Investigating the Role of TP53 in Peripheral T-Cell Lymphoma-GATA3 Subtype

Introduction: Non-Hodgkin Lymphoma (NHL) accounts for 4.1% of all cancers in the United States. Peripheral T-Cell Lymphoma (PTCL) consists of ~10-15% of all NHL in the Western world. 30-50% of these PTCLs are not classifiable/diagnosed and are instead designated as PTCL-Not Otherwise Specified (PTCL-NOS). The two major molecular subgroups within PTCL-NOS are PTCL-TBX21 and PTCL-GATA3, determined by their distinct T-helper (TH) transcriptional programs. GATA3 and TBX21 are the master-transcriptional regulators of TH2- and TH1-cell differentiation, respectively. The overall survival analysis of PTCL-NOS cases illustrates the clinical outcome of PTCL-GATA3 cases are significantly lower than PTCL-TBX21 cases over a broad timeframe. Thus, the need for understanding the underlying mechanism and finding therapeutic targets is at the utmost importance. Background: TP53 mutations and/or TP53 loss deletions are frequent in PTCL-GATA3 cases, compared to PTCL-TBX21. TP53 is a protein that is essential in cycle regulation but also acts as a tumor suppressor. It stops cells from dividing if they have mutated or damaged DNA. Due to the high mutation rates observed in this subtype, we believe TP53 could play a major role in this mechanism. Therefore, it was important to focus on the TP53-GATA3 interaction at the genomic level. Prior studies using chromatin immunoprecipitation (ChIP)-qPCR on the intron 3 full GATA3 region suggested there was more TP53 binding in this intron region compared to other regions. Therefore, we designed a research strategy to determine the specific binding regions of TP53-GATA3 interaction and the function of the TP53 binding.https://digitalcommons.unmc.edu/surp2023/1003/thumbnail.jp

Effect of Different Levels of Phosphorus and Sulphur on Seed & Stover Yield of Soybean (Glycine max L. Merill) under 'Eutrochrepts'

A field experiment was conducted at KVK, Srinagar during two consecutive kharif seasons of 2010 and 2011 to study the “Effect of phosphorus and sulphur on yield and quality of soybean (Glycine max L. Merill) under Eutrochrepts”. The experiment was laid down under 16 treatment combinations viz four levels of phosphorus (0, 30, 60, 90 kg P2O5 ha-1) and four levels of sulphur (0,15, 30, 45 kg S ha-1) in randomized complete block design with three replications .The soil of the experimental site was typic Eutrochrepts, silty clay loam in texture having pH 7.18, EC 0.18 dSm-1, organic carbon 0.74 per cent, available N, P, K 250.52, 11.45, 120.62, kg ha-1, respectively. Soil was sufficient in available Fe, Cu, Mn and deficient in available Zn and sulphur. Total and organic phosphorus content in soil was 345 and 173 ppm, respectively while as total and organic sulphur content was 232 and 162 ppm, respectively. Both seed and stover yield of soybean increased significantly due to individual as well as combined application of phosphorus and sulphur. Combined application of 45 kg S with 90 kg P2O5 produced highest seed (24.39 q ha-1) and stover (43.51 q ha-1) yield of soybean. Application of increasing levels of both phosphorus and sulphur resulted in a significant increase in macro and micronutrient content of soybean seed. With application of 90 kg P2O5 ha-1, maximum nutrient content of N, P, K, Ca, Mg and S in seed was 6.42, 0.56, 1.876, 0.324 0.440, 0.466 per cent, respectively while as Fe, Cu, Mn was 100.01, 2.86 and 3.74 mg kg-1, respectively

Soybean and Sustainable Agriculture for Food Security

Global food security is under-challenged due to over increasing human population, limited cropland, and risk of climate change. Therefore, an appropriate agricultural policy framework needs to be developed for food security that should be sustainable economically and ecologically. Nitrogen (N) is a crucial element that controls the growth productivity of crop plants. N accounts for around 78 volume per cent of the atmosphere but all crop plants cannot use it directly. Agricultural land is mostly dominated by cereals (e.g. rice, wheat, maize) which have specifically high N demand as compared to food legumes. Soybean exemplifies the most significant and cultivated food legume, presently cultivated worldwide under varying climatic conditions. It plays a significant role in global food security as well as agricultural sustainability due to a high seed protein and oil concentration, and low reliance on N fertilization. Soybean enriches soil health by fixing atmospheric N through biological nitrogen fixation (BNF), the most productive and economical system for N fixation and crop production, associated with more intensive production systems. However, the efficiency of BNF depends on several factors. This study is focused to develop more reliable guidelines for managing BNF by using the potential of natural agro-ecosystems

Evaluation Criteria for the Suitability of Apple Cultivation in Kashmir Valley, India

The study aims to provide viable criteria to assess land suitability for apple growing in Kashmir Valley, India. It used a Delphi survey and the analytical hierarchical process (AHP) approach to determine factors influencing apple production. The evaluation criteria were obtained through multiple rounds of the Delphi survey of stakeholders. The Delphi outcome was extended to enable prioritization of the criteria, using a pair-wise comparison process. Results show that experts value physical and economic considerations (accounting for 87% of the overall weight) more than social factors. Furthermore, location-specific factors (i.e., cost-benefit ratio and landholding size) have significant bearings on land suitability for apple in the study area. The Delphi-AHP method proved to be useful as it incorporated core issues of agricultural land use by creating a common framework for suitability evaluation and eliminated uncertainties in the decision-making process

Economic and Profitability Analysis of Walnut Production in Kashmir Valley, India

The Jammu and Kashmir union territory is the largest producer of walnuts in India, and this crop provides an important source of livelihood for many farmers. This study aims to measure the economic efficiency and profitability of walnut orchards and explore constraints in cultivation in the Kashmir Valley. It relies on a crosssectional database collected from 240 walnut growers in the study area during the 2018/19 production period. Results reveal that walnut cultivation is highly labor-intensive as it incurs 80 percent of total production costs. The cost-benefit ratio of 1:5.35 per hectare indicates better economic prospects for the walnut industry in Kashmir Valley. The factors affecting productivity include farmyard manure, labor, chemical fertilizers, plant density, women participation, and information. The regression coefficients of production analysis, marginal value product, and marginal factor cost ratio indicate that there is ample scope for the expansion of walnut cultivation in the research area. However, walnut growers are confronted by several problems that tend to be location specific. The study calls for policy intervention concerning improved access to extension services, credit, and farmer training programs to boost walnut production in the study region

Screening Technique Based on Seed and Early Seedling Parameters for Cold Tolerance of Selected F₂-Derived F₃ Rice Genotypes under Controlled Conditions

The cold tolerance studies were carried out in a bi-parental F2 population of a cross between tolerant and susceptible parents (SKUA-529 and HEERA, respectively). The purpose was to screen the individuals of a population for primary cold-tolerance-related attributes. The information generated has a direct application and use in identifying cold tolerance quantitative trait loci (QTLs) and further can be used for genotyping with an appropriate marker system. The screening was carried out on F2-derived F3 seeds and F3 plants for seedling and agronomic traits, respectively. Two tests measuring cold tolerance were conducted. In experiment I, seeds were germinated for 28 days at 13 °C and 7 days at 28 °C, and in experiment II, the seeds were germinated for 72 h at 28 °C, 96 h at 13 °C, and once more for 72 h at 28 °C. Coleoptile length, germination percentage, and radical reduction percentages were all measured in experiment I. The radicle and coleoptile regeneration in experiment II were measured after the cold period. The improvement in cold tolerance was achieved through radicle regrowth, as evidenced by the difference between the second and first measurements. The individual lines from the F2:3 population that recorded high germination (%) were #21, #13, #14, and #15. The percentage of coleoptile length (PERCOL %) was observed to be between the ranges of 23.33% to 53.00%. The reduction in coleoptile length (REDCOL %) was also obtained, and there was less reduction in #15, #16, and #14 and it had a range between 38.46% and 75%. Radicle regrowth (REDRAG) was high at 13 °C in #7, #11, #30, #35, and #36. Survival of the seedling range was between 33.33% and up to 100%, and the highest survival rate was observed in #16. The main objective of this rotation in temperature was to emulate field conditions where there has been a drop in temperature. The evaluations were done for primary cold stress tolerance traits, and it was found that most of these traits exhibited high variability. The mapping population developed may be utilized to generate a linkage map and locate QTLs for tolerance to cold stress in rice. Further, the identified donors for cold tolerance may be utilized for breeding programs aimed at the transfer of low-temperature stress tolerance into susceptible backgrounds. In general, a genotype with improved seedling germination rates, growth rates, and leaf yellowing scores; high seedling survival; lesser reduction in coleoptile length and in radicle development; and recovery following a cold shock at the seedling stage demonstrated its cold resistance. Genotypes with a low germination percentage, a greater number of days to germination, slow growth rate and higher leaf yellowing score, high reduction in coleoptile and radicle growth, and reduced seedling survival indicated cold susceptibility

Screening Technique Based on Seed and Early Seedling Parameters for Cold Tolerance of Selected F2-Derived F3 Rice Genotypes under Controlled Conditions

The cold tolerance studies were carried out in a bi-parental F2 population of a cross between tolerant and susceptible parents (SKUA-529 and HEERA, respectively). The purpose was to screen the individuals of a population for primary cold-tolerance-related attributes. The information generated has a direct application and use in identifying cold tolerance quantitative trait loci (QTLs) and further can be used for genotyping with an appropriate marker system. The screening was carried out on F2-derived F3 seeds and F3 plants for seedling and agronomic traits, respectively. Two tests measuring cold tolerance were conducted. In experiment I, seeds were germinated for 28 days at 13 °C and 7 days at 28 °C, and in experiment II, the seeds were germinated for 72 h at 28 °C, 96 h at 13 °C, and once more for 72 h at 28 °C. Coleoptile length, germination percentage, and radical reduction percentages were all measured in experiment I. The radicle and coleoptile regeneration in experiment II were measured after the cold period. The improvement in cold tolerance was achieved through radicle regrowth, as evidenced by the difference between the second and first measurements. The individual lines from the F2:3 population that recorded high germination (%) were #21, #13, #14, and #15. The percentage of coleoptile length (PERCOL %) was observed to be between the ranges of 23.33% to 53.00%. The reduction in coleoptile length (REDCOL %) was also obtained, and there was less reduction in #15, #16, and #14 and it had a range between 38.46% and 75%. Radicle regrowth (REDRAG) was high at 13 °C in #7, #11, #30, #35, and #36. Survival of the seedling range was between 33.33% and up to 100%, and the highest survival rate was observed in #16. The main objective of this rotation in temperature was to emulate field conditions where there has been a drop in temperature. The evaluations were done for primary cold stress tolerance traits, and it was found that most of these traits exhibited high variability. The mapping population developed may be utilized to generate a linkage map and locate QTLs for tolerance to cold stress in rice. Further, the identified donors for cold tolerance may be utilized for breeding programs aimed at the transfer of low-temperature stress tolerance into susceptible backgrounds. In general, a genotype with improved seedling germination rates, growth rates, and leaf yellowing scores; high seedling survival; lesser reduction in coleoptile length and in radicle development; and recovery following a cold shock at the seedling stage demonstrated its cold resistance. Genotypes with a low germination percentage, a greater number of days to germination, slow growth rate and higher leaf yellowing score, high reduction in coleoptile and radicle growth, and reduced seedling survival indicated cold susceptibility

The miR-141/200c-STAT4 Axis Contributes to Leukemogenesis by Enhancing Cell Proliferation in T-PLL

T-prolymphocytic leukemia (T-PLL) is a rare and mature T-cell malignancy with characteristic chemotherapy-refractory behavior and a poor prognosis. Molecular concepts of disease development have been restricted to protein-coding genes. Recent global microRNA (miR) expression profiles revealed miR-141-3p and miR-200c-3p (miR-141/200c) as two of the highest differentially expressed miRs in T-PLL cells versus healthy donor-derived T cells. Furthermore, miR-141/200c expression separates T-PLL cases into two subgroups with high and low expression, respectively. Evaluating the potential pro-oncogenic function of miR-141/200c deregulation, we discovered accelerated proliferation and reduced stress-induced cell death induction upon stable miR-141/200c overexpression in mature T-cell leukemia/lymphoma lines. We further characterized a miR-141/200c-specific transcriptome involving the altered expression of genes associated with enhanced cell cycle transition, impaired DNA damage responses, and augmented survival signaling pathways. Among those genes, we identified STAT4 as a potential miR-141/200c target. Low STAT4 expression (in the absence of miR-141/200c upregulation) was associated with an immature phenotype of primary T-PLL cells as well as with a shortened overall survival of T-PLL patients. Overall, we demonstrate an aberrant miR-141/200c-STAT4 axis, showing for the first time the potential pathogenetic implications of a miR cluster, as well as of STAT4, in the leukemogenesis of this orphan disease

The miR-141/200c-STAT4 Axis Contributes to Leukemogenesis by Enhancing Cell Proliferation in T-PLL

T-prolymphocytic leukemia (T-PLL) is a rare and mature T-cell malignancy with characteristic chemotherapy-refractory behavior and a poor prognosis. Molecular concepts of disease development have been restricted to protein-coding genes. Recent global microRNA (miR) expression profiles revealed miR-141-3p and miR-200c-3p (miR-141/200c) as two of the highest differentially expressed miRs in T-PLL cells versus healthy donor-derived T cells. Furthermore, miR-141/200c expression separates T-PLL cases into two subgroups with high and low expression, respectively. Evaluating the potential pro-oncogenic function of miR-141/200c deregulation, we discovered accelerated proliferation and reduced stress-induced cell death induction upon stable miR-141/200c overexpression in mature T-cell leukemia/lymphoma lines. We further characterized a miR-141/200c-specific transcriptome involving the altered expression of genes associated with enhanced cell cycle transition, impaired DNA damage responses, and augmented survival signaling pathways. Among those genes, we identified STAT4 as a potential miR-141/200c target. Low STAT4 expression (in the absence of miR-141/200c upregulation) was associated with an immature phenotype of primary T-PLL cells as well as with a shortened overall survival of T-PLL patients. Overall, we demonstrate an aberrant miR-141/200c-STAT4 axis, showing for the first time the potential pathogenetic implications of a miR cluster, as well as of STAT4, in the leukemogenesis of this orphan disease