Fine Tuning a Well-Oiled Machine: Influence of NK1.1 and NKG2D on NKT Cell Development and Function

Natural killer T cells (NKT) represent a group of CD1d-restricted T-lineage cells that provide a functional interface between innate and adaptive immune responses in infectious disease, cancer, allergy and autoimmunity. There have been remarkable advances in understanding the molecular events that underpin NKT development in the thymus and in the complex array of functions in the periphery. Most functional studies have focused on activation of T cell antigen receptors expressed by NKT cells and their responses to CD1d presentation of glycolipid and related antigens. Receiving less attention has been several molecules that are hallmarks of Natural Killer (NK) cells, but nonetheless expressed by NKT cells. These include several activating and inhibitory receptors that may fine-tune NKT development and survival, as well as activation via antigen receptors. Herein, we review the possible roles of the NK1.1 and NKG2D receptors in regulating development and function of NKT cells in health and disease. We suggest that pharmacological alteration of NKT activity should consider the potential complexities commensurate with NK1.1 and NKG2D expressio

Graphene Quantum Dots - From Emergence to Nanotheranostic Applications

Quantum dots are at the cutting edge of nanotechnology development. Due to their unique optical and physical properties, they have potential applications in many avenues of medicine and biotechnology. With the advancements in nano-sciences, novel applications of quantum dots are constantly being explored for drug delivery and bioimaging. Graphene quantum dots (GQDs) are nanoparticles of graphene with properties of quantum dots as well as graphene. GQDs have ignited remarkable research interest in the field of medicine and biology and are considered as well-suited candidates for nanotheranostic applications due to their excellent biocompatibility and tunable physicochemical properties. The promising emerging implications of GQD platforms for diagnostics and therapeutics advances are the basis of this chapter

Ayurveda and Siddha systems polyherbal formulations to treat COVID-19 caused by SARS-CoV-2 and brief insight on application of Molecular Docking and SWISS Target prediction tools to study efficacy of active molecules

Ayurveda and  Siddha systems are the two ancient medical systems originated in India more than 4000 years ago had given many formulary and treatment methods against influenza like infections. Kabasura churan from Siddha system and Maha sudharshan churan from the Ayurvedic system are the two major formulations along with many other individual herbs mentioned in the texts to treat Influenza like infections. Kabasura churan and Maha Sudarshan churan both have antipyretic, analgesic and anti-inflammatory effects. Both formulations were prepared according to Siddha and Ayurvedic texts. Herbs mentioned in both formulations like Turmeric, Tulsi (Basil), Kalmegh (Andrographis), Black Pepper, Liquorice (Mulethi), and Dronapushpi (Leucas) etc., had direct antiviral effect. Herbs like Aswagandha, Ginger, Guduchi (Tinospora), Kulanjan (Galangal) etc., had immunomodulatory and anti-inflammatory effect. Active compounds from different herbs were selected to study their antiviral activity through molecular docking algorithm. Application of modern of tools like Bioinformatics and Highthroughput screening methods can predict the efficacy of the ancient documented formulations and can be compared as per their literature. Compounds like curcumin, Glycyrrhizin, Ursolic acid, Quercetin, Andrographolide, Coumarins etc. were showed polyspecific activity like inhibition of Spike protein, Furin, Main Protease (Mpro) and Papain like Proteases (PLpro). Thus we propose use of Kabasura churan and Maha Sudharshan churan as alternative complementary medicine as a palliative treatment against COVID-19 caused by SARS-CoV-2 by conducting proper Randomized Clinical Trial

Immunization of Mice with Anthrax Protective Antigen Limits Cardiotoxicity but Not Hepatotoxicity Following Lethal Toxin Challenge

Protective immunity against anthrax is inferred from measurement of vaccine antigen-specific neutralizing antibody titers in serum samples. In animal models, in vivo challenges with toxin and/or spores can also be performed. However, neither of these approaches considers toxin-induced damage to specific organ systems. It is therefore important to determine to what extent anthrax vaccines and existing or candidate adjuvants can provide organ-specific protection against intoxication. We therefore compared the ability of Alum, CpG DNA and the CD1d ligand alpha-galactosylceramide (alphaGC) to enhance protective antigen-specific antibody titers, to protect mice against challenge with lethal toxin, and to block cardiotoxicity and hepatotoxicity. By measurement of serum cardiac Troponin I (cTnI), and hepatic alanine aminotransferase (ALT), and aspartate aminotransferase (AST), it was apparent that neither vaccine modality prevented hepatic intoxication, despite high Ab titers and ultimate survival of the subject. In contrast, cardiotoxicity was greatly diminished by prior immunization. This shows that a vaccine that confers survival following toxin exposure may still have an associated morbidity. We propose that organ-specific intoxication should be monitored routinely during research into new vaccine modalities

Neodymium Isotope Constraints on the Origin of TTGs and High-K Granitoids in the Bundelkhand Craton, Central India : Implications for Archaean Crustal Evolution

The Bundelkhand craton in central India consists mainly of abundant high-K granitoids formed at the Archaean-Proterozoic boundary and several enclosed rafts of TTGs (tonalite-trondhjemite-granodiorites) up to 3.5 Ga. Therefore, the Bundelkhand craton is a key locality for studies on Archaean crustal growth and the emergence of multisource granitoid batholiths that stabilised a supercontinent at 2.5 Ga. Based on their geochemical characteristics, the high-K granitoids are divided into low silica-high Mg (sanukitoids and hybrids) and high silica-low Mg (anatectic) groups. We aim to provide new insights into the role of juvenile versus crustal sources in the evolution of the TTG, sanukitoid, hybrid, and anatectic granitoids of the Bundelkhand craton by comparing their key geochemical signatures with new Nd isotope evidence on crustal contributions and residence times. The ages and geochemical signatures as well as epsilon Nd(t) values and Nd model ages of TTGs point towards partial melting of a juvenile or short-lived mafic crust at different depths. Paleoarchaean TTGs show short crustal residence times and contributions from the newly formed crust, whereas Neoarchaean TTGs have long crustal residence times and contributions from the Paleoarchaean crust. This may reflect the transition from melting in a primitive oceanic plateau (3.4-3.2 Ga) in plume settings, resulting in a Paleoarchaean protocontinent, to 2.7 Ga subduction and island arc accretion along the protocontinent. The 2.5 Ga high-K granitoids formed at convergent subduction settings by partial melting of the mantle wedge and preexisting crust. Sanukitoids and hybrid granitoids originated in the mantle, the latter showing stronger crustal contributions, whereas abundant anatectic granitoids were products of pure crustal melting. Our Nd data and geochemical signatures support a change from early mafic sources to strong crust-mantle interactions towards the A-P boundary, probably reflecting the onset of supercontinent cycles.Peer reviewe

Identification of mirtrons in rice using MirtronPred: a tool for predicting plant mirtrons.

article i nfo Studies from flies and insects have reported the existence of a special class of miRNA, called mirtrons that are produced from spliced-out introns in a DROSHA-independent manner. The spliced-out lariat is debranched and refolded into a stem-loop structure resembling the pre-miRNA, which can then be processed by DICER into mature ~21 nt species. The mirtrons have not been reported from plants. In this study, we present Mir- tronPred, a web based server to predict mirtrons from intronic sequences. We have used the server to predict 70 mirtrons in rice introns that were put through a stringent selection filter to shortlist 16 best sequences. The prediction accuracy was subsequently validated by northern analysis and RT-PCR of a predicted Os- mirtron-109. The target sequences for this mirtron were also found in the rice degradome database. The pos- sible role of the mirtron in rice regulon is discussed. The MirtronPred web server is available at http://bioinfo. icgeb.res.in/mirtronPred

Zika Virus- Emergence, Evolution, Pathology, Diagnosis, and Control: Current Global Scenario and Future Perspectives- A Comprehensive Review

This review converses the Zika virus which has attained global concern due to its rapid pandemic potential and impact on humans. Though Zika virus was first isolated in 1947, till the recent large-scale outbreak which occurred in Micronesia, in 2007, the virus was placed into the innocuous pathogen category. The World Health Organization on 1 February 2016 declared it as a Public Health Emergency of International Concern.\u27 Of the note, American as well as Pacific Island strains/isolates is relatively closer to Asian lineage strains. The African and American strains share more than 87.5% and 95% homologies with Asian strains/isolates, respectively. Asian strains form independent clusters, except those isolated from China, suggesting relatively more diversity than African strains. Prevention and control are mainly aimed at the vector population (mosquitoes) with Aedes aegypti being the main species. Surveys in Africa and Asia indicated seropositivity in various animal species. However, so far its natural reservoir is unknown. There is an urgent need to understand why Zika virus has shifted from being a virus that caused mild illness to unforeseen birth defects as well as autoimmune-neurological problems. Unfortunately, an effective vaccine is not available yet. Availability of cryo-electron microscopy based on 3.8 angstrom resolution revealing mature Zika virus structure and the probable virus attachment site to host cell would provide critical insights into the development of antiviral treatments and vaccines

Heterogeneity in HIV and cellular transcription profiles in cell line models of latent and productive infection: implications for HIV latency.

BackgroundHIV-infected cell lines are widely used to study latent HIV infection, which is considered the main barrier to HIV cure. We hypothesized that these cell lines differ from each other and from cells from HIV-infected individuals in the mechanisms underlying latency.ResultsTo quantify the degree to which HIV expression is inhibited by blocks at different stages of HIV transcription, we employed a recently-described panel of RT-ddPCR assays to measure levels of 7 HIV transcripts ("read-through," initiated, 5' elongated, mid-transcribed/unspliced [Pol], distal-transcribed [Nef], polyadenylated, and multiply-sliced [Tat-Rev]) in bulk populations of latently-infected (U1, ACH-2, J-Lat) and productively-infected (8E5, activated J-Lat) cell lines. To assess single-cell variation and investigate cellular genes associated with HIV transcriptional blocks, we developed a novel multiplex qPCR panel and quantified single cell levels of 7 HIV targets and 89 cellular transcripts in latently- and productively-infected cell lines. The bulk cell HIV transcription profile differed dramatically between cell lines and cells from ART-suppressed individuals. Compared to cells from ART-suppressed individuals, latent cell lines showed lower levels of HIV transcriptional initiation and higher levels of polyadenylation and splicing. ACH-2 and J-Lat cells showed different forms of transcriptional interference, while U1 cells showed a block to elongation. Single-cell studies revealed marked variation between/within cell lines in expression of HIV transcripts, T cell phenotypic markers, antiviral factors, and genes implicated in latency. Expression of multiply-spliced HIV Tat-Rev was associated with expression of cellular genes involved in activation, tissue retention, T cell transcription, and apoptosis/survival.ConclusionsHIV-infected cell lines differ from each other and from cells from ART-treated individuals in the mechanisms governing latent HIV infection. These differences in viral and cellular gene expression must be considered when gauging the suitability of a given cell line for future research on HIV. At the same time, some features were shared across cell lines, such as low expression of antiviral defense genes and a relationship between productive infection and genes involved in survival. These features may contribute to HIV latency or persistence in vivo, and deserve further study using novel single cell assays such as those described in this manuscript

Polymorphism and epitope sharing between the alleles of merozoite surface protein-1 of Plasmodium falciparum among Indian isolates

<p>Abstract</p> <p>Background</p> <p>The C-terminal region of merozoite surface protein-1 (MSP-1) is one of the leading candidates for vaccination against the erythrocytic stages of malaria. However, a major concern in the development of MSP-1 based malaria vaccine is the polymorphism observed in different geographical <it>Plasmodium falciparum </it>isolates. To explore whether the sequence heterogeneity of PfMSP-1 leads to variation in naturally acquired anti-MSP-1₁₉antibodies, the present study was undertaken to study PfMSP-1₁₉sequence polymorphism in malaria-endemic villages in eastern India and also carried out a competition enzyme-linked immunosorbent assay using three PfMSP-1₁₉variant forms.</p> <p>Methods</p> <p>The sequence variations in the C-terminal region of PfMSP-1₁₉were determined in a malaria endemic region. Three PfMSP-1₁₉variants were produced in <it>Escherichia coli </it>(PfMSP1₁₉QKNG-L, PfMSP1₁₉EKNG-L and PfMSP1₁₉ETSR-F) and an immunodepletion assay was carried out using the corresponding patients' sera.</p> <p>Results</p> <p>Results revealed predominance of PfMAD20 allele among Indian field isolates. Seven PfMSP-1₁₉variant forms were isolated in a singe geographical location. Three of PfMSP-1₁₉variant forms when expressed in <it>E. coli </it>showed presence of cross-reaction as well as variant specific antibodies in malaria infected patient sera.</p> <p>Conclusion</p> <p>The present study demonstrates the existence of allele specific antibodies in <it>P. falciparum</it>-infected patient sera, however their role in protection requires further investigation. These results thereby, suggest the importance of a multi-allelic PfMSP-1₁₉based vaccine for an effective malaria control.</p