Search

Aspergillus fumigatus (A. fumigatus) is a medically important opportunistic fungus that may lead to invasive aspergillosis in humans with weak immune system. Proteomic profiling of this fungus on exposure to itraconazole (ITC), an azole antifungal drug, may lead to identification of its molecular targets and better understanding on the development of drug resistance against ITC in A. fumigatus. Here, proteome analysis was performed using 2-DE followed by mass spectrometric analysis which resulted in identification of a total of 259 unique proteins. Further, proteome profiling of A. fumigatus was carried out on exposure to ITC, 0.154 μg/ml, the minimum inhibitory concentration (MIC50). Image analysis showed altered levels of 175 proteins (66 upregulated and 109 downregulated) of A. fumigatus treated with ITC as compared to the untreated control. Peptide mass fingerprinting led to the identification of 54 proteins (12 up-regulated and 42 down-regulated). The differentially expressed proteins include proteins related to cell stress, carbohydrate metabolism and amino acid metabolism. We also observed four proteins, including nucleotide phosphate kinase (NDK), that are reported to interact with calcineurin, a protein involved in regulation of cell morphology and fungal virulence. Comparison of differentially expressed proteins on exposure to ITC with artemisinin (ART), an antimalarial drug with antifungal activity1, revealed a total of 26 proteins to be common among them suggesting that common proteins and pathways are targeted by these two antifungal agents. The proteins targeted by ITC may serve as important leads for development of new antifungal drugs. [ABSTRACT FROM AUTHOR]

2-Benzylidene-1-tetralones, obtained via of 1-tetralones with aromatic aldehydes, in one pot condensation with thiosemicarbazide/semicarbazide and α-haloketones in the presence of trifluoroethanol and conc. HCl gives rise to a series of new substituted-3,3a,4,5-tetrahydro-2 H-benzo[ g]indazol-2yl-thiazoles. The condensation was also carried out in two steps, and the intermediates 3-substituted-3,3a,4,5-tetrahydro-2 H-benzo[ g]indazole-2-carbothioamides/carboxamides, obtained in the first step by the reaction of 2-bezylidene-1-tetralones with thiosemicarbazide/semicarbazide, on reaction with α-haloketones gives rise to indazolyl-thiazoles. A detailed X-ray diffractometry of (3a R)-3-phenyl-3,3a,4,5-tetrahydro-2 H-benzo[ g]indazole-2-carbothioamide were carried out to establish its crystal structure. Further, density functional theory studies on (3a R)-3-phenyl-3,3a,4,5-tetrahydro-2 H-benzo[ g]indazole-2-carbothioamide and its regioisomer were carried out. There is good correlation between the theoretical and experimental spectral data. The antibacterial and antifungal activities of the selected compounds were examined, and some are found to exhibit excellent activities. [ABSTRACT FROM AUTHOR]

A short two-step synthesis of substituted dihydro-1 H-pyrazolo[3,4- d]thiazoles from 4-thiazolidinones is described. 4-Thiazolidinones are easily synthesized by the reaction of thiosemicarbazones of carbonyl compounds and chloroacetic acid. Upon treatment with Lawesson's reagent and dimethylformamide-dimethylacetal, 5-dimethylaminomethylene-3-methylthiazolidine-4-thiones are formed, which undergo condensation with hydrazine derivatives to furnish substituted dihydro-1 H-pyrazolo[3,4- d]thiazoles. The structure of the synthesized compounds was established by elemental analysis and analysis of spectral data. [ABSTRACT FROM AUTHOR]

In order to develop the relationship between soil test and response of lentil to applied fertilizers under Integrated Plant Nutrition System (STCR-IPNS), a field experiment was conducted on Aquic Hapludoll of Uttarakhand during Rabi 2009-10 following Ramamoorthy's targeted yield model. Using the data on grain yield, initial soil test values on available NPK, doses of fertilizers and farm yard manure (FYM) applied and NPK uptake, the basic parameters viz., nutrient requirement, contribution from soil, fertilizers and FYM were computed. It was found that 5.24, 0.72 and 3.58 kg of N, P and K respectively were required for producing one quintal of grain. The percent contribution of nutrients from soil, fertilizer and FYM were 32.01, 43.02 and 11.02 for N; 30.0, 32.03 and 8.04 for P; 31.06, 42.01 and 9.00 for K respectively. Making use of these basic parameters, fertilizer prescription equations were developed for lentil (var. PL-5) and an estimate of fertilizer doses were formulated for a range of soil test values and desired yield targets under NPK alone and IPNS (NPK plus FYM). Coefficient of determination (R²) was significant (0.805 **) between yield and soil test values. Verification trial was also conducted to test the validity of fertilizer prescription equations in next season i.e. Rabi 2010- 11. The variation in yield obtained from targeted yield ranged from -5.0 to +1.9%.The farmer's practice of fertilizer application was least efficient to produce grain yield of lentil in comparison to other treatments. Highest response ratio was found with farm yard manure 10 t ha-1+ yield target 16 q ha-1. [ABSTRACT FROM AUTHOR]

Field experiment was conducted at Norman E. Borlaug Crop Research Centre, Govind Ballabh Pant University of Agriculture and Technology, Pantnagar during 2008-09 to study the effect of integrated nutrient management on wheat under rice-wheat cropping system in a Mollisol. Twelve treatments were replicated twice in split plot design with 12 main and 2 sub plots. Plant height, number of tillers, wheat grain and straw yield were noted. Nutrient content (N, P, K & S) in wheat and nutrient uptake (N, P, K & S) by wheat were determined. Partial replacement of N through FYM and wheat and moong straw resulted in significant improvement in nutrient concentration as well as their uptake and wheat yield. The treatments with 100% N or NPK and 50% N applied through moong straw were better than all other treatments and moong straw proved the best among organic sources of N studied in respect of its effect on wheat yield & nutrient status in plant. [ABSTRACT FROM AUTHOR]

Response of wheat to twenty four selected treatment combinations of four levels of N, P, K and three levels of FYM with simultaneous variation in initially available nutrients was studied under soil-test-crop-response calibration in Aquic Hapludoll during 2005-07. To produce 100 kg of grain, 2.72, 0.49, 2.67 kg of N, P, K were required. Per cent contribution of nutrients each through soil, chemical fertilizer and FYM were also computed. Yield and soil analysis data were utilized to formulate prescription equations for varying yield targets. Significant R2 (0.914) was observed between yield and soil test values and fertilizer nutrients. N correlated most with grain yield and quality parameters. Verification trial was also conducted in next season, revealed the highest response and benefiticost ratio were found to be with yield target 4.5 t/ha + FYM @ 101/ha, with a targeted yield variation of -2.78 to +0.9%. [ABSTRACT FROM AUTHOR]

Allergenic/antigenic proteins are known to induce Type I and Type III hypersensitivity reactions leading to allergic bronchopulmonary aspergillosis (ABPA) in immunocompetent host. The common structural features or intrinsic properties of the allergens/antigens leading to allergenicity in a host are not well understood. In the current report, comparative analysis of proteins on two dimensional gel electrophoresis (2D-3) and specific IgE immunoblots of A. fumigatus secretory proteins (1st, 2nd and 3rd week culture filtrate proteins) was carried out. We observed a total of 159 proteins in 1st, 2nd and 3rd week culture filtrates of A. fumigatus. Specific IgE immunoreactivity was observed in 75 proteins with different intensity. Third week culture filtrate showed maximum number of proteins, 142, and specific IgE immunoreactive proteins, 65. MALDI-TOF analysis resulted in putative identification of two allergens as hypothetical protein YBL057c from Saccharomyces cereviseae and unnamed protein product from Debaryomyces hansenii (similar to IPF14568 of Candida albicans). Identification of a repertoire of specific IgE immunoreactive proteins will facilitate the studies on structure-function relationship of these proteins relevant for diagnosis and pathogenesis. [ABSTRACT FROM AUTHOR]

Background: Meningioma is the most prevalent primary intracranial brain tumor and accounts for one-third of all CNS tumors. Meningioma is known to be the most common yet life-threatening brain tumor with a higher recurrence rate. Globally, there is an increase in the healthcare burden due to meningioma and hence in its research. The present clinical approach includes surgical resection, chemotherapy, and radiation therapies to which the malignancy does not seem to respond efficiently. Targeted therapies and molecular markers provide elite patient treatment and care for individuals suffering from meningiomas as compared to conventional measures. Although there is proteomic data on meningioma the knowledge of potential biomarkers differentiating the grades is scarce. To identify the best set of biomarkers, validation of reported markers in large and independent sample cohorts in the future is necessary., Methods: A total of 12 samples, 3 each of control (which made pool 1) Meningioma grade I (which made 2 sets: pool 2 and pool 3), and Meningioma grade II (which made pool 4) were taken for LC-MS/MS. After this, the expression of three proteins was checked by immunocytochemistry, flow cytometry, and western blotting., Results: Protein expression was analyzed using various techniques like mass spectrometry, immunocytochemistry, flow cytometry, and western blotting. Mass spectrometry is the most commonly used standard and reliable technique for identifying and quantifying protein expression. We got three highly upregulated proteins namely AK2, COL1A1, and PLG using this technique. The biomarker potential of these proteins was further checked by ICC, western blotting, and flow cytometry. Three important proteins were found to be upregulated namely AK2 (Adenylate Kinase 2), COL1A1 (Collagen 1A1), and PLG (Plasminogen). The order of increased protein expression was control < MG grade I < MG grade II according to mass spectrometry and western blotting. In immunocytochemistry, we found that COL1A1 expression increases significantly with grades in comparison to control. Similarly, AK2 and PLG also showed little increase but not as much as COL1A1. In flow cytometry, PLG showed higher upregulation in grades than control. While AK2 and COL1A1 showed little increase in expression in grades than control. All techniques, especially mass spectrometry and western blotting presented higher expression of these proteins in grades as compared to control., Conclusions: In the quest to find a suitable therapeutic marker, this study incorporates quantitative labeling and detection followed by flow cytometry, Immunocytochemistry, and western blotting for early diagnosis and treatment of meningioma. The article further explores the efficacy of some proteins namely AK2, COL1A1 & PLG to be the targeted molecules., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Glioblastoma multiforme (GBM) is one of the most lethal brain tumors with an inadequately understood pathophysiology. Biomarkers that guide accurate diagnosis and treatment decisions would greatly support precision medicine for GBM. Previous studies of GBM have focused on signaling pathways such as epidermal growth factor receptor (EGFR), platelet-derived growth factor receptors (PDGFRs), notch, wnt, and others, identified with single omics technology platforms (genomics, transcriptomics, or proteomics), but not with their integrated use. In this context, we report here a multi-omics pathway view, expanded through integration of the expression data at transcriptomic and proteomic levels, followed by selection of a functionally related group of proteins such as kinases deregulated in GBM. By using this strategy, we observed a highly significant enrichment of the gonadotropin-releasing hormone (GnRH) signaling pathway that was not deciphered with single omics datasets. The curation of the GnRH pathway with extensive literature analysis brought about a comprehensive annotation of the pathway, which included several additional pathway members that were not previously annotated. A targeted search resulted in identification of additional nonkinase members of the pathway in the GBM multi-omics datasets. We found evidence of GnRH receptor expression in GBM and other cancers. We offer here an updated generic pathway map of GnRH signaling, show its enrichment in the context of GBM, and discuss its plausible cross-connectivity with EGFR, wnt, calcium, and focal adhesion kinase signaling pathways that were earlier shown to be the top deregulated pathways in GBM. In conclusion, this study demonstrates the promise of multi-omics research and analyses to better understand complex cancers and suggests continued efforts and research in this direction in the field of integrative biology.