Under pressure from neutralising antibodies induced by vaccination or infection the SARS-CoV-2 spike gene has become a hotspot for evolutionary change, leading to the failure of all mAbs developed for clinical use. Most potent antibodies bind to the receptor binding domain which has become heavily mutated. Here we study responses to a conserved epitope in sub-domain-1 (SD1) of spike which have become more prominent because of mutational escape from antibodies directed to the receptor binding domain. Some SD1 reactive mAbs show potent and broad neutralization of SARS-CoV-2 variants. We structurally map the dominant SD1 epitope and provide a mechanism of action by blocking interaction with ACE2. Mutations in SD1 have not been sustained to date, but one, E554K, leads to escape from mAbs. This mutation has now emerged in several sublineages including BA.2.86, reflecting selection pressure on the virus exerted by the increasing prominence of the anti-SD1 response.

Hypoxia is mainly caused by cardiopulmonary disease or high-altitude exposure. We used a driving simulator to investigate whether breathing hypoxic gas influences driving behaviors in healthy subjects. Fifty-two healthy subjects were recruited in this study, approved by the Science and Engineering Ethical Committee. During simulated driving experiments, driving behaviors, breathing frequency, oxygen saturation (SpO2 ), and heart rate variability (HRV) were analyzed. Each subject had four driving sessions; a 10-min practice and three 20-min randomized interventions: normoxic room air (21% FIO2 ) and medical air (21% FIO2 ) and hypoxic air (equal to 15% FIO2 ), analyzed by repeated measures ANOVA. Driving behaviors and HRV frequency domains showed no significant change. Heart rate (HR; p < 0.0001), standard deviation of the RR interval (SDRR; p = 0.03), short-term HRV (SD1; p < 0.0001), breathing rate (p = 0.01), and SpO2 (p < 0.0001) were all significantly different over the three gas interventions. Pairwise comparisons showed HR increased during hypoxic gas exposure compared to both normoxic interventions, while SDRR, SD1, breathing rate, and SpO2 were lower. Breathing hypoxic gas (15% FiO2 , equivalent to 2710 m altitude) may not have a significant impact on driving behavior in healthy subjects. Furthermore, HRV was negatively affected by hypoxic gas exposure while driving suggesting further research to investigate the impact of breathing hypoxic gas on driving performance for patients with autonomic dysfunction.

The 'Improved White Ponni' (IWP) rice variety, which is susceptible to lodging, leading to yield losses. Our primary goal is to develop new rice lines with non-lodging traits, enhancing stem strength and resistance to adverse conditions. Additionally, we aim to improve yield-contributing agronomic traits, benefiting farmers, food security, and the environment. Our work contributes to scientific knowledge and addresses a significant issue in Southern Indian rice cultivation. In the present study, early and semi-dwarf early mutants of IWP were developed without altering the native grain quality traits using gamma ray-mediated mutagenesis. The seeds (500) were irradiated with γ-rays after fixing the Lethal Dose 50 (LD50), and selection for semi-dwarfism and earliness was imposed on a large M2 population. The selected traits were confirmed by evaluating the M3 lines at morpho-physiological, biochemical, and molecular levels. The response of mutants to gibberellic acid has been studied, which identified responsive mutants as well as slow-responding mutant lines including IWP-11-2, IWP-48-2, IWP-50-11, and IWP-33-2. Agar plate assay indicated low α- amylase content in IWP-50-11, IWP-33-2, IWP-43-1, IWP-47-2, and IWP-18-1. The scanning electron microscopy demonstrated that the mutants displayed an increased cellular dimension in comparison to the wild type. In dwarf mutants, null alleles were observed for the SD1 gene-specific primers which depicts gene undergone mutation. Further sequencing revealed the presence of single nucleotide polymorphisms in the SD1 gene resulting in semi-dwarfism in the mutant IWP-D-1. The impact of a defective gibberellic acid-mediated signaling pathway in mutants to produce a novel high-yielding and early maturing semi-dwarf rice variety.

This longitudinal study aimed to analyze the influence of physical activity (PA) on the relationship between body adiposity and cardiac autonomic modulation (CAM) in women survivors of breast cancer. We collected body adiposity through electrical bioimpedance considering body fat percentage (BFP), CAM through heart rate variability (considering RMSSD, SDNN, PNN50, LF (m2), HF (m2), SD1 indexes and SD1/SD2 ratio) and PA through a questionnaire in 64 participants (58.0 ± 9.6 years), recruited through the local association of support for breast cancer and by direct indications from city mastologists. After insertion of PA into the multivariate statistical model, significant attenuation was observed in the relationship between body adiposity and CAM for the indices: SDNN (β = -0.94; 95 percent CI: -1.93; 0.04; p = .060) and SD1/SD2 (β = -0.01;95 percent CI = -0.02; 0.001; p = .065). In conclusion, it was observed that PA was able to mitigate the relationships between BFP and CAM (considering SDNN index and SD1/SD2 ratio) in breast cancer survivors.

Familial hypobetalipoproteinemias (FHBL) are rare genetic diseases characterized by lipid malabsorption. We focused on abetalipoproteinemia (FHBL-SD1) and chylomicron retention disease (FHBL-SD3), caused by mutations in microsomal triglyceride transfer protein (MTTP) and SAR1B genes, respectively. Treatments include a low-fat diet and high-dose fat-soluble vitamin supplementations. However, patients are not supplemented in carotenoids, a group of lipid-soluble pigments essential for eye health. Our aim was to evaluate carotenoid absorption and status in the context of hypobetalipoproteinemia. We first used knock-out Caco-2/TC7 cell models of FHBL-SD1 and FHBL-SD3 to evaluate carotenoid absorption. We then characterized FHBL-SD1 and FHBL-SD3 patient status in the main dietary carotenoids and compared it to that of control subjects. In vitro results showed a significant decrease in basolateral secretion of α- and β-carotene, lutein, and zeaxanthin (-88.8 ± 2.2 % to -95.3 ± 5.8 %, -79.2 ± 4.4 % to -96.1 ± 2.6 %, -91.0 ± 4.5 % to -96.7 ± 0.3 % and -65.4 ± 3.6 % to -96.6 ± 1.9 %, respectively). Carotenoids plasma levels in patients confirmed significant deficiencies, with decreases ranging from -89 % for zeaxanthin to -98 % for α-carotene, compared to control subjects. Given the continuous loss in visual function despite fat-soluble vitamin treatment in some patients, carotenoid supplementation may be of clinical utility. Future studies should assess the correlation between carotenoid status and visual function in aging patients and investigate whether carotenoid supplementation could prevent their visual impairment.