Integrative RNA-Seq analysis of Capsicum annuum L.-Phytophthora capsici L. pathosystem reveals molecular cross-talk and activation of host defence response.

Chili pepper (Capsicum annuum L.) is economically one of the most important spice. But, it's productivity is highly affected by the pathogen, Phytophthora capsici L. Our current understanding of the molecular mechanisms associated with the defence response in C. annuum-P. capsici pathosystem is limited. The current study used RNA-seq technology to dissect the genes associated with defence response against P. capsici infection in two contrasting landraces, i.e. GojamMecha_9086 (Resistant) and Dabat_80045 (Susceptible) exposed to P. capsici infection. The transcriptomes from four leaf samples (RC, RI, SC and SI) of chili pepper resulted in a total of 118,879 assembled transcripts along with 52,384 pooled unigenes. The enrichment analysis of the transcripts indicated 23 different KEGG pathways under five main categories. Out of 774 and 484 differentially expressed genes (DEGs) of two landraces (under study), respectively, 57 and 29 DEGs were observed as associated with defence responses against P. capsici infection in RC vs. RI and SC vs. SI leaf samples, respectively. qRT-PCR analysis of six randomly selected genes validated the results of Illumina NextSeq500 sequencing. A total of 58 transcription factor families (bHLH most abundant) and 2095 protein families (Protein kinase most abundant) were observed across all the samples with maximum hits in RI and SI samples. Expression analysis revealed differential regulation of genes associated with defence and signalling response with shared coordination of molecular function, cellular component and biological processing. The results presented here would enhance our present understanding of the defence response in chili pepper against P. capsici infection, which the molecular breeders could utilize to develop resistant chili genotypes. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12298-021-01122-y.

Pharmacological preconditioning with phosphodiestrase inhibitor: an answer to stem cell survival against ischemic injury through JAK/STAT signaling.

Stem cell transplantation in regenerative medicine has been widely used in various disorders including cardiovascular diseases (CVD) and emerging next-generation therapy. However, transplanted stem cell encountered ischemia/reperfusion (IR) injury which is a major challenge for stem cell survival. During the acute phase after myocardial infarction (MI) cytokine-rich hostile microenvironment, extensive immune cell infiltration and lack of oxygen have been a bottleneck in cell-based therapy. During prolonged ischemia, intracellular pH and ATP level decrease results in anaerobic metabolism and lactate accumulation. Consequentially, ATPase-dependent ion transport becomes dysfunctional, contributing to calcium overload and cell death by apoptosis and necrosis. Although O2 level revitalizes upon reperfusion, a surge in the generation of reactive oxygen species (ROS) occurs with neutrophil infiltration in ischemic tissues further aggravating the injury. Ischemic preconditioning (IPC) of stem cells with a repeated short cycle of IR results in the release of chemical signals such as NO, ROS, and adenosine which triggers a cascade of signaling events that activates protein kinase C (PKC), Src protein tyrosine kinases, and nuclear factor κB (NF-κB) and subsequently increased synthesis of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), Heme oxygenase-1 [HO-1], aldose reductase, Mn superoxide dismutase, and anti-apoptotic genes (Mcl-1, BCl-xL, c-FLIPL, c-FLIPS). Pharmacological preconditioning uses a phosphodiestrase inhibitor, another mode of protecting stem cell or heart per se from impending ischemic injury in two phases. During the early phase of cardioprotection (2 h), PC leads to increased expression of survival factors like BCl2/Bax ratio while late phase (24 h) showed activation of the JAK/STAT survival pathway. Phosphorylation of STAT3 at two crucial residues, Tyr-705 and Ser-727, allows its entry inside the nucleus and upregulates the expression of protein kinase G-1 (PKG1) which evokes cardioprotective signaling. To confirm, heart-specific conditional STAT3 knockout mice undergone IR surgery, abolishing late-phase cardioprotective effects.

A draft genome sequence of the pulse crop chickpea (Cicer arietinum L.).

Cicer arietinum L. (chickpea) is the third most important food legume crop. We have generated the draft sequence of a desi-type chickpea genome using next-generation sequencing platforms, bacterial artificial chromosome end sequences and a genetic map. The 520-Mb assembly covers 70% of the predicted 740-Mb genome length, and more than 80% of the gene space. Genome analysis predicts the presence of 27,571 genes and 210 Mb as repeat elements. The gene expression analysis performed using 274 million RNA-Seq reads identified several tissue-specific and stress-responsive genes. Although segmental duplicated blocks are observed, the chickpea genome does not exhibit any indication of recent whole-genome duplication. Nucleotide diversity analysis provides an assessment of a narrow genetic base within the chickpea cultivars. We have developed a resource for genetic markers by comparing the genome sequences of one wild and three cultivated chickpea genotypes. The draft genome sequence is expected to facilitate genetic enhancement and breeding to develop improved chickpea varieties.

Lumacaftor as a potential repurposed drug in targeting breast cancer stem cells: insights from in silico study.

CONTEXT: Breast cancer stem cells (BCSCs) are a small subset of cells within breast tumors with characteristics similar to normal stem cells. Despite advancements in chemotherapy and targeted therapy for breast cancer, the prognosis for breast cancer patients has remained poor due to drug resistance, reoccurrence, and metastasis. Growing evidence suggests that deregulation of the self-renewal pathways, like the Wnt signaling pathway mediated by ß-catenin, plays a crucial role in the survival of breast cancer stem cells. Targeting the Wnt signaling pathway in breast cancer stem cells offers a promising avenue for developing effective therapeutic strategies targeting these cells, potentially leading to improved patient outcomes and reduced tumor recurrence. METHODS: For this purpose, we have screened a 1615 FDA-approved drug library against our target protein, ß-catenin, which is involved in the Wnt signaling pathway using molecular docking analysis, molecular dynamics (MD) simulations, and molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) calculations. RESULTS: Molecular docking studies showed that the Lumacaftor- ß-catenin complex had the lowest docking score of - 8.7 kcal/mol towards ß-catenin protein than the reference inhibitor. Molecular dynamic simulations and MM/PBSA calculations were also performed for the Lumacaftor-ß-catenin complex to establish the stability of the interactions involved. Considering its promising attributes and encouraging results, Lumacaftor holds significant potential as a novel therapeutic option to target BCSCs. This study opens avenues for further investigation and may pave the way for developing therapeutic potential in breast cancer treatment. Further confirmation is warranted through in vitro and clinical studies to validate the findings of this study.

Sesame (Sesamum indicum L.).

Sesame (Sesamum indicum L.) is an important oilseed crop grown in India, China, Korea, Russia, Turkey, Mexico, South America, and several countries of Africa. Sesame seeds are rich in oil, proteins, unsaturated fatty acids, vitamins, minerals, and folic acid. Nearly 70% of the world's sesame is processed into oil and meal, while the remainder is channeled to food and confectionery industries. Production of sesame is limited by several fungal diseases, water logging, salinity, and shattering of seed capsules during harvest. Introgression of useful genes from wild species into cultigens by conventional breeding has not been successful due to postfertilization barriers. The only alternative for the improvement of S. indicum is to transfer genes from other sources through genetic transformation techniques. Here, we describe a simple, fast, and reproducible method for the Agrobacterium-mediated genetic transformation of S. indicum which may be employed for the transfer of desirable traits into this economically important oilseed crop.

Microwave assisted synthesis, characterization and biocidal activities of some new chelates of carbazole derived Schiff bases of cadmium and tin metals.

This study is planned to report the advancement of green microwave approach in the fabrication of a new series of biologically potent (N^X, where X=O/S) donor Schiff bases and their cadmium(II) and tin(II) complexes. The ligands and their metal complexes have been characterized in terms of elemental analysis, molar ionic conductance, magnetic moment and spectral (IR, UV-Vis, NMR ((1)H, (119)Sn), FAB-mass, thermal and XRD) data. The data revealed that the ligands coordinated to the metal center via nitrogen and oxygen/sulfur atoms and form an octahedral arrangement of the ligands around central metal atom. All compounds were evaluated for their in vitro antimicrobial activities against two pathogenic bacteria Bacillus subtilis and Escherichia coli and two fungi Aspergillus niger and Aspergillus flavus by standard disc diffusion method. The discs were stored in an incubator at 37°C. The compounds were dissolved in DMF at 500 and 1000 ppm concentrations for screening biocidal activity. The compounds were dissolved in DMF to get the 100 and 200 ppm concentration of test solutions for screening fungicidal activity. The inhibition zone around each disc was measured (in mm) after 24 h and 96 h for biocidal and fungicidal activities respectively.