Search

A pot experiment was conducted in the Department of Soil Science and Agricultural Chemistry, Institute of Agricultural Sciences B.H.U., Varanasi, India during kharif season of 2012 to investigate the efficacy in enhancing uptake of nutrients and yield of rice crop grown in an alluvial soil. The treatments comprised of four levels of rice husk biochar (RHB) (i.e. 0, 1.8, 3.6 and 7.2 g kg-1 soil), two levels of plant growth promoting rhizobacteria (PGPR) (uninoculated and inoculated) and two levels of N, P, K and Zn fertilizers (100% and 75% of RDF). One of the important findings of the investigation pointed beneficial effects of RHB could be exploited if it was applied along with PGPR. Combined application of RHB (3.6 g kg-1 soil) along with PGPR was produced significantly higher rice yield and uptake of nutrients in rice. Inoculation with PGPR also resulted in significantly higher rice yield, nutrients uptake and their availability in soil over uninoculated conditions. [ABSTRACT FROM AUTHOR]

Phosphorus often limits the achievement of high crop yields in low P supplying soils, where P is strongly fixed and largely unavailable for crop uptake. These soils may not be low in total P, but most of it is present in a form of extremely low solubility of Fe/ Al or Ca phosphate. This may result in low P uptake. Even varieties of same species differ in their P efficiency i.e. ability to grow well at low P supply. These differences in P efficiency may be based on differences in the internal P requirement, the uptake efficiency and/or the rate of shoot growth. Several researchers have reported that differences in P efficiency are based on size and type of the root system i.e. root length, root radius and root hair density and rate of shoot growth rate . This shows that a number of reasons may contribute to differences in P efficiency among plants, and that those differences may arise at different stages of the growing cycle. Therefore, the aim of this study was to determine the phosphorus efficiency of wheat, maize and pea, the factors and mechanisms responsible for the observed differences in P efficiency by measuring shoot and root properties during the growing cycle. To achieve these objectives, pot experiments were conducted with wheat, maize and pea during November 2011 to May 2013 in an acid soil of eastern Uttar Pradesh at the Department of Soil Science & Agricultural Chemistry, Institute of Agricultural Sciences, BHU, Varanasi, India. Main problem of this soil is a low fertilizer use efficiency due to P fixation mainly by oxide and hydro-oxide of iron and aluminum, which are abundant in this soil .The soil has 14 - 16 %clay, organic carbon, 0.35 % and pH (H2O)5.3. Treatments consisted of three P levels, P-0 (unfertilized, without P ), P-50 (50 mg P/kg soil) and P-200 (200 mg P/kg soil) as potassium di hydrogen phosphate, four harvest intervals (covering the whole crop growth period) and 4 replications for wheat, maize and pea. Comparing the P uptake of different species at limiting P supply, i.e. mainly on the unfertilized plot, maize was able to absorb significantly higher amount compared to wheat or pea. From the model calculation it is pertinent that at P-0, in most cases the measured influx was higher, in maize up to nine times, than the calculated influx. For pea it was almost five times and in wheat it was close to three times. Reasonably good agreement between calculated and measured P influx into the roots of all crops was obtained at medium as well as high P levels. [ABSTRACT FROM AUTHOR]

A field experiment was conducted during kharif season of 2013 to find out the effect of mulching and NPK levels on pearl millet (Pennisetum glaucum) in bael (Aegle marmelos) based agri-horti system under rainfed condition of Vindhyan region. There were twelve treatment combinations comprised of three levels of mulching (no mulch, wheat straw mulch and dust mulch) and four levels of RDF NPK (50%, 75%, 100%, 125%). The experiment was laid out under split-plot design with three replications. Significant improvement was recorded in growth and yield attributes viz., plant height, number of leaves per plant, number of tillers per plant, dry matter accumulation per plant, number of ears per plant, ear length, number of grains per ear, 1000-grain weight, grain yield, stover yield, harvest index (%), nutrient uptake and economic returns. Significantly higher yield of pearl millet (1908 kg/ha) was observed in the plot that received 125% RDF, which was found at par with the 100% RDF and in case of mulching, the maximum yield was observed with dust mulch (1942 kg/ha) than all other treatments. The application of dust mulch and 125% of the recommended dose of fertilizer (RDF) NPK (T12) treatment have distinct superiority as compared to all other treatments under bael based agri-horti system and more suitable for moisture conservation practice in pearl millet. [ABSTRACT FROM AUTHOR]

After the group exercise, one of the experts apprised the audience about gender vulnerability to climate change and the role of women in climate change mitigation. One member of the Block Development Council, Papoli village pointed out that climate change awareness and resilience building programmes for women would certainly provide a roadmap for adaptive measures to minimize the impacts of climate change. The Gram Pradhan, Papoli highlighted key issues of the impact of climate change on women and suggested development of a framework to mitigate climate change impacts. [Extracted from the article]

The Indian law ministry released a consultation paper in April 2010 inviting comments on proposed amendments to the Indian Arbitration Act. While based on the Model Law, the interpretation of the Indian Act in 15 years since enactment has created serious divergence from transnational standards. A unique absurdity is the delimited application of the Act to even arbitrations seated outside India. Merits review has crept in through innovative means. Public policy defence is read as the repository of all residual powers. The proposals identify the problems, but do they walk the talk? This article analyses the contours of these problems in detail and puts the proposals to test. The conclusion in most cases is that the proposal covers a fraction of the whole issue it attempts to deal with. This article contains suggestions that could help complete the task and align Indian arbitral regime to transnational standards on these issues. [ABSTRACT FROM PUBLISHER]

The current study was conducted at the different villages of the Arajiline block of Varanasi district, Uttar Pradesh, India during November, 2022-June, 2023 to evaluate the variability of soil properties and nutrient indexof soils. The random sampling technique was used to collect 40 soil samples at different locations with the help of GPS at 0-15 cm depth. The collected soil samples were air-dried in shade at room temperature, passed through a 2 mm filter paper, and analyzed for different physico-chemical properties. The result revealed that the TS (range 8.2-81.3%), VFS (range 4.2-35.5%), Silt (range 10.1-54.2%), Clay (range 7.7-38.8%), BD (range 1.08-1.45 g cm-3), PD (range 2.04-2.33), Porosity (range 30.24-51.56%) pH (range 6.4-7.8), EC (range 0.1-0.3 dS m-1), OC (0.2-0.6%), and available N, P, K, S, Ca, and Mg varied from 130.12-260.30 kg ha-1, 14.2-23.2 kg ha-1, 145.0-240.0 kg ha-1, 7.5-17.6 kg ha-1, 3.8-8.2 cmol(P+)/kg, and 2.1-4.1 cmol(P+)/kg, respectively. The findings indicated that the studied soils were slightly acidic to moderately acidic and free from salinity hazards; 70% of the soil samples were low in organic carbon, 30% were medium in organic carbon, and 100% of the soil samples were low in available N and medium in available P, K, and S. 100% of soil samples were found to be sufficient in exchangeable Ca and Mg. The findings of this research could help in crop nutrient management, fertilizer recommendation, and decision-making for increasing agricultural production and farmer profitability. [ABSTRACT FROM AUTHOR]

Interactions between cells in the stroma and epithelium facilitate prostate stem cell activity and tissue regeneration capacity. Numerous molecular signal transduction pathways, including the induction of sonic hedgehog (Shh) to activate the Gli transcription factors, are known to mediate the cross-talk of these two cellular compartments. However, the details of how these signaling pathways regulate prostate stem and progenitor cell activity remain elusive. Here we demonstrate that, although cell-autonomous epithelial Shh-Gli signaling is essential to determine the expression levels of basal cell markers and the renewal potential of epithelial stem and progenitor cells, stromal Gli signaling regulates prostate stem and progenitor cell activity by increasing the number and size of prostate spheroids in vitro. Blockade of stromal Gli signaling also inhibited prostate tissue regeneration in vivo. The inhibition of stromal Gli signaling suppressed the differentiation of basal and progenitor cells to luminal cells and limited prostate tubule secretory capability. Additionally, stromal cells were able to compensate for the deficiency of epithelial Shh signaling in prostate tissue regeneration. Mechanistically, suppression of Gli signaling increased the signaling factor transforming growth factor β (TGFβ) in stromal cells. Elevation of exogenous TGFβ1 levels inhibited prostate spheroid formation, suggesting that a stromal Gli-TGFβ signaling axis regulates the activity of epithelial progenitor cells. Our study illustrates that Gli signaling regulates epithelial stem cell activity and renewal potential in both epithelial and stromal compartments. [ABSTRACT FROM AUTHOR]

Dysregulated pre-mRNA splicing is an emerging Achilles heel of cancers and myelodysplasias. To expand the currently limited portfolio of small-molecule drug leads, we screened for chemical modulators of the U2AF complex, which nucleates spliceosome assembly and is mutated in myelodysplasias. A hit compound specifically enhances RNA binding by a U2AF2 subunit. Remarkably, the compound inhibits splicing of representative substrates and stalls spliceosome assembly at the stage of U2AF function. Computational docking, together with structure-guided mutagenesis, indicates that the compound bridges the tandem U2AF2 RNA recognition motifs via hydrophobic and electrostatic moieties. Cells expressing a cancer-associated U2AF1 mutant are preferentially killed by treatment with the compound. Altogether, our results highlight the potential of trapping early spliceosome assembly as an effective pharmacological means to manipulate pre-mRNA splicing. By extension, we suggest that stabilizing assembly intermediates may offer a useful approach for small-molecule inhibition of macromolecular machines. [Display omitted] • A small molecule binds to U2AF2 and promotes its association with splice site RNA • Promoting the U2AF2-RNA complex stalls the initial stages of spliceosome assembly • The small molecule exacerbates pre-mRNA splicing defects of U2AF1 mutant cells • Cancer-relevant U2AF1 mutant cells are preferentially killed by the small molecule Many cancers and myelodysplasias are associated with pre-mRNA splicing defects. Chatrikhi et al. describe a hit compound that stalls pre-mRNA splicing at the initial stages of spliceosome assembly by binding to U2AF2 and promoting U2AF2-RNA association. Treatment with the molecule alters splicing and preferentially kills cells expressing a cancer-relevant U2AF1 mutant. [ABSTRACT FROM AUTHOR]

RNA splicing factor (SF) gene mutations are commonly observed in patients with myeloid malignancies. Here we showed that SRSF2- and U2AF1-mutant leukemias are preferentially sensitive to PARP inhibitors (PARPi), despite being proficient in homologous recombination repair. Instead, SF-mutant leukemias exhibited R-loop accumulation that elicited an R-loop-associated PARP1 response, rendering cells dependent on PARP1 activity for survival. Consequently, PARPi induced DNA damage and cell death in SF-mutant leukemias in an R-loop-dependent manner. PARPi further increased aberrant R-loop levels, causing higher transcription-replication collisions and triggering ATR activation in SF-mutant leukemias. Ultimately, PARPi-induced DNA damage and cell death in SF-mutant leukemias could be enhanced by ATR inhibition. Finally, the level of PARP1 activity at R-loops correlated with PARPi sensitivity, suggesting that R-loop-associated PARP1 activity could be predictive of PARPi sensitivity in patients harboring SF gene mutations. This study highlights the potential of targeting different R-loop response pathways caused by spliceosome gene mutations as a therapeutic strategy for treating cancer., Significance: Spliceosome-mutant leukemias accumulate R-loops and require PARP1 to resolve transcription-replication conflicts and genomic instability, providing rationale to repurpose FDA-approved PARP inhibitors for patients carrying spliceosome gene mutations., (©2023 American Association for Cancer Research.)

Purpose: To investigate the antibiotic resistance and genetic profile of ceftriaxone-resistant Salmonella Typhi isolated from the blood culture of two paediatric cases of typhoid fever and one from the stool culture of their household contact, in North India., Methods: In this study, whole-genome sequencing was carried out with paired-end 2 ​× ​150 bp reads on Illumina MiSeq (Illumina, USA) employing v2 and v3 chemistry. To check data quality, adapters and low-quality sequences were removed through Trimmomatic-v0.36. High quality reads were then assembled de novo using A5-miseq pipeline. For further refinement, reference-guided contig ordering and orienting were performed on the scaffold assemblies using ABACAS (http://abacas.sourceforge.net/). The assembled genome was annotated using Prokka v1.12 to identify and annotate the gene content. Plasmid replicons in bacterial isolates were identified by PlasmidFinder, whereas mobile genetic elements were predicted using Mobile Element Finder. Referenced-based SNP tree with maximum likelihood method was built with CSI phylogeny v1.4., Results: All three isolates exhibited resistance to ceftriaxone, cefixime, ciprofloxacin, ampicillin, and co-trimoxazole, while demonstrating sensitivity to azithromycin and chloramphenicol. The whole-genome sequencing of these strains revealed the presence of blaCTX-M-15 gene for cephalosporin resistance in addition to gyrA, qnr and IncY plasmid replicon. A 5 ​kb IS91 Sbo1 gene cassette (IncY plasmid) was identified which carried extended spectrum β-lactamase blaCTX-M-15, blaTEM-1D (resistance to ampicillin and cephalosporin), sul2, dfrA14 (resistant to trimethoprim-sulfamethoxazole) and qnrS (resistant to ciprofloxacin). These isolates belong to H58 lineage and grouped as sequence type 1 (ST1) on multilocus sequence typing (MLST) analysis., Conclusion: In the present study we report the isolation of blaCTX-M-15 positive S. Typhi from two paediatric patients presenting with fever and one from stool culture of their contact from North India and highlight the need for further investigations to understand the different factors contributing to ceftriaxone resistance in Salmonella Typhi., (Copyright © 2023 Indian Association of Medical Microbiologists. Published by Elsevier B.V. All rights reserved.)

Background: The CLSI annual update of its M100 document is eagerly awaited every year. This year's update, the M100-Ed33, was published in February, and will significantly affect clinical practices., Objective: To highlight and explain the rationale of the changes and their clinical impact., Content: The major changes this year are mostly focused on PK/PD data, selective and cascade reporting of the antibiotics and therapy related comments. The CLSI has moved away from its classical grouping of antibiotics (A, B, U, O) to a tier-based approach (Tier 1, 2, 3, 4) which will aid in cascade reporting during an antibiotic susceptibility testing (AST). Rather than non-fastidious, fastidious and anaerobe grouping, the tables have been made organism specific. The aminoglycosides breakpoints have been changed for both Enterobacterales and Pseudomonas aeruginosa while for P. aeruginosa, the breakpoints of piperacillin - tazobactam (TZP) are also updated. These updates are mostly based on attainment of drug plasma level for bacterial stasis rather than bactericidal effect of the antibiotics. It is noteworthy, that these breakpoint changes are made, keeping in view that the aminoglycosides for all organisms should be used in combination therapy. For P. aeruginosa, gentamicin has been removed, while amikacin has been restricted for urinary isolates only., Competing Interests: Declaration of competing interest Rai S reports a relationship with AIIMS Mangalagiri that includes: employment., (Copyright © 2023 Indian Association of Medical Microbiologists. Published by Elsevier B.V. All rights reserved.)

Purpose: Metastatic hormone receptor-positive (HR+) breast cancer initially responds to serial courses of endocrine therapy, but ultimately becomes refractory. Elacestrant, a new generation FDA-approved oral selective estrogen receptor degrader (SERD) and antagonist, has demonstrated efficacy in a subset of women with advanced HR+breast cancer, but there are few patient-derived models to characterize its effect in advanced cancers with diverse treatment histories and acquired mutations., Methods: We analyzed clinical outcomes with elacestrant, compared with endocrine therapy, among women who had previously been treated with a fulvestrant-containing regimen from the recent phase 3 EMERALD Study. We further modeled sensitivity to elacestrant, compared with the currently approved SERD, fulvestrant in patient-derived xenograft (PDX) models and cultured circulating tumor cells (CTCs)., Results: Analysis of the subset of breast cancer patients enrolled in the EMERALD study who had previously received a fulvestrant-containing regimen indicates that they had better progression-free survival with elacestrant than with standard-of-care endocrine therapy, a finding that was independent estrogen receptor (ESR1) gene mutations. We modeled elacestrant responsiveness using patient-derived xenograft (PDX) models and in ex vivo cultured CTCs derived from patients with HR+breast cancer extensively treated with multiple endocrine therapies, including fulvestrant. Both CTCs and PDX models are refractory to fulvestrant but sensitive to elacestrant, independent of mutations in ESR1 and Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha (PIK3CA) genes., Conclusion: Elacestrant retains efficacy in breast cancer cells that have acquired resistance to currently available ER targeting therapies. Elacestrant may be an option for patients with HR+/HER2- breast cancer whose disease progressed on fulvestrant in the metastatic setting., Translational Relevance: Serial endocrine therapy is the mainstay of management for metastatic HR+breast cancer, but acquisition of drug resistance highlights the need for better therapies. Elacestrant is a recently FDA-approved novel oral selective estrogen receptor degrader (SERD), with demonstrated efficacy in the EMERALD phase 3 clinical trial of refractory HR+breast cancer. Subgroup analysis of the EMERALD clinical trial identifies clinical benefit with elacestrant in patients who had received prior fulvestrant independent of the mutational status of the ESR1 gene, supporting its potential utility in treating refractory HR+breast cancer. Here, we use pre-clinical models, including ex vivo cultures of circulating tumor cells and patient-derived xenografts, to demonstrate the efficacy of elacestrant in breast cancer cells with acquired resistance to fulvestrant., (© 2023. The Author(s).)

Prostate stem/progenitor cells (PrSCs) are responsible for adult prostate tissue homeostasis and regeneration. However, the related regulatory mechanisms are not completely understood. In this study, we examined the role of heparan sulfate (HS) in PrSC self-renewal and prostate regeneration. Using an in vitro prostate sphere formation assay, we found that deletion of the glycosyltransferase exostosin 1 (Ext1) abolished HS expression in PrSCs and disrupted their ability to self-renew. In associated studies, we observed that HS loss inhibited p63 and CK5 expression, reduced the number of p63+- or CK5+-expressing stem/progenitor cells, elevated CK8+ expression and the number of differentiated CK8+ luminal cells and arrested the spheroid cells in the G1/G0 phase of cell cycle. Mechanistically, HS expressed by PrSCs (in cis) or by neighboring cells (in trans) could maintain sphere formation. Furthermore, HS deficiency upregulated transforming growth factor β (TGFβ) signaling and inhibiting TGFβ signaling partially restored the sphere-formation activity of the HS-deficient PrSCs. In an in vivo prostate regeneration assay, simultaneous loss of HS in both epithelial cell and stromal cell compartments attenuated prostate tissue regeneration, whereas the retention of HS expression in either of the two cellular compartments was sufficient to sustain prostate tissue regeneration. We conclude that HS preserves self-renewal of adult PrSCs by inhibiting TGFβ signaling and functions both in cis and in trans to maintain prostate homeostasis and to support prostate regeneration., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)