Manipulating epigenetic diversity in crop plants: Techniques, challenges and opportunities.

Epigenetic modifications act as conductors of inheritable alterations in gene expression, all while keeping the DNA sequence intact, thereby playing a pivotal role in shaping plant growth and development. This review article presents an overview of techniques employed to investigate and manipulate epigenetic diversity in crop plants, focusing on both naturally occurring and artificially induced epialleles. The significance of epigenetic modifications in facilitating adaptive responses is explored through the examination of how various biotic and abiotic stresses impact them. Further, environmental chemicals are explored for their role in inducing epigenetic changes, particularly focusing on inhibitors of DNA methylation like 5-AzaC and zebularine, as well as inhibitors of histone deacetylation including trichostatin A and sodium butyrate. The review delves into various approaches for generating epialleles, including tissue culture techniques, mutagenesis, and grafting, elucidating their potential to induce heritable epigenetic modifications in plants. In addition, the ground breaking CRISPR/Cas is emphasized for its accuracy in targeting specific epigenetic changes. This presents a potent tools for deciphering the intricacies of epigenetic mechanisms. Furthermore, the intricate relationship between epigenetic modifications and non-coding RNA expression, including siRNAs and miRNAs, is investigated. The emerging role of exo-RNAi in epigenetic regulation is also introduced, unveiling its promising potential for future applications. The article concludes by addressing the opportunities and challenges presented by these techniques, emphasizing their implications for crop improvement. Conclusively, this extensive review provides valuable insights into the intricate realm of epigenetic changes, illuminating their significance in phenotypic plasticity and their potential in advancing crop improvement.

The Impacts and Changes Related to the Cancer Drug Resistance Mechanism.

BACKGROUND: Cancer drug resistance remains a difficult barrier to effective treatment, necessitating a thorough understanding of its multi-layered mechanism. OBJECTIVE: This study aims to comprehensively explore the diverse mechanisms of cancer drug resistance, assess the evolution of resistance detection methods, and identify strategies for overcoming this challenge. The evolution of resistance detection methods and identification strategies for overcoming the challenge. METHODS: A comprehensive literature review was conducted to analyze intrinsic and acquired drug resistance mechanisms, including altered drug efflux, reduced uptake, inactivation, target mutations, signaling pathway changes, apoptotic defects, and cellular plasticity. The evolution of mutation detection techniques, encompassing clinical predictions, experimental approaches, and computational methods, was investigated. Strategies to enhance drug efficacy, modify pharmacokinetics, optimizoptimizee binding modes, and explore alternate protein folding states were examined. RESULTS: The study comprehensively overviews the intricate mechanisms contributing to cancer drug resistance. It outlines the progression of mutation detection methods and underscores the importance of interdisciplinary approaches. Strategies to overcome drug resistance challenges, such as modulating ATP-binding cassette transporters and developing multidrug resistance inhibitors, are discussed. The study underscores the critical need for continued research to enhance cancer treatment efficacy. CONCLUSION: This study provides valuable insights into the complexity of cancer drug resistance mechanisms, highlights evolving detection methods, and offers potential strategies to enhance treatment outcomes.

Assessment of pathogen removal efficiency of vertical flow constructed wetland treating septage.

Septage refers to the semi-liquid waste material that accumulates in septic tanks and other onsite sanitation systems. It is composed of a complex mixture of human excreta, wastewater, and various solid particles. Septage is a potential source of water pollution owing to presence of high organic content, significant pathogen concentrations, and a range of nutrients like nitrogen and phosphorus. The harmful impacts of septage pollution poses significant risks to public health through the contamination of drinking water sources, eutrophication of water bodies and spread of water borne diseases. Conventional septage treatment technologies often face limitations such as high operational costs, energy requirements, and the need for extensive infrastructure. Therefore, with an aim to treat septage through an alternative cost effective and energy-efficient technology, a laboratory-scale constructed wetland (CW) system (0.99 m2) consisting of a sludge drying bed and a vertical flow wetland bed was utilized for the treatment of septage. The sludge drying bed and vertical flow beds were connected in series and filled with a combination of gravel with varying sizes (ranging from 5 to 40 mm) and washed sand. Canna indica plants were cultivated on both beds to facilitate phytoremediation process. The system was operated with intermittent dosing of 30 Ltrs of septage every day for 2 months. The HRT of the system was fixed at 48 h. The average inlet loads of Biochemical Oxygen Demand (BOD5), Chemical Oxygen Demand (COD), and Total Suspended Solids (TSS) were measured as 150 ± 65.7 g m-2 day-1, 713 ± 443.9 g m-2 day-1, and 309 ± 66.3 g m-2 day-1, respectively. After treatment, the final effluent had an average load of 6 g m-2 day-1 for BOD5, 15 g m-2 day-1 for COD, and 51 g m-2 day-1 for TSS, indicating that the CW system achieved an average removal efficiency of 88% for BOD, 87% for COD, and 65% for TSS. The average load of total coliforms and helminthes eggs in the influent was recorded as 4 × 108 Colony-Forming Units (CFU) m-2 day-1 and 3 × 107 eggs m-2 day-1, respectively. However, the CW system demonstrated significant effectiveness in reducing microbial contamination, with an average removal efficiency of 99% for both total coliforms and helminthes eggs. The vertical flow constructed wetland system, equipped with pretreatment by sludge drying bed, has proven to be efficient in treatment of septage.

Rifampicin-induced ER stress and excessive cytoplasmic vacuolization instigate hepatotoxicity via alternate programmed cell death paraptosis in vitro and in vivo.

AIMS: Rifampicin-induced hepatotoxicity is a primary cause of drug-induced liver injury (DILI), posing a significant challenge to its continued clinical application. Moreover, the mechanism underlying rifampicin-induced hepatotoxicity remains unclear. MAIN METHODS: Human hepatocyte line-17 (HHL-17) cells were treated with an increasing dose of rifampicin for 24 h, and male Wistar rats were given rifampicin [150 mg/kg body weight (bw)] orally for 28 days. Viability assay, protein expression, and cell death assays were analyzed in vitro. Moreover, liver serum markers, body/organ weight, H&E staining, protein expression, etc., were assayed in vivo. KEY FINDINGS: Rifampicin induced a dose-dependent hepatotoxicity in HHL-17 cells (IC50; 600 µM), and increased the serum levels of liver injury markers, e.g., alanine transaminase (ALT) and aspartate transaminase (AST) in rats. Rifampicin-induced cell death was non-apoptotic and non-necroptotic both in vitro and in vivo. Further, excessive cellular vacuolization and reduced expression of Alix protein confirmed the induction of paraptosis both in vitro and in vivo. In addition, a significant increase in the endoplasmic reticulum (ER) stress markers (e.g., BiP, CHOP, and total polyubiquitinated proteins) was detected, demonstrating the induction of ER stress and altered protein homeostasis. Interestingly, rifampicin-induced hepatotoxicity was associated with the inhibition of autophagy and enhanced reactive oxygen species (ROS) generation in HHL-17 cells. Furthermore, inhibition of protein synthesis by cycloheximide (CHX) suppressed paraptosis by alleviating rifampicin-induced ER stress and ROS generation. SIGNIFICANCE: Rifampicin-induced hepatotoxicity involves ER stress-driven paraptosis as a novel mechanism of its toxicity that may be targeted to protect liver cells from rifampicin toxicity.

Defective quality control autophagy in Hyperhomocysteinemia promotes ER stress and consequent neuronal apoptosis through proteotoxicity.

Homocysteine (Hcy), produced physiologically in all cells, is an intermediate metabolite of methionine and cysteine metabolism. Hyperhomocysteinemia (HHcy) resulting from an in-born error of metabolism that leads to accumulation of high levels of Hcy, is associated with vascular damage, neurodegeneration and cognitive decline. Using a HHcy model in neuronal cells, primary cortical neurons and transgenic zebrafish, we demonstrate diminished autophagy and Hcy-induced neurotoxicity associated with mitochondrial dysfunction, fragmentation and apoptosis. We find this mitochondrial dysfunction is due to Hcy-induced proteotoxicity leading to ER stress. We show this sustained proteotoxicity originates from the perturbation of upstream autophagic pathways through an aberrant activation of mTOR and that protetoxic stress act as a feedforward cues to aggravate a sustained ER stress that culminate to mitochondrial apoptosis in HHcy model systems. Using chemical chaperones to mitigate sustained ER stress, Hcy-induced proteotoxicity and consequent neurotoxicity were rescued. We also rescue neuronal lethality by activation of autophagy and thereby reducing proteotoxicity and ER stress. Our findings pave the way to devise new strategies for the treatment of neural and cognitive pathologies reported in HHcy, by either activation of upstream autophagy or by suppression of downstream ER stress. Video Abstract.

An In-vitro Evaluation of Retention Force of All PEEK, All Zirconia and Zirconia-PEEK Telescopic Attachment for Mandibular Overdentures.

The objective of this study is to compare retention capacity of mandibular implant-supported overdenture with all zirconia, zirconia-PEEK, and all PEEK telescopic attachments. Sixty acrylic resin models of mandible were used. Telescopic attachment system was made up of all zirconia, all PEEK, and zirconia-PEEK. Evaluation of retention force was done using universal testing machine. Obtained data were statistically evaluated. Highest initial force value was obtained with zirconia-PEEK group. All PEEK and zirconia-PEEK groups showed significantly decreased final retention values in comparison to their initial values. Zirconia can be regarded as the material of choice for telescopic crown, whereas polyetheretherketone and zirconia-PEEK telescopic crowns showed retention loss over a period of time.

Development and evaluation of Hedyotis corymbosa (L.) extract containing phytosomes: a preclinical approach for treatment of neuropathic pain in rodent model.

PURPOSE: The study was aimed to encapsulate Hedyotis corymbosa extract (HCE) into phytosomes to improve its therapeutic efficacy in neuropathic pain by enhancing the bioavailability of chief chemical constituent Hedycoryside -A (HCA). METHODS: For preparing phytosomes complexes (F1, F2, and F3), HCE and phospholipids were reacted in disparate ratio. F2 was chosen to assess its therapeutic efficacy in neuropathic pain induced by partial sciatic nerve ligation. Nociceptive threshold and oral bioavailability were also estimated for F2. RESULTS: Particle size, zeta potential and entrapment efficiency for F2 were analysed as 298.1 ± 1.1 nm, -3.92 ± 0.41 mV and 72.12 ± 0.72% respectively. F2 gave enhanced relative bioavailability (158.92%) of HCA along with a greater neuroprotective potential showing a significant antioxidant effect and augmentation (p < 0.05) in nociceptive threshold with the diminution in damage to nerves. CONCLUSION: F2 is an optimistic formulation for enhancing the HCE delivery for the effective treatment of neuropathic pain.

Crosstalk between epigenetics and tumor promoting androgen signaling in prostate cancer.

Prostate cancer (PCa) is one of the major health burdens among all cancer types in men globally. Early diagnosis and efficacious treatment options are highly warranted as far as the incidence of PCa is concerned. Androgen-dependent transcriptional activation of androgen receptor (AR) is central to the prostate tumorigenesis and therefore hormonal ablation therapy remains the first line of treatment for PCa in the clinics. However, the molecular signaling engaged in AR-dependent PCa initiation and progression is infrequent and diverse. Moreover, apart from the genomic changes, non-genomic changes such as epigenetic modifications have also been suggested as critical regulator of PCa development. Among the non-genomic mechanisms, various epigenetic changes such as histones modifications, chromatin methylation and noncoding RNAs regulations etc. play decisive role in the prostate tumorigenesis. Given that epigenetic modifications are reversible using pharmacological modifiers, various promising therapeutic approaches have been designed for the better management of PCa. In this chapter, we discuss the epigenetic control of tumor promoting AR signaling that underlies the mechanism of prostate tumorigenesis and progression. In addition, we have discussed the approaches and opportunities to develop novel epigenetic modifications based therapeutic strategies for targeting PCa including castrate resistant prostate cancer (CRPC).

Chloroquine synergizes doxorubicin efficacy in cervical cancer cells through flux impairment and down regulation of proteins involved in the fusion of autophagosomes to lysosomes.

Drug repurposing holds abundant opportunity in the development of novel anticancer drugs. Chloroquine (CQ), a FDA approved anti-malarial drug, is demonstrated to enhance anticancer efficacy of standard anticancer drugs including doxorubicin (DOX) in several types of cancer cells. Here, we aimed to exploit the chemosensitizing effects of CQ against DOX in human cervical cancer (HeLa) cells that remains to be investigated yet. We show that a combination of DOX (40 nM) and CQ (40 µM) resulted in a synergistic cytotoxicity (combination index; CI < 1) in HeLa cells compared to the DOX or CQ alone. Synergistic effect of the combination (DOX + CQ) was associated with the impaired autophagic flux and enhanced apoptosis. Following treatment with the combination (DOX + CQ), the level of p62/SQSTM and LC-3II proteins was increased, while a decrease was noted in the expression of LAMP-2, Syntaxin17, Rab 5, and Rab 7 proteins that play critical roles in the fusion of autophagosomes to lysosomes. Autophagy inhibition by combination (DOX + CQ) enhanced the apoptotic cell death synergistically by increasing the cleavage of procaspase-3 and PARP1. Further, a prior incubation of HeLa cells with Z-VAD-FMK (a pan-caspase inhibitor) for 4 h, suppressed the combination (DOX + CQ)-induced cell death. Our data suggest that a combination of DOX + CQ had a better anti-cancer efficacy in HeLa cells than either of the drugs alone. Thus, CQ, as a repurposed drug, may hold the potential to synergize anticancer effects of DOX in cervical cancer cells.

Bisphenol A exposure induces metastatic aggression in low metastatic MCF-7 cells via PGC-1α mediated mitochondrial biogenesis and epithelial-mesenchymal plasticity.

AIMS: The frequency of estrogen receptor alpha (ERα)-positive breast cancers and their metastatic progression is prevalent in females globally. Aberrant interaction of estrogen-like endocrine-disrupting chemicals (EDCs) is highly implicated in breast carcinogenesis. Studies have shown that single or acute exposures of weak EDCs such as bisphenol A (BPA) may not have a substantial pro-carcinogenic/metastatic effect. However, repeated exposure to EDCs is expected to strongly induce carcinogenic/metastatic progression, which remains to be studied. MAIN METHODS: Low metastatic ERα-positive human breast cancer cells (MCF-7) were exposed to nanomolar doses of BPA every 24 h (up to 200 days) to study the effect of repeated exposure on metastatic potential. Following the designated treatment of BPA, markers of epithelial-mesenchymal transition (EMT), migration and invasion, mitochondrial biogenesis, ATP levels, and peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC-1α) knockdown assays were performed. KEY FINDINGS: A repeated exposure of low dose BPA induced stable epithelial-mesenchymal plasticity in MCF-7 cells to augment migration and invasion in the ERα-dependent pathway. Repeated exposures of BPA increased the levels of several mesenchymal markers such as N-cadherin, vimentin, cluster of differentiation 44 (CD44), slug, and alpha-smooth muscle actin (α-SMA), whereas reduced the level of E-cadherin drastically. BPA-induced mitochondrial biogenesis favored metastatic aggression by fulfilling bioenergetics demand via PGC-1α/NRF1/ERRα signaling. Knockdown of PGC-1α resulted in suppressing both mitochondrial biogenesis and EMT in BPA exposed MCF-7 cells. SIGNIFICANCE: Repeated exposures of low dose BPA may induce metastatic aggression in ERα-positive breast cancer cells via PGC-1α-mediated mitochondrial biogenesis and epithelial-mesenchymal plasticity.

Cancer cell's internal and external warriors: Autophagosomes and exosomes.

"That survival instinct, that will to live, that need to get back to life again, is more powerful than any consideration of taste, decency, politeness, manners, civility, anything. It's such a powerful force." This quote by famous director Danny Boyle is a perfect analogy to describe the cancer cell's inexhaustible drive to persist against all odds. In order to adapt to a hostile environment, the cancer cells rely on multiple mechanisms including immune escape, epithelial to mesenchymal transition, angiogenesis, extravasation, autophagy, exosome release among others. Cancer cells depute their internal and external warriors, autophagosomes and exosomes, to dwell in the belligerent tumor microenvironment. It is quite reasonable for a cancer cell, striving to survive, to invest in pathways that will provide the maximum advantage. Autophagy is an important cellular degradation pathway, while the exosome pathway provides an alternative cargo disposal mechanism to maintain the homeostasis and cell survival. While autophagic degradation provides the essential nutrients to rapidly dividing cells, exosomal secretion ensures that the tumor microenvironment is attuned to accommodate the swiftly expanding tumor mass. Studies have revealed that exosomes secreted by cancer cells can modulate autophagy in recipient cells, while autophagy can influence the biogenesis of exosomes. Autophagy and exosome crosstalk is extremely complex and it is only beginning to be recognized and documented. This review is focused on discussing the roles of autophagy and exosomes in the cancer cell's adaptation to the tumor microenvironment and how the two pathways are coordinately regulated to facilitate cancer cell survival.

Characterization of Microwave-Controlled Polyacrylamide Graft Copolymer of Tamarind Seed Polysaccharide.

The main objective of the study was to prepare tamarind seed polysaccharide grafted copolymers of polyacrylamide (TSP-g-Am) using a 32 factorial design. Tamarind seed polysaccharide (TSP) was extracted, and grafted copolymer of TSP was prepared using polyacrylamide as copolymer and ceric ammonium nitrate as initiator. Various batches (F1-F9) of TSP-g-Am were prepared, among which F1 showed highest grafting efficiency; hence, the prepared TSP-g-Am (F1) was evaluated for grafting efficiency, conversion, effect of initiator and further characterized using SEM analysis, contact angle determination, DSC analysis, swelling index, swelling and deswelling, and chemical resistance. The contact angle of TSP was found to be 81 ± 2, and that of TSP-g-Am (F1) was found to be 74 ± 2, which indicates that the wetting ability of the grafted copolymer was less than that of the native polymer. The results of thermal analysis indicated that TSP-g-Am had a more stable molecular structure than TSP. The morphology of the grafted polymer was observed from SEM images, and it was observed that the particles was asymmetrical. Antimicrobial activity was also found in the grafted copolymer. The present study concludes that the TSP-g-Am showed an excellent performance in thermal stability and swelling capacity compared with TSP. The detailed structural characteristics, as well as the excellent thermal stability and swelling capacities, will make it beneficial to use the synthesised copolymer as a precursor for the production of large-scale eco-friendly advanced materials with a wide range of applications, acting as a stabiliser, thickener, binder, release retardant, modifier, suspending agent, viscosity enhancer, emulsifying agent, or carrier for novel drug delivery systems in oral, buccal, colon, and ocular systems, and in nanofabrication and wound dressing, and it is also becoming an important part of food, cosmetics, confectionery, and bakery.

A Comparative Clinical Evaluation of Effectiveness of Platelet-Rich Plasma, Synthetic Allograft, and Bioresorbable Xenograft During Immediate Implant Placement.

BACKGROUND: The use of an appropriate graft material helps in an adequate amount of osseointegration. The objective of this study was to compare the efficacy of platelet-rich plasma (PRP), a synthetic allograft (PerioGlas), and Bio-Oss, a bioresorbable xenograft in immediate implant procedures. METHODS: In this randomized, prospective study, 90 patients were categorized into three groups with 30 samples in each as Group A: patients who received PRP with an immediate implant; Group B: immediate implants with synthetic allograft (PerioGlas); and Group C: patients with immediate implants placed using bioresorbable xenograft (Bio-Oss). Postoperative follow-up was done based on plaque and gingival index, measurement of probing depths, and resorption of bone. Obtained data were statistically analyzed using the "one-way analysis of variance (ANOVA)" test. RESULTS: Inter-group statistical comparisons between gingival and plaque indices at three, six, and 12 months of follow-up in the study groups demonstrated no statistical significance (p > 0.05). The mean probing depths and resorption of bone at three, six, and 12 months of follow-up were statistically nonsignificant (p > 0.05) on the inter-group comparison. CONCLUSION: It could be concluded from the present study that there is no statistical superiority observed among PRP, PerioGlas, or Bio-Oss in terms of their usage as a graft material along with immediate implant placement procedure.

WheatQTLdb V2.0: a supplement to the database for wheat QTL.

We recently developed a database for hexaploid wheat QTL (WheatQTLdb; www.wheatqtldb.net), which included 11,552 QTL affecting various traits of economic importance. However, that database did not include valuable QTL from other wheat species and/or progenitors of hexaploid wheat. Therefore, an updated and improved version of wheat QTL database (WheatQTLdb V2.0) was developed, which now includes information on hexaploid wheat (Triticum aestivum) and the following seven other related species: T. durum, T. turgidum, T. dicoccoides, T. dicoccum, T. monococcum, T. boeoticum, and Aegilops tauschii. WheatQTLdb V2.0 includes a much-improved list of QTL, including 27,518 main effect QTL, 202 epistatic QTL, and 1321 metaQTL. This newly released WheatQTLdb V2.0 also has additional valuable options to search and choose the QTL, category-wise, and trait-wise data for their use in research or breeding programs.

Meta-QTLs and candidate genes for stripe rust resistance in wheat.

In bread wheat, meta-QTL analysis was conducted using 353 QTLs that were available from earlier studies. When projected onto a dense consensus map comprising 76,753 markers, only 184 QTLs with the required information, could be utilized leading to identification of 61 MQTLs spread over 18 of the 21 chromosomes (barring 5D, 6D and 7D). The range for mean R2 (PVE %) was 1.9% to 48.1%, and that of CI was 0.02 to 11.47 cM; these CIs also carried 37 Yr genes. Using these MQTLs, 385 candidate genes (CGs) were also identified. Out of these CGs, 241 encoded known R proteins and 120 showed differential expression due to stripe rust infection at the seedling stage; the remaining 24 CGs were common in the sense that they encoded R proteins as well as showed differential expression. The proteins encoded by CGs carried the following widely known domains: NBS-LRR domain, WRKY domains, ankyrin repeat domains, sugar transport domains, etc. Thirteen breeders' MQTLs (PVE > 20%) including four pairs of closely linked MQTLs are recommended for use in wheat molecular breeding, for future studies to understand the molecular mechanism of stripe rust resistance and for gene cloning.

Isolation of new phytometabolites from Alpinia galanga willd rhizomes.

The current research was aimed to isolate newer phyto-metabolites from rhizomes of Alpinia galanga plant. Study involved preparation of Alpinia galanga rhizome methanolic extract, followed by normal phase column chromatography assisted isolation of new phytometabolites (using different combinations of chloroform and methanol), and characterization (by UV, FTIR, 13C-NMR, 1H-NMR, COSY, DEPT and Mass spectrometry). The isolation and characterization experiment offered two phytometabolites: an ester (Ag-1) and tetrahydronapthalene type lactone (Ag-2). Present study concludes and reports the two phytometabolites, benzyl myristate (Ag-1) and 3-Methyl-6α, 8ß-diol-7-carboxylic acid tetralin-11, 9ß-olide (Ag-2) for the first time in Alpinia galanga rhizome. The study recommends that these phytometabolites Ag-1 and Ag-2 can be utilized as effective analytical biomarkers for identification, purity and quality control of this plant in future.

Lessons from implementation research on community management of Possible Serious Bacterial Infection (PSBI) in young infants (0-59 days), when the referral is not feasible in Palwal district of Haryana, India.

BACKGROUND: Neonatal sepsis is a major cause of death in India, which needs hospital management but many families cannot access hospitals. The World Health Organization and the Government of India developed a guideline to manage possible serious bacterial infection (PSBI) when a referral is not feasible. We implemented this guideline to achieve high coverage of treatment of PSBI with low mortality. METHODOLOGY: The implementation research study was conducted in over 50 villages of Palwal district, Haryana during August 2017-March 2019 and covered a population of 199143. Policy dialogue with central, state and district health authorities was held before initiation of the study. A baseline assessment of the barriers in the implementation of the PSBI intervention was conducted. The intervention was implemented in the program setting. The research team collected data throughout and also co-participated in the implementation of the intervention for the first six months to identify bottlenecks in the health system and at the community level. RE-AIM framework was utilized to document implementation strategies of PSBI management guideline. Implementation strategies by the district technical support unit (TSU) included: (i) empower mothers and families through social mobilization to improve care-seeking of sick young infants 0-59 days of age, (ii) build capacity through training and build confidence through technical support of health staff at primary health centers (PHC), community health centers (CHC) and sub-centers to manage young infants with PSBI signs and (iii) improve performance of accredited social health activists (ASHAs). FINDINGS: A total of 370 young infants with signs of PSBI were identified and managed in 5270 live births. Treatment coverage was 70% assuming that 10% of live births would have PSBI within the first two months of life. Mothers identified 87.6% (324/370) of PSBI cases. PHCs and CHCs became functional and managed 150 (40%) sick young infants with PSBI. Twenty four young infants (7-59days) who had only fast breathing were treated with oral amoxicillin without a referral. Referral to a hospital was refused by 126 (84%); 119 had clinical severe infection (CSI), one 0-6 days old had fast breathing and six had critical illness (CI). Of 119 CSI cases managed on outpatient injection gentamicin and oral amoxicillin, 116 (96.7%) recovered, 55 (45.8%) received all seven gentamicin injections and only one died. All 7-59 day old infants with fast breathing recovered, 23 on outpatient oral amoxicillin treatment; and 19 (79%) received all doses. Of 65 infants managed at either district or tertiary hospital, two (3.1%) died, rest recovered. Private providers managed 155 (41.9%) PSBI cases, all except one recovered, but sub-classification and treatment were unknown. Sub-centers could not be activated to manage PSBI. CONCLUSION: The study demonstrated resolution of implementation bottlenecks with existing resources, activated PHCs and CHCs to manage CSI and fast breathers (7-59 day old) on an outpatient basis with low mortality when a referral was not feasible. TSU was instrumental in these achievements. We established the effectiveness of oral amoxicillin alone in 7-59 days old fast breathers and recommend a review of the current national policy.

Biopurification of dairy farm wastewater through hybrid constructed wetland system: Groundwater quality and health implications.

Groundwater is under heavily threat owing to enormous infilteration of dairy farm originated wastewater into it. The anoxic environment in the groundwater due to mixing of organic rich wastewater can produce significant alterations in the groundwater quality. It is therefore necessary to treat such wastewaters before discharging to surrounding areas. Therefore, in this study we evaluated a hybrid constructed wetland (CW) system(40 m2 area) consisting of three beds, i.e. Vertical (16 m2) - Horizontal (18 m2) - Vertical (6 m2) connected in series for the treatment of dairy farm wastewater under typical high humid climate in northern India. Tropical perennial plant such as Arundo donax L. was grown on both vertical beds, whereas Hibiscus esculentus L. and Solanum melongena L. were grown on the horizontal bed of the system.The average purification of TSS, BOD3, total N, and P was significant (p < 0.05) in HF bed and recorded as 92.2 ± 6.1, 95 ± 3.8, 83.6 ± 9.0 and 86.1 ± 10.0% respectively.The average load of BOD3, total N, and P in the influent and effluent was recorded (with no significant differences, p > 0.05) as 7.0 ± 7.17, 1.9 ± 0.7, 0.72 ± 0.5 g m-2 day-1and 0.3 ± 0.2, 0.3 ± 0.2 and 0.04 ± 0.01 g m-2 day-1 respectively.The average values of total biomass content of Arundo donax L. were differed significantly and recorded as 0.31 ± 0.06, 0.43 ± 0.17, and 0.43 ± 0.16 g g-1 fresh wt. in control, VF-1, and VF-2 respectively. Therefore, the hybrid CW system can be efficiently used for the treatment of dairy farm wastewater with implications on groundwater and health. Future research may focus on performance analysis of upgraded combined anaerobic reactor and hybrid CW system planted with series of macrophytes for on-site treatment of high strength dairy farm wastewater in tropical regions.

WheatQTLdb: a QTL database for wheat.

During the last three decades, QTL analysis in wheat has been conducted for a variety of individual traits, so that thousands of QTL along with the linked markers, their genetic positions and contribution to phenotypic variation (PV) for concerned traits are now known. However, no exhaustive database for wheat QTL is currently available at a single platform. Therefore, the present database was prepared which is an exhaustive information resource for wheat QTL data from the published literature till May, 2020. QTL data from both interval mapping and genome-wide association studies (GWAS) have been included for the following classes of traits: (i) morphological traits, (ii) N and P use efficiency, (iii) traits for biofortification (Fe, K, Se, and Zn contents), (iv) tolerance to abiotic stresses including drought, water logging, heat stress, pre-harvest sprouting and salinity, (v) resistance to biotic stresses including those due to bacterial, fungal, nematode and insects, (vi) quality traits, and (vii) a variety of physiological traits, (viii) developmental traits, and (ix) yield and its related traits. For the preparation of the database, literature was searched for data on QTL/marker-trait associations (MTAs), curated and then assembled in the form of WheatQTLdb. The available information on metaQTL, epistatic QTL and candidate genes, wherever available, is also included in the database. Information on QTL in this WheatQTLdb includes QTL names, traits, associated markers, parental genotypes, crosses/mapping populations, association mapping panels and other useful information. To our knowledge, WheatQTLdb prepared by us is the largest collection of QTL (11,552), epistatic QTL (107) and metaQTL (330) data for hexaploid wheat to be used by geneticists and plant breeders for further studies involving fine mapping, cloning, and marker-assisted selection (MAS) during wheat breeding.