The NFκB signaling system in the generation of B-cell subsets: from germinal center B cells to memory B cells and plasma cells

Memory B cells and antibody-secreting cells are the two prime effector B cell populations that drive infection- and vaccine-induced long-term antibody-mediated immunity. The antibody-mediated immunity mostly relies on the formation of specialized structures within secondary lymphoid organs, called germinal centers (GCs), that facilitate the interactions between B cells, T cells, and antigen-presenting cells. Antigen-activated B cells may proliferate and differentiate into GC-independent plasmablasts and memory B cells or differentiate into GC B cells. The GC B cells undergo proliferation coupled to somatic hypermutation of their immunoglobulin genes for antibody affinity maturation. Subsequently, affinity mature GC B cells differentiate into GC-dependent plasma cells and memory B cells. Here, we review how the NFκB signaling system controls B cell proliferation and the generation of GC B cells, plasmablasts/plasma cells, and memory B cells. We also identify and discuss some important unanswered questions in this connection

HISTOARCHITECTURAL ANOMALIES INDUCED BY ANTIBIOTIC FLORFENICOL IN COMMERCIALLY IMPORTANT CATFISH PANGASIANODON HYPOPHTHALMUS

Antibiotics are widely used to prevent and treat bacterial infections, increasing aquaculture productivity. However, their imprudent use can lead to unintended consequences, including pathological alterations in vital organs of aquatic organisms. The safety of florfenicol following in-feed administration at 10 times the recommended dose and three times the recommended period in Pangasianodon hypophthalmus was studied. Florfenicol induced significant histoarchitectural anomalies as observed from the photomicrographs of double-stained sections of various tissues, including gills, liver, and kidneys of P. hypophthalmus, following in-feed administration at graded doses, viz., 0mg, 10mg, 30mg, 50mg and 100 mg/kg biomass–1 day–1 for 30 days, i.e., three times the recommended therapeutic duration. Gills exhibited lamellar fusion, epithelial lifting, and hyperplasia indicative of respiratory distress. There were hepatocellular vacuolation, degeneration, and congestion, suggesting impaired hepatic integrity. The kidney sections demonstrated tubular degeneration, necrosis, and interstitial inflammation implying renal dysfunction. These changes were prominent at higher doses, mostly in 50 mg and 100 mg groups, and in the extended duration of the treatment, underscoring the potential adverse effects of florfenicol on the histological integrity and physiological homeostasis of P. hypophthalmus. As the catfish species holds significant economic value in Asian aquaculture, understanding the impacts of antibiotic exposure is crucial for sustainable fish farming practices. Implementing appropriate antibiotic usage protocols and monitoring strategies can mitigate the risks associated with antibiotic-induced pathological alterations in commercially important aquatic species

Effects of Bt-cotton on biological properties of Vertisols in central India

Growing areas under transgenic crops have created a concern over their possible adverse impact on the soil ecosystem. This study evaluated the effect of Bt-cotton based cropping systems on soil microbial and biochemical activities and their functional relationships with active soil carbon pools in Vertisols of central India (Nagpur, Maharastra, during 2012–2013). Culturable groups of soil microflora, enzymatic activities and active pools of soil carbon were measured under different Bt-cotton based cropping systems (e.g. cotton-soybean, cotton-redgram, cotton-wheat, cotton-vegetables and cotton-fallow). Significantly higher counts of soil heterotrophs (5.7–7.9 log cfu g−1soil), aerobic N-fixer (3.9–5.4 log cfu g−1soil) and P-solubilizer (2.5−3.0 log cfu g−1soil) were recorded in Bt-cotton soils. Similarly, soil enzymatic activities, viz. dehydrogenase (16.6–22.67 µg TPF g−1 h−1), alkaline phosphatase (240–253 µg PNP g−1 h−1) and fluorescein di-acetate hydrolysis (14.6–18.0 µg fluorescein g−1 h−1), were significantly higher under Bt-cotton-soybean system than other Bt- and non-Bt-cotton based systems in all crop growth stages. The growth stage-wise order of soil microbiological activities were: boll development > harvest > vegetative stage. Significant correlations were observed between microbiological activities and active carbon pools in the rhizosphere soil. The findings indicated no adverse effect of Bt-cotton on soil biological properties

Design, Synthesis and Study of Peptidomimetic Inhibitors against Different Cellular Targets

In the living system thousands of biochemical processes occur spontaneously. All such biochemical processes are not same for different ways of living kingdom. Some biochemical pathways are unique for a specific type of organism. Moreover in many pathological conditions some of these processes are aberrant, inappropriate or poorly regulated. Many of such biochemical processes have been very rigorously studied by the scientific communities. It is already known that the protein-protein and protein-nucleic acid interactions play many crucial roles in many biological processes. The ability to interfere such interactions would, therefore, provide many attractive opportunities for the treatment of human disease. Three biochemical pathways have been taken to address for disruptions of specific protein–protein or protein nucleic acid interactions by peptidomimetics. The translation of Hepatitis C Virus (HCV) poly-protein is mediated through interaction of human La protein with HCV-IRES near initiator AUG. It was earlier demonstrated that RNA recognition motif 2 (RRM2) of La protein interacts with HCV-IRES near initiator AUG and facilitates translation of hepatitis C virus (HCV). So the interface of HCV-IRES near initiator AUG and RRM2 of La protein is a very good drug target. NF-κB family proteins have been constitutively active in almost all tumor tissues. Suppression of NF-κB in cancer cell lines inhibits proliferation, causes cell cycle arrest, and leads to apoptosis, indicating the crucial role of NF-κB in cell proliferation and survival. What causes the constitutive activation of NF-κB in tumor cells is incompletely understood. IKK complex plays a very crucial role in the activation of NF-κB family proteins. It consists of IKKα, IKKβ, and IKKγ subunit proteins. Upon phosphorylation of IKK complex it phosphorylates IκBs protein consequently NF-κB family proteins are activated. By disruption of the IKK complex NF-κB pathway can be controlled hence uncontrolled proliferation of tumor tissues. Majority of bacteria and all archaea, which do not possess GlnRS, the accurate translation of the genetic code of Gln occurs through a two-step process. In the first step, tRNAGln is misacylated with glutamic acid by a non-discriminating GluRS, and then the mischarged Glu-tRNAGln is transformed into Gln-tRNAGln by Glu-tRNAGln–dependent amidotransferase (Glu-AdT). Glu-AdT converts Glu-tRNAGln into Gln-tRNAGln by initially activating Glu-tRNAGln into γ-phosphoryl-Glu-tRNAGln at the expense of ATP, which is subsequently transamidated into Gln-tRNAGln using ammonia generated by hydrolysis of glutamine. The active site of Glu-AdT (gatCAB present in mycobacterium) for hydrolysis of glutamine is a hot spot for drug target against mycobacterium. This thesis attempts to develop peptidomimetic inhibitors to disrupt such specific protein-protein and protein-nucleic acid interactions occurs in such hot spots for drug target

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Not AvailableChanos chanos commonly known as Milkfish, a euryhaline benthopelagic, amphidromous, tropical species under the order Gonorynchiformes is a monotypic species from the family Chanidae, inhabiting marine as well as brackish waters. Milkfish is mostly found in offshore marine waters and shallow coastal embayment; reported to very often enter into estuaries and freshwater streams. In reef-associated coasts or islands, they occur as small to large schools. Milkfish is considered the national fish of the Philippines and locally known as ‘Bangus’. It is considered delicious, can grow fast, and tolerate wide ranges of salinity. Culture of milkfish in brackishwater ponds and pens is an age-old practice and mainly followed in the countries like Philippines, Taiwan, Indonesia, and pacific island countries. During the year 2014, global milkfish production was 10 lakh MT, and the main contributors were Philippines, Taiwan, and Indonesia. In Indian open waters, Milkfish is available in almost all the brackishwater lagoons and estuaries along both the east and west coasts of India. Culture of milkfish is done mainly in brackish water, coastal, and estuarine water bodies in a traditional way. Culture of milkfish mainly depends on natural seed resources, and is not done in an organized manner due to the non-availability of quality seeds. Recently ICAR-CIBA successfully bred and standardized breeding techniques of milkfish. In India, as per the report of MPEDA (1997) at least 20 million, wild-caught seeds of the species are collected every year from the natural water bodies for farming purposes which is considered one of the reasons for the depletion of natural population stocks. Present status of Milkfish fishery in India is discussed in this communication along with the management strategies for its improvement.Not Availabl

Structural Determinant of Human La Protein Critical for Internal Initiation of Translation of Hepatitis C Virus RNA

Human La protein has been implicated in facilitating internal ribosome entry site (IRES)-mediated translation of hepatitis C virus (HCV). Earlier, we demonstrated that the RNA recognition motif (RRM) encompassing residues 112 to 184 of La protein [La (112-184)] interacts with the HCV IRES near the initiator AUG codon. A synthetic peptide, LaR2C (24-mer), derived from La RRM (112-184), retains RNA binding ability, competes with La protein binding to the HCV IRES, and inhibits translation. The peptide interferes with the assembly of 48S complexes, resulting in the accumulation of preinitiation complexes that are incompetent for the 60S ribosomal subunit joining. Here, nuclear magnetic resonance spectroscopy of the HCV IRES-bound peptide complex revealed putative contact points, mutations that showed reduced RNA binding and translation inhibitory activity. The residues responsible for RNA recognition were found to form a turn in the RRM (112-184) structure. A 7-mer peptide comprising this turn showed significant translation inhibitory activity. The bound structure of the peptide inferred from transferred nuclear Overhauser effect experiments suggests that it is a β turn. This conformation is significantly different from that observed in the free RRM (112-184) NMR structure, suggesting paths toward a better-stabilized mimetic peptide. Interestingly, addition of hexa-arginine tag enabled the peptide to enter Huh7 cells and showed inhibition of HCV IRES function. More importantly, the peptide significantly inhibited replication of the HCV monocistronic replicon. Elucidation of the structural determinant of the peptide provides a basis for developing small peptidomimetic structures as potent anti-HCV therapeutics

A cyclic peptide mimic of an RNA recognition motif of human La protein is a potent inhibitor of hepatitis C virus

Due to limited available therapeutic options, developing new lead compounds against hepatitis C virus is an urgent need. Human La protein stimulates hepatitis C virus translation through interaction with the hepatitis C viral RNA. A cyclic peptide mimicking the beta-turn of the human La protein that interacts with the viral RNA was synthesized. It inhibits hepatitis C viral RNA translation significantly better than the corresponding linear peptide at longer post-treatment times. The cyclic peptide also inhibited replication as measured by replicon RNA levels using real time RT-PCR. The cyclic peptide emerges as a promising lead compound against hepatitis C

Structural Determinant of Human La Protein Critical for Internal Initiation of Translation of Hepatitis C Virus RNA ▿ †

Human La protein has been implicated in facilitating internal ribosome entry site (IRES)-mediated translation of hepatitis C virus (HCV). Earlier, we demonstrated that the RNA recognition motif (RRM) encompassing residues 112 to 184 of La protein [La (112-184)] interacts with the HCV IRES near the initiator AUG codon. A synthetic peptide, LaR2C (24-mer), derived from La RRM (112-184), retains RNA binding ability, competes with La protein binding to the HCV IRES, and inhibits translation. The peptide interferes with the assembly of 48S complexes, resulting in the accumulation of preinitiation complexes that are incompetent for the 60S ribosomal subunit joining. Here, nuclear magnetic resonance spectroscopy of the HCV IRES-bound peptide complex revealed putative contact points, mutations that showed reduced RNA binding and translation inhibitory activity. The residues responsible for RNA recognition were found to form a turn in the RRM (112-184) structure. A 7-mer peptide comprising this turn showed significant translation inhibitory activity. The bound structure of the peptide inferred from transferred nuclear Overhauser effect experiments suggests that it is a β turn. This conformation is significantly different from that observed in the free RRM (112-184) NMR structure, suggesting paths toward a better-stabilized mimetic peptide. Interestingly, addition of hexa-arginine tag enabled the peptide to enter Huh7 cells and showed inhibition of HCV IRES function. More importantly, the peptide significantly inhibited replication of the HCV monocistronic replicon. Elucidation of the structural determinant of the peptide provides a basis for developing small peptidomimetic structures as potent anti-HCV therapeutics

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Not AvailableOrganic farming is an emerging option to protect the soil health by replenishing the rapidly depleting organic matter under t ropical soil condition to ensure production sustenance. Present study evaluates the effect of indigenous organic preparation panchagavya, cattle dung manure and biodynamic preparations on nitrate reductase activity, chlorophyll content, phyllospheric microbial count, soil microbial activity as well as growth and yield of wheat crop. Amongst, all the organic preparations viz. panchagavya, cattle dung manure, Biodynamic compost, BD500 and Cow Pat Pit, liquid preparation panchagavya contained low amou nt of plant nutrients. The highest count of bacteria (log10cfu 9.39 per ml) and aerobic nitrogen fixers (log10cfu 7.35 per ml) were found in Panchagavya. Improvement in grain yield of wheat with application of panchagavya and other organics was recorded however; compared to inorganic fertilizer treatment, reduction in grain yield to the extent of 35.42% in panchagavya 9.1% in integrated nutrient management, 12.7% in conventional organic treatment and 16.3% in biodynamic treatment indicated less nutrient supplementing potential of organics in short term as evidenced by lower leaf chlorophyll content and nitrate reducta se activity. Enhancement in phyllospheric microbial population and soil dehydrogenase activity with organic application suggested favorable impact of application of organics.Not Availabl