Understanding the nature of blast resistance in combined bacterial leaf blight and blast gene pyramided lines of rice variety tellahamsa.

BACKGROUND: Rice blast and bacterial leaf blight (BLB) are the most limiting factors for rice production in the world which cause yield losses typically ranging from 20 to 30% and can be as high as 50% in some areas of Asia especially India under severe infection conditions. METHODS AND RESULTS: An improved line of Tellahamsa, TH-625-491 having two BLB resistance genes (xa13 and Xa21) and two blast resistance genes (Pi54 and Pi1) with 95% Tellahamsa genome was used in the present study. TH-625-491 was validated for all four target genes and was used for backcrossing with Tellahamsa. Seventeen IBC1F1 plants heterozygous for all four target genes, 19 IBC1F2 plants homozygous for four, three and two gene combinations and 19 IBC1F2:3 plants also homozygous for four, three and two gene combinations were observed. Among seventeen IBC1F1 plants, IBC1F1-62 plant recorded highest recurrent parent genome (97.5%) covering 75 polymorphic markers. Out of the total of 920 IBC1F2 plants screened, 19 homozygous plants were homozygous for four, three and two target genes along with bacterial blight resistance. Background analysis was done in all 19 homozygous IBC1F2 plants possessing BLB resistance (possessing xa13, Xa21, Pi54 and Pi1 in different combinations) with five parental polymorphic SSR markers. IBC1F2-62-515 recovered 98.5% recurrent parent genome. The four, three and two gene pyramided lines of Tellahamsa exhibited varying resistance to blast. CONCLUSIONS: Results show that there might be presence of antagonistic effect between bacterial blight and blast resistance genes since the lines with Pi54 and Pi1 combination are showing better resistance than the combinations with both bacterial blight and blast resistance genes.

Structural insights into the modulation Of SOD1 aggregation By a fungal metabolite Phialomustin-B: Therapeutic potential in ALS.

Amyotrophic lateral sclerosis (ALS) is a fatal human motor neuron disease leading to muscle atrophy and paralysis. Mutations in superoxide dismutase 1 (SOD1) are associated with familial ALS (fALS). The SOD1 mutants in ALS have a toxic-gain of function by destabilizing the functional SOD1 homodimer, consequently inducing fibril-like aggregation with a cytotoxic non-native trimer intermediate. Therefore, reducing SOD1 oligomerization via chemical modulators is an optimal therapy in ALS. Here, we report the discovery of Phialomustin-B, an unsaturated secondary metabolite from the endophytic fungus Phialophora mustea, as a modulator of SOD1 aggregation. The crystal structure of the SOD1-Phialomustin complex refined to 1.90 Å resolution demonstrated for the first time that the ligand binds to the dimer interface and the lateral region near the electrostatic loop. The aggregation analyses of SOD1WT and the disease mutant SOD1A4V revealed that Phialomustin-B reduces cytotoxic trimerization. We propose that Phialomustin-B is a potent lead molecule with therapeutic potential in fALS.

Heparin vs Saline Infusion to Maintain Patency of Arterial Catheters in Children: A Randomized, Double-Blind, Noninferiority Trial.

OBJECTIVE: To determine whether normal saline flush solution is noninferior to heparinised saline for maintaining the patency of arterial intravascular catheters in children. METHODS: A single centre, double blind, parallel group, noninferiority, randomized control study was conducted in the Pediatric Intensive Care Unit of Kanchi Kamakoti CHILDS Trust hospital, a tertiary children's hospital, Chennai, India. 92 children requiring arterial catheters for more than 12 hours were randomized to receive either normal saline or heparinized saline (1 U/ml) flush solution. Primary outcome was a noninferiority comparison between normal saline and heparinised saline in maintaining the patency of arterial catheters using the proportion of occlusion of arterial catheters as primary endpoint. Secondary outcome was mean duration of patency of arterial catheters in each treatment group. RESULTS: Ninety-two children with a median (interquartile range, age of 84 (33.5-132) months and 52% males were enrolled. 15.2% of catheters in the heparin group and 17.4% of catheters in the normal saline group were occluded (P = 0.77). The 95% upper confidence interval for the difference in proportion was 0.148 (+14.8%), establishing noninferiority (< 15%). The median (IQR) duration of a patent arterial catheter was 47 (27.75 - 94.5) hours in the heparin group and 35.50 (24.50 - 62) hours in the normal saline group (P = 0.10). Comparison of duration of patency using Kaplan Meier survival analysis and log rank test showed no statistically significant difference. There were no serious adverse events noted in either group. CONCLUSIONS: Our data suggests that normal saline is noninferior to heparinized saline infusion in maintaining the patency of arterial lines in children. This may benefit clinicians worldwide as normal saline would be a safer and cost-effective option.

Native bio-control agents from the rice fields of Telangana, India: characterization and unveiling the potential against stem rot and false smut diseases of rice.

The stem rot caused by Sclerotium hydrophilum and false smut caused by Ustilaginoidea virens are two of the major production constraints in rice cultivation in India and other countries. Stem rot and false smut can be effectively controlled with synthetic fungicides. However, the indiscriminate use of chemical fungicides may cause development of resistance among the pathogens. In addition to this, synthetic fungicides also exhibit harmful impacts on the environment. Exploiting microbe-based alternatives for managing plant diseases diminishes public concerns about the ill effects of pesticide usage in crops. In this regard, the present study was designed to investigate the potential of native microbial biocontrol agents (BCAs) from rice rhizosphere for the sustainable management of stem rot and false smut diseases in rice. Potential BCAs and pathogens were identified and characterized through morphological, biochemical, and sanger sequencing techniques. Bio-efficacy tests of potential BCAs against stem rot and false smut diseases on rice under glasshouse conditions indicated higher seed vigour index of the treated seeds, significant improvement in the growth of the seedling, increased dry weight, reduction in percentage disease index viz., 70.03% (stem rot) and 69.24% (false smut) over the control plants. Phytohormones indole acetic acid (IAA), abscisic acid (ABA), gibberellic acid (GA), salicylic acid (SA), and zeatin (tZ) were detected and quantified in the four potential BCAs using liquid chromatography- tandem mass spectrometry (LC-MS/MS). Scanning electron microscopy (SEM) studies revealed the endophytic nature of the strains in rice. The study indicated a positive correlation between the diversity and concentration of phytohormones released by the bioagents and enhanced plant growth promotion and disease suppression in rice.

Chlorhexidine as a Keap1-Nrf2 inhibitor: a new target for an old drug for Parkinson's disease therapy.

Oxidative stress plays a vital role in the pathophysiology of most neurodegenerative diseases such as Parkinson's disease (PD). The Keap1-Nrf2-ARE pathway, one of the internal defense mechanisms, curbs the reactive oxygen species (ROS) generated in the cellular environment. The pathway leads to the expression of antioxidant genes such as HO-1, GCLC, and NQO1, which act as cellular redox switches and protect the cellular environment. Keap1, the negative regulator of Nrf2, is a potential therapeutic target for treating age-related neurodegenerative diseases. Tecfidera (Dimethyl fumarate), used in the intervention for relapsing multiple sclerosis, is the only commercial drug known to regulate the Nrf2 function. Here, we have identified a repurposing drug, chlorhexidine (LBP125), through ligand-based pharmacophore development and screening against the DrugBank, as a potential inhibitor of the ß-propeller domain of Keap1 (Keap1-DC). Chlorhexidine, an antimicrobial agent, is widely used as a mouthwash, skin cleanser, and intervening bacterial infection during childbirth. The biochemical assay confirmed a significant binding affinity of 30 µM and competitively inhibited the Nrf2 peptide interaction. Moreover, chlorhexidine also exerts cytoprotection in a neurotoxic cell model of PD through Keap1-Nrf2 disruption leading to nuclear translocation of Nrf2 and expression of downstream genes, HO-1, and NQO1. Hence, the chemical scaffold of chlorhexidine is a potential lead to develop new chemical libraries with drug-like properties for treating PD.Communicated by Ramaswamy H. Sarma.

Mesoporous calcium hydroxide nanoparticle synthesis from waste bivalve clamshells and evaluation of its adsorptive potential for the removal of Acid Blue 113 dye.

Calcium hydroxide nanoadsorbent was prepared from waste bivalve clamshells and used for the adsorptive removal of Acid Blue 113 (AB113) dye. The morphology, elemental nature, functional groups, and thermal stability of the nanoadsorbent were characterized by various methods. The nanoadsorbent had a high monolayer adsorption capacity (153.53 mg/g) for AB113 dye. Langmuir and Temkin isotherms better fitted (R2 > 0.95) the experimental data. The adsorption rate followed pseudo-second-order kinetics (R2 > 0.99). The thermodynamic study ascertained spontaneous and exothermic adsorption. This study confirmed the possibility of using calcium hydroxide as an adsorbent to effectively remove AB113 dye from aqueous solutions.

Adsorptive removal of AB113 dye using green synthesized hydroxyapatite/magnetite nanocomposite.

In the present study, magnetite nanoparticles (Fe3O4NPs) synthesized using Thunbergia grandiflora leaf extract as a reducing agent were doped with hydroxyapatite sourced from waste bivalve clamshells to produce hydroxyapatite/magnetite nanocomposite (HA/Fe3O4NPs). The magnetic nanocomposite was examined using several characterization techniques. The results of XRD and FESEM, analysis showed HA/Fe3O4NPs have a crystalline phase and irregular spherical particles respectively. EDAX and FTIR confirmed the presence of specific elements and functional groups of both iron oxide and hydroxyapatite nanoparticles respectively. The surface area and superparamagnetic property of the composite were determined by BET and VSM analysis. Central Composite Design (CCD) was used to optimize the adsorption process to remove of AB113 from aqueous solutions. The optimal adsorption efficiency was found out to be 94.38% at pH 8, AB113 dye concentration 54 ppm, HA/Fe3O4NPs dose 84 mg, and an agitation speed of 174 rpm. The monolayer Langmuir isotherm was the best model with a sorption capacity of 109.98 mg/g which was higher than the reported values. The pseudo-second-order kinetic model displayed a good fit with an R2 = 0.99. Thermodynamic parameters were assessed which confirmed the exothermic adsorption process. Therefore, the synthesized magnetic nanocomposite can be employed as a novel nanoadsorbent for the removal of anionic dyes from waste effluents.

Screening of Asymptomatic Healthcare Workers for SARS-COV-2 for Occult Infections: A Cross-Sectional Study.

Introduction The SARS-CoV-2 illness (COVID-19) has spread around the world, primarily through person-to-person transmission, and is a serious public health concern. Based on the severity of illness symptoms, SARS-CoV-2 infection can be classified as either apparent or occult. To date, real-time reverse transcription polymerase chain reaction (RT-PCR) on respiratory specimens, particularly nasopharyngeal and oropharyngeal swabs, or nasopharyngeal wash or aspirate, has been the gold standard for the identification of COVID-19. A negative RT-PCR does not necessarily rule out SARS-CoV-2 infection. Occult COVID-19 infections could least be identified with RT-PCR. Aims and objectives To assess the prevalence of possible occult COVID-19 infection in healthcare personnel by RT-PCR and serology testing for SARS-CoV-2 virus. Methods A cross-sectional study was conducted on health care workers at a tertiary care hospital in South India during the period from October 2020 to January 2021. None of the study participants were vaccinated against COVID-19 during the study period. Nasopharyngeal swabs collected for RT-PCR were tested using Cobas 480 platform (Roche, Basel, Switzerland). Peripheral blood venous sampling was performed to collect EDTA (ethylenediaminetetraacetic acid) and plain samples. SARS-CoV-2 IgG antibodies against spike proteins were estimated using ECI Vitros platform (Ortho Clinical Diagnostics, Raritan, USA). Results The mean age of study participants was 34.78 years (SD±9.51) with an age range of 19-69 years. The study participants were stratified into age groups of 19-25 years, 26-40 years, 41-60 years, and above 60 years, gender, ABO and Rh blood groups, and occupational and further based on their area of work as Covid and Non-Covid for the purpose of statistical analysis. Total 190 samples from healthcare workers (HCWs) were tested for RT-PCR using nasopharyngeal swabs collected at the time of enrolment into the study, and all the 190 samples tested negative for RT-PCR. Among 190 HCW samples screened for SARS-CoV-2-IgG antibodies, 48 (25.3%) were found reactive for IgG antibodies while 142 (74.7%) were found non-reactive. Conclusion Our study findings suggested that using RT-PCR testing, which may only identify those with a prolonged viral shedding period and minimum viral loads, the proportion of asymptomatic/occult infections could be underestimated.

Mucosa-adherent Pediococcus Pentosaceus I44 isolated from healthy human and effect of oleic acid on its probiotic properties.

With the aim of selectively isolating and understanding the cultivable lactic acid bacteria that are autochthonous to human gut, biopsy samples were collected from the terminal ileum and caecum of healthy volunteers who underwent routine colonoscopy procedure. The use of tissue samples (over stool samples) provides for a better expression of the autochthonous bacterial population of the human gut. The strains that were stable after many rounds of sub-culture were identified and studied further. One such ileal isolate, a Gram-positive, catalase-negative cocci was identified to be Pediococcus pentosaceus I44. It was studied for its gastric tolerance, bile tolerance and surface properties, and reported here. The effect of tween-80, oleic acid, extra virgin olive oil and sesame oil on the aforementioned properties of P. pentosaceus I44 was also analysed. The isolate was able to survive well in simulated gastric fluid of pH 3.0 followed by treatment in simulated intestinal fluid with a survival percentage of around 70%. It was, however, unable to withstand pH 2.0 even in the presence of supplements. It showed good tolerance to bile stress (1% w/v), and its cell surface was found to be hydrophilic. P. pentosaceus I44 showed good aggregation of 87% after 24 h, with oleic acid having a significant effect on the isolate's aggregation potential. P. pentosaceus I44 is one of the few mucosa-bound cultivable bacteria that are adapted for survival in human colon. Studying and analysing such isolates might provide useful insights into their role in metabolism and health.

Demographic profile, clinical characteristics and medical management patterns of Indian coronary artery disease patients: a nationwide urban-based, real-world, retrospective, observational electronic medical record study- report of baseline data.

Background: This is the first detailed Indian electronic medical record (EMR)-based real-world observational study to understand the clinical characteristics, associated comorbidities/risk factors and treatment(s) of CAD patients across India.Methods: EMR data of adult Indians (aged ≥ 18 years) diagnosed with CAD was retrospectively analyzed.Results: The majority of the participants had stable IHD (93%), were men (68.5% in ACS, 59.8% in stable IHD), most common age group was 40-64 years in ACS (56.6%) and stable IHD (51.4%). Both are common in metros (ACS 52%, 62% stable IHD). There is a high frequency of hypertension (38.2% in ACS, 59% in stable IHD) and diabetes mellitus (32.3% in ACS, 57.6% in stable IHD). Most common treatments are antiplatelet drugs and lipid-lowering drugs (96%).Conclusions: In India, stable IHD is the most prevalent form in vast majority of patients. The patients with CAD are mostly males, are mainly located in metros and majority fall between the age group of 40-64. The major comorbidities are hypertension and diabetes mellitus. Sociodemographic and clinical characteristics for CAD in India may not be similar to what is reported from the west. There is a significant difference in drug usage and adherence to guidelines in India for CAD.

Detection of SARS-CoV-2 in the air from hospitals and closed rooms occupied by COVID-19 patients

To understand air transmission characteristics of SARS-CoV-2 and risks for health care personnel and visitors to hospitals, we analyzed air samples collected from various enclosures in hospitals at Hyderabad and Mohali and performed closed room experiments with COVID-19 positive individuals. We collected 64 air samples from COVID and non-COVID areas of various hospitals and 17 samples from closed rooms occupied by COVID patients. 4 samples from COVID care areas were positive for SARS-CoV-2 with no obvious predilection towards ICU/non-ICU areas in the hospital samples. In the closed room experiments, where one or more COVID-19 patients spent a short duration of time, one sample - collected immediately after the departure of three symptomatic patients from the room - was positive. Our results indicate that the chance of picking up SARS-CoV-2 in the air is directly related to a number of COVID positive cases in the room, their symptomatic status, and the duration of exposure and that the demarcation of hospital areas into COVID and non-COVID areas is a successful strategy to prevent cross infections. In neutral environmental conditions, the virus does not seem to spread farther away from the patients, especially if they are asymptomatic, giving an objective evidence for the effectiveness of physical distancing in curbing the spread of the epidemic.

Consensus document: management of heart failure in type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is a known predisposing factor for heart failure (HF). The growing burden of these two conditions and their impact on health of the individual and on society in general needs urgent attention from the health care professionals. Availability of multiple treatment choices for managing T2DM and HF may make therapeutic decisions more complex for clinicians. Recent cardiovascular outcome trials of antidiabetic drugs have added very robust evidence to effectively manage subjects with this dual condition. This consensus statement provides the prevalence trends and the impact of this dual burden on patients. In addition, it concisely narrates the types of HF, the different treatment algorithms, and recommendations for physicians to comprehensively manage such patients.

A review on adsorptive removal of dyes from wastewater by hydroxyapatite nanocomposites.

Dye removal from wastewater is of prominence due to its hostile effects on human health and the environment. The complex structure of the dye molecule is responsible for its difficulty in removal. Adsorption is found to be a promising technique to eliminate dye wastes due to its high removal capacity at low concentration. Among different adsorbents used, hydroxyapatite is a biocompatible adsorbent that is relatively efficient in both anionic and cationic dye removal. Recently, modification of hydroxyapatite by doping with other materials to increase its removal efficiency has gained much attention. This review summarizes compilation of recent literature on the removal of anionic and cationic dye by different hydroxyapatite nanocomposites, comparison of adsorption capacities of different hydroxyapatite nanocomposites, the possible adsorption mechanism of removal of dyes, the general isotherm, and kinetic and thermodynamic studies explaining the type of adsorption and the characteristics, advantages, and limitations of adsorbents.

Multiple Genome Wide Association Mapping Models Identify Quantitative Trait Nucleotides for Brown Planthopper (Nilaparvata lugens) Resistance in MAGIC Indica Population of Rice.

Brown planthopper (BPH), one of the most important pests of the rice (Oryza sativa) crop, becomes catastrophic under severe infestations and causes up to 60% yield loss. The highly disastrous BPH biotype in the Indian sub-continent is Biotype 4, which also known as the South Asian Biotype. Though many resistance genes were mapped until now, the utility of the resistance genes in the breeding programs is limited due to the breakdown of resistance and emergence of new biotypes. Hence, to identify the resistance genes for this economically important pest, we have used a multi-parent advanced generation intercross (MAGIC) panel consisting of 391 lines developed from eight indica founder parents. The panel was phenotyped at the controlled conditions for two consecutive years. A set of 27,041 cured polymorphic single nucleotide polymorphism (SNPs) and across-year phenotypic data were used for the identification of marker-trait associations. Genome-wide association analysis was performed to find out consistent associations by employing four single and two multi-locus models. Sixty-one SNPs were consistently detected by all six models. A set of 190 significant marker-associations identified by fixed and random model circulating probability unification (FarmCPU) were considered for searching resistance candidate genes. The highest number of annotated genes were found in chromosome 6 followed by 5 and 1. Ninety-two annotated genes identified across chromosomes of which 13 genes are associated BPH resistance including NB-ARC (nucleotide binding in APAF-1, R gene products, and CED-4) domain-containing protein, NHL repeat-containing protein, LRR containing protein, and WRKY70. The significant SNPs and resistant lines identified from our study could be used for an accelerated breeding program to develop new BPH resistant cultivars.

Rational discovery of a SOD1 tryptophan oxidation inhibitor with therapeutic potential for amyotrophic lateral sclerosis.

Formation of Cu, Zn superoxide dismutase 1 (SOD1) protein inclusions within motor neurons is one of the principal characteristics of SOD1-related amyotrophic lateral sclerosis (ALS). A hypothesis as to the nature of SOD1 aggregation implicates oxidative damage to a solvent-exposed tryptophan as causative. Here, we chart the discovery of a phenanthridinone based compound (Lig9) from the NCI Diversity Set III by rational methods by in silico screening and crystallographic validation. The crystal structure of the complex with SOD1, refined to 2.5 Å, revealed that Lig9 binds the SOD1 ß-barrel in the ß-strand 2 and 3 region which is known to scaffold SOD1 fibrillation. The phenanthridinone moiety makes a substantial π-π interaction with Trp32 of SOD1. The compound possesses a significant binding affinity for SOD1 and inhibits oxidation of Trp32; a critical residue for SOD1 aggregation. Thus, Lig9 is a good candidate from which to develop a new library of SOD1 aggregation inhibitors through protection of Trp32 oxidation. Communicated by Ramaswamy H. Sarma.

Prevention of Histological Changes after Colonic Diversion in Rats: An Experimental Study.

AIM: To determine the beneficial effects of Glutamine, Psyllium, Short Chain Fatty Acids (SCFA), and Maharishi Amrit Kalash (MAK), in preventing the histological changes after diversion colostomy. MATERIAL AND METHODS: After ethical clearance, male wistar rats (n=40) underwent diversion colostomy. Rats were divided into five groups of 8 rats each. Each group was given, after diversion colostomy, per rectally, one of the five agents being tested as an enema (3 ml/kg/day). Group I: Normal saline. Group II: Glutamine Group III: Psyllium, Group IV: MAK. Group V: Short chain fatty acid. The rats were euthanised 45 days after performing diversion colostomy. Morphometrical analysis of defunctionalised colon was done. Statistical analysis was done using SSPS statistical analysis software. RESULTS: On comparison with Group I epithelial cell height and mucosal thickness was significantly higher in Group II. Muscularis externae thickness was significantly higher in Group III on comparison with Group I. Group V had least inflammatory changes. CONCLUSIONS: Atrophic and inflammatory changes in the diverted colon can be prevented by per rectal administration of Glutamine, Psyllium and Short chain fatty acids.

Absent Infra-renal Inferior Vena Cava Presenting with Varicose Veins.

Inferior vena cava (IVC) anomalies were rare and usually asymptomatic. Among these, anomalies absence of infra-renal IVC is the rarest anomaly. Absence of infra-renal IVC may present with symptoms of venous insufficiency and idiopathic deep vein thrombosis. Contrast enhanced CT and MRI abdomen play crucial role in diagnosing these anomalies. These patients can be managed conservatively or by venous bypass. Identification of these anomalies is important to avoid surgeries for varicose veins.

Indium triflate catalysed 3-aza-Cope rearrangement of amino acid derived α,ß-unsaturated esters to alkylidene oxindoles.

The first examples of amino acid derived α,ß-unsaturated esters to Z-alkylidene oxindoles via 3-aza-Cope rearrangement using In(OTf)3 are reported.

Hypersomnolence-hyperkinetic movement disorder in a child with compound heterozygous mutation in 4-aminobutyrate aminotransferase (ABAT) gene.

Deficiency of gamma-amino-butyrate aminotransferase (ABAT) is a rare inherited disorder. A six-month-old girl presented with hyper-somnolence, hyperkinetic movements of distal extremities during wakefulness, hypotonia, bi-pyramidal signs, and impaired response to sound and visual stimuli. Brain MRI at five months showed restricted diffusion along the internal capsule and genu of corpus callosum. A follow up MRI at 18months, showed hyperintensities in brainstem, external and internal capsule, 'trilaminated' appearance of posterior limb of internal capsule and dysmyelination of sub-cortical white matter. MRS showed a peak between 2.2ppm and 2.4ppm, corresponding to glutamine, glutamate and GABA. EEG was normal at six months but showed multifocal epileptiform discharges at 18months. Targeted exome sequencing revealed compound heterozygous missense variations in ABAT resulting in its reduced function. We report the novel association of hypersomnolence and hyperkinetic movement disorder with ABAT variations thus expanding the clinical spectrum of this uncommon neuro-metabolic disorder and discuss the emerging role of GABA in pathways regulating sleep-wake cycle and movement disorders.

Possible role of Epoxyeicosatrienoic acid in prevention of oxidative stress mediated neuroinflammation in Parkinson disorders.

Parkinson's disease (PD) is a multifactorial neurodegenerative disease involving oxidative stress, neuroinflammation and apoptosis. Epoxyeicosatrienoic acids (EETs) are arachidonic acid metabolites and they play a role in cytoprotection by modulating various cell signaling pathways. This cytoprotective role of EETs are well established in cerebral stroke, cardiac failure, and hypertension, and it is due to their ability to attenuate oxidative stress, endoplasmic reticulum stress, inflammation, caspase activation and apoptosis. The actions of EETs in brain closely parallel the effects which is observed in the peripheral tissues. Since many of these effects could potentially contribute to neuroprotection, EETs are, therefore, one of the potential therapeutic candidates in PD. Therefore, by increasing the half life of endogenous EETs in vivo via inhibition of sEH, its metabolizing enzyme can, therefore, constitutes an important therapeutic strategy in PD.