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Background: The recent outbreak of the novel SARS-CoV-2 across the globe and the absence of specific drug against this virus lead the scientific community to look into some alternative indigenous treatments. India as a hub of Ayurvedic and medicinal plants can shed light on its treatment using specific active bio-molecules from these plants. Objectives: Keeping our herbal resources in mind, we were interested to inquire whether some phytochemicals from Indian spices and medicinal plants can be used as alternative therapeutic agents in contrast to synthetic drugs. Materials and methods: We used in silico molecular docking approach to test whether bioactive molecules of herbal origin such as hyperoside, nimbaflavone, ursolic acid, 6-gingerol, 6-shogaol and 6-paradol, curcumin, catechins and epigallocatechin, α-Hederin, piperine could bind and potentially block the Mproenzyme of the SARS-CoV-2 virus. Results: Ursolic acid showed the highest docking score (−8.7 kcal/mol) followed by hyperoside (−8.6 kcal/mol), α-Hederin (−8.5 kcal/mol) and nimbaflavone (−8.0 kcal/mol). epigallocatechin, catechins, and curcumin also exhibited high binding affinity (Docking score −7.3, −7.1 and −7.1 kcal/mol) with the Mpro. The remaining tested phytochemicals exhibited moderate binding and inhibitory effects. Conclusion: This finding provides a basis for biochemical assay of tested bioactive molecules on SARS-CoV-2 virus.

Maternal risk factors and their interactions with each other that associate chromosome 21 nondisjunction are intriguing and need incisive study to be resolved. We determined recombination profile of nondisjoined chromosome 21 and maternal genotypes for four selected polymorphic variants from the folate regulators genes stratifying the women according to the origin of segregation error and age at conception. We conducted association study for genotype and maternal addiction to smokeless chewing tobacco, usually chopped tobacco leaves or paste of tobacco leaves with the incidence of Down syndrome birth. Additionally, we designed various logistic regression models to explore the effects of maternal genotype, maternal habit of smokeless chewing tobacco, maternal age at conception and all possible interactions among them on chromosome 21 nondisjunction. We found folate regulator gene mutations are associated with maternal meiosis II error. Regression models revealed smokeless chewing tobacco and folate polymorphic/mutant risk genotype interact with each other to increase the risk of reduced and single peri-centromeric recombination events on chromosome 21 that nondisjoined at meiosis II in the oocytes and the effect is maternal age independent. We inferred maternal folate polymorphic/mutant risk genotypes and habit of smokeless chewing tobacco interact with each other and increase the risk of meiosis II error in oocytes in maternal age-independent manner.

Maternal risk factors and their interactions with each other that associate chromosome 21 nondisjunction are intriguing and need incisive study to be resolved. We determined recombination profile of nondisjoined chromosome 21 and maternal genotypes for four selected polymorphic variants from the folate regulators genes stratifying the women according to the origin of segregation error and age at conception. We conducted association study for genotype and maternal habit of smoke less chewing tobacco with the incidence of Down syndrome birth. Additionally, we designed various logistic regression models to explore the effects of genotype, smokeless chewing tobacco habit, maternal age at conception and all possible interactions among them on chromosome 21 nondisjunction. We found folate regulator gene mutations are associated with maternal meiosis II error. Regression models revealed smokeless chewing tobacco and folate regulator mutant genotypes interact with each other to increase the risk of reduced and peri-centromeric recombination events on chromosome 21 that nondisjoined at meiosis II in the oocytes and the effect is maternal age independent. We inferred maternal polymorphic genotypes and habit of smokeless chewing tobacco interact with each other and increase the risk of meiosis II error in oocytes in maternal age-independent manner.

Background The recent outbreak of novel SARs CoVid-2 across the globe and absence of specific drug against this virus lead the scientific community to look into some alternative indigenous treatments. India as a hub of ayurvedic and medicinal plants can shed light on its treatment using specific active bio-molecules from these plants. Objectives Keeping our herbal resources in mind we were interested to inquire whether some phytochemicals from Indian spices and medicinal plants can be used as alternative therapeutic agents in contrast to synthetic drugs. Materials and methods We used in-silico molecular docking approach to test whether bioactive molecules of herbal origin such as Hyperoside, Nimbaflavone, Ursolic acid, 6-gingerol, 6-shogaol& 6-paradol, Curcumin, Catechins&Epigallocatechin, α-Hederin, Piperine could bind and potentially block theMproenzyme of Sars-CoV-2 virus. Results Ursolic acid showed the highest docking score (-8.7 kcal/mol) followed by Hyperoside (-8.6kcal/mol), α-Hederin (-8.5 kcal/mol) and Nimbaflavone (-8.0kcal/mol). Epigallocatechin, Catechins, and Curcumin also exhibited high binding affinity (Docking score -7.3, -7.1 and -7.1 kcal/mol) with the Mpro. Rest of the tested phytochemicals exhibited moderate binding and inhibitory effects. Conclusion This finding provides a basis for biochemical assay on Sars-CoV-2 virus.

Altered patterns of recombination on 21q have long been associated with the nondisjunction chromosome 21 within oocytes and the increased risk of having a child with Down syndrome. Unfortunately the genetic etiology of these altered patterns of recombination have yet to be elucidated. We for the first time genotyped the gene MCM9, a candidate gene for recombination regulation and DNA repair in mothers with or without children with Down syndrome. In our approach, we identified the location of recombination on the maternal chromosome 21 using short tandem repeat markers, then stratified our population by the origin of meiotic error and age at conception. We observed that twenty-five out of forty-one single nucleotide polymorphic sites within MCM9 exhibited an association with meiosis I error (N = 700), but not with meiosis II error (N = 125). This association was maternal age-independent. Several variants exhibited aprotective association with MI error, some were neutral. Maternal age stratified characterization of cases revealed that MCM9 risk variants were associated with an increased chance of reduced recombination on 21q within oocytes. The spatial distribution of single observed recombination events revealed no significant change in the location of recombination among women harbouring MCM9 risk, protective, or neutral variant. Additionally, we identified a total of six novel polymorphic variants and two novel alleles that were either risk imparting or protective against meiosis I nondisjunction. In silico analyses using five different programs suggest the risk variants either cause a change in protein function or may alter the splicing pattern of transcripts and disrupt the proportion of different isoforms of MCM9 products within oocytes. These observations bring us a significant step closer to understanding the molecular basis of recombination errors in chromosome 21 nondisjunction within oocytes that leads to birth of child with Down syndrome., Author summary We studied MCM9 variations in the genome of women with a Down syndrome child by stratifying the women based on MCM9 genotypes, meiotic error group, and their age of conception. We identified polymorphisms are associated with reduced recombination and nondisjunction of chromosome 21 at the meiosis I stage of oogenesis in a maternal age-independent manner. But these variants do not affect the position of chiasma formation. In Silico analyses revealed the presence of MCM9 variants that may cause alteration in protein function due to amino acid substitution. We also identified splice variants in MCM9. We hypothesize that the polymorphisms in MCM9 predispose women to experience reduced recombination on chromosome 21 in oocytes at meiosis I, which ultimately leads to the birth of a child with Down syndrome.

Background: People with Down syndrome (DS) are one of the highest risk groups for mortality associated with COVID-19, but outcomes may differ across countries due to different co-morbidity profiles, exposures, and societal practices, which could have implications for disease management. This study is designed to identify differences in clinical presentation, severity, and treatment of COVID-19 between India and several high-income countries (HICs). Methods: We used data from an international survey to examine the differences in disease manifestation and management for COVID-19 patients with DS from India vs HIC. De-identified survey data collected from April 2020 to August 2021 were analysed. Results: COVID-19 patients with DS from India were on average nine years younger than those from HICs. Comorbidities associated with a higher risk for severe COVID-19 were more frequent among the patients from India than from HICs. Hospitalizations were more frequent among patients from India as were COVID-19-related medical complications. Treatment strategies differed between India and HICs, with more frequent use of antibiotics in India. The average severity score of 3.31 was recorded for Indian DS in contrast to 2.3 for European and 2.04 for US cases. Conclusions: Presentation and outcomes of COVID-19 among individuals with DS were more severe for patients from India than for those from HIC. Global efforts should especially target vaccination campaigns and other risk-reducing interventions for individuals with DS from low-income countries. PH is supported by University Grant Commission, India (UGC/21/06/2015 (i)EU-V). SG is supported by Government of West Bengal (DST, WB) Grant No. SG/WBDST/S&T 1000114/2016 and UGC-UPEII, DST-PURSE programs (Grant No. UGC/859/UPE-2 BIO). AH is supported by the HERCULES Center (NIEHS P30ES019776) and the LuMind IDSC Foundation. The REDCap survey and database management system at Emory University was supported by Library Information Technology Services grant support (UL1 TR000424). ACSC is supported by the Alana USA Foundation, Awakening Angels Foundation, and the Infectious Diseases Society of America (IDSA). MD is supported by the Centre for Genomic Regulation Severo Ochoa excellence grant, the CIBER of Rare Diseases, DURSI 2017SGR595, and acknowledges the Spanish Ministry of Science, Innovation and Universities (MSIU) to the EMBL partnership, the Centro de Excelencia Severo Ochoa and CERCA (GenCat). AS is supported by the MRC (MR/ S011277/1; MR/S005145/1; MR/R024901/1), Lumind IDSC, The LeJeune Foundation and the European Commission (H2020 SC1 Gene overdosage and comorbidities during the early lifetime in Down syndrome GO-DS21- 848077). ML was supported by the National Institute for Health Research (NIHR) Biomedical Research Centre based at UCL Great Ormond Street Institute of Child Health/Great Ormond Street Hospital NHS Foundation Trust). DRdeA was partially supported by Spanish Fondo de Investigacion Sanitaria-Instituto Carlos III (FIS-ISCIII), grant No. PI19/00634; BAC has research support from Various Grateful Families of Patients. The Research Programme on Biomedical Informatics (GRIB) is a member of the Spanish National Bioinformatics Institute (INB), funded by ISCIII and EDER (PT17/0009/ 0014). The DCEXS is a ‘Unidad de Excelencia Marí a de Maeztu’, funded by the AEI (CEX2018-000782-M). The GRIB is also supported by the Agencia de G d ’AjutsUniversitarisi de Recerca (AGAUR), Generalitat de Catalunya (2017 SGR 00519). This study was also supported by the Fondo de InvestigacionesSanitario (FIS), Instituto de Salud Carlos III (PI18/00335 to MCI, PI14/ 01126 and PI17/01019 to JF), partly jointly funded by Fondo Europeo de Desarrollo Regional, Union Europea, Una manera de hacer Europa; the Jerome Lejeune Foundation (No.1319 Cycle 2019B to MCI); the National Institutes of Health (NIA grants 1R01AG056850 – 01A1; R21AG056974 and R01AG061566 to JF); Departament de Salut de la Generalitat de Catalunya, PlaEstrategic de RecercaiInnovaci o enSalut (SLT006/17/00119 to JF); and Fundacio La Marat o de TV3 (20141210 to JF).