Unraveling the genetic potential of native rice (Oryza sativa L.) landraces for tolerance to early-stage submergence.

Direct-seeded rice (DSR) is a promising alternative to the traditional puddled rice system. It has become more popular among rice growers as a result of socioeconomic shifts and global climate change. Although DSR offers advantages, rice plants experience greater anaerobic stress at sowing from unpredicted rainfall. Rice is unique among cereals in its ability to germinate under anaerobiosis. The coleoptile of rice rapidly elongates above the water surface to obtain more oxygen and enhance vigorous seedling growth. A panel of 115 landraces and four check varieties were subjected to anaerobic stress with a water level of 10 cm for up to 15 days. The present study observed significant variation in anaerobic germination percentage (AGP) (10%-100%) and anaerobic vigor index (AVI) (150-4,433). Landraces Karuthakar, Poovan samba, Mattaikar, Edakkal, Manvilayan, and Varappu kudainchan were identified as genotypes tolerant to early water submergence. The shoot and root length of susceptible landraces were significantly lower than the tolerant landraces under hypoxia condition, implying that landraces with longer shoots and roots had a higher survival rate. The response index substantiated this. The results clearly show that tolerant and moderately tolerant landraces possessed higher mean values for root and shoot lengths than susceptible landraces. The landraces grouped under the long-bold category had superior AGP and AVI scores to other grain type groups. This raises the possibility that differences in kernel breadth, which is linked to grain type, could affect anaerobic germination potential. Molecular confirmation using gene-specific markers, viz., DFR, TTP_G4, RM478, RM208, and RM24161, for which the polymorphic information content (PIC) value ranged from 0.36 (RM478) to 0.68 (RM206) suggests that this diverse panel of landraces must be assessed further using advanced molecular tools to precisely clarify the genetic mechanism behind this phenomenon. The tolerant landraces thus identified may become donors in breeding programs. The introduction of these traits would contribute to the development of rice varieties tolerant to anaerobic stress, resulting in sustainable yields. This solution could promote the DSR system across the world.

Antibody response to SARS-CoV-2 mRNA vaccine in lung cancer patients: Reactivity to vaccine antigen and variants of concern.

PurposeWe investigated SARS-CoV-2 mRNA vaccine-induced binding and live-virus neutralizing antibody response in NSCLC patients to the SARS-CoV-2 wild type strain and the emerging Delta and Omicron variants. Methods82 NSCLC patients and 53 healthy adult volunteers who received SARS-CoV-2 mRNA vaccines were included in the study. Blood was collected longitudinally, and SARS-CoV-2-specific binding and live-virus neutralization response to 614D (WT), B.1.617.2 (Delta), B.1.351 (Beta) and B.1.1.529 (Omicron) variants were evaluated by Meso Scale Discovery (MSD) assay and Focus Reduction Neutralization Assay (FRNT) respectively. We determined the longevity and persistence of vaccine-induced antibody response in NSCLC patients. The effect of vaccine-type, age, gender, race and cancer therapy on the antibody response was evaluated. ResultsBinding antibody titer to the mRNA vaccines were lower in the NSCLC patients compared to the healthy volunteers (P=<0.0001). More importantly, NSCLC patients had reduced live-virus neutralizing activity compared to the healthy vaccinees (P=<0.0001). Spike and RBD-specific binding IgG titers peaked after a week following the second vaccine dose and declined after six months (P=<0.001). While patients >70 years had lower IgG titers (P=<0.01), patients receiving either PD-1 monotherapy, chemotherapy or a combination of both did not have a significant impact on the antibody response. Binding antibody titers to the Delta and Beta variants were lower compared to the WT strain (P=<0.0001). Importantly, we observed significantly lower FRNT50 titers to Delta (6-fold), and Omicron (79-fold) variants (P=<0.0001) in NSCLC patients. ConclusionsBinding and live-virus neutralizing antibody titers to SARS-CoV-2 mRNA vaccines in NSCLC patients were lower than the healthy vaccinees, with significantly lower live-virus neutralization of B.1.617.2 (Delta), and more importantly, the B.1.1.529 (Omicron) variant compared to the wild-type strain. These data highlight the concern for cancer patients given the rapid spread of SARS-CoV-2 Omicron variant.

Whole-genome comparative analysis reveals genetic mechanisms of disease resistance and heat tolerance of tropical Bos indicus cattle breeds.

Bos indicus cattle breeds have been naturally selected for thousands of years for disease resistance and thermo-tolerance. However, the genetic mechanisms underlying these specific inherited characteristics must be elucidated. Hence, in this study, a whole-genome comparative analysis of the Bos indicus cattle breeds Kangayam, Tharparkar, Sahiwal, Red Sindhi, and Hariana of the Indian subcontinent was conducted. Genetic variant identification analysis revealed 155 851 012 SNPs and 10 062 805 InDels in the mapped reads across all Bos indicus cattle breeds. The functional annotation of 17 252 genes that comprised both SNPs and InDels, with high functional impact on proteins, was carried out. The functional annotation results revealed the pathways involved in the innate immune response, including toll-like receptors, retinoic acid-inducible gene I-like receptors, NOD-like receptors, Jak-STAT signaling pathways, and non-synonymous variants in the candidate immune genes. We also identified several pathways involved in the heat shock response, hair and skin properties, oxidative stress response, osmotic stress response, thermal sweating, feed intake, metabolism, and non-synonymous variants in the candidate thermo-tolerant genes. These pathways and genes directly or indirectly contribute to the disease resistance and thermo-tolerance adaptations of Bos indicus cattle breeds.

Decades-old renin inhibitors are still struggling to find a niche in antihypertensive therapy. A fleeting look at the old and the promising new molecules.

Hypertension is a diverse illness interlinked with cerebral, cardiovascular (CVS) and renal abnormalities. Presently, the malady is being treated by focusing on Renin- angiotensin system (RAS), voltage-gated calcium channels, peripheral vasodilators, renal and sympathetic nervous systems. Cardiovascular and renal abnormalities are associated with the overactivation of RAS, which can be constrained by angiotensin- converting enzyme inhibitors (ACEIs), angiotensin II (Ang-II) -AT1 receptor blockers (ARBs) and renin inhibitors. The latter is a new player in the old system. The renin catalyzes the conversion of angiotensinogen to Angiotensin I (Ang-I). This can be overcome by inhibiting renin, a preliminary step, eventually hinders the occurrence of the cascade of events in the RAS. Various peptidomimetics, the first-generation renin inhibitors developed six decades ago have limited drug-like properties as they suffered from poor intestinal absorption, high liver first-pass metabolism and low oral bioavailability. The development of chemically diverse molecules from peptides to nonpeptides expanded the horizon to achieving direct renin inhibition. Aliskiren, a blockbuster drug that emerged as a clinical candidate and got approved by the US FDA in 2007 was developed by molecular modeling studies. Aliskiren indicated superior to average efficacy and with minor adverse effects relative to other RAS inhibitors. However, its therapeutic use is limited by poor oral bioavailability of less than 2% that is similar to first-generation peptidic compounds. In this review, we present the development of direct renin inhibitors (DRIs) from peptidic to nonpeptidics that lead to the birth of aliskiren, its place in the treatment of cardiovascular diseases and its limitations.

Meta-analysis of mammary RNA seq datasets reveals the molecular understanding of bovine lactation biology.

A better understanding of the biology of lactation, both in terms of gene expression and the identification of candidate genes for the production of milk and its components, is made possible by recent advances in RNA seq technology. The purpose of this study was to understand the synthesis of milk components and the molecular pathways involved, as well as to identify candidate genes for milk production traits within whole mammary transcriptomic datasets. We performed a meta-analysis of publically available RNA seq transcriptome datasets of mammary tissue/milk somatic cells. In total, 11 562 genes were commonly identified from all RNA seq based mammary gland transcriptomes. Functional annotation of commonly expressed genes revealed the molecular processes that contribute to the synthesis of fats, proteins, and lactose in mammary secretory cells and the molecular pathways responsible for milk synthesis. In addition, we identified several candidate genes responsible for milk production traits and constructed a gene regulatory network for RNA seq data. In conclusion, this study provides a basic understanding of the lactation biology of cows at the gene expression level.