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

RNA Aptamers Rescue Mitochondrial Dysfunction in a Yeast Model of Huntington’s Disease

Huntington’s disease (HD) is associated with the misfolding and aggregation of mutant huntingtin harboring an elongated polyglutamine stretch at its N terminus. A distinguishing pathological hallmark of HD is mitochondrial dysfunction. Any strategy that can restore the integrity of the mitochondrial environment should have beneficial consequences for the disease. Specific RNA aptamers were selected that were able to inhibit aggregation of elongated polyglutamine stretch containing mutant huntingtin fragment (103Q-htt). They were successful in reducing the calcium overload, which leads to mitochondrial membrane depolarization in case of HD. In one case, the level of Ca2+ was restored to the level of cells not expressing 103Q-htt, suggesting complete recovery. The presence of aptamers was able to increase mitochondrial mass in cells expressing 103Q-htt, along with rescuing loss of mitochondrial genome. The oxidative damage to the proteome was prevented, which led to increased viability of cells, as monitored by flow cytometry. Thus, the presence of aptamers was able to inhibit aggregation of mutant huntingtin fragment and restore mitochondrial dysfunction in the HD cell model, confirming the advantage of the strategy in a disease-relevant parameter. Keywords: calcium homeostasis, intramers, membrane depolarization, mitochondrial mass, oxidative damage, reactive oxygen specie

Engineering novel synthetic strategy to develop mesocarbon microbeads for multi-functional applications

To assess the challenge of affordable technology, present synthetic strategies can be extended to new low-cost synthesis and processing methods that have potential to tailor the properties of the materials. Here we report, a novel method for the synthesis of mesocarbon microbeads (MCMB) through a preprocessing involved pyrolysis technique. The resulting MCMB is compressed into a product and effects of heat treatment temperature on different properties of MCMB is studied. The use of MCMB for the electromagnetic interference (EMI) shielding is new and hence, the effect of heat treatment temperature on EMI shielding effectiveness is studied in X-band. It is observed that EMI shielding effectiveness increases to -39.6 dB on increasing the heat treatment temperature. The high conductivity of MCMB plate heat treated up to 2500 degrees C contributes to highly conducting networks. Additionally, to investigate the electrochemical performance of MCMB as an anode material for lithium ion batteries, 2500 degrees C heat treated MCMB powder is used to fabricate the electrode. The MCMB electrode exhibits high discharge capacity of 345 mAh g(-1) with a stable capacity for over 50 cycles and good rate capability. Thus, MCMB synthesized by this novel approach can be used for the development of high performance anode materials for Li-ion batteries

Integration of MCMBs/MWCNTs with Fe3O4 in a flexible and light weight composite paper for promising EMI shielding applications

Insights into advances in portable and flexible electronic devices can be gained from the integration of magnetic nanoparticles with light weight and flexible conductive supports, especially in cases where the thickness of the material is challenging for future electromagnetic interference shielding applications. Here we report the fabrication of flexible shielding materials made up of Fe3O4 nanoparticles incorporated mesocarbon microbeads and multiwalled carbon nanotubes (MCMBs/MWCNTs) composite paper for efficient electromagnetic interference (EMI) shielding in the X-band frequency region (8.2-12.4 GHz). The incorporation of Fe3O4 nanoparticles in the MCMBs/MWCNTs composite paper significantly increases its interfacial polarization and anisotropy energy, which leads to an excellent absorption dominated EMI shielding effectiveness (SE) of -80 dB at 0.5 mm thickness. The composite paper also exhibits improved magnetic properties coupled with enhanced dielectric properties that increase with increasing concentration of Fe3O4 nanoparticles. Our measurements have provided a regime for designing conductive networks with advantages of light weight and flexibility, with promising EMI shielding applications

Copper-Catalyzed Tandem Synthesis of Indolo‑, Pyrrolo[2,1‑<i>a</i>]isoquinolines, Naphthyridines and Bisindolo/Pyrrolo[2,1‑<i>a</i>]isoquinolines via Hydroamination of <i>ortho</i>-Haloarylalkynes Followed by C‑2 Arylation

An efficient approach for the copper-catalyzed regioselective tandem synthesis of diversely substituted indolo­[2,1-<i>a</i>]­isoquinolines <b>11a</b>–<b>r</b>, pyrrolo­[2,1-<i>a</i>]­isoquinolines <b>12a</b>–<b>d</b>, and indolo-, pyrrolo­[2,1-<i>f</i>]­[1,6]­naphthyridines <b>14a</b>–<b>f</b> via preferential addition of the heterocyclic amines onto the <i>ortho</i>-haloarylalkynes over <i>N</i>-arylation followed by intramolecular C-2 arylation is described. The scope of the developed chemistry was successfully extended for the direct synthesis of bisindolo-, pyrrolo­[2,1-<i>a</i>]­isoquinolines <b>15a</b>–<b>g</b>, a regioisomer of the bisindolo­[1,2-<i>a</i>]­quinolines used as organic single-crystal field-effect transistor. Hydroxymethyl benzotriazole, which is an inexpensive and air stable compound, has been used as a ligand to carry out this one-step conversion of simple, readily available starting materials into an interesting class of heterocyclic compounds

Copper-Catalyzed Tandem Synthesis of Indolo‑, Pyrrolo[2,1‑<i>a</i>]isoquinolines, Naphthyridines and Bisindolo/Pyrrolo[2,1‑<i>a</i>]isoquinolines via Hydroamination of <i>ortho</i>-Haloarylalkynes Followed by C‑2 Arylation

An efficient approach for the copper-catalyzed regioselective tandem synthesis of diversely substituted indolo­[2,1-<i>a</i>]­isoquinolines <b>11a</b>–<b>r</b>, pyrrolo­[2,1-<i>a</i>]­isoquinolines <b>12a</b>–<b>d</b>, and indolo-, pyrrolo­[2,1-<i>f</i>]­[1,6]­naphthyridines <b>14a</b>–<b>f</b> via preferential addition of the heterocyclic amines onto the <i>ortho</i>-haloarylalkynes over <i>N</i>-arylation followed by intramolecular C-2 arylation is described. The scope of the developed chemistry was successfully extended for the direct synthesis of bisindolo-, pyrrolo­[2,1-<i>a</i>]­isoquinolines <b>15a</b>–<b>g</b>, a regioisomer of the bisindolo­[1,2-<i>a</i>]­quinolines used as organic single-crystal field-effect transistor. Hydroxymethyl benzotriazole, which is an inexpensive and air stable compound, has been used as a ligand to carry out this one-step conversion of simple, readily available starting materials into an interesting class of heterocyclic compounds

Copper-Catalyzed Tandem Synthesis of Indolo‑, Pyrrolo[2,1‑<i>a</i>]isoquinolines, Naphthyridines and Bisindolo/Pyrrolo[2,1‑<i>a</i>]isoquinolines via Hydroamination of <i>ortho</i>-Haloarylalkynes Followed by C‑2 Arylation

An efficient approach for the copper-catalyzed regioselective tandem synthesis of diversely substituted indolo­[2,1-<i>a</i>]­isoquinolines <b>11a</b>–<b>r</b>, pyrrolo­[2,1-<i>a</i>]­isoquinolines <b>12a</b>–<b>d</b>, and indolo-, pyrrolo­[2,1-<i>f</i>]­[1,6]­naphthyridines <b>14a</b>–<b>f</b> via preferential addition of the heterocyclic amines onto the <i>ortho</i>-haloarylalkynes over <i>N</i>-arylation followed by intramolecular C-2 arylation is described. The scope of the developed chemistry was successfully extended for the direct synthesis of bisindolo-, pyrrolo­[2,1-<i>a</i>]­isoquinolines <b>15a</b>–<b>g</b>, a regioisomer of the bisindolo­[1,2-<i>a</i>]­quinolines used as organic single-crystal field-effect transistor. Hydroxymethyl benzotriazole, which is an inexpensive and air stable compound, has been used as a ligand to carry out this one-step conversion of simple, readily available starting materials into an interesting class of heterocyclic compounds

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Not AvailableFive hundred and eighty hybrid parents, 320 R- and 260 B-lines, derived from 6 pearl millet breeding programs in India, genotyped following RAD-GBS (about 0.9 million SNPs) clustered into 12 R- and 7 B-line groups. With few excep- tions, hybrid parents of all the breeding programs were found distributed across all the marker-based groups suggesting good diversity in these programs. Three hundred and twenty hybrids generated using 37 (22 R and 15 B) representative parents, evaluated for grain yield at four locations in India, showed significant differences in yield, heterosis, and combining ability. Across all the hybrids, mean mid- and better-parent heterosis for grain yield was 84.0% and 60.5%, respectively. Groups G12 B × G12 R and G10 B × G12 R had highest heterosis of about 10% over best check hybrid Pioneer 86M86. The parents involved in heterotic hybrids were mainly from the groups G4R, G10B, G12B, G12R, and G13B. Based on the heterotic performance and combining ability of groups, 2 B-line (HGB-1 and HGB-2) and 2 R-line (HGR-1 and HGR-2) heterotic groups were identified. Hybrids from HGB-1 × HGR-1 and HGB-2 × HGR-1 showed grain yield heterosis of 10.6 and 9.3%, respectively, over best hybrid check. Results indicated that parental groups can be formed first by molecular markers, which may not predict the best hybrid combination, but it can reveal a practical value of assigning existing and new hybrid pearl millet parental lines into heterotic groups to develop high-yielding hybrids from the different heterotic groups.Not Availabl