Pathogenesis of Alzheimer's Disease and Diversity of 1,2,3-Triazole Scaffold in Drug Development: Design Strategies, Structural Insights, and Therapeutic Potential.

Alzheimer's disease is a most prevalent form of dementia all around the globe and currently poses a significant challenge to the healthcare system. Currently available drugs only slow the progression of this disease rather than provide proper containment. Identification of multiple targets responsible for this disease in the last three decades established it as a multifactorial neurodegenerative disorder that needs novel multifunctional agents for its management and the possible reason for the failure of currently available single target clinical drugs. 1,2,3-Triazole is a miraculous nucleus in medicinal chemistry and the first choice for development of multifunctional hybrid molecules. Apart from that, it is an integral component of various drugs in clinical trials as well as in clinical practice. This review is focused on the pathogenesis of Alzheimer's disease and 1,2,3-triazole containing derivatives developed in recent decades as potential anti-Alzheimer's agents. The review will provide (A) precise insight of various established targets of Alzheimer's disease including cholinergic, amyloid, tau, monoamine oxidases, glutamate, calcium, and reactive oxygen species hypothesis and (B) design hypothesis, structure-activity relationships, and pharmacological outcomes of 1,2,3-triazole containing multifunctional anti-Alzheimer's agents. This review will provide a baseline for various research groups working on Alzheimer's drug development in designing potent, safer, and effective multifunctional anti-Alzheimer's candidates of the future.

The hidden players: Shedding light on the significance of post-translational modifications and miRNAs in Alzheimer's disease development.

Alzheimer's disease (AD) is the most prevalent, expensive, lethal, and burdening neurodegenerative disease of this century. The initial stages of this disease are characterized by a reduced ability to encode and store new memories. Subsequent cognitive and behavioral deterioration occurs during the later stages. Abnormal cleavage of amyloid precursor protein (APP) resulting in amyloid-beta (Aß) accumulation along with hyperphosphorylation of tau protein are the two characteristic hallmarks of AD. Recently, several post-translational modifications (PTMs) have been identified on both Aß as well as tau proteins. However, a complete understanding of how different PTMs influence the structure and function of proteins in both healthy and diseased conditions is still lacking. It has been speculated that these PTMs might play vital roles in the progression of AD. In addition, several short non-coding microRNA (miRNA) sequences have been found to be deregulated in the peripheral blood of Alzheimer patients. The miRNAs are single-stranded RNAs that control gene expression by causing mRNA degradation, deadenylation, or translational repression and have been implicated in the regulation of several neuronal and glial activities. The lack of comprehensive understanding regarding disease mechanisms, biomarkers, and therapeutic targets greatly hampers the development of effective strategies for early diagnosis and the identification of viable therapeutic targets. Moreover, existing treatment options for managing the disease have proven to be ineffective and provide only temporary relief. Therefore, understanding the role of miRNAs and PTMs in AD can provide valuable insights into disease mechanisms, aid in the identification of biomarkers, facilitate the discovery of novel therapeutic targets, and inspire innovative treatments for this challenging condition.

Photoswitchable Azoheteroarene-Based Chelating Ligands: Light Modulation of Properties, Aqueous Solubility and Catalysis.

We report the design and synthesis of eight photoswitchable phenylazopyridine- and phenylazopyrazole-based molecular systems as chelation-type light-controllable ligands. Besides the studies on fundamental photoisomerization behaviour, the ligands were also screened for light-tuneable properties such as photochromism, phase transition, and solubility, especially in the aqueous medium. This investigation demonstrates how the modulation of aqueous solubility can be achieved through photoisomerization and can further be utilized towards controlling the amount of catalytically active Cu(I) species in the aqueous conditions. Through this approach, light control over the catalytic activity was achieved for Cu-catalyzed azide-alkyne cycloaddition (CuAAC) reactions, along with a partial recovery of the catalytically active species.

The Current Landscape of Bioactive Molecules against DENV: A Systematic Review.

With a 30-fold increase in incidence over the previous 50 years, dengue fever is now the most widespread viral disease transmitted by mosquitoes in the world. The intricate interaction of the human defense system, hereditary predisposition, and specific bitterness elements is more likely to be the pathogenesis of dengue. There are presently no viable treatments for dengue. Synthetic drugs which are used against this ailment also show major side effects. There must be a deeper understanding of the underlying mechanism generating severe symptoms to develop auguring markers, cutting-edge diagnostics, and treatments and finally a well-rounded and secure antiserum. Hence, the aim is to search for safer and more potent drugs derived from plants. Plants or herbs are mainly targeting replication or its enzyme or specific stereotypes, though an exact mechanism of phytoconstituents interfering with the viral replication is still undiscovered. The present attempt provided the update with the objective to bringing up forward pathophysiological eventualities involved in dengue virus along with the naturally derived treatment relevant to provide the impregnable therapy by evading the noxious symptoms for dengue fever. Governor's plum, Cryptocarya chartacea, magnolia berry, and Chinese ginger are such plants exhibiting many effective phytoconstituents against DENV and can be further explored for novel drug discovery by medicinal scientists.

The chickpea root rot complex in Saskatchewan, Canada- detection of emerging pathogens and their relative pathogenicity.

Chickpea fields in Saskatchewan, one of the three Canadian prairie provinces, have suffered from major health issues since 2019, but no definitive cause has been determined. Field surveys were conducted in Saskatchewan in 2020 and 2021 in order to develop a better understanding of root rot pathogens associated with chickpea. Root samples were analyzed for the presence of 11 potential chickpea root rot pathogens using end-point PCR. Fusarium redolens, F. solani and F. avenaceum were the most prevalent pathogen species detected in both survey years. The cause of Fusarium wilt in chickpea, F. oxysporum f. sp. ciceris, was not detected in either year, nor were Phytophthora spp. and Verticillium albo-atrum. Berkeleyomyces sp. was detected in one field in each year, and Verticillium dahliae was detected in several fields sampled in 2021. These two pathogens have not been reported previously on chickpea in Saskatchewan. The prevalence of Fusarium species obtained from 2021 root isolations was similar to that determined by molecular tests, with frequent isolation of F. redolens, F. oxysporum, F. avenaceum and F. solani. A series of indoor pathogenicity testing compared root disease severity caused by a selection of 16 isolates of six Fusarium species and single isolates of V. dahliae, Berkeleyomyces sp. and Macrophomina phaseolina. Results showed that select isolates of F. avenaceum were the most aggressive of the Fusarium isolates on chickpea. Despite relatively low inoculum density, a highly aggressive isolate of F. avenaceum caused severe stunting and more root rot symptoms than single isolates of V. dahliae, Berkeleyomyces sp. and M. phaseolina under the test conditions.

Bacterial metabolite butyrate in modulating sorafenib-targeted microRNAs to curtail its resistance in hepatocellular carcinoma.

BACKGROUND AND AIM: The host dietary fibre is fermented into short-chain fatty acids (SCFA) by intestinal microbiota as bacterial metabolites like propionate, acetate and butyrate. Among these metabolites, the role of butyrate is well documented to provide energy to intestinal epithelial cells. Also, butyrate has anti-inflammatory and anti-tumour properties and decrease in its level by unbalanced diet can develops cancer. Lately, some research has suggested that sodium butyrate as an inhibitor of histone deacetylase (HDAC) may have anticancer potential for hepatocellular carcinoma (HCC), the most common type of liver cancer. Since, HCC is asymptomatic it is usually diagnosed at its advanced stage. Sorafenib with antiproliferative and antiangiogenic effects is the first line of treatment in advanced HCC. However, prolonged drug treatment to HCC patients develops adaptive resistance towards the sorafenib. Sorafenib resistance can also be enhanced by differentially expressed microRNAs. However, the significance of butyrate in HCC sorafenib resistance and its association with sorafenib-targeted microRNAs is yet to be unfurled. Here, an attempt has been made to explore the role of bacterial metabolite butyrate on sorafenib resistant HCC as well as on sorafenib-targeted microRNAs (miR-7641 and miR-199) to curtail sorafenib resistance in HCC. METHODS: Initially, in-silico analysis was performed using Human Metabolome Database (HMDB) so to identify specific butyrate producing faecal bacteria. Then, their specific 16s rRNA expression was compared between HCC patients and healthy individuals using qRT-PCR. Additionally, the cell viability (MTT) and apoptosis assays were performed in both parental and sorafenib resistant HepG2 cells to evaluate the role of sodium butyrate in sorafenib resistant HCC. Moreover, the association of sodium butyrate with sorafenib-targeted miR-7641 and miR-199 was also assessed using real time PCR, cell viability, cell apoptosis and transfection assays. RESULTS: In silico analysis demonstrated Roseburia cecical, Roseburia intestinalis, Eubacterium rectal, Faecalibacterium prausnitzii as specific butyrate producing faecal bacteria and their 16s rRNA expression was downregulated in HCC patients. In vitro study revealed the presence of sodium butyrate also decreased the cell viability as well as enhanced cell apoptosis of both parental and resistant HepG2 cells. Interestingly, sodium butyrate also decreased the expression of both sorafenib-targeted miR-7641 and miR-199. Further, combination of both sodium butyrate and antimiR-7641 or antimiR-199 also increased apoptosis and decreased viability of resistant cells. CONCLUSION: This is first study to unravel the association of butyrate producing bacteria with HCC patients and the significance of bacterial metabolite butyrate as anti-tumour in sorafenib resistant hepatocellular carcinoma. The study also demonstrated the plausible new aspects of bacterial metabolite butyrate association with sorafenib-targeted miRNAs (miR-7641 and miR-199). Hence, the study highlighted the therapeutic potential of bacterial metabolite butyrate that might improve the clinical management of hepatocellular carcinoma.

Selenocoxib-3, a novel anti-inflammatory therapeutic effectively resolves colitis.

Ulcerative colitis (UC) is an idiopathic, chronic and relapsing colonic inflammatory disease. Despite the involvement of diverse intricate mechanisms, COX mediated inflammatory pathway is crucial in the pathophysiology of colitis. Thus, COX inhibition is imperative for managing colitis-associated inflammation. However, the use of COX inhibitory classical non-steroidal anti-inflammatory drugs (NSAIDs) for inflammation resolution has been linked to sudden increased flare-ups. Therefore, considering the anti-inflammatory and pro-resolution effects of antioxidant and essential trace element Selenium (Se), a Seleno-derivative of Celecoxib called Selenocoxib-3 was characterized and evaluated for its favourable pharmacokinetics, safety margins and anti-inflammatory therapeutic potential in DSS-induced experimental colitis. The serum pharmacokinetic profiling [elimination rate constant (K) and clearance (Cl) and toxicity profiling suggested enhanced efficacy, therapeutic potential and lesser toxicity of Selenocoxib-3 as compared to its parent NSAID Celecoxib. In vivo studies demonstrated that Selenocoxib-3 efficiently resolves the gross morphological signs of DSS-induced colitis such as diarrhoea, bloody stools, weight loss and colon shortening. Further, intestinal damage evaluated by H & E staining and MPO activity suggested of histopathological disruptions, such as neutrophil infiltration, mucodepletion and cryptitis, by Selenocoxib-3. The expression profiles of COX-1/2 demonstrated mitigation of pro-inflammatory mediators thereby promoting anti-inflammatory efficacy of Selenocoxib-3 when compared with Celecoxib. The current study suggests translational applicability of Se-containing novel class of COX inhibitors for efficiently managing inflammatory disorders such as UC.

Therapeutic Modalities in Head-Neck Neoplasia and Prognostication: A Review.

Neoplasia of the head and the neck necessitates intervention, surgical or otherwise, as the site and stage of the pathology may dictate. The various therapeutic modalities employed and prognosis has been reviewed.

miR-23b-3p Modulating Cytoprotective Autophagy and Glutamine Addiction in Sorafenib Resistant HepG2, a Hepatocellular Carcinoma Cell Line.

BACKGROUND: Hepatocellular carcinoma (HCC) is the second most common malignancy with increasing cancer deaths worldwide. HCC is mainly diagnosed at its advanced stage, and treatment with FDA-approved sorafenib, the multikinase inhibitor drug, is advised. Acquired resistance against sorafenib develops through several pathways involving hypoxia, autophagy, high glycolysis, or glutaminolysis. Small non-coding RNAs, similar to microRNAs (miRNAs), are also known to affect sorafenib resistance in HCC. However, there is a lack of information regarding the significance of differentially expressed miRNA (if any) on autophagy and glutamine regulation in sorafenib-resistant HCC. METHODS: The expression of autophagy and glutaminolysis genes was checked in both parental and sorafenib resistant HepG2 cell lines by real-time PCR. MTT and Annexin/PI assays were also performed in the presence of inhibitors such as chloroquine (autophagy inhibitor) and BPTES (glutaminolysis inhibitor). Next generation sequencing and in silico analysis were performed to select autophagy and glutamine addiction-specific microRNA. Selected miRNA were transfected into both HepG2 cells to examine its effect on autophagy and glutamine addiction in regulating sorafenib-resistant HCC. RESULTS: Our in vitro study depicted a higher expression of genes encoding autophagy and glutaminolysis in sorafenib-resistant HepG2 cells. Moreover, inhibitors for autophagy (chloroquine) and glutaminolysis (BPTES) showed a diminished level of cell viability and augmentation in cell apoptosis of sorafenib-resistant HepG2 cells. NGS and real-time PCR demonstrated the downregulated expression of miR-23b-3p in sorafenib-resistant cells compared to parental cells. In silico analysis showed that miR-23b-3p specifically targeted autophagy through ATG12 and glutaminolysis through GLS1. In transfection assays, mimics of miR-23b-3p demonstrated reduced gene expression for both ATG12 and GLS1, decreased cell viability, and increased cell apoptosis of sorafenib-resistant HepG2 cells, whereas the antimiRs of miR-23b-3p demonstrated contrasting results. CONCLUSION: Our study highlights the cytoprotective role of autophagy and glutamine addiction modulated by miR-23b-3p (tumor suppressor), suggesting new approaches to curb sorafenib resistance in HCC.

Sunflower protein isolates-composition, extraction and functional properties.

The demand of proteins from both plant and animal origin is growing throughout the world. But the proteins obtained from animals have an environmental effect and are expensive in market. Sunflower seeds are particularly intriguing among plant proteins since they are widely available have high protein content, nutritive value and functionalities. The quantity of anti-nutritional components in sunflower has been shown very low as compared to other plant sources. The governing factor which decides the applicability of sunflower proteins is its functional properties despite the absence of anti-nutritional compounds. The emulsification properties are comparable to soy protein isolates which increases the use of sunflower protein. However, foaming and gelling properties are not promising. But these properties can be improved by modification of proteins and eventually can be used for specific applications.

Enhanced photo-degradation of N-methyl-2-pyrrolidone (NMP): Influence of matrix components, kinetic study and artificial neural network modelling.

This study investigates the degradation of N-methyl-2-pyrrolidone (NMP) by UV-C and UV-C/PMS-treatment processes. The degradation of NMP was less than 2% by UV-C photolysis. To enhance the degradation, PMS was used as a source of sulphate (SO4• -) and hydroxyl (HO•) radicals in the UV-C photolysis treatment system. The operational parameters such as initial pH and concentration of NMP and PMS and water matrix elements were studied to understand their effects on degradation. At pH = 6.3, λ = 260 nm, initial concentration of NMP = 10 mg/L, PMS = 300 mg/L and carbonate ion = 150 mg/L, the degradation of NMP was found to be 97.5%, along with 26.86% of TOC removal. The bicarbonate ions, nitrate ions, and chloride ions showed the inhibitory effect on the degradation of NMP. The NMP degradation was governed by pseudo first order kinetics. SO4• - was found to be the dominating degradation species through the radical quenching studies. The intermediates formed during the degradation were identified through LC-MS analysis, and a degradation pathway was proposed. The experimental data was successfully validated through the application of the developed ANN model. The R2 between expected and experimental outcomes was 0.97. The developed ANN model was successful in predicting the degradation of NMP in the given reaction conditions with the prediction accuracy of 90.91% and RMSE of 3.54.

Efficacy of Brentuximab Vedotin and Nivolumab in Refractory or Relapsed Hodgkin Lymphoma: A Systematic Review.

The central dilemma in treating patients with refractory or relapsed classical Hodgkin lymphoma (RRHL) is the developed resistance to chemotherapy. In recent years, significant advances have been made with the introduction of targeted immunotherapy such as brentuximab vedotin (BV) and nivolumab (NV). As monotherapy, BV and NV have demonstrated high response rates but with an opportunity for disease progression. In other studies, BV or NV is given in combination with chemotherapy as a bridge to hematopoietic stem cell transplantation for curative therapy. This review will investigate the effect of BV and NV as single agents, in combination with each other, or given concurrently with chemotherapy on the response and survival rate of patients with RRHL.

Subsets of cancer cells expressing CX3CR1 are endowed with metastasis-initiating properties and resistance to chemotherapy.

Metastasis-initiating cells (MICs) display stem cell-like features, cause metastatic recurrences and defy chemotherapy, which leads to patients' demise. Here we show that prostate and breast cancer patients harbor contingents of tumor cells with high expression of CX3CR1, OCT4a (POU5F1), and NANOG. Impairing CX3CR1 expression or signaling hampered the formation of tumor spheroids by cell lines from which we isolated small subsets co-expressing CX3CR1 and stemness-related markers, similarly to patients' tumors. These rare CX3CR1High cells show transcriptomic profiles enriched in pathways that regulate pluripotency and endowed with metastasis-initiating behavior in murine models. Cancer cells lacking these features (CX3CR1Low) were capable of re-acquiring CX3CR1-associated features over time, implying that MICs can continuously emerge from non-stem cancer cells. CX3CR1 expression also conferred resistance to docetaxel, and prolonged treatment with docetaxel selected CX3CR1High phenotypes with de-enriched transcriptomic profiles for apoptotic pathways. These findings nominate CX3CR1 as a novel marker of stem-like tumor cells and provide conceptual ground for future development of approaches targeting CX3CR1 signaling and (re)expression as therapeutic means to prevent or contain metastasis initiation.

Soil Properties and Weed Dynamics in Wheat as Affected by Rice Residue Management in the Rice-Wheat Cropping System in South Asia: A Review.

The rice-wheat cropping system (RWCS) has substantially contributed in making India self-sufficient in food grain production; however, rice residue management is of great concern, threatening the sustainability of this system. Rice residue is invariably disposed of by farmers through open burning. In addition to environmental pollution, residue burning of rice also leads to loss of soil nutrients. One of the alternatives to overcome these problems and sustain the RWCS is managing the rice residues in the field itself. Rice residue retention has variable effects on agricultural pests (namely, weeds, insect pests, diseases, and rodents) in the RWCS. High weed infestation in the RWCS results in high consumption of herbicides, which leads to several ecological problems and evolution of herbicide resistance. The shift from intensive tillage to conservation tillage causes major changes in weed dynamics and herbicide efficacy. Incorporation of rice residue reduces weed density and helps in improving soil physical, chemical, and biological properties. Rice residue retention on the surface or mulching reduces weed density and the biomass of both grass and broadleaf weeds in wheat crop as compared to its removal. Long-term field studies involving the use of rice residue as a component of integrated weed management strategies are needed to be done in the RWCS.

Culturable endophytic Pseudomonas fluorescens Z1B4 isolated from Zanthoxylum alatum Roxb. with stress-tolerance and plant growth-promoting potential.

Endophytes are an important constituent of sustainable agriculture because of their ability to produce a large number of agriculturally important metabolites. A salt-tolerant fluorescent green pigment-producing endophytic bacterium was isolated on 2.5% NaCl-supplemented nutrient agar from the leaf samples of Zanthoxylum alatum Roxb. The isolate Z1B4 was identified as Pseudomonas fluorescens based on morphological features, fatty acid methyl ester analysis, biochemical tests, and 16S rRNA gene sequencing. P. fluorescens Z1B4 showed positive results for tricalcium phosphate solubilization; 1-aminocyclopropane-1-carboxylate (ACC) deaminase activity; and production of auxins, siderophores, hydrogen cyanide, and ammonia. P. fluorescens Z1B4 also showed strong antagonistic activity against Curvularia lunata (MTCC 283), Fusarium verticillioides (MTCC 3322), and Alternaria alternata (MTCC 1362) and exhibited stress tolerance to a wide range of temperature and pH and concentrations of NaCl and calcium salts. Under natural conditions, following inoculation with the isolate Z1B4, a significant increase in the growth of pea and maize test plants in pots was observed compared to that of uninoculated control plants. The rifampicin-resistant mutant Z1B4Rif was recovered from the roots, shoots, and leaves of the test plants, indicating that the isolated endophytic bacterium can grow well within different plant tissues. The present study indicated that the endophytic bacterium P. fluorescens Z1B4 can be used as a bacterial inoculant in stressed environments for sustainable agriculture.

mRNA localization, reaction centre biogenesis and thylakoid membrane targeting in cyanobacteria.

The thylakoid membranes of cyanobacteria form a complex intracellular membrane system with a distinctive proteome. The sites of biogenesis of thylakoid proteins remain uncertain, as do the signals that direct thylakoid membrane-integral proteins to the thylakoids rather than to the plasma membrane. Here, we address these questions by using fluorescence in situ hybridization to probe the subcellular location of messenger RNA molecules encoding core subunits of the photosystems in two cyanobacterial species. These mRNAs cluster at thylakoid surfaces mainly adjacent to the central cytoplasm and the nucleoid, in contrast to mRNAs encoding proteins with other locations. Ribosome association influences the distribution of the photosynthetic mRNAs on the thylakoid surface, but thylakoid affinity is retained in the absence of ribosome association. However, thylakoid association is disrupted in a mutant lacking two mRNA-binding proteins, which probably play roles in targeting photosynthetic proteins to the thylakoid membrane.

Structural and functional insights about unique extremophilic bacterial lipolytic enzyme from metagenome source.

In the present investigation, a lipid hydrolyzing gene RPK01 was cloned from metagenome source of hot spring. Expression and purification of recombinant protein revealed single purified protein band of ~24 KDa on 12% SDS-PAGE, and is well corroborated with the deduced molecular weight of protein as calculated from its amino acid sequence. The purified protein displayed high activity towards short chain fatty acids and was found to be completely stable at 30°C till 3h, it further retained ~40% activity at 50°C and 60°C temperature till 3h. Additionally, the pH stability assay showed its functionality in broad range of pH, with maximum stability observed at pH 2.0, it decreases from pH 4.0 to pH 12.0, and nearly showed 40% activity in these pH values. Both circular dichroism and intrinsic Trp fluorescence studies revealed conformational stability of protein structure at wide range of temperature and pH. Enzyme activity enhances in presence of non-ionic surfactants like Tween 20 and TritonX-100. Further, inhibitors of the active site residues including PMSF and DEPC alone were unable to inhibit enzyme activity, while cumulative presence of calcium and inhibitors reduces enzyme activity to 90%, indicating conformational changes in the protein. Molecular simulation dynamics analysis revealed a calcium binding site near the lid helix of this protein(Asn75-Ile80).

Vimentin as a potential therapeutic target in sorafenib resistant HepG2, a HCC model cell line.

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is the most common liver cancer with high mortality rate in patients suffering from liver diseases. The drug of choice used in advanced-stage of HCC is sorafenib. However, adaptive resistance has been observed in HCC patients undergoing long-term sorafenib treatment, lowering its effectiveness. Hence, it is important to overcome drug resistance to improve overall management of HCC. Here, we have identified a candidate biomarker for sorafenib resistance in a HCC model cell line, HepG2. METHODS: Initially, comparative proteomic profiling of parental HepG2 [HepG2 (P)] and sorafenib-resistant HepG2 [HepG2 (R)] cells was performed via MALDI (matrix-assisted laser desorption/ionization) which revealed the deregulation of vimentin in HepG2 (R) cells. Gene and protein level expression of vimentin was also observed through quantitative real-time polymerase chain reaction (qRT PCR) and fluorescence-activated cell sorting (FACS), respectively. Furthermore, withaferin A was used to study regulation of vimentin expression and its significance in sorafenib resistance. RESULTS: Both gene and protein level of vimentin expression was found to be downregulated in HepG2 (R) in comparison to HepG2 (P). Interestingly, the study demonstrated that withaferin A further lowered the expression of vimentin in HepG2 (R) cells in a dose-dependent manner. Also, inhibition of vimentin lowered ABCG2 expression and decreased cell viability in parental as well as sorafenib resistant HepG2 cells. CONCLUSION: Hence, our study for the first time highlighted the probable therapeutic potential of vimentin in sorafenib resistant HepG2, a HCC model cell line.

Seroprevalence of measles, mumps & rubella antibodies among 5-10 years old children in north India.

Background & objectives: : Globally, there is an effort to eliminate the measles and control rubella as these diseases lead to considerable morbidity and mortality especially among under-five children and are important public health problems. This study was aimed to estimate the seroprevalence of measles, mumps and rubella (MMR) antibodies among children of age 5-10 yr in Chandigarh, north India, to provide evidence on prevalent immunity levels. Methods: : This cross-sectional study was conducted in Chandigarh, among 196 randomly selected healthy children (5-10 yr), who received either one or two doses of measles or MMR combination vaccine. Socio-economic background and immunization history were recorded. Blood sample (2 ml) was collected to estimate the MMR IgG antibody titres by using ELISA kits. Results: : Protective seroprevalence of MMR antibodies was 40.8, 75.5 and 86.2 per cent, respectively. The geometric mean titres of MMR IgG antibodies in the study children were 11.3, 50.6 and 54.3 international units (IU)/ ml, respectively. The proportion of seroprotected children for measles was significantly higher among those who had received two or more doses (46.4%) of measles vaccine compared to those who had received single dose (35.6%) (P <0.001). About 16 per cent of children had received single dose of MMR vaccine. Among these, 71.4 and 100 per cent were seroprotected against mumps and rubella, respectively. Interpretation & conclusions: : A large proportion of children aged 5-10 yr lacked protective immunity against measles (60%); about one-fourth (15-25%) were susceptible to infection with mumps and rubella virus. Mumps vaccination may be considered to be included in National Immunization Schedule for children with periodic serosurveillance.

GABA (γ-aminobutyric acid), as a thermo-protectant, to improve the reproductive function of heat-stressed mungbean plants.

Rising global temperatures are proving to be detrimental for the agriculture. Hence, strategies are needed to induce thermotolerance in food crops to sustain the food production. GABA (γ-aminobutyric acid), a non-protein amino acid, can partially protect plants from high-temperature stress. This study hypothesises that declining GABA concentrations in the cells of heat-stressed mungbean plants increases the heat-sensitivity of reproductive function. Mungbean plants were grown in a natural, outdoor environment (29.3/16.1 ± 1 °C as mean day/night temperature, 1350-1550 µmol m-2 s-1 light intensity, 60-65% as mean relative humidity) until the start of the reproductive stage. Subsequently, two temperature treatments were imposed in a controlled environment-control (35/23 °C) and heat stress (45/28 °C)-at about 800 µmol m-2 s-1 light intensity and 65-70% as mean relative humidity, until pod maturity. In heat-stressed (HS) plants, endogenous GABA concentrations in leaf and anther samples had declined by 49 and 60%, respectively, and to a much lesser degree in the plants, exogenously supplemented with 1 mM GABA. The reproductive function of GABA-treated heat-stressed plants improved significantly in terms of pollen germination, pollen viability, stigma receptivity and ovule viability, compared to untreated HS controls. In addition, GABA-treated heat-stressed plants had less damage to membranes, photosynthetic machinery (chlorophyll concentration, chlorophyll fluorescence, RuBisCO activity were functionally normal) and carbon assimilation (sucrose synthesis and its utilisation) than the untreated HS controls. Leaf water status improved significantly with GABA application, including enhanced accumulation of osmolytes such as proline and trehalose due to increase in the activities of their biosynthetic enzymes. GABA-treated heat-stressed plants produced more pods (28%) and seed weight (27%) plant-1 than the untreated controls. This study is the first to report the involvement of GABA in protecting reproductive function in mungbean under heat stress, as a result of improved leaf turgor, carbon fixation and assimilation processes, through the augmentation of several enzymes related to these physiological processes.