Metabotyping of docosahexaenoic acid - Treated alzheimer's disease cell model

10.1371/journal.pone.0090123PLoS ONE92-POLN

SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion

Abstract: The B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)1. In vitro, B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and eightfold less sensitive to vaccine-elicited antibodies, compared with wild-type Wuhan-1 bearing D614G. Serum neutralizing titres against B.1.617.2 were lower in ChAdOx1 vaccinees than in BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies to the receptor-binding domain and the amino-terminal domain. B.1.617.2 demonstrated higher replication efficiency than B.1.1.7 in both airway organoid and human airway epithelial systems, associated with B.1.617.2 spike being in a predominantly cleaved state compared with B.1.1.7 spike. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike. We also observed that B.1.617.2 had higher replication and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 130 SARS-CoV-2-infected health care workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era

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Not AvailableBipolaris with Bipolaris maydis as type species is well known pathogen causing serious diseases i.e. Brown spot of rice [B. oryzae (Breda de Haan) Shoemaker], Brown stripe of sugarcane [B.stenospila (Drechsler) Shoemaker] and Southern leaf blight [B. maydis (Nisikado and Miyake) Shoemaker] of maize. Identification of organism is very difficult both by morphology and molecular. There have been no much studies to identify potential gene regions to group different Bipolaris species. In present investigation, 24 Bipolaris isolates belonging to five different species were used for multi regions (ITS, tef-1, β-tubulin, LSU and SSU) phylogenetic analysis to know the potential region to cluster the same species. ITS was found to be the best in species discrimination followed by tef-1and β-tubulin. LSU and SSU were unable to segregate Bipolaris species.Not Availabl

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Not AvailableFourty-two sporulating isolates of Drechslera, Helminthosporium, Bipolaris and Exserohilum obtained from Indian Type Culture Collection, New Delhi were used in this study. Macroscopic and microscopic studies revealed that, the isolates were assembled into two major groups and three sub-groups; there was a lot of variation in the cultural characters.In group I (28 isolates) aerial mycelium was fluffy, cottony and whitish gray in colour and there was wide variation in radial growth of the isolates [8.45 cm in D19 to 2.2 cm in D7]. In group II (14 isolates), most of the cultures were black in colour and texture was smooth in which radial growth was highest in E7 (8.65 cm) and lowest in D42 (6.25 cm). It was found that germination from two or more cells of conidia separates Drechslerafrom Bipolaris and Exserohilum. Whereas, presence of strongly protuberant hilum structure differentiates between Exserohilum and Bipolaris isolates. Thirteen of the isolates having strongly protuberant hilum structure were grouped into the genus Exserohilum. Remaining 29 isolates were considered as the genus Bipolaris group with no protuberant hilum.Not Availabl

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Not AvailableBipolaris with Bipolaris maydis as type species is well known pathogen causing serious diseases i.e. Brown spot of rice [B. oryzae (Breda de Haan) Shoemaker], Brown stripe of sugarcane [B.stenospila (Drechsler) Shoemaker] and Southern leaf blight [B. maydis (Nisikado and Miyake) Shoemaker] of maize. The identification of organism is very difficult both by morphology and molecular. There have been no such studies to identify potential gene regions to group different Bipolaris species. In the present investigation, 24 Bipolaris isolates belonging to five different species were used for multi regions (ITS, tef-1, β-tubulin, LSU and SSU) phylogenetic analysis to know the potential region to cluster the same species. ITS was found to be the best in species discrimination followed by tef-1and β-tubulin. LSU and SSU were unable to segregate Bipolaris species.Not Availabl

Cerebrospinal fluid from amyotrophic lateral sclerosis patients causes fragmentation of the Golgi apparatus in the neonatal rat spinal cord

We have previously shown in our laboratory that cerebrospinal fluid from ALS patients (ALS-CSF) contains putative toxic factor(s). In the present study we determined the effect of ALS-CSF on the integrity of the Golgi apparatus of spinal motor neurons in the neonatal rats. CSF was injected intrathecally into three-day-old rat pups and subsequently the ultrastructural changes in the motor neurons were studied after 48 h, 1, 2 and 3 weeks. We observed that ALS-CSF causes fragmentation of the Golgi apparatus in a considerable number of motor neurons in the spinal cord. This was further confirmed when motor neurons were stained with an antibody against a medial Golgi protein (MG160). Thus, we suggest that the putative toxin(s) present in ALS-CSF may cause impairment in the protein processing leading to motor neuron deat

(−)-Deprenyl alleviates the degenerative changes induced in the neonatal rat spinal cord by CSF from amyotrophic lateral sclerosis patients

Previous studies from our laboratory suggest the presence of toxic factor(s) in the cerebrospinal fluid (CSF) of patients with amyotrophic lateral sclerosis (ALS) which induces degenerative changes in the spinal cord neurons. The present work was carried out to investigate the role of (−)-deprenyl in attenuating these degenerative changes. CSF samples from ALS and non-ALS neurological patients were injected into the spinal subarachnoid space of 3-day-old rat pups, followed by a single dose (0.01/mg/kg body weight) of (−)-deprenyl, administered 24 h after CSF injection. After a further period of 24 h, the rats were sacrificed and the spinal cord sections were stained with antibodies against phosphorylated neurofilament (NF, SMI-31 antibody) and glial fibrillary acidic protein (GFAP). Activity of lactate dehydrogenase (LDH) was also measured. (−)-Deprenyl injection resulted in a significant (61%) decrease in the number of SMI-31 stained neuronal soma in the ventral horn of the spinal cord of ALS CSF exposed rats. This was accompanied by a reduction in the astrocytes immunoreactive for GFAP. There was also a significant (35%) decrease in the LDH activity following (−)-deprenyl treatment. These results suggest that (−)-deprenyl may confer neuroprotection against the toxic factor(s) present in ALS CSF

BA.1, BA.2 and BA.2.75 variants show comparable replication kinetics, reduced impact on epithelial barrier and elicit cross-neutralizing antibodies.

The Omicron variant of SARS-CoV-2 is capable of infecting unvaccinated, vaccinated and previously-infected individuals due to its ability to evade neutralization by antibodies. With multiple sub-lineages of Omicron emerging in the last 12 months, there is inadequate information on the quantitative antibody response generated upon natural infection with Omicron variant and whether these antibodies offer cross-protection against other sub-lineages of Omicron variant. In this study, we characterized the growth kinetics of Kappa, Delta and Omicron variants of SARS-CoV-2 in Calu-3 cells. Relatively higher amounts infectious virus titers, cytopathic effect and disruption of epithelial barrier functions was observed with Delta variant whereas infection with Omicron sub-lineages led to a more robust induction of interferon pathway, lower level of virus replication and mild effect on epithelial barrier. The replication kinetics of BA.1, BA.2 and BA.2.75 sub-lineages of the Omicron variant were comparable in cell culture and natural infection in a subset of individuals led to a significant increase in binding and neutralizing antibodies to the Delta variant and all the three sub-lineages of Omicron but the level of neutralizing antibodies were lowest against the BA.2.75 variant. Finally, we show that Cu2+, Zn2+ and Fe2+ salts inhibited in vitro RdRp activity but only Cu2+ and Fe2+ inhibited both the Delta and Omicron variants in cell culture. Thus, our results suggest that high levels of interferons induced upon infection with Omicron variant may counter virus replication and spread. Waning neutralizing antibody titers rendered subjects susceptible to infection by Omicron variants and natural Omicron infection elicits neutralizing antibodies that can cross-react with other sub-lineages of Omicron and other variants of concern

Data_Sheet_1_Dysregulated metal ion homeostasis underscores non-canonical function of CD8+ T cell during COVID-19.ZIP

IntroductionSeveral efforts have been made to describe the complexity of T cell heterogeneity during the COVID-19 disease; however, there remain gaps in our understanding in terms of the granularity within.MethodsFor this attempt, we performed a single-cell transcriptomic analysis of 33 individuals (4 healthy, 16 COVID-19 positive patients, and 13 COVID-19 recovered individuals).ResultsWe found CD8+ T cell-biased lymphopenia in COVID-19 patients compared to healthy and recovered individuals. We also found an optimal Th1/Th2 ratio, indicating an effective immune response during COVID-19. Expansion of activated CD4+ T and NK T was detected in the COVID-19-positive individuals. Surprisingly, we found cellular and metal ion homeostasis pathways enriched in the COVID-19-positive individuals compared to the healthy and recovered in the CD8+ T cell populations (CD8+ TCM and CD8+ TEM) as well as activated CD4+ T cells.DiscussionIn summary, the COVID-19-positive individuals exhibit a dynamic T cell mediated response. This response may have a possible association with the dysregulation of non-canonical pathways, including housekeeping functions in addition to the conventional antiviral immune response mediated by the T cell subpopulation. These findings considerably extend our insights into the heterogeneity of T cell response during and post-SARS-CoV-2 infection.</p

Clinico-Genomic Analysis Reveals Mutations Associated with COVID-19 Disease Severity: Possible Modulation by RNA Structure

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) manifests a broad spectrum of clinical presentations, varying in severity from asymptomatic to mortality. As the viral infection spread, it evolved and developed into many variants of concern. Understanding the impact of mutations in the SARS-CoV-2 genome on the clinical phenotype and associated co-morbidities is important for treatment and preventionas the pandemic progresses. Based on the mild, moderate, and severe clinical phenotypes, we analyzed the possible association between both, the clinical sub-phenotypes and genomic mutations with respect to the severity and outcome of the patients. We found a significant association between the requirement of respiratory support and co-morbidities. We also identified six SARS-CoV-2 genome mutations that were significantly correlated with severity and mortality in our cohort. We examined structural alterations at the RNA and protein levels as a result of three of these mutations: A26194T, T28854T, and C25611A, present in the Orf3a and N protein. The RNA secondary structure change due to the above mutations can be one of the modulators of the disease outcome. Our findings highlight the importance of integrative analysis in which clinical and genetic components of the disease are co-analyzed. In combination with genomic surveillance, the clinical outcome-associated mutations could help identify individuals for priority medical support