Delhi, the national capital of India, experienced multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreaks in 2020 and reached population seropositivity of >50% by 2021. During ...April 2021, the city became overwhelmed by COVID-19 cases and fatalities, as a new variant, B.1.617.2 (Delta), replaced B.1.1.7 (Alpha). A Bayesian model explains the growth advantage of Delta through a combination of increased transmissibility and reduced sensitivity to immune responses generated against earlier variants (median estimates: 1.5-fold greater transmissibility and 20% reduction in sensitivity). Seropositivity of an employee and family cohort increased from 42% to 87.5% between March and July 2021, with 27% reinfections, as judged by increased antibody concentration after a previous decline. The likely high transmissibility and partial evasion of immunity by the Delta variant contributed to an overwhelming surge in Delhi.
The ethnic diversity of India provides a unique opportunity to study the history of the origin of mutations of genetic disorders. Spinocerebellar ataxia type 27B (SCA27B), a recently identified ...dominantly inherited cerebellar disorder is caused by GAA-repeat expansions in intron 1 of Fibroblast Growth Factor 14 (FGF14). Predominantly reported in the European population, we aimed to screen this mutation and study the founder haplotype of SCA27B in Indian ataxia patients.BACKGROUNDThe ethnic diversity of India provides a unique opportunity to study the history of the origin of mutations of genetic disorders. Spinocerebellar ataxia type 27B (SCA27B), a recently identified dominantly inherited cerebellar disorder is caused by GAA-repeat expansions in intron 1 of Fibroblast Growth Factor 14 (FGF14). Predominantly reported in the European population, we aimed to screen this mutation and study the founder haplotype of SCA27B in Indian ataxia patients.We have undertaken screening of GAA repeats in a large Indian cohort of ~ 1400 uncharacterised ataxia patients and kindreds and long-read sequencing-based GAA repeat length assessment. High throughput genotyping-based haplotype analysis was also performed. We utilized ~ 1000 Indian genomes to study the GAA at-risk expansion alleles.METHODSWe have undertaken screening of GAA repeats in a large Indian cohort of ~ 1400 uncharacterised ataxia patients and kindreds and long-read sequencing-based GAA repeat length assessment. High throughput genotyping-based haplotype analysis was also performed. We utilized ~ 1000 Indian genomes to study the GAA at-risk expansion alleles.We report a high frequency of 1.83% (n = 23) of SCA27B in the uncharacterized Indian ataxia cohort. We observed several biallelic GAA expansion mutations (n = 5) with younger disease onset. We observed a risk haplotype (AATCCGTGG) flanking the FGF14-GAA locus over a 74 kb region in linkage disequilibrium. We further studied the frequency of this risk haplotype across diverse geographical population groups. The highest prevalence of the risk haplotype was observed in the European population (29.9%) followed by Indians (21.5%). The observed risk haplotype has existed through ~ 1100 generations (~ 22,000 years), assuming a correlated genealogy.FINDINGSWe report a high frequency of 1.83% (n = 23) of SCA27B in the uncharacterized Indian ataxia cohort. We observed several biallelic GAA expansion mutations (n = 5) with younger disease onset. We observed a risk haplotype (AATCCGTGG) flanking the FGF14-GAA locus over a 74 kb region in linkage disequilibrium. We further studied the frequency of this risk haplotype across diverse geographical population groups. The highest prevalence of the risk haplotype was observed in the European population (29.9%) followed by Indians (21.5%). The observed risk haplotype has existed through ~ 1100 generations (~ 22,000 years), assuming a correlated genealogy.This study provides valuable insights into SCA27B and its Upper Paleolithic origin in the Indian subcontinent. The high occurrence of biallelic expansion is probably relevant to the endogamous nature of the Indian population.INTERPRETATIONThis study provides valuable insights into SCA27B and its Upper Paleolithic origin in the Indian subcontinent. The high occurrence of biallelic expansion is probably relevant to the endogamous nature of the Indian population.
The cobalt oxide (Co3O4) nanomaterials were prepared by coprecipitation synthesis technique by maintaining the pH of the mother solution at 7, 8, and 9. The prepared nanomaterials were subjected to ...structural and optical characterizations, and the results were examined. The optical absorption spectral studies reveal that the two absorption bands indicate ligand–metal coordination. The photoluminescence spectra contain emission peak at 488 and 745 nm due to size and shape of the synthesized materials. The magnetic nature of the samples was identified from the hysteresis loop traced by vibrating sample magnetometry (VSM). The Fourier transform infrared (FT-IR) spectrum of Co3O4 nanomaterials reveals two sharp bands absorbed in 584 and 666 cm-1. This ascribes to the Co-O and O-Co-O stretching, respectively. As the pH of the solution varied from 7 to 10, the SEM image authenticates the transformation of Co3O4 nanomaterials morphology from spherical to cubic to agglomerated shape. From the UV-Vis spectra, two absorption bands around 473 nm and 762 nm are observed for the materials prepared at pH 7 and 8. But at pH 9, these two peaks were shifted towards higher wavelengths 515 nm and 777 nm. The observed ferromagnetic nature of Co3O4 nanomaterials clearly show the role of surface spins and surface morphology on the magnetic properties of Co3O4 nanomaterials. The cyclic voltammetry (CV) curves show the rectangular type of voltammogram. This is an indication of good charge propagation with the electrodes. The Nyquist plots of Co3O4 nanomaterials have a semicircle in the high frequency region and a vertical line in the low frequency region. The results suggest that Co3O4 is found to be a promising material for the fabrication of light-emitting diodes, solar cells, and optoelectronic devices.
Co-infection with ancillary pathogens is a significant modulator of morbidity and mortality in infectious diseases. There have been limited reports of co-infections accompanying SARS-CoV-2 ...infections, albeit lacking India specific study. The present study has made an effort toward elucidating the prevalence, diversity and characterization of co-infecting respiratory pathogens in the nasopharyngeal tract of SARS-CoV-2 positive patients. Two complementary metagenomics based sequencing approaches, Respiratory Virus Oligo Panel (RVOP) and Holo-seq, were utilized for unbiased detection of co-infecting viruses and bacteria. The limited SARS-CoV-2 clade diversity along with differential clinical phenotype seems to be partially explained by the observed spectrum of co-infections. We found a total of 43 bacteria and 29 viruses amongst the patients, with 18 viruses commonly captured by both the approaches. In addition to SARS-CoV-2, Human Mastadenovirus, known to cause respiratory distress, was present in a majority of the samples. We also found significant differences of bacterial reads based on clinical phenotype. Of all the bacterial species identified, ∼60% have been known to be involved in respiratory distress. Among the co-pathogens present in our sample cohort, anaerobic bacteria accounted for a preponderance of bacterial diversity with possible role in respiratory distress.
Clostridium botulinum
,
Bacillus cereus
and
Halomonas
sp. are anaerobes found abundantly across the samples. Our findings highlight the significance of metagenomics based diagnosis and detection of SARS-CoV-2 and other respiratory co-infections in the current pandemic to enable efficient treatment administration and better clinical management. To our knowledge this is the first study from India with a focus on the role of co-infections in SARS-CoV-2 clinical sub-phenotype.
The monomer 1-(isopropylamino)-3-(1-naphthyloxy)-2-propanoacrylate (IANOPA) and monomer 1-(isopropylamino)-3-(1-naphthyloxy)-2-propanomethacrylate (IANOPMA) were synthesized by treating ...1-(isopropylamino)-3-(1-naphthyloxy)-2-propanol with acryloylchloride/methacryloyl chloride. The above esterification reactions were carried out in the presence of triethylamine. By employing the free radical polymerization method, the synthesized monomers were converted into polymers by using an initiator 2, 2′-azobisisobutyronitrile in the presence of nitrogen environment at 70±2°C. The monomers and polymers were characterized by various techniques such as FT-IR, UV, 1H NMR, and 13C NMR spectroscopic analyses. Further, differential scanning calorimetry (DSC) was used to estimate the glass transition temperature (Tg). Gel permeation chromatography (GPC) was used to estimate the molecular weight of the polymers. In addition, monomer and polymer surfaces’ morphology was analyzed using SEM analysis. As a primary application, the effectiveness of synthesized monomers and polymers was explored as antibacterial agents against gram-positive bacteria (Staphylococcus aureus) and gram-negative bacteria (Pseudomonas aeruginosa) which were measured from their inhibitory zone diameters. Further, the synthesized polymers, poly-IANOPA and poly-IANOPMA, were utilized for the uptake ability study of heavy metal ions such as Zn2+, Cu2+, Ni2+, and Pb2+ present in water sources by equilibrium method.
Of significant interest was the downregulation of MAL (MYD88 adaptor-like), an integral component of Toll-like receptor (TLR) signalling during pathogen invasion,7 and TRIM16, which regulates ...inflammasome activity through NLRP1-dependent production of IL-1B (Interleukin) and IL-18.8 ECM1, HSPB8, TGM3, TMPRSS11B, ITGA2, SLC20A2, ANXA11, S100A10 and IGFP3 were significantly downregulated in mortality patients, highlighting the possibility of a suboptimal innate immune response. Enrichment of pathways associated with antiviral inflammatory immune signalling (Figure 2D) and protein–protein interaction analysis highlighting the cellular stress response (Figure 2E,F) highlights the state of active defence in moderate patients and a suboptimal immune response in mortality. A possible counteractive effect is observed by the upregulation of HSPA1A, where HSPA1A leads to inhibition of-Nuclear factor kappa B (NF-κB)-regulated NLR family pyrin domain containing 3 (NLRP3) inflammasome activation, thereby preventing exacerbation of inflammation.10 The mechanism for the deregulated host response due to downregulation of MAL and TRIM16 in mortality patients is also depicted in Figure 4A.
Acetophenone derivatives are eco-friendly corrosion inhibitors to prevent corrosion of mild steel (MS) in acidic medium. In this work, the inhibition effect of 3-nitroacetophenone (3-NA) on the ...corrosion of MS in acidic medium (1 N HCl) was investigated using weight loss measurements, electrochemical measurements, scanning electron microscopy, energy-dispersive X-ray spectroscopy, and quantum chemistry analysis. The studies were performed using different concentrations of inhibitors and at different temperatures. The results indicated that the inhibition efficiency of 3-NA increases with an increase in inhibitor concentration and reaches to a maximum of 64% at inhibitor concentration of 250 ppm at 30°C. The potentiodynamic polarization measurement indicated that 3-NA acts as mixed category of interdict. The adsorption of 3-NA on MS surface followed the Langmuir adsorption isotherm. The mode of adsorption of 3-NA on MS surface was further studied by quantum chemical calculations based on density functional theory (DFT). The results plainly revealed that 3-NA performs fairly as corrosion interdict for MS in acidic medium.
India first detected SARS-CoV-2, causal agent of COVID-19 in late January 2020, imported from Wuhan, China. From March 2020 onwards, the importation of cases from countries in the rest of the world ...followed by seeding of local transmission triggered further outbreaks in India.
We used ARTIC protocol-based tiling amplicon sequencing of SARS-CoV-2 (n=104) from different states of India using a combination of MinION and MinIT sequencing from Oxford Nanopore Technology to understand how introduction and local transmission occurred.
The analyses revealed multiple introductions of SARS-CoV-2 genomes, including the A2a cluster from Europe and the USA, A3 cluster from Middle East and A4 cluster (haplotype redefined) from Southeast Asia (Indonesia, Thailand and Malaysia) and Central Asia (Kyrgyzstan). The local transmission and persistence of genomes A4, A2a and A3 was also observed in the studied locations. The most prevalent genomes with patterns of variance (confined in a cluster) remain unclassified, and are here proposed as A4-clade based on its divergence within the A cluster.
The viral haplotypes may link their persistence to geo-climatic conditions and host response. Multipronged strategies including molecular surveillance based on real-time viral genomic data is of paramount importance for a timely management of the pandemic.
Spinocerebellar Ataxia type-12 (SCA12) is a neurodegenerative disease caused by tandem CAG repeat expansion in the 5′-UTR/non-coding region of PPP2R2B. Molecular pathology of SCA12 has not been ...studied in the context of CAG repeats, and no appropriate models exist. We found in human SCA12-iPSC-derived neuronal lineage that expanded CAG in PPP2R2B transcript forms nuclear RNA foci and were found to sequester variety of proteins. Further, the ectopic expression of transcript containing varying length of CAG repeats exhibits non-canonical repeat-associated non-AUG (RAN) translation in multiple frames in HEK293T cells, which was further validated in patient-derived neural stem cells using specific antibodies. mRNA sequencing of the SCA12 and control neurons have shown a network of crucial transcription factors affecting neural fate, in addition to alteration of various signaling pathways involved in neurodevelopment. Altogether, this study identifies the molecular signatures of SCA12 disorder using patient-derived neuronal cell lines.
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•RNA foci are found in the patient-derived neural cell lines of SCA12•Expanded CAG in PPP2R2B transcript binds key nuclear proteins•Polyglutamine and polyserine RAN proteins are expressed in SCA12•IPA and mRNA sequencing analysis revealed affected pathways in SCA12
Molecular biology; Neuroscience
Twelve patients from seven unrelated South Indian families with a limb-girdle muscular dystrophy-congenital myasthenic syndrome (LGMD/CMS) phenotype and recessive inheritance underwent deep clinical ...phenotyping, electrophysiological evaluation, muscle histopathology, and next-generation sequencing/Sanger sequencing–based identification of the genetic defect. Homozygosity mapping was performed using high-throughput genome-wide genotyping for mapping the mutation and to evaluate the founder effect. The age of disease onset among patients ranged from childhood to 40 years of age. The key clinical manifestations observed were progressive fatigable limb-girdle weakness, muscle hypertrophy/atrophy, and preferential weakness in a dystrophic pattern. The ages at last follow-up ranged from 30 to 64 years; nine were independently ambulant, two required assistance, and one was wheelchair-bound. Lower limb muscle MRI showed varying degrees of fat replacement in the glutei, hamstrings, anterior leg muscles, and medial gastrocnemius. All patients showed significant decrement on repetitive nerve stimulation (RNS). Muscle biopsy in 7 patients revealed varying degrees of dystrophic and neurogenic changes. Treatment with pyridostigmine and/or salbutamol resulted in variable improvement in 10 patients. Genetic analysis showed an identical homozygous GMPPB mutation c.1000G > A (p.Asp334Asn) in all affected patients. A region of homozygosity (6Mbp) was observed flanking the c.1000G > A change in carrier chromosomes. This study identifies c.1000G > A in GMPPB as a common founder mutation in an ethnic community of South Indian descent with milder yet variable degree of clinical presentation of GMPPB-associated LGMD-CMS.