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Abstract Maize is gaining impetus in non-traditional and non-conventional seasons such as off-season, primarily due to higher demand and economic returns. Maize varieties directed for growing in the winter season of South Asia must have cold resilience as an important trait due to the low prevailing temperatures and frequent cold snaps observed during this season in most parts of the lowland tropics of Asia. The current study involved screening of a panel of advanced tropically adapted maize lines to cold stress during vegetative and flowering stage under field conditions. A suite of significant genomic loci (28) associated with grain yield along and agronomic traits such as flowering (15) and plant height (6) under cold stress environments. The haplotype regression revealed 6 significant haplotype blocks for grain yield under cold stress across the test environments. Haplotype blocks particularly on chromosomes 5 (bin5.07), 6 (bin6.02), and 9 (9.03) co-located to regions/bins that have been identified to contain candidate genes involved in membrane transport system that would provide essential tolerance to the plant. The regions on chromosome 1 (bin1.04), 2 (bin 2.07), 3 (bin 3.05–3.06), 5 (bin5.03), 8 (bin8.05–8.06) also harboured significant SNPs for the other agronomic traits. In addition, the study also looked at the plausibility of identifying tropically adapted maize lines from the working germplasm with cold resilience across growth stages and identified four lines that could be used as breeding starts in the tropical maize breeding pipelines.

Arsenic is a ubiquitous element that occurs either as a pure element or as a component of many minerals, sulfur, and metals. Elemental arsenic and its compounds are carcinogenic, mutagenic, and teratogenic for living organisms in the environment at elevated levels. Global reports of arsenic contamination in soil and groundwater are frequent. Reports also indicate arsenic contamination in the groundwater and soil of the Rohtak district of Haryana state. The present work was designed to check whether agrochemicals could be a possible source of arsenic contamination in the study area, as no geogenic sources of arsenic were reported. In total, 82 samples of commonly used agrochemicals differing in compositions and brands were collected and analyzed by the fluorescence method using the Fluorat-02-4M Analyzer. Phosphate fertilizers were found to be highly contaminated; the highest amount of arsenic was reported in N: P: K (0:52:34) with a mean value of 345 ppb, followed by N: P: K (12:32:16) with a mean value of 292 ppb, followed by diammonium phosphate with a mean value of 252 ppb. Organic fertilizers show comparatively low values. Arsenic content in various pesticides ranged from 6 ppb to 228 ppb. Despite the ban on arsenic- containing pesticides, nearly all agrochemicals contain it. Research indicates that farmers should reduce their use of chemical fertilizers and promote the use of organic fertilizers instead. [ABSTRACT FROM AUTHOR]

Therapeutic antibodies have predominantly been IgG‐based. However, the ongoing clinical trial of MOv18 IgE has highlighted the potential of using IgE antibodies in cancer therapy. While extensive studies targeting IgG glycosylation resulted in a rational basis for the development of enhanced biotherapeutics, IgE glycosylation remains an area with limited analyses. Previous studies on the role of IgE glycosylation present conflicting data with one study emphasizing the importance of N275 and T277 residues for FcεRI binding whereas another asserts the nonsignificance of IgE glycosylation in receptor interaction. While existing literature underscores the significance of glycans at the N275 position for binding to FcεR1 receptor and initiation of anaphylaxis, the role of other IgE glycosylation sites in folding or receptor binding remains elusive. This study systematically investigates the functional significance of N‐linked glycosylation sites in the heavy chain of IgE which validates the pivotal role of N275 residue in IgE secretion and stability. Replacement of this asparagine to non‐amine group moieties does not affect IgE function in vitro, yet substitution with aspartic acid compromises antibody yield. The deglycosylated IgE variant exhibits superior efficacy, challenging the conventional importance of glycosylation for effector function. In summary, our study unveils an intricate relationship between N‐glycosylation sites and the structural–functional dynamics of IgE antibodies. Furthermore, it offers novel insights into the IgE scaffold, paving the way for the development of more effective and stable IgE‐based therapeutics. [ABSTRACT FROM AUTHOR]

Unpredictable weather vagaries in the Asian tropics often increase the risk of a series of abiotic stresses in maize-growing areas, hindering the efforts to reach the projected demands. Breeding climate-resilient maize hybrids with a cross-tolerance to drought and waterlogging is necessary yet challenging because of the presence of genotype-by-environment interaction (GEI) and the lack of an efficient multi-trait-based selection technique. The present study aimed at estimating the variance components, genetic parameters, inter-trait relations, and expected selection gains (SGs) across the soil moisture regimes through genotype selection obtained based on the novel multi-trait genotype–ideotype distance index (MGIDI) for a set of 75 tropical pre-released maize hybrids. Twelve traits including grain yield and other secondary characteristics for experimental maize hybrids were studied at two locations. Positive and negative SGs were estimated across moisture regimes, including drought, waterlogging, and optimal moisture conditions. Hybrid, moisture condition, and hybrid-by-moisture condition interaction effects were significant (p ≤ 0.001) for most of the traits studied. Eleven genotypes were selected in each moisture condition through MGIDI by assuming 15% selection intensity where two hybrids, viz., ZH161289 and ZH161303, were found to be common across all the moisture regimes, indicating their moisture stress resilience, a unique potential for broader adaptation in rainfed stress-vulnerable ecologies. The selected hybrids showed desired genetic gains such as positive gains for grain yield (almost 11% in optimal and drought; 22% in waterlogging) and negative gains in flowering traits. The view on strengths and weaknesses as depicted by the MGIDI assists the breeders to develop maize hybrids with desired traits, such as grain yield and other yield contributors under specific stress conditions. The MGIDI would be a robust and easy-to-handle multi-trait selection process under various test environments with minimal multicollinearity issues. It was found to be a powerful tool in developing better selection strategies and optimizing the breeding scheme, thus contributing to the development of climate-resilient maize hybrids.

In most of developing countries, open dumpsites are frequently opted as the best choice to get rid of waste, but this type of practice has severe threats to the environment. This may be considered as one of the factors in contamination of soil and groundwater. The study examined the arsenic and physicochemical properties of soil around a municipal waste dumpsite in Rohtak city, Haryana. For Rohtak city, leachate secretion and generation of various gases at landfill site may be a factor in contamination of soil around the dumpsite. 13 samples of soil were collected from the surrounding area of dumpsite within 2 km area. Soil samples were tested for various parameters like pH, EC, moisture content, bulk density, water holding capacity, organic matter, chloride and arsenic. The pH values of the various samples of different locations ranged from 7.14 to 8.34, EC ranged from 1034-9536 add μS/cm with a mean value of 3484 μS/cm, organic matter of the soil samples of present study ranged from 1.26 to 3.16%. Water holding capacity of soil samples ranged from 51.02% to 59.14%, moisture content was found from 3.12 to 13.86%, bulk density was found from 1.28-1.89 g/cm³. Range of chloride content was 358-4165 mg/ kg with mean value 1679 mg/kg. Higher level of arsenic contamination is found in the surrounding soil samples, ranged from 410 ppb to 840 ppb with mean value of 618 ppb which may be due to leachate secretion at dumpsite area that make soil unsuitable for agricultural purposes. [ABSTRACT FROM AUTHOR]

Simple Summary: Triple-negative breast cancer (TNBC) is characterized by the absence of estrogen receptors, progesterone receptors, and human epidermal receptors. This lack of receptors renders TNBC unsuitable for targeted-based treatment, making it the most fatal and aggressive subtype of breast cancer. TNBC has a greater relapse rate, worse prognosis, and increased metastasis rate compared to non-TNBC because of its tendency to resist apoptosis, a programmed cell death triggered by most chemotherapeutic drugs, producing anticancer efficacy. This work describes two new drugs, TPH104c, and TPH104m, that induce a non-apoptotic form of cell death in TNBC. The incubation of TNBC cells with TPH104c or TPH104m causes cellular expansion and rupture without producing apoptotic characteristics, such as nuclear fragmentation, apoptotic blebbing, or caspase activation. TPH104c and TPH104m decreased the mitochondrial protein, division regulator, and dynamin-related protein 1 (DRP1). The level of DRP1 in TNBC cells affects the magnitude of cytotoxicity produced by TPH104c and TPH104m. Apoptosis induction with taxanes or anthracyclines is the primary therapy for TNBC. Cancer cells can develop resistance to anticancer drugs, causing them to recur and metastasize. Therefore, non-apoptotic cell death inducers could be a potential treatment to circumvent apoptotic drug resistance. In this study, we discovered two novel compounds, TPH104c and TPH104m, which induced non-apoptotic cell death in TNBC cells. These lead compounds were 15- to 30-fold more selective in TNBC cell lines and significantly decreased the proliferation of TNBC cells compared to that of normal mammary epithelial cell lines. TPH104c and TPH104m induced a unique type of non-apoptotic cell death, characterized by the absence of cellular shrinkage and the absence of nuclear fragmentation and apoptotic blebs. Although TPH104c and TPH104m induced the loss of the mitochondrial membrane potential, TPH104c- and TPH104m-induced cell death did not increase the levels of cytochrome c and intracellular reactive oxygen species (ROS) and caspase activation, and cell death was not rescued by incubating cells with the pan-caspase inhibitor, carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]-fluoromethylketone (Z-VAD-FMK). Furthermore, TPH104c and TPH104m significantly downregulated the expression of the mitochondrial fission protein, DRP1, and their levels determined their cytotoxic efficacy. Overall, TPH104c and TPH104m induced non-apoptotic cell death, and further determination of their cell death mechanisms will aid in the development of new potent and efficacious anticancer drugs to treat TNBC. [ABSTRACT FROM AUTHOR]

β-secretase 1, one of the most important proteins, is an aspartate protease. This membrane-associated protein is used for treating Alzheimer's disease (AD). Several inhibitors have been pursued against β-secretase 1, but they still have not resulted effectively. Virtual screening based on pharmacophores has been shown to be useful for lead optimization and hit identification in the preliminary phase of developing a new drug. Here, we screen the commercially available databases to find the hits against β-secretase 1 for drug discovery against AD. Virtual screening for 200,000 compounds was done using the database from the Vitas-M Laboratory. The phase screen score was utilized to assess the screened hits. Molecular docking was performed on compounds with phase scores >1.9. According to the study, the 66H ligand of the crystal structure has the maximum performance against β-secretase 1. The redocking of the co-crystal ligand showed that the docked ligand was seamlessly united with the crystal structure. The reference complex had three hydrogen bonds with Asp93, Asp289, and Gly291; one van der Waals interaction with Gly74; and three hydrophobic interactions. After equilibration, the RMSD of the reference compound sustained a value of ~1.5 A until 30 ns and then boosted to 2.5 A. On comparison, the RMSD of the S1 complex steadily increased to ~2.5 A at 15 ns, displayed slight aberrations at approximately ~2.5-3 A until 80 ns, and then achieved steadiness toward the end of the simulation. The arrangements of proteins stayed condensed during the mockup when bonded to these complexes as stable Rg values showed. Furthermore, the MM/GBSA technique was employed to analyze both compounds' total binding free energies ^Gtotal). Our research study provides a new understanding of using 66H as anti-βsecretase 1 for drug development against AD. [ABSTRACT FROM AUTHOR]

Dendrites are tree-like structures with tiny spines specialized to receive excitatory synaptic transmission. Spino-dendritic plasticity, driven by neural activity, underlies the maintenance of neuronal connections crucial for proper circuit function. Abnormalities in dendritic morphology are frequently seen in epilepsy. However, the exact etiology or functional implications are not yet known. Therefore, to better comprehend the structure-function significance of this dendritic pathology in epilepsy, it is necessary to identify the common spino-dendritic disturbances present in both human and experimental models. Here, we describe the dendritic and spine structural profiles found across human refractory epilepsy as well as in animal models of developmental, acquired, and genetic epilepsies. [ABSTRACT FROM AUTHOR]

HLA‐B*13:01:01:12 differs from HLA‐B*13:01:01:01 by a single nucleotide. [ABSTRACT FROM AUTHOR]

We have studied the nonlinear interaction between two different eigen modes in suspended carbon nanotube resonators. It was found that the mode coupling in suspended carbon nanotubes was dominated by single electron-tunneling process. For suspended carbon nanotube resonator at low temperatures using quantum dot embedded in the nanotube as detector, the interaction was found between two different eigen modes. For nanotube resonators in the coulomb blockade regime the nonlinear modal interaction was dominated by single electron tunneling as opposed to displacement induced tension. A strongly enhanced mode coupling was observed in the coulomb blockade regime which was of the order of magnitude larger than in conventional micro resonators. The obtained results found in good agreement with previously obtained results. [ABSTRACT FROM AUTHOR]

Medicinal plants are rich in bioactive components that are utilized to treat various human ailments. They are crucial to healing as well. Phytochemical constituents are responsible for the medicinal activity of plant species. Phytochemical screening is an important step in identifying bioactive compounds present in particular medicinal plants. Hence, in this present work, phytochemical screening of leaf extract of some traditional medicinal plants, namely Cannabis sativa, Ricinus communis, and Bryophyllum pinnatum was carried out. The solvent extracts of the leaves of respective plants were prepared using the Soxhlet apparatus with acetone, chloroform, petroleum ether, and aqueous solvents. Qualitative phytochemical analysis of plants included tests for reducing sugars, flavonoids, steroids, glycosides, polyphenols, tannins, terpenoids, and coumarins. All eight tested phytoconstituents were found present in all three plants in any solvent extracts. Aqueous extract confirmed the presence of a maximum number of phytoconstituents in C. sativa in comparison to other solvents. Acetone confirmed the maximum and chloroform confirmed the minimum number of phytoconstituents in R. communis, while chloroform confirmed the maximum and aqueous extract confirmed the minimum number of phytoconstituents in B. pinnatum. These phytochemicals may be a source of innovative plant-based medications because their existence is connected with the therapeutic potential of these plants. [ABSTRACT FROM AUTHOR]