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Liver has exceptional regeneration capacity which makes live donor liver transplantation a good surgical option for patients waiting for donors. Hepatic veins play major role in transplantation surgeries. Variations of hepatic veins can have great impact on surgical approach and outcome of the surgery. In the present study, total number of hepatic veins, presence and absence of accessory veins and confluence with its varied patterns were studied. We found maximum cases with 2 and 3 major hepatic veins which indicate presence of confluence. Confluence between left and middle hepatic veins was highest with 38% of total 54% of cases with confluence. We also found confluence between middle and accessory hepatic vein which is not mentioned in any present classifications. In addition, we have measured confluence length and diameter which holds significance in hepatic resection and anastomosis. The mean confluence length was 0.88±0.39 cm while mean confluence diameter was 0.57±0.20 cm. We found accessory hepatic veins in 15% of cases. The knowledge of this surgical anatomy and associated variations is of paramount importance in liver transplantation, radiological interventional procedures of liver and hepatic tumor resection procedures.
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The coexistence of Systemic Lupus Erythematosus (SLE) and Inflammatory Bowel Disease (IBD) is a rare and hard-to-diagnose multisystem autoimmune disorder. Allopathic treatment approaches often fall short in managing both conditions simultaneously, as specific medications targeting this dual manifestation are lacking. In such instances, herbal medicine can offer a potential solution through its holistic approach. Ocimum tenuiflorum (O. tenuiflorum) a rich source of bioactive compounds belonging to Lamiaceae family. This study employs network pharmacology and molecular modelling to unveil the multi-target and multi-pathway mechanisms of O. tenuiflorum as a complementary therapy. A total of 423 common targets were obtained, among which AKT1, TNF, SRC, EGFR, HIF1A, HSP9AA, BCL2, and STAT3 were identified as the key targets. Lastly, molecular modelling validated the strong binding affinity between O. tenuiflorum 's compounds and the identified targets. In conclusion, these investigations provide new insight for further study of O. tenuiflorum towards the management of SLE and IBD.
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BACKGROUND: Systemic lupus erythematosus is a chronic autoimmune inflammatory disease characterized by multiple symptoms. The phenolic acids and other flavonoids in Nelumbo nucifera have anti-oxidants, anti-inflammatory, and immunomodulatory activities that are essential for managing SLE through natural sources. This study employs network pharmacology to unveil the multi-target and multi-pathway mechanisms of Nelumbo nucifera as a complementary therapy. The findings are validated through molecular modeling, which includes molecular docking followed by a molecular dynamics study. METHODS: Active compounds and targets of SLE were obtained from IMPPAT, KNApAcKFamily and SwissTargetPrediction databases. SLE-related targets were retrieved from GeneCards and OMIM databases. A protein-protein interaction (PPI) network was built to screen out the core targets using Cytoscape software. ShinyGO was used for GO and KEGG pathway enrichment analyses. Interactions between potential targets and active compounds were assessed by molecular docking and molecular dynamics simulation study. RESULTS: In total, 12 active compounds and 1190 targets of N. nucifera's were identified. A network analysis of the PPI network revealed 10 core targets. GO and KEGG pathway enrichment analyses indicated that the effects of N. nucifera are mediated mainly by AGE-RAGE and other associated signalling pathways. Molecular docking indicated favourable binding affinities, particularly leucocianidol exhibiting less than -4.5 kcal/mol for all 10 targets. Subsequent molecular dynamics simulations of the leucocianidol-ESR1 complex aimed to elucidate the optimal binding complex's stability and flexibility. CONCLUSIONS: Our study unveiled the potential therapeutic mechanism of N. nucifera in managing SLE. These findings provide insights for subsequent experimental validation and open up new avenues for further research in this field.
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Background Drug-resistant tuberculosis is a major health issue around the world. The time it takes to find a sputum-positive patient is a major risk factor for the spread of tuberculosis, and many things can indicate a longer time to culture conversion. Also, there is strong proof that poor nutrition is linked to infectious diseases. So, this study aimed to look into the link between a person's body mass index (BMI) and the change of a sputum culture within three months in people who have rifampicin-resistant (RR)/multidrug-resistant (MDR)-tuberculosis (TB) kept on a bedaquiline-based regimen. Materials and methods The Department of Respiratory Medicine at King George's Medical University, Lucknow, hosted an observational, analytical, prospective, single-center study from May 2020 to April 2021. The study included 105 people who had been identified with RR/MDR-TB and were on an optimized background regimen that included a bedaquiline-based regimen. The result we were interested in was sputum culture conversion within three months, and we looked at how BMI related to that outcome. Analytical analyses utilized Pearson's chi-square test for categorical variables and the t-test for continuous variables. Differences with a P-value of <0.05 were considered significant. SPSS software (version 18.0, IBM Corp., Armonk, NY, USA) was used for all analyses, with missing data not replaced or credited. Results A total of 105 people who met the inclusion and exclusion criteria were analyzed. The patients had a mean age of 33.34 years and were mostly male 61 (58%). Fifty-eight (58; 55%) patients lived in rural areas. Most patients had fever 77 (73%), cough 72 (69%), and weight loss 66 (63%). Sixty-nine (69; 66%) patients had a history of TB. Fifty-seven patients had a BMI of <18.5 kg/m2, and 48 patients had with BMI of ≥18.5. At the end of the study, 75/105 patients converted their sputum culture. Of the 105 patients, 57 (54%) had a low BMI (less than 18.5 kg/m2). Among the 57 patients with a BMI of <18.5 kg/m2, only 28 (46%) achieved sputum culture conversion after 3 months while 29 (60%) of 48 with BMI ≥18.5 achieved sputum culture conversion after 3 months. Among the patients with a BMI <18.5, 15/57 (26%) tested positive for sputum culture after three months. In patients with a BMI of ≥18.5, only 4/48 (8%) patients tested positive for sputum culture after three months. Conclusion In patients with drug-resistant tuberculosis, low BMI (<18.5 kg/m2) was an independent risk factor for failing to convert sputum cultures within three months.
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India's rich diversity encompasses individuals from varied geographical, cultural, and ethnic backgrounds. In the field of population genetics, comprehending the genetic diversity across distinct populations plays a crucial role. This study presents significant findings from genetic data obtained from the Sikkimese population of India. Autosomal markers were crucial for evaluating forensic parameters, with a combined paternity index of 1 × 109. Notably, Penta E emerged as a distinguishing marker for individual identification in the Sikkim population. Fst genetic distance values revealed insights into genetic isolation among different groups, enhancing our understanding of population dynamics in the central Himalayan region. The NJ-based phylogenetic tree highlighted close genetic relationships, of the Sikkim population with the Nepalese population surrounding neighbouring Himalayan populations providing glimpses into common ancestry. In summary, this study contributes valuable data to population genetics and underscores the importance of genetic variation in comprehending population dynamics and forensic applications.
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Variación Genética , Genética de Población , Filogenia , Dinámica Poblacional , Humanos , India , Sikkim , Masculino , Repeticiones de Microsatélite/genética , Etnicidad/genética , FemeninoRESUMEN
Background: There is no accepted way to define difficult donor hepatectomy (DiffDH) during open right live donor hepatectomy (ORLDH). There are also no studies exploring association between DiffDH and early donor outcomes or reliable pre-operative predictors of DiffDH. Methods: Consecutive ORLDH performed over 18 months at a single center were included. Intraoperative parameters were used to develop an objective definition of DiffDH. The impact of DiffDH on early postoperative outcomes and achievement of textbook outcome (TO) was evaluated. Donor morphometry data on axial and coronal sections of donor computed tomography (CT) at the level of portal bifurcation were collected. Donor and graft factors predictive of DiffDH were evaluated using univariate and multivariate logistic regression. Results: One-hundred-eleven donors (male: 40.5%, age: 34 ± 9.5 years) underwent ORLDH during the study period. The difficulty score was constructed using five intraoperative parameters, i.e., operating time, transection time, estimated blood loss, need for intraoperative vasopressors, and need for Pringle maneuver. Donors were classified as DiffDH (score ≥ 2) or standard donor hepatectomy (StDH) (score <2). Twenty-nine donors (26%) were classified as DiffDH. DiffDH donors suffered greater all-cause morbidity (P = 0.004) but not major morbidity (Clavien-Dindo score >2; P = 0.651), more perioperative transfusion (P = 0.013), increased postoperative systemic inflammatory response syndrome (P = 0.034), delay in achieving full oral diet (P = 0.047), and a 70% reduced chance of achieving TO as compared to StDH (P = 0.007). On logistic regression analysis, increasing right lobe anteroposterior depth (RLdepth) was identified as an independent predictor of DiffDH (Odds ratio: 2.0 (95% confidence interval = 1.2, 3.3), P < 0.006). Receiver operating characteristic curve analysis identified an RLdepth of >14 cm as the best predictor of DiffDH (sensitivity:79%, specificity: 66%, area under curve = 0.803, P < 0.001). Conclusion: We report a novel definition of DiffDH and show that it is associated with worse postoperative outcomes, including a lesser chance of achieving TO. We also report that DiffDH can be predicted from readily available donor CT parameters.
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BACKGROUND: Heat stress is a detrimental abiotic stress that limits the development of many plant species and is linked to a variety of cellular and physiological problems. Heat stress affects membrane fluidity, which leads to negative effects on cell permeability and ion transport. Research reveals that heat stress causes severe damage to cells and leads to rapid accumulation of reactive oxygen species (ROS), which could cause programmed cell death. METHODS AND RESULTS: This current study aimed to validate the role of Triticum aestivum Salt Stress Root Protein (TaSSRP) in plants' tolerance to heat stress by modulating its expression in tobacco plants. The Relative Water Content (RWC), total chlorophyll content, and Membrane Stability Index (MSI) of the seven distinct transgenic lines (T0 - 2, T0 - 3, T0 - 6, T0 - 8, T0 - 9, T0 - 11, and T0 - 13), increased in response to heat stress. Despite the fact that the same tendency was detected in wild-type (WT) plants, changes in physio-biochemical parameters were greater in transgenic lines than in WT plants. The expression analysis revealed that the transgene TaSSRP expressed from 1.00 to 1.809 folds in different lines in the transgenic tobacco plants. The gene TaSSRP offered resistance to heat stress in Nicotiana tabacum, according to the results of the study. CONCLUSION: These findings could help to improve our knowledge and understanding of the mechanism underlying thermotolerance in wheat, and the novel identified gene TaSSRP could be used in generating wheat varieties with enhanced tolerance to heat stress.
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Regulación de la Expresión Génica de las Plantas , Respuesta al Choque Térmico , Nicotiana , Proteínas de Plantas , Plantas Modificadas Genéticamente , Triticum , Nicotiana/genética , Nicotiana/metabolismo , Triticum/genética , Triticum/metabolismo , Plantas Modificadas Genéticamente/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Respuesta al Choque Térmico/genética , Especies Reactivas de Oxígeno/metabolismo , Raíces de Plantas/metabolismo , Raíces de Plantas/genética , Termotolerancia/genética , Clorofila/metabolismo , Tolerancia a la Sal/genéticaRESUMEN
Since 2020, African swine fever (ASF) has affected all pig breeds in Northeast India except Doom pigs, a unique indigenous breed from Assam and the closest relatives of Indian wild pigs. ASF outbreaks result in significant economic losses for pig farmers in the region. Based on sequencing and phylogenetic analysis of the B646L (p72) gene, it has been determined that ASFV genotype II is responsible for outbreaks in this region. Recent studies have shown that MYD88, LDHB, and IFIT1, which are important genes of the immune system, are involved in the pathogenesis of ASFV. The differential expression patterns of these genes in surviving ASFV-infected and healthy Doom breed pigs were compared to healthy controls at different stages of infection. The ability of Doom pigs to withstand common pig diseases, along with their genetic resemblance to wild pigs, make them ideal candidates for studying tolerance to ASFV infection. In the present study, we investigated the natural resistance to ASF in Doom pigs from an endemic area in Northeast India. The results of this study provide important molecular insights into the regulation of ASFV tolerance genes.
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Virus de la Fiebre Porcina Africana , Fiebre Porcina Africana , Brotes de Enfermedades , Filogenia , Animales , Fiebre Porcina Africana/virología , Fiebre Porcina Africana/epidemiología , Fiebre Porcina Africana/inmunología , Virus de la Fiebre Porcina Africana/genética , Virus de la Fiebre Porcina Africana/inmunología , India/epidemiología , Porcinos , Brotes de Enfermedades/veterinaria , Genotipo , Factor 88 de Diferenciación Mieloide/genética , Resistencia a la Enfermedad/genéticaRESUMEN
Background and Objectives: Malaria was the first ever reported case of transfusion transmitted infection (TTI). Transfusion transmissible malaria (TTM) can result in febrile transfusion reaction in the recipient. TTM can be fatal if the blood transfusion recipient is from vulnerable population i.e. pregnant women or young children. Therefore, the present study was done to estimate the seroprevalence of malaria parasitemia among blood donors in Garhwal region. Materials and Methods: Study subjects were healthy blood donors who had passed the screening criteria for blood donation. Donors with a history of malaria were temporarily deferred for 3 months following full recovery. Screening of the donated blood units for malaria parasite was done using immunochromatography based rapid diagnostic test. Thin smear examination was performed for malaria parasite species identification. Results: A total of 1984 blood donations were screened for TTI. The seroprevalence of HBV, HCV HIV and syphilis was 0.3% (n=6), 0.25% (n=5), 0% (n=0) and 0% (n=0) respectively. The seroprevalence of malaria parasite was 0.05% (n=1). Plasmodium vivax was identified upon thin smear examination. The donor reactive for malaria parasite was a replacement donor and gave no recent history of fever or any past history of malaria. Conclusion: Meticulous donor screening combined with rapid diagnostic tests for malaria parasite is the most practical strategy to prevent TTM in Garhwal region of India.
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Otitis media is a common childhood disease in developing countries and is the most important cause of preventable hearing loss among Indian children. To study the knowledge, attitude, and practices regarding risk factors for otitis media among caretakers of children in Puducherry. This was a questionnaire based descriptive cross-sectional study conducted from April 2023 to June 2023. All the caregivers of children aged 2-12 years presented or diagnosed with otitis media under our inclusion criteria were interviewed. Overall, most caretakers displayed good knowledge (67%), positive attitude (62%) and good care-seeking practices (49%). There was a positive correlation with sociodemographic parameters. The odd's ratio for overcrowding was high (OR = 4, p = 0.042 for knowledge and attitude, OR = 3.929, p = 0.041 for practices). Higher score was seen among middle class with odd's ratio 1.417 for knowledge and attitude and 4.875 for practices (p = 0.041). Graduate parents had higher score with the odd's ratio that was statistically significant. Most of the caregivers had a good knowledge regarding symptoms of otitis media and an acceptable level of caregivers' attitude and care seeking practices. Higher scores were associated with overcrowding, socioeconomic status, parental education. Improvement in risk factors and providing health education will reduce prevalence of OM in children and thereby reduce preventable hearing loss in children. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-024-04551-9.
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Proficiency in surface anatomy knowledge plays a pivotal role in fostering complication-free and efficacious clinical practice across a wide spectrum of healthcare specialties. This comprehensive understanding and adept utilization of surface anatomy principles serve as the linchpin for deciphering normal anatomical structures within medical imaging and the aptitude to articulate the topographical attributes, visual characteristics, and interrelations of palpable anatomical entities. Despite the advent of advanced direct visualization techniques, such as ultrasound guidance, which assist in interventional procedures, clinicians have not relinquished the indispensable requirement for pertinent surface anatomy knowledge to ensure the successful and secure execution of procedures. Regrettably, evidence-based surface anatomy remains an underemphasized facet in the pedagogy of anatomical sciences. The current narrative review underscores the various methodologies employed in imparting surface anatomy education to students. However, it is noteworthy that no singular, unequivocal best practice has emerged for the teaching and acquisition of surface anatomy knowledge. Therefore, as custodians of anatomical education, there is a pressing need to innovate and amalgamate contemporary pedagogical approaches with state-of-the-art technologies to furnish students with evidence-based surface anatomy insights, thereby enhancing comprehension, retention, and the lasting utility of this essential domain of medical knowledge.
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Attention mechanism has recently gained immense importance in the natural language processing (NLP) world. This technique highlights parts of the input text that the NLP task (such as translation) must pay "attention" to. Inspired by this, some researchers have recently applied the NLP domain, deep-learning based, attention mechanism techniques to predictive maintenance. In contrast to the deep-learning based solutions, Industry 4.0 predictive maintenance solutions that often rely on edge-computing, demand lighter predictive models. With this objective, we have investigated the adaptation of a simpler, incredibly fast and compute-resource friendly, "Nadaraya-Watson estimator based" attention method. We develop a method to predict tool-wear of a milling machine using this attention mechanism and demonstrate, with the help of heat-maps, how the attention mechanism highlights regions that assist in predicting onset of tool-wear. We validate the effectiveness of this adaptation on the benchmark IEEEDataPort PHM Society dataset, by comparing against other comparatively "lighter" machine learning techniques - Bayesian Ridge, Gradient Boosting Regressor, SGD Regressor and Support Vector Regressor. Our experiments indicate that the proposed Nadaraya-Watson attention mechanism performed best with an MAE of 0.069, RMSE of 0.099 and R2 of 83.40 %, when compared to the next best technique Gradient Boosting Regressor with figures of 0.100, 0.138, 66.51 % respectively. Additionally, it produced a lighter and faster model as well.â¢We propose a Nadaraya-Watson estimator based "attention mechanism", applied to a predictive maintenance problem.â¢Unlike the deep-learning based attention mechanisms from the NLP domain, our method creates fast, light and high-performance models, suitable for edge computing devices and therefore supports the Industry 4.0 initiative.â¢Method validated on real tool-wear data of a milling machine.
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Understanding the stability of thin liquid trilayer films is of direct relevance to applications such as multilayer coatings and polymer processing. The stability of trilayer films can also be used to provide insights into emulsion dynamics, such as the rupture of the thin film formed between two droplets during coalescence. Often, emulsions are laden with surfactants and other additives, which can be present in one or both phases as well as at the interfaces between the liquids. In experimental studies, complicating factors such as variations in droplet sizes, curvatures, and collision processes make it difficult to specifically isolate the influence of surfactant transport on droplet coalescence and film rupture. The present work addresses this issue by systematic consideration of a model problem involving a thin liquid trilayer film. Surfactant is soluble in either the outer layers or the inner layer, corresponding to surfactant soluble in the droplets or the continuous phase. Rupture of the inner layer is driven by van der Waals forces. Lubrication theory is applied to derive coupled nonlinear evolution equations describing the perturbations to the interface positions and the surfactant concentrations. Our findings reveal that surfactant better stabilizes the film when soluble in the inner layer, and the stabilizing effect is more pronounced when the outer layers are thicker. These findings are consistent with experimental observations involving emulsions, where emulsions tend to be more stable when surfactant is in the continuous phase rather than in the droplets, with the distinction being more pronounced when droplets are larger.
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Over the past decade, there have been accumulating reports from researchers, farmers, and field extension personnel on the increasing incidence and spread of onion basal rot in India. Onion basal rot disease is mainly caused by Fusarium spp. This study aimed to validate the information on the active prevalence of F. falciforme and F. acutatum causing Fusarium basal rot (FBR) in Maharashtra. A survey was conducted, and the infected plants/bulbs were collected from fields of 38 locations comprising five districts of Maharashtra, namely, Nashik, Aurangabad, Solapur, Ahmednagar, and Pune, in 2023. This disease was prevalent in high-moisture and high-oil-temperature conditions and the symptoms were observed in most of the fields, with the FBR incidence ranging from 17 to 41%. The available data of basal rot incidence from 1998 to 2022 were analyzed, based on which the prevalence of FBR was 11-50%. Tissue from the infected samples of onion bulbs was used for the isolation. The identification was performed based on colony morphology and microscopic features and confirmed through molecular markers using ITS and Tef-1α gene primers. Of the ten Fusarium isolates collected from selected locations, six species were confirmed as F. acutatum and four as F. falciforme. The pathogenicity tests performed with onion seedlings and bulbs under moist conditions proved that both F. acutatum and F. falciforme independently could cause basal rot disease symptoms but with different degrees of virulence. Koch's postulates were confirmed by reisolating the same pathogens from the infected plants. Thus, the active prevalence of FBR was confirmed in Maharashtra and also, to the best of our knowledge, this is the first report of F. falciforme and F. acutatum causing basal rot of onion independently in Maharashtra, India.
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INTRODUCTION: Reducing the healing period after surgical placement of dental implants can facilitate the loading of dental prostheses. AIM: The aim is to compare the osteogenic potential of unmodified titanium disks with titanium disks that were surface-modified or hydrogel-coated. MATERIALS AND METHODOLOGY: One hundred eight titanium disks (Ø6 × 2-mm) were divided into three groups: (1) unmodified titanium as control (Ti-C); (2) sandblasted and acid-etched (Ti-SLA), and (3) coated with tamarind kernel polysaccharide hydrogel grafted with acrylic acid (Ti-TKP-AA). The osteogenic potential and cytotoxic effect of various groups of titanium were compared using human osteoblasts Saos-2. The surface topography of the titanium disks and morphology of osteoblasts grown on disks were investigated by scanning electron microscopy (n = 3). Cell attachment to the disks and actin expression intensity were investigated by confocal imaging (n = 3). Cytotoxicity was quantified by cell viability assay (n = 9). Osteoblast maturation was determined by alkaline phosphatase assay (n = 9). Cell mineralization was quantified by Alizarin red staining (n = 9). One-way analysis of variance followed by Tukey's multiple comparisons test was used for intergroup comparisons (α= 0.05). RESULTS: The surface modifications on Ti-SLA and Ti-TKP-AA support better morphology and proliferation of osteoblasts than Ti-C (P< 0.001) and significantly higher levels of actin cytoskeleton accumulation (P< 0.0001). Ti-TKP-AA showed a significantly higher maturation rate than Ti-C (P< 0.001). Ti-TKP-AA showed > twofold increased mineralization than Ti-C and Ti-SLA (P< 0.001). CONCLUSIONS: TKP-AA hydrogel-coated titanium promotes faster osteoblast proliferation, maturation, and mineralization than SLA-treated or untreated titanium. These advantages can be explored for achieving early osseointegration and prosthetic loading of titanium dental implants.
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BACKGROUND: Wheat rusts are important biotic stresses, development of rust resistant cultivars through molecular approaches is both economical and sustainable. Extensive phenotyping of large mapping populations under diverse production conditions and high-density genotyping would be the ideal strategy to identify major genomic regions for rust resistance in wheat. The genome-wide association study (GWAS) population of 280 genotypes was genotyped using a 35 K Axiom single nucleotide polymorphism (SNP) array and phenotyped at eight, 10, and, 10 environments, respectively for stem/black rust (SR), stripe/yellow rust (YR), and leaf/brown rust (LR). RESULTS: Forty-one Bonferroni corrected marker-trait associations (MTAs) were identified, including 17 for SR and 24 for YR. Ten stable MTAs and their best combinations were also identified. For YR, AX-94990952 on 1A + AX-95203560 on 4A + AX-94723806 on 3D + AX-95172478 on 1A showed the best combination with an average co-efficient of infection (ACI) score of 1.36. Similarly, for SR, AX-94883961 on 7B + AX-94843704 on 1B and AX-94883961 on 7B + AX-94580041 on 3D + AX-94843704 on 1B showed the best combination with an ACI score of around 9.0. The genotype PBW827 have the best MTA combinations for both YR and SR resistance. In silico study identifies key prospective candidate genes that are located within MTA regions. Further, the expression analysis revealed that 18 transcripts were upregulated to the tune of more than 1.5 folds including 19.36 folds (TraesCS3D02G519600) and 7.23 folds (TraesCS2D02G038900) under stress conditions compared to the control conditions. Furthermore, highly expressed genes in silico under stress conditions were analyzed to find out the potential links to the rust phenotype, and all four genes were found to be associated with the rust phenotype. CONCLUSION: The identified novel MTAs, particularly stable and highly expressed MTAs are valuable for further validation and subsequent application in wheat rust resistance breeding. The genotypes with favorable MTA combinations can be used as prospective donors to develop elite cultivars with YR and SR resistance.
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Basidiomycota , Resistencia a la Enfermedad , Estudio de Asociación del Genoma Completo , Enfermedades de las Plantas , Polimorfismo de Nucleótido Simple , Triticum , Triticum/genética , Triticum/microbiología , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/genética , Resistencia a la Enfermedad/genética , Basidiomycota/fisiología , Fenotipo , Genes de Plantas , Genotipo , Puccinia/fisiología , Sitios de Carácter CuantitativoRESUMEN
Currently, more than 55 million people around the world suffer from dementia, and Alzheimer's Disease and Related Dementias (ADRD) accounts for nearly 60-70% of all those cases. The spread of Alzheimer's Disease (AD) pathology and progressive neurodegeneration in the hippocampus and cerebral cortex is strongly correlated with cognitive decline in AD patients; however, the molecular underpinning of ADRD's causality is still unclear. Studies of postmortem AD brains and animal models of AD suggest that elevated endoplasmic reticulum (ER) stress may have a role in ADRD pathology through altered neurocellular homeostasis in brain regions associated with learning and memory. To study the ER stress-associated neurocellular response and its effects on neurocellular homeostasis and neurogenesis, we modeled an ER stress challenge using thapsigargin (TG), a specific inhibitor of sarco/endoplasmic reticulum Ca2+ ATPase (SERCA), in the induced pluripotent stem cell (iPSC)-derived neural stem cells (NSCs) of two individuals from our Mexican American Family Study (MAFS). High-content screening and transcriptomic analysis of the control and ER stress-challenged NSCs showed that the NSCs' ER stress response resulted in a significant decline in NSC self-renewal and an increase in apoptosis and cellular oxidative stress. A total of 2300 genes were significantly (moderated t statistics FDR-corrected p-value ≤ 0.05 and fold change absolute ≥ 2.0) differentially expressed (DE). The pathway enrichment and gene network analysis of DE genes suggests that all three unfolded protein response (UPR) pathways, protein kinase RNA-like ER kinase (PERK), activating transcription factor-6 (ATF-6), and inositol-requiring enzyme-1 (IRE1), were significantly activated and cooperatively regulated the NSCs' transcriptional response to ER stress. Our results show that IRE1/X-box binding protein 1 (XBP1) mediated transcriptional regulation of the E2F transcription factor 1 (E2F1) gene, and its downstream targets have a dominant role in inducing G1/S-phase cell cycle arrest in ER stress-challenged NSCs. The ER stress-challenged NSCs also showed the activation of C/EBP homologous protein (CHOP)-mediated apoptosis and the dysregulation of synaptic plasticity and neurotransmitter homeostasis-associated genes. Overall, our results suggest that the ER stress-associated attenuation of NSC self-renewal, increased apoptosis, and dysregulated synaptic plasticity and neurotransmitter homeostasis plausibly play a role in the causation of ADRD.
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Enfermedad de Alzheimer , Estrés del Retículo Endoplásmico , Humanos , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Células-Madre Neurales/metabolismo , Células-Madre Neurales/patología , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Endorribonucleasas/genética , Endorribonucleasas/metabolismo , Células Madre Pluripotentes Inducidas/metabolismo , Tapsigargina/farmacología , Demencia/genética , Demencia/metabolismo , Demencia/patología , eIF-2 Quinasa/genética , eIF-2 Quinasa/metabolismo , Masculino , Factor de Transcripción Activador 6/metabolismo , Factor de Transcripción Activador 6/genética , Neurogénesis , Proteína 1 de Unión a la X-Box/metabolismo , Proteína 1 de Unión a la X-Box/genética , Femenino , Respuesta de Proteína Desplegada , Factor de Transcripción CHOPRESUMEN
The study of human cadavers is essential for teaching, advanced training, and research in medical and anatomical sciences. Medical institutions around the globe presently face a scarcity of cadaver supplies. For the majority of countries, unclaimed bodies are still the primary source of cadavers despite guidelines issued by the International Federation of Associations of Anatomists, which discourage the use of unclaimed bodies. This self-funded study aims to conduct a review of the existing national and international laws safeguarding the several rights of a deceased person. The study also reviewed the existing anatomy acts (and related acts) across various countries that facilitate cadaver supply for anatomy education and research. According to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, an online search for publications in four medical databases (PubMed, Scopus, Web of Sciences, and Google Scholar) was conducted from 1950 till 2022. A research review protocol was registered in PROSPERO prospectively (registration ID: CRD42023469534) using the Mesh terms like cadaver, anatomy education, dead person and rights, body donation program, unclaimed bodies, and anatomy acts. After the application of the eligibility criteria, 149 publications were shortlisted. After reviewing all the shortlisted articles, laws, and guidelines, using the data extraction checklist prepared by both authors, five international laws, three supreme court case decisions, two high court case decisions, four Indian penal Code Sections, and 22 anatomy acts were selected. Articles from other medical databases could not be reviewed, which was the limitation of this study. The anatomy/human tissue/tissue transplantation acts and advisories from regulatory bodies of individual African, Middle-Eastern, and European countries could not be retrieved. The review findings will emphasize the distinctions between India's anatomy acts and those of other developed nations, thereby broadening our perspective as we propose a model anatomy act for uniform implementation across the country to streamline the procurement of cadavers.
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High-power impulse magnetron sputtering (HiPIMS) plus kick is a physical vapor deposition method that employs bipolar microsecond-scale voltage pulsing to precisely control the ion energy during sputter deposition. HiPIMS plus kick for AlN deposition is difficult since nitride deposition is challenged by low surface diffusion and high susceptibility to ion damage. In this current study, a systematic examination of the process parameters of HiPIMS plus kick was conducted. Under optimized main negative pulsing conditions, this study documented that a 25 V positive kick biasing for AlN deposition is ideal for optimizing a high quality film, as shown by X-ray diffraction and transmission electron microscopy as well as optimal thermal conductivity while increasing high speed deposition (25 nm/min) and obtaining ultrasmooth surfaces (rms roughness = 0.5 nm). HiPIMS plus kick was employed to deposit a single-texture 1 µm AlN film with a 7.4° rocking curve, indicating well oriented grains, which correlated with high thermal conductivity (121 W/m·K). The data are consistent with the optimal kick voltage enabling enhanced surface diffusion due to ion-substrate collisions without damaging the AlN grains.
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Complex fluids including colloidal suspensions, microgels, and entangled wormlike micelles (WLMs) can develop heterogeneous flow regions under imposed steady shear. In some of these systems, the evolution to this flow state from rest is accompanied by flow reversal - when a portion of the fluid moves opposite to the imposed flow direction. Flow reversal was proposed to occur in shear startup when (1) the fluid has significant elasticity, and (2) the flow becomes heterogeneous immediately following the stress overshoot [McCauley et al., J. Rheol., 2023, 67, 661-681]. To verify this hypothesis, a new method is developed for measuring flow heterogeneity. Upon cessation of the imposed flow, elasticity and flow heterogeneity cause retraction of the fluid, which is quantified with particle tracking velocimetry. Flow is stopped at key times during shear startup in two systems: a gel-like WLM that exhibits flow reversal before heterogeneous flow and a viscoelastic, fluid-like WLM that does not. The degree of flow heterogeneity is inferred from the shape and magnitude of velocity profiles measured during retraction. Flow heterogeneity develops earlier in gel-like WLMs - supporting the proposed flow reversal criteria. For comparison, heterogeneous Couette flows described with the upper-convected Maxwell or Germann-Cook-Beris models are analyzed. These theoretical flow problems confirm that stark differences in rheological properties across the flow geometry can cause significant fluid retraction and reproduce key features of the experimentally observed retraction. This new method can be used to extract quantitative information about spatially heterogeneous flows in viscoelastic complex fluids, whether or not flow reversal occurs.