Identification of Novel QTLs/Defense Genes in Spring Wheat Germplasm Panel for Seedling and Adult Plant Resistance to Stem Rust and Their Validation Through KASP Marker Assays.

Stem rust is one of the major diseases threatening wheat production globally. To identify novel resistance quantitative trait loci (QTLs), we performed 35K Axiom Array SNP genotyping assays on an association mapping panel of 400 germplasm accessions, including Indian landraces, in conjunction with phenotyping for stem rust at seedling and adult plant stages. Association analyses using three genome wide association study (GWAS) models (CMLM, MLMM, and FarmCPU) revealed 20 reliable QTLs for seedling and adult plant resistance. Among these 20 QTLs, five QTLs were found consistent with three models, i.e., four QTLs on chromosome 2AL, 2BL, 2DL, and 3BL for seedling resistance and one QTL on chromosome 7DS for adult plant resistance. Further, we identified a total of 21 potential candidate genes underlying QTLs using gene ontology analysis, including a leucine rich repeat receptor (LRR) and P-loop nucleoside triphosphate hydrolase, which have a role in pathogen recognition and disease resistance. Furthermore, four QTLs (Qsr.nbpgr-3B_11, QSr.nbpgr-6AS_11, QSr.nbpgr-2AL_117-6, and QSr.nbpgr-7BS_APR) were validated through KASP located on chromosomes 3B, 6A, 2A, and 7B. Out of these QTLs, QSr.nbpgr-7BS_APR was identified as a novel QTL for stem rust resistance which has been found effective in both seedling as well as the adult plant stages. Identified novel genomic regions and validated QTLs have the potential to be deployed in wheat improvement programs to develop disease resistant varieties for stem rust and can diversify the genetic basis of resistance.

Multi-locus genome-wide association studies (ML-GWAS) reveal novel genomic regions associated with seedling and adult plant stage leaf rust resistance in bread wheat (Triticum aestivum L.).

Leaf rust is one of the important diseases limiting global wheat production and productivity. To identify quantitative trait nucleotides (QTNs) or genomic regions associated with seedling and adult plant leaf rust resistance, multilocus genome-wide association studies (ML-GWAS) were performed on a panel of 400 diverse wheat genotypes using 35 K single-nucleotide polymorphism (SNP) genotyping assays and trait data of leaf rust resistance. Association analyses using six multi-locus GWAS models revealed a set of 201 significantly associated QTNs for seedling and 65 QTNs for adult plant resistance (APR), explaining 1.98-31.72% of the phenotypic variation for leaf rust. Among these QTNs, 51 reliable QTNs for seedling and 15 QTNs for APR were consistently detected in at least two GWAS models and were considered reliable QTNs. Three genomic regions were pleiotropic, each controlling two to three pathotype-specific seedling resistances to leaf rust. We also identified candidate genes, such as leucine-rich repeat receptor-like (LRR) protein kinases, P-loop containing nucleoside triphosphate hydrolase and serine-threonine/tyrosine-protein kinases (STPK), which have a role in pathogen recognition and disease resistance linked to the significantly associated genomic regions. The QTNs identified in this study can prove useful in wheat molecular breeding programs aimed at enhancing resistance to leaf rust and developing next-generation leaf rust-resistant varieties.

Tuning Cationic Micelle Properties with an Antioxidant Additive: A Molecular Perspective.

In this work, we characterize the micellization and morphology transition induced in aqueous cetyltrimethylammonium bromide (CTAB) solution by the addition of the antioxidant propyl gallate (PG) using tensiometry, rheology, and small-angle neutron scattering (SANS) techniques combined with the molecular dynamics (MD) simulation approach. The adsorption of CTAB at the air-water interface in the presence of varying [PG] revealed a progressive decrease in the critical micelle concentration (CMC), while the changes in different interfacial parameters indicated enhancement of the hydrophobicity induced by PG in the CTAB micellar system. The dynamic rheology behavior indicated an increase in the flow viscosity (η) as a function of [PG]. Moreover, the rheological components (storage modulus, G', and loss modulus, G″) depicted the viscoelastic features. SANS measurements depicted the existence of ellipsoidal micelles with varying sizes and aggregation number (Nagg) as a function of [PG] and temperature. Computational simulation performed using density functional theory (DFT) calculations and molecular dynamics (MD) provided an insight into the atomic composition of the examined system. The molecular electrostatic potential (MEP) analysis depicted a close proximity of CTAB, i.e., emphasized favorable interactions between the quaternary nitrogen of CTAB and the hydroxyl group of the PG monomer, further validated by the two-dimensional nuclear Overhauser enhancement spectroscopy (2D-NOESY), which showed the penetration of PG inside the CTAB micelles. In addition, various dynamic properties, viz., the radial distribution function (RDF), the radius of gyration (Rg), and solvent-accessible surface area (SASA), showed a significant microstructural evolution of the ellipsoidal micelles in the examined CTAB-PG system, where the changes in the micellar morphology with a more elongated hydrophobic chain and the increased Rg and SASA values indicated the notable intercalation of PG in the CTAB micelles.

Glycemic index of millet based food mix and its effect on pre diabetic subjects.

Diet plays an important role in management of diabetes and foods having low glycemic index are gaining more importance as they delay the release of glucose in the blood. It is essential to develop low glycemic food mix from regionally available ingredients for use in daily dietaries. Hence, the present study was undertaken to assess the glycemic index of the traditional recipes prepared from developed millet based food mix and their effect on pre diabetic subjects. The developed millet based food mix had appreciable amount of protein (19.41 g/100 g) and dietary fibre (21.11 g/100 g). The traditional recipes viz., roti, dosa and dumpling (mudde) prepared from developed mix exhibited higher acceptance with good sensory parameters and are comparable to regional preparations. The glycemic index was found to be 37, 48 and 53 for dosa, mudde and roti respectively with a glycemic load of 11.05, 18.43 and 18.09. However, all the three developed products showed the relatively lower glycemic index (< 55) and moderate glycemic load of < 20. Further, dietary intervention on pre diabetic subjects revealed that there was a significant reduction in FBS (120.50 ± 18.73 to 97.81 ± 20.00) and HbA1c (6.14 ± 0.30 to 5.67 ± 0.40) indicating their preferable option in the management of diabetes mellitus.

Plasma anti-α-galactoside antibody binds to serine- and threonine-rich peptide sequence of apo(a) subunit in Lp(a).

Lipoprotein(a) immune complexes [Lp(a) IC] of varying particle density obtained by ultracentrifugation of plasma from normal healthy donors were markedly dominated by IgG. Lp(a) and immunoglobulins were liberated from plasma Lp(a) IC by treatment with melibiose, a sugar specific for circulating anti-α-galactoside antibody (anti-Gal). Upon incubation with plasma lipoprotein fraction anti-Gal but not the α-glucoside-specific antibody from human plasma formed de novo IC with Lp(a). Binding of Lp(a) sugar-reversibly enhanced the fluorescence of FITC-labeled anti-Gal as did binding of α-galactoside-containing glycoproteins. This effect apparently due to conformational shift in the Fc region of the antibody was also produced by apo(a) subunit separated from Lp(a) and de-O-glycosylated apo(a) but not by any other plasma lipoproteins or by Lp(a) pre-incubated with the O-glycan-specific lectin jacalin. O-Glycans and their terminal sialic acid moieties in apo(a) of circulating Lp(a)-anti-Gal IC, in contrast to those in pure Lp(a), were inaccessible to jacalin and anion exchange resin, respectively. Unlike other plasma lipoproteins, Lp(a) inhibited Griffonia simplicifolia isolectin B4 which also accommodates serine- and threonine-rich peptide sequence (STPS) as surrogate ligand to α-galactosides at its binding site. Results suggest that anti-Gal recognizes STPS in the O-glycan-rich regions of apo(a) subunit in Lp(a) which contains no α-linked galactose.

Share of Adult Suicides After Recent Jail Release.

Importance: Although people released from jail have an elevated suicide risk, the potentially large proportion of this population in all adult suicides is unknown. Objective: To estimate what percentage of adults who died by suicide within 1 year or 2 years after jail release could be reached if the jail release triggered community suicide risk screening and prevention efforts. Design, Setting, and Participants: This cohort modeling study used estimates from meta-analyses and jail census counts instead of unit record data. The cohort included all adults who were released from US jails in 2019. Data analysis and calculations were performed between June 2021 and February 2024. Main Outcomes and Measures: The outcomes were percentage of total adult suicides within years 1 and 2 after jail release and associated crude mortality rates (CMRs), standardized mortality ratios (SMRs), and relative risks (RRs) of suicide in incarcerated vs not recently incarcerated adults. Taylor expansion formulas were used to calculate the variances of CMRs, SMRs, and other ratios. Random-effects restricted maximum likelihood meta-analyses were used to estimate suicide SMRs in postrelease years 1 and 2 from 10 jurisdictions. Alternate estimate was computed using the ratio of suicides after release to suicides while incarcerated. Results: Included in the analysis were 2019 estimates for 7 091 897 adults (2.8% of US adult population; 76.7% males and 23.3% females) who were released from incarceration at least once, typically after brief pretrial stays. The RR of suicide was 8.95 (95% CI, 7.21-10.69) within 1 year after jail release and 6.98 (95% CI, 4.21-9.76) across 2 years after release. A total of 27.2% (95% CI, 18.0%-41.7%) of all adult suicide deaths occurred in formerly incarcerated individuals within 2 years of jail release, and 19.9% (95% CI, 16.2%-24.1%) of all adult suicides occurred within 1 year of release (males: 23.3% [95% CI, 20.8%-25.6%]; females: 24.0% [95% CI, 19.7%-36.8%]). The alternate method yielded slightly larger estimates. Another 0.8% of adult suicide deaths occurred during jail stays. Conclusions and Relevance: This cohort modeling study found that adults who were released from incarceration at least once make up a large, concentrated population at greatly elevated risk for death by suicide; therefore, suicide prevention efforts focused on return to the community after jail release could reach many adults within 1 to 2 years of jail release, when suicide is likely to occur. Health systems could develop infrastructure to identify these high-risk adults and provide community-based suicide screening and prevention.

Effect of long-term yoga training on autonomic function among the healthy adults.

Background: Autonomic dysfunction is one of the major complications in noncommunicable diseases, and there are studies to prove yoga practice improves cardiac autonomic function. So, this present study was done to compare the autonomic functions among yoga practitioners and nonyoga practitioners. Methods: This cross-sectional comparative study was initiated among 68 healthy volunteers of both sexes, after recruiting them based on inclusion and exclusion criteria in the age group of 17-30 yrs. The autonomic reactivity tests like resting heart rate, response of heart rate to standing, Valsalva maneuver, and response of heart rate to deep breathing, response of BP to standing, and sustained hand-grip were done. Results: In the autonomic reactivity test, resting heart rate (80.92 ± 11.76 vs 69.24 ± 10.64) and sustained handgrip (16.30 ± 4.53 vs 10.20 ± 3.67) significantly decreased (P < 0.05) in the participants of the yoga group compared to control group. Deep breathing test, Valsalva maneuver, 30:15 ratio in lying to standing, and BP response to standing test did not show any significant difference between the groups (P > 0.05). Conclusion: The present study revealed diminished sympathetic activity and improved parasympathetic activity among the regular yoga practicing participants. It can be practiced regularly to reduce stress and prevent lifestyle-associated disorders in the future.

Arsenite causes down-regulation of Akt and c-Fos, cell cycle dysfunction and apoptosis in glutathione-deficient cells.

Arsenic is a well-known environmental toxicant but the mechanism by which it causes cytotoxicity is poorly understood. Arsenite induces apoptosis in glutathione (GSH)-deficient GCS-2 cells by causing cell cycle dysfunction and down-regulating critical signaling pathways. This study was designed to examine the effect of arsenite on redox-sensitive phosphatidylinositol 3-kinase (PI3K)/Akt, a signaling pathway involved in cell survival and growth, and transcription factor, activating protein-1 (AP-1). Arsenite significantly diminished Akt and c-Fos levels and caused accelerated degradation of these proteins by ubiquitnation. Arsenite also induced cell cycle arrest and apoptosis. The cell cycle arrest involved the down-regulation of cyclin A2, cyclin D1, cyclin E, cyclin dependent kinases (CDK) 2, CDK4, and CDK6. Apoptosis involved down-regulation of anti-apoptotic proteins Bcl-2, Bcl-xL, survivin, and inhibitor of apoptosis protein (IAP) and up-regulation of pro-apoptotic protein Bax. Taken together, our results suggest that a possible mechanism of arsenite-induced toxicity under low/no GSH conditions, is to negatively regulate GCS-2 cell proliferation by attenuating Akt and AP-1 by ubiquitination and causing cell cycle dysfunction and apoptosis.

Cardiovascular and stroke disease risk among doctors: a cross-sectional study.

The leading causes of death in the world are cardiovascular disease (CVD) and stroke according to the World Health Organization, as is also the case in India. There is also a high prevalence of major conventional risk factors in India, where 18.3%, 9.0% and 14.1% of adults are diagnosed with hypertension, diabetes and smoking, respectively. The aim of the present study was to look at the risk of CVD among doctors in our country using a validated tool developed by the National Health Service (NHS) in the UK, the QRISK3 calculator.

Disease burden of adverse childhood experiences across 14 states.

OBJECTIVE: To examine whether the relationship between Adverse Childhood Experiences (ACEs) and health outcomes is similar across states and persists net of ACEs associations with smoking, heavy drinking, and obesity. METHODS: We use data from the Behavioral Risk Factor Surveillance System for 14 states. Logistic regressions yield estimates of the direct associations of ACEs exposure with health outcomes net of health risk factors, and indirect ACEs-health associations via health risk factors. Models were estimated for California (N = 22,475) and pooled data from 13 states (N = 110,076), and also separately by state. RESULTS: Exposure to ACEs is associated with significantly higher odds of smoking, heavy drinking, and obesity. Net of these health risk factors, there was a significant and graded relationship in California and the pooled 13-state data between greater ACEs exposure and odds of depression, asthma, COPD, arthritis, and cardiovascular disease. Four or more ACEs were less consistently associated across states with cancer and diabetes and a dose-response relationship was also not present. There was a wide range across individual states in the percentage change in health outcomes predicted for exposure to 4+ ACEs. ACEs-related smoking, heavy drinking, and obesity explain a large and significant proportion of 4+ ACEs associations with COPD and cardiovascular disease, however some effect, absent of risk behavior, remained. CONCLUSIONS: ACE's associations with most of the health conditions persist independent of behavioral pathways but only asthma, arthritis, COPD, cardiovascular disease, and depression consistently exhibit a dose-response relationship. Our results suggest that attention to child maltreatment and household dysfunction, mental health treatment, substance abuse prevention and promotion of physical activity and healthy weight outcomes might mitigate some adverse health consequences of ACEs. Differences across states in the pattern of ACEs-health associations may also indicate fruitful areas for prevention.

Adult health burden and costs in California during 2013 associated with prior adverse childhood experiences.

OBJECTIVES: To estimate the adult health burden and costs in California during 2013 associated with adults' prior Adverse Childhood Experiences (ACEs). METHODS: We analyzed five ACEs-linked conditions (asthma, arthritis, COPD, depression, and cardiovascular disease) and three health risk factors (lifetime smoking, heavy drinking, and obesity). We estimated ACEs-associated fractions of disease risk for people aged 18+ for these conditions by ACEs exposure using inputs from a companion study of California Behavioral Risk Factor Surveillance System data for 2008-2009, 2011, and 2013. We combined these estimates with published estimates of personal healthcare spending and Disability-Adjusted-Life-Years (DALYs) in the United States by condition during 2013. DALYs captured both the years of healthy life lost to disability and the years of life lost to deaths during 2013. We applied a published estimate of cost per DALY. RESULTS: Among adults in California, 61% reported ACEs. Those ACEs were associated with $10.5 billion in excess personal healthcare spending during 2013, and 434,000 DALYs valued at approximately $102 billion dollars. During 2013, the estimated health burden per exposed adult included $589 in personal healthcare expenses and 0.0224 DALYs valued at $5,769. CONCLUSIONS: Estimates of the costs of childhood adversity are far greater than previously understood and provide a fiscal rationale for prevention efforts.

Publisher Correction: The HIV protease inhibitor darunavir prevents kidney injury via HIV-independent mechanisms.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

p53 regulates Hsp90beta during arsenite-induced cytotoxicity in glutathione-deficient cells.

p53, a tumor suppressor and transcription factor, is a critical modulator in the cellular response to stress. Exposure of glutathione-deficient GCS-2 cells to arsenite significantly phosphorylated and stabilized p53. In addition, p53 transcriptionally repressed Hsp90beta gene expression. Mutation analysis revealed a p53 binding site in the 5' flanking region responsible for the regulation of Hsp90beta gene. Electrophoretic mobility shift assay showed that p53 is bound to Hsp90beta promoter region. ATM kinase, a major determinant in the modulation of p53 specifically affected its phosphorylation at Ser-15. ATM kinase-mediated phosphorylation of p53 is regulated through phosphorylation of Chk2. Down-regulation of ATM and Chk2 by their small interfering RNAs (siRNAs) attenuated the arsenite-induced phosphorylation of p53 and restored Hsp90beta mRNA levels. Taken together, these findings suggest that arsenite acts through ATM and Chk2 to induce phosphorylation of p53. This results in the transcriptional repression of Hsp90beta, under GSH-deficient conditions which may play a role in arsenic-mediated pathogenesis.

In vivo studies of the ceramic coated titanium alloy for enhanced osseointegration in dental applications.

This paper reports the effect of the various ceramic coatings viz., hydroxyapatite (HA) and partially stabilized zirconia (PSZ) on the bond strength between the bone and implant, and cell compatibility of screw-shaped Ti-6Al-7Nb dental implants. Electrophoretic deposition technique (EPD) was used to obtain a uniform coating of one of the three types of ceramic layers (HA, PSZ and 50%HA + 50%PSZ) on the screws. Structural investigations were carried out on the prepared HA powder and the modified surfaces of the Ti-6Al-7Nb alloy using different techniques, namely X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR). The in vivo studies were performed by the implantation of screw-shaped uncoated and coated implants in the tibia of white New Zealand rabbits. To understand the bone-implant interface, biomechanical test was carried out after 2, 6 and 18 weeks healing periods. There was increased mechanical strength (torque value) of bone-implant interface with time, and the highest increment in the bond strength was recorded for implants coated with a 50% HA and 50% PSZ. Histological results show that the coated Ti-6Al-7Nb screws after 18 weeks of the implantation seem to be well-tolerated by the bone since no adverse tissue reaction was evident. However, there was a faster reaction of bone towards the coated implants compared to the uncoated one. The histochemical stain studies shows higher cellular activity and mature bone formation on all the samples.

The HIV protease inhibitor darunavir prevents kidney injury via HIV-independent mechanisms.

HIV-associated nephropathy (HIVAN) is a rapidly progressive kidney disease that is caused by HIV infection of renal epithelial cells with subsequent expression of viral genes, including vpr. Antiretroviral therapy ameliorates HIVAN without eradicating HIV from the kidneys and the mechanism by which it protects kidneys is poorly understood. Since HIV protease inhibitors have "off target" cellular effects, we studied whether darunavir, the most commonly prescribed protease inhibitor, protects kidneys from HIV-induced injury via mechanisms independent of HIV protease and viral replication. Renal epithelial cells were transduced with lentiviruses encoding HIV (lacking protease and reverse transcriptase), Vpr, or vector control. Darunavir attenuated HIV and Vpr-induced activation of Stat3, Src, Erk, and cytokines, which are critical for HIVAN pathogenesis. We then studied HIV-transgenic mice, which develop HIVAN in the absence of HIV protease or reverse transcriptase. Mice were treated with darunavir, zidovudine, darunavir + zidovudine, or control. Darunavir and darunavir + zidovudine reduced albuminuria and histologic kidney injury and normalized expression of dysregulated proteins. RNA-seq analyses demonstrated that darunavir suppressed HIV-induced upregulation of immune response genes in human kidney cells. These data demonstrate that darunavir protects against HIV-induced renal injury via mechanisms that are independent of inhibition of HIV protease.

Paying for Hemodialysis in Kerala, India: A Description of Household Financial Hardship in the Context of Medical Subsidy.

INTRODUCTION: Many low- and middle-income countries are implementing strategies to increase dialysis availability as growing numbers of people reach end-stage renal disease. Despite efforts to subsidize care, the economic sustainability of chronic dialysis in these settings remains uncertain. We evaluated the association of medical subsidy with household financial hardship related to hemodialysis in Kerala, India, a state with high penetrance of procedure-based subsidies for patients on dialysis. METHODS: Patients on maintenance hemodialysis at 15 facilities in Kerala were administered a questionnaire that ascertained demographics, dialysis details, and household finances. We estimated direct and indirect costs of hemodialysis, and described the use of medical subsidy. We evaluated whether presence of subsidy (private, charity, or government-sponsored) was associated with lower catastrophic health expenditure (defined as ≥40% of nonsubsistence expenditure spent on dialysis) or distress financing. RESULTS: Of the 835 patients surveyed, 759 (91%) reported their households experienced catastrophic health expenditure, and 644 (77%) engaged in distress financing. Median dialysis-related expenditure was 80% (25th-75th percentile: 60%-90%) of household nonsubsistence expenditure. Government subsidies were used by 238 (29%) of households, 139 (58%) of which were in the lowest income category. Catastrophic health expenditure was present in 215 (90%) of households receiving government subsidy and 332 (93%) without subsidy. CONCLUSIONS: Provision of medical subsidy in Kerala, India was not associated with lower rates of household financial hardship related to long-term hemodialysis therapy. Transparent counseling on impending costs and innovative strategies to mitigate household financial distress are necessary for persons with end-stage renal disease in resource-limited settings.

Inpatient rehabilitation after deep brain stimulator placement: a case series.

This case series describes the inpatient rehabilitation of two medically complex patients with Parkinson's disease (PD) who had undergone deep brain stimulator (DBS) placement. Most patients may not require inpatient rehabilitation. However, a short rehabilitation stay might be of use to patients who need to be weaned off medications or who need frequent adjustments of their deep brain stimulators. This is the first case series to describe the inpatient rehabilitation of patients with deep brain stimulators.

Glutathione protects cells against arsenite-induced toxicity.

To understand the role of glutathione (GSH) in the protection of cells from arsenite toxicity, we studied the mechanism of apoptotic cell death in cells genetically unable to synthesize GSH (GCS-2 cells). Arsenite stimulated an increase in protein ubiquitination in GCS-2 cells while the wild-type cells were unaffected. Arsenite treatment increased lipid peroxidation and induced ubiquitination of molecular chaperone Hsp90 and impaired its ability to bind cochaperone p50(Cdc-37) and client proteins Plk-1 and Cdk-4 in GCS-2 cells. Treatment with arsenite also partially inhibited proteasome activity in GCS-2 cells. In these cells stably transfected with GFP(u) (a reporter consisting of a short degron fused to the COOH-terminus of GFP), intracellular fluorescence increased, suggesting the accumulation of GFP aggregates. GCS-2 cells underwent apoptosis accompanied by release of cytochrome c into the cytoplasm. Taken together, these data suggest that a possible mechanism of arsenite-induced apoptosis is the accumulation of ubiquitinated proteins and impairment of the protein degradative pathway. Further, protection from arsenite-induced ubiquitination is mediated by GSH and to a lesser extent by available reducing equivalents in the cells.

Substance abuse and the uninsured worker in the United States.

Although millions of US workers lack health insurance, the relationship of insurance coverage with substance abuse and access to workplace treatment services remains unexplored. Our analysis shows uninsured workers have higher rates of heavy drinking and illicit drug use than insured workers. Young and part-time workers are, moreover, less likely to have insurance coverage than workers with lower substance abuse risks. Compared to the insured, uninsured workers have less access to employee assistance programs (EAPs) and less drug and alcohol testing by employers. The effectiveness of workplace substance abuse programs and policies designed for insured populations is untested among uninsured workers. Issues include EAP effectiveness with referrals to public treatment and the return on investment for adding coverage of substance abuse treatment. Workers in countries with universal health insurance but inadequate treatment capacity may face similar problems to uninsured workers in the US.