High-affinity, neutralizing antibodies to SARS-CoV-2 can be made without T follicular helper cells

T follicular helper (Tfh) cells are the conventional drivers of protective, germinal center (GC)-based antiviral antibody responses. However, loss of Tfh cells and GCs has been observed in patients with severe COVID-19. As T cell-B cell interactions and immunoglobulin class switching still occur in these patients, non-canonical pathways of antibody production may be operative during SARS-CoV-2 infection. We found that both Tfh-dependent and -independent antibodies were induced against SARS-CoV-2 infection, SARS-CoV-2 vaccination, and influenza A virus infection. Even though Tfh-independent antibodies to SARS-CoV-2 had evidence of reduced somatic hypermutation, they were still high-affinity, durable, and reactive against diverse spike-derived epitopes and were capable of neutralizing both homologous SARS-CoV-2 and the B.1.351 (beta) variant of concern. Indeed, we found by epitope mapping and BCR sequencing that Tfh cells focused the B cell response and therefore, in the absence of Tfh cells, a more diverse clonal repertoire was maintained. These data support an alternative pathway for the induction of B cell responses during viral infection that enables effective, neutralizing antibody production to complement traditional GC-derived antibodies that might compensate for GCs damaged by viral inflammation

Facile one-pot synthesis of CuO nanospheres: Sensitive electrochemical determination of hydrazine in water effluents

Hydrazine (HZ) is massively used in several industrial applications. Adsorption of HZ through human skin creates carcinogenicity by disturbing the human organ system and thus, the quantification of HZ levels in environmental water samples is highly needed. The present work describes the short-term development of copper oxide nanospheres (CuO NS) by one-step wet chemical approach and their implementation on glassy carbon electrode (GCE) for the sensitive and selective quantification of the environmentally hazardous HZ. The CuO NS formation was identified by X-ray diffraction (XRD), field-emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM) and UV-visible spectroscopy. SEM images exhibited the uniform CuO NS with an average size of 85 nm. The linker-free CuO NS modified GCE offered high electrocatalytic activity against HZ determination by showing the linear range determination in the range of 0.5 to 500 µM, with the detection limit of 63 nM (S/N=3), and sensitivity of 894.28 µA mM-1 cm-2. Further, the developed HZ sensor displayed excellent repeatability and reproducibility and was successfully exploited for the determination of HZ in real environmental samples, implying that GCE/CuO-NS is a confident and low-cost electrochemical platform for HZ determination

Performance and Emission Characteristics of Diesel Fuelled Homogeneous Charge Compression Ignition (HCCI) Engine

ABSTRACT: An experimentally investigation is carried out to analysis the performance and emission characteristics of Homogeneous charge compression ignition engine (HCCI). Over the past decades many researcher have been discussed about working of HCCI engine. The HCCI engine is a suitable replacement for compression ignition engine (CI). This paper experimentally investigate the performance and emission characteristics of a HCCI engine at different load with constant speed and compare with convention CI engine. In this research, the HCCI mode engine uses the port fuel injection (PFI) for preparing the homogeneous air-fuel mixture. The results show that the specific fuel consumption is decreased for diesel fuelled HCCI mode engine compared to DI-CI engine. The brake thermal efficiency of HCCI mode engine is even as same or slightly increased. From the result observed that the value of oxides of nitrogen (NOx) and particulate matter (PM) emissions are very low than the DI diesel engine. The rate of reduction of NOx and PM are about 20% and 5% respectively. But the exhaust emission of un burnt hydrocarbon (UHC) and carbon monoxide (CO) are higher than DI mode diesel engine

ProtRepeatsDB: a database of amino acid repeats in genomes

BACKGROUND: Genome wide and cross species comparisons of amino acid repeats is an intriguing problem in biology mainly due to the highly polymorphic nature and diverse functions of amino acid repeats. Innate protein repeats constitute vital functional and structural regions in proteins. Repeats are of great consequence in evolution of proteins, as evident from analysis of repeats in different organisms. In the post genomic era, availability of protein sequences encoded in different genomes provides a unique opportunity to perform large scale comparative studies of amino acid repeats. ProtRepeatsDB is a relational database of perfect and mismatch repeats, access to which is designed as a resource and collection of tools for detection and cross species comparisons of different types of amino acid repeats. DESCRIPTION: ProtRepeatsDB (v1.2) consists of perfect as well as mismatch amino acid repeats in the protein sequences of 141 organisms, the genomes of which are now available. The web interface of ProtRepeatsDB consists of different tools to perform repeat s; based on protein IDs, organism name, repeat sequences, and keywords as in FASTA headers, size, frequency, gene ontology (GO) annotation IDs and regular expressions (REGEXP) describing repeats. These tools also allow formulation of a variety of simple, complex and logical queries to facilitate mining and large-scale cross-species comparisons of amino acid repeats. In addition to this, the database also contains sequence analysis tools to determine repeats in user input sequences. CONCLUSION: ProtRepeatsDB is a multi-organism database of different types of amino acid repeats present in proteins. It integrates useful tools to perform genome wide queries for rapid screening and identification of amino acid repeats and facilitates comparative and evolutionary studies of the repeats. The database is useful for identification of species or organism specific repeat markers, interspecies variations and polymorphism

Effective Communication Protocols for Verification on SoC Using FPGA

ABSTRACT A System on Chip (SoC) is an integrated circuit that integrates all components of a computer or other electronic system into a single chip. It may contain digital, analog, mixed-signal, and often radio frequency functions all on a single chip substrate. Traditionally, Engineers have employed simulation acceleration, emulation and/or an FPGA prototype to verify and debug both hardware and software for SOC design prior to tape out. So that design effective communication protocols are important for efficient verification on SOC.A serial communication interface based on FPGA (Field Programmable Gate Array) has been designed in this paper, used for data communication with other equipment. It guarantees the realization of the serial communication function under the condition of without any increasing in hardware resources

UV photodecomposition of zinc acetate for the growth of ZnO nanowires

The thermal annealing of zinc precursors to form suitable seed layers for the growth of ZnO nanowires is common. However, the process is relatively long and involves high temperatures which limit substrate choice. In this study the use of a low temperature, ultra-violet (UV) exposure is demonstrated for photodecomposition of zinc acetate precursors to form suitable seed layers. Comparisons are made between ZnO nanowire growth performed on seed layers produced through thermal annealing and exposure to UV. The dependence of growth density and nanowire diameter on UV exposure time is investigated. Growth quality is confirmed with energy dispersive x-ray (EDX) and x-ray diffraction analyses. The chemical composition of the exposed layers is investigated with EDX and x-ray photoelectron spectroscopy (XPS). Atomic force microscopy (AFM) is utilized to investigate morphological changes with respect to UV exposure. The diameter and density of the resultant growth was found to be strongly dependent on the UV exposure time. UV exposure times of only 25–30 s led to maximum density of growth and minimum diameter, significantly faster than thermal annealing. EDX, XPS and AFM analyses of the seed layers confirmed decomposition of the zinc precursor and morphological changes which influenced the growth

Influence of Growth Time on Zinc Oxide Nano Rods Prepared By Dip Coating Method

ABSTRACT: The Dip coating method was used for the preparation of ZnO nano rods and their structural, morphological, optical and photoluminescence properties were taken for study. ZnO seed layer thin films were prepared by dip coating method on well cleaned glass substrates. ZnO seed-coated glass substrates were immersed in aqueous solution of zinc nitrate and hexamethylenetetramine (HMT) at three different growth time of 3, 4 and 5 hours at low temperature of 90°C. 0.02 mol of Zinc nitrate and 0.2 mol of Hexamethylenetetramine (HMT) on 1:10 molar concentration were used for the growth of Zinc oxide nano rods. The growth time influence on the surface morphology of the films was examined. The structure of the ZnO nano rod was studied with X-ray diffraction. The surface morphology was studied with Scanning Electron Microscope. The absorption and transmittance was studied with UVVis spectrophotometer. The excitation studies were examined with photoluminescence spectroscopy. Experimental results have shown that prepared ZnO nano rods by this method have increase in c-axis orientation due to increase in growth time

Homozygosity Mapping and Genetic Analysis of Autosomal Recessive Retinal Dystrophies in 144 Consanguineous Pakistani Families.

PurposeThe Pakistan Punjab population has been a rich source for identifying genes causing or contributing to autosomal recessive retinal degenerations (arRD). This study was carried out to delineate the genetic architecture of arRD in the Pakistani population.MethodsThe genetic origin of arRD in a total of 144 families selected only for having consanguineous marriages and multiple members affected with arRD was examined. Of these, causative mutations had been identified in 62 families while only the locus had been identified for an additional 15. The remaining 67 families were subjected to homozygosity exclusion mapping by screening of closely flanking microsatellite markers at 180 known candidate genes/loci followed by sequencing of the candidate gene for pathogenic changes.ResultsOf these 67 families subjected to homozygosity mapping, 38 showed homozygosity for at least one of the 180 regions, and sequencing of the corresponding genes showed homozygous cosegregating mutations in 27 families. Overall, mutations were detected in approximately 61.8 % (89/144) of arRD families tested, with another 10.4% (15/144) being mapped to a locus but without a gene identified.ConclusionsThese results suggest the involvement of unmapped novel genes in the remaining 27.8% (40/144) of families. In addition, this study demonstrates that homozygosity mapping remains a powerful tool for identifying the genetic defect underlying genetically heterogeneous arRD disorders in consanguineous marriages for both research and clinical applications

Genome assemblies across the diverse evolutionary spectrum of Leishmania protozoan parasites

We report the high-quality draft assemblies and gene annotations for 13 species and/or strains of the protozoan parasite gener

Natural product (L)-gossypol inhibits colon cancer cell growth by targeting RNA-binding protein Musashi-1

Musashi-1 (MSI1) is an RNA-binding protein that acts as a translation activator or repressor of target mRNAs. The best-characterized MSI1 target is Numb mRNA, whose encoded protein negatively regulates Notch signaling. Additional MSI1 targets include the mRNAs for the tumor suppressor protein APC that regulates Wnt signaling and the cyclin-dependent kinase inhibitor P21WAF−1. We hypothesized that increased expression of NUMB, P21 and APC, through inhibition of MSI1 RNA-binding activity might be an effective way to simultaneously downregulate Wnt and Notch signaling, thus blocking the growth of a broad range of cancer cells. We used a fluorescence polarization assay to screen for small molecules that disrupt the binding of MSI1 to its consensus RNA binding site. One of the top hits was (−)-gossypol (Ki = 476 ± 273 nM), a natural product from cottonseed, known to have potent anti-tumor activity and which has recently completed Phase IIb clinical trials for prostate cancer. Surface plasmon resonance and nuclear magnetic resonance studies demonstrate a direct interaction of (−)-gossypol with the RNA binding pocket of MSI1. We further showed that (−)-gossypol reduces Notch/Wnt signaling in several colon cancer cell lines having high levels of MSI1, with reduced SURVIVIN expression and increased apoptosis/autophagy. Finally, we showed that orally administered (−)-gossypol inhibits colon cancer growth in a mouse xenograft model. Our study identifies (−)-gossypol as a potential small molecule inhibitor of MSI1-RNA interaction, and suggests that inhibition of MSI1's RNA binding activity may be an effective anti-cancer strategy