line MDA-MB-468. Through the fine-tuning of 1, cyclic and acyclic amines at 4-position of the pyrimidine core were turned out to be crucial for the selectivity. An extensive analysis of structure-activity relationships of the analogs revealed that aminoalkyl groups at the end of the propyl chain are amenable to modification. Among the newly synthesized analogs, compound 38, bearing 4-chloropiperidinyl and cyclohexyl groups, was found to be the most potent and selective, and was about three times more potent and selective than 1 was against the TNBC cells.     

变豆菜属15种植物的果实微形态特征及其分类学意义

采用扫描电镜对来自北美和东亚的变豆菜属植物(美国7个种,中国8个种)的果实表面微形态进行观察,结合前人对伞形科其他类群果实微形态特征的研究及近年来分子系统学证据,对变豆菜属的种间分类进行研究。结果显示,变豆菜属植物果实的形态大小、皮刺弯曲程度和果柄蜡质纹饰丰富多样。研究表明变豆菜属是一个自然类群,果实表面钩刺结构有利于该属植物的传播及扩散,果实微形态特征具有分类学价值,可作为种间分类的依据。根据变豆菜属果实表面微形态特征,编制了该属植物分种检索表。     

火龙果转录组测序、基因表达与功能分析

利用高通量测序技术对火龙果(Hylocereus undulatus Britt)红肉品种‘大红二号’的花芽、果实和枝条不同发育阶段的基因表达进行研究。结果显示,转录组测序共获得468.68 Gb原始数据(Raw data),从头组装获得239 152条转录本和162 519条unigene,约53.74%的unigene得到注释。分别在43 506条和16 251条unigene中检测到600 283个SNP位点和56 147个SSR位点。基因表达分析结果表明,在火龙果不同组织Fl510、Fl513、Fl514、Fl518、F711、F715、S513、S419中分别有31、7、5、152、17、63、17、8个特异表达的unigene。通过GO和KEGG富集分析,发现了一些组织特异的GO条目和代谢通路,如在Fl510中富集的类萜骨架生物合成代谢通路等。本研究还对参与花发育的候选基因进行了鉴定和表达分析,他们包括COL基因、FT-like基因、分生组织决定基因和器官决定基因等。     

脂肪来源干细胞治疗心肌梗死的现状及策略

急性心肌梗死是最常见的心血管疾病之一,由于冠状动脉供血不全导致心肌细胞大量坏死、生存微环境恶化,近期可发生心肌细胞机械-电生理功能紊乱,远期可导致心力衰竭。目前的临床治疗方法虽能在一定程度上改善心功能,减轻心室重塑,但由于心肌细胞再生能力有限,心脏功能难以完全恢复正常。近年来,脂肪来源干细胞移植治疗急性心肌梗死受到广泛关注,但由于移植后细胞的存留和存活率普遍较低,总体治疗效果并不理想。本文对目前脂肪来源干细胞治疗急性心肌梗死的现况及提高其疗效的途径和方法作一综述。     

Sources of Nitrogen in Combination with Systems of Irrigation Influence the Productivity of Modern Rice (<i>Oryza sativa</i> L.) Cultivars during Dry Season in Sub-Tropical Environment

In irrigated agricultural systems, nitrogen (N) and water are the vital resources for sustainability of the crop production in the modern era of climate change. The current study aimed to assess the impact of water and N management on the productivity of irrigated rice cultivars. In the context, a field observation was done at the research farm of Bangladesh Agricultural University, Mymensingh, during dry seasons in consecutive two years (2018–2019 and 2019–2020). The experiments were set up following split-plot design assigning water management in the main plots, nitrogen management in the sub-plots, and the cultivars were approved in the split-split plot with three replications. After two years observation, it was revealed that rice cultivar Binadhan-8 gave the maximum value of leaf area index, number effective tillers hill^-1 and grains panicle^-1 which lead to the higher grain yield (GY). Substantial relationships were observed among the concentration of N, growth, total dry matter (TDM) and N content, N uptake, N utilization effectiveness, and GY. However, with little exception, the Combined effect of water and N, cultivars and water management were varied significantly for all parameters. Finally, the results of the current study concluded that application of irrigation at 8 days after the disappearance of ponded water and source of 105 kg N ha^-1 from PU + Poultry manure are the best management approach for the excellent performance of rice cultivar Binadhan-8.     

Biological Control of Root-Knot Nematode <i>Meloidogyne incognita</i> in <i>Psoralea corylifolia</i> Plant by Enhancing the Biocontrol Efficacy of <i>Trichoderma harzianum</i> Using Press Mud

Meloidogyne incognita is a plant pathogen causing root-knot disease and loss of crop yield. The present study aimed to use Trichoderma harzianum as a biocontrol agent against plant-parasitic nematodes and used press mud, which is a solid waste by-product of sugarcane, as a biocontrol agent and biofertilizer. Therefore, the combined application of T. harzianum and press mud may enhance nematode control and plant growth. Elemental analysis of press mud using scanning electron microscopy (SEM) integrated with an Energy Dispersive X-ray (EDX) analyzer revealed the presence of different elements such as C, O, Mg, Si, P, K, Ca, Cu and Zn. In addition, a greenhouse study was conducted to investigate the combined effects of press mud and T. harzianum on M. incognita reproduction and growth and the biochemical features of Psoralea corylifolia. The results showed that plant length, dry biomass, leaf area, the number of seeds per plant, chlorophyll a, chl b, carotenoid content, nitrate reductase, carbonic anhydrase, and nitrogen content were significantly increased (P ≤ 0.05) in the T2 plants (plants were treated with 100 g of press mud + 50 mL T. harzianum before one week of M. incognita inoculation), over inoculated plants (IC). Antioxidant enzyme activity of ascorbate peroxidase (APX), catalase (CAT), peroxidase (POD), and superoxide dismutase (SOD) in the foliage of P. corylifolia was significantly increased when plants were treated with press mud + T. harzianum. A significant reduction in the number of egg masses, nematode population, and root-knot index (RKI) was found in plants with T2 plants. These results suggest that the combined application of T. harzianum and press mud has the potential to control the M. incognita infection and can be used as an environmentally safe alternative to chemical nematicides and also help in the removal of sugarcane waste that causes environmental pollution.     

MarkerML – Marker Feature Identification in Metagenomic Datasets Using Interpretable Machine Learning

Identification of environment specific marker-features is one of the key objectives of many metagenomic studies. It aims to identify such features in microbiome datasets that may serve as markers of the contrasting or comparable states. Hypothesis testing and black-box machine learnt models which are conventionally used for identification of these features are generally not exhaustive, especially because they generally do-not provide any quantifiable relevance (context) of/between the identified features. We present MarkerML web-server, that seeks to leverage the emergence of interpretable machine learning for facilitating the contextual discovery of metagenomic features of interest. It does so through a comprehensive and automated application of the concept of Shapley Additive Explanations in companionship to the compositionality accounted hypothesis testing for the multi-variate microbiome datasets. MarkerML not only helps in identification of marker-features, but also enables insights into the role and inter-dependence of the identified features in driving the decision making of the supervised machine learnt model. Generation of high quality and intuitive visualizations spanning prediction effect plots, model performance reports, feature dependency plots, Shapley and abundance informed cladograms (Sungrams), hypothesis tested violin plots along-with necessary provisions for excluding the participant bias and ensuring reproducibility of results, further seek to make the platform a useful asset for the scientists in the field of microbiome (and even beyond). The MarkerML web-server is freely available for the academic community at https://microbiome.igib.res.in/markerml/.