Kupyaphores are zinc homeostatic metallophores required for colonization of Mycobacterium tuberculosis.

Mycobacterium tuberculosis (Mtb) endures a combination of metal scarcity and toxicity throughout the human infection cycle, contributing to complex clinical manifestations. Pathogens counteract this paradoxical dysmetallostasis by producing specialized metal trafficking systems. Capture of extracellular metal by siderophores is a widely accepted mode of iron acquisition, and Mtb iron-chelating siderophores, mycobactin, have been known since 1965. Currently, it is not known whether Mtb produces zinc scavenging molecules. Here, we characterize low-molecular-weight zinc-binding compounds secreted and imported by Mtb for zinc acquisition. These molecules, termed kupyaphores, are produced by a 10.8 kbp biosynthetic cluster and consists of a dipeptide core of ornithine and phenylalaninol, where amino groups are acylated with isonitrile-containing fatty acyl chains. Kupyaphores are stringently regulated and support Mtb survival under both nutritional deprivation and intoxication conditions. A kupyaphore-deficient Mtb strain is unable to mobilize sufficient zinc and shows reduced fitness upon infection. We observed early induction of kupyaphores in Mtb-infected mice lungs after infection, and these metabolites disappeared after 2 wk. Furthermore, we identify an Mtb-encoded isonitrile hydratase, which can possibly mediate intracellular zinc release through covalent modification of the isonitrile group of kupyaphores. Mtb clinical strains also produce kupyaphores during early passages. Our study thus uncovers a previously unknown zinc acquisition strategy of Mtb that could modulate host-pathogen interactions and disease outcome.

Electrically Controlled High Sensitivity Strain Modulation in MoS2 Field-Effect Transistors via a Piezoelectric Thin Film on Silicon Substrates.

Strain can modulate bandgap and carrier mobilities in two-dimensional (2D) materials. Conventional strain-application methodologies relying on flexible/patterned/nanoindented substrates are limited by low thermal tolerance, poor tunability, and/or scalability. Here, we leverage the converse piezoelectric effect to electrically generate and control strain transfer from a piezoelectric thin film to electromechanically coupled 2D MoS2. Electrical bias polarity change across the piezo film tunes the nature of strain transferred to MoS2 from compressive (∼0.23%) to tensile (∼0.14%) as verified through Raman and photoluminescence spectroscopies and substantiated by density functional theory calculations. The device architecture, on silicon substrate, integrates an MoS2 field-effect transistor on a metal-piezoelectric-metal stack enabling strain modulation of transistor drain current (130×), on/off ratio (150×), and mobility (1.19×) with high precision, reversibility, and resolution. Large, tunable tensile (1056) and compressive (-1498) strain gauge factors, electrical strain modulation, and high thermal tolerance promise facile integration with silicon-based CMOS and micro-electromechanical systems.

Spinocerebellar ataxia type 27B (SCA27B) in India: insights from a large cohort study suggest ancient origin.

BACKGROUND: The ethnic diversity of India provides a unique opportunity to study the history of the origin of mutations of genetic disorders. Spinocerebellar ataxia type 27B (SCA27B), a recently identified dominantly inherited cerebellar disorder is caused by GAA-repeat expansions in intron 1 of Fibroblast Growth Factor 14 (FGF14). Predominantly reported in the European population, we aimed to screen this mutation and study the founder haplotype of SCA27B in Indian ataxia patients. METHODS: We have undertaken screening of GAA repeats in a large Indian cohort of ~ 1400 uncharacterised ataxia patients and kindreds and long-read sequencing-based GAA repeat length assessment. High throughput genotyping-based haplotype analysis was also performed. We utilized ~ 1000 Indian genomes to study the GAA at-risk expansion alleles. FINDINGS: We report a high frequency of 1.83% (n = 23) of SCA27B in the uncharacterized Indian ataxia cohort. We observed several biallelic GAA expansion mutations (n = 5) with younger disease onset. We observed a risk haplotype (AATCCGTGG) flanking the FGF14-GAA locus over a 74 kb region in linkage disequilibrium. We further studied the frequency of this risk haplotype across diverse geographical population groups. The highest prevalence of the risk haplotype was observed in the European population (29.9%) followed by Indians (21.5%). The observed risk haplotype has existed through ~ 1100 generations (~ 22,000 years), assuming a correlated genealogy. INTERPRETATION: This study provides valuable insights into SCA27B and its Upper Paleolithic origin in the Indian subcontinent. The high occurrence of biallelic expansion is probably relevant to the endogamous nature of the Indian population.

Investigation of RFC1 tandem nucleotide repeat locus in diverse neurodegenerative outcomes in an Indian cohort.

An intronic bi-allelic pentanucleotide repeat expansion mutation, (AAGGG)400-2000, at AAAAG repeat locus in RFC1 gene, is known as underlying genetic cause in cases with cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) and late-onset sporadic ataxia. Biallelic positive cases carry a common recessive risk haplotype, "AAGA," spanning RFC1 gene. In this study, our aim is to find prevalence of bi-allelic (AAGGG)exp in Indian ataxia and other neurological disorders and investigate the complexity of RFC1 repeat locus and its potential association with neurodegenerative diseases in Indian population-based cohorts. We carried out repeat number and repeat type estimation using flanking PCR and repeat primed PCR (AAAAG/AAAGG/AAGGG) in four Indian disease cohorts and healthy controls. Haplotype assessment of suspected cases was done by genotyping and confirmed by Sanger sequencing. Blood samples and consent of all the cases and detailed clinical details of positive cases were collected in collaboration with A.I.I.M.S. Furthermore, comprehension of RFC1 repeat locus and risk haplotype analysis in Indian background was performed on the NGS data of Indian healthy controls by ExpansionHunter, ExpansionHunter Denovo, and PHASE analysis, respectively. Genetic screening of RFC1-TNR locus in 1998 uncharacterized cases (SCA12: 87; uncharacterized ataxia: 1818, CMT: 93) and 564 heterogenous controls showed that the frequency of subjects with bi-allelic (AAGGG)exp are 1.15%, < 0.05%, 2.15%, and 0% respectively. Two RFC1 positive sporadic late-onset ataxia cases, one bi-allelic (AAGGG)exp and another, (AAAGG)~700/(AAGGG)exp, had recessive risk haplotype and CANVAS symptoms. Long normal alleles, 15-27, are significantly rare in ataxia cohort. In IndiGen control population (IndiGen; N = 1029), long normal repeat range, 15-27, is significantly associated with A3G3 and some rare repeat motifs, AGAGG, AACGG, AAGAG, and AAGGC. Risk-associated "AAGA" haplotype of the original pathogenic expansion of A2G3 was found associated with the A3G3 representing alleles in background population. Apart from bi-allelic (AAGGG)exp, we report cases with a new pathogenic expansion of (AAAGG)exp/(AAGGG)exp in RFC1 and recessive risk haplotype. We found different repeat motifs at RFC1 TNR locus, like AAAAG, AAAGG, AAAGGG, AAAAGG, AAGAG, AACGG, AAGGC, AGAGG, and AAGGG, in Indian background population except ACAGG and (AAAGG)n/(AAGGG)n. Our findings will help in further understanding the role of long normal repeat size and different repeat motifs, specifically AAAGG, AAAGGG, and other rare repeat motifs, at the RFC1 locus.

Genetics of 67 patients of suspected primary ciliary dyskinesia from India.

Data are limited on the genetic profile of primary ciliary dyskinesia (PCD) from developing countries. Here, we report one of the first study on genetic profile of patients with suspected PCD from India. In this prospective cross-sectional study, we enrolled 162 children with suspected PCD. We recorded clinical features, relevant laboratory tests for PCD and performed whole exome sequencing (WES). We are reporting 67 patients here who had positive variant/s on WES. We had 117 variants in 40 genes among 67 patients. Among the 108 unique variants, 33 were categorized as pathogenic or likely pathogenic (P/LP). We had nine novel variants in out cohort. The 29 definite PCD cases, diagnosed by composite reference standards, had variants in 16 genes namely LRRC6/DNAAF11 (5), DNAH5 (3), CCDC39 (3), HYDIN (3), DNAH11 (2), CCDC40 (2), CCDC65 (2) and one each DNAAF3, DNAAF2, CFAP300, RPGR, CCDC103, CCDC114, SPAG1, DNAI1, and DNAH14. To conclude, we identified 108 unique variants in 40 genes among 67 patients. The common genes involved in definite cases of PCD in Indian patients were LRRC6, DNAH5, CCDC39, and HYDIN. Our findings suggest a need to develop a separate genetic panel for PCD in the Indian population.

Interacting Trimagnetic Ensembles for Enhanced Magnetic Resonance Transverse Relaxivity.

An ensemble of nanosystems can be considered to improve magnetic resonance imaging (MRI) transverse relaxivity. Herein, an interacting superparamagnetic competing structure of an isotropic-anisotropic trimagnetic hybrid nanosystem, γ-Fe2O3@δ-MnO2@NiFe2O4, is considered for MRI relaxivity exploration. The interacting superparamagnetic system reveals fascinating dynamic magnetic behavior, where flower-shaped two-dimensional flakes are decorated over nanoparticles. The hybrid nanosystem exhibits modulated shape anisotropy with spin blocking and energy barrier broadening, which help in achieving faster MR transverse relaxivity. The hierarchical architecture ensemble of the trimagnetic landscape shows effective MR transverse relaxivity with a transverse (r2)/longitudinal (r1) relaxivity of 61.5 and potential cell viability. The competing trimagnetic system with regulated activation energy is found to be the underlying reason for such signal enhancement in MRI contrast efficiency. Hence, this study displays a novel pathway correlating MR transverse relaxivity with dynamic magnetic behavior and competing landscape of hierarchical trimagnetic ensembles.

Integrative Modulation of Magnetic Resonance Transverse and Longitudinal Relaxivity in a Cell-Viable Bimagnetic Ensemble, γ-Fe2O3@ZnFe2O4.

The potential application of magnetic nanosystems as magnetic resonance imaging (MRI) contrast agents has been thoroughly investigated. This work seeks to attain robust MRI-contrast efficiency by designing an interacting landscape of a bimagnetic ensemble of zinc ferrite nanorods and maghemite nanoparticles, γ-Fe2O3@ZnFe2O4. Because of competing spin clusters and structural anisotropy triggered by isotropic γ-Fe2O3 and anisotropic ZnFe2O4, γ-Fe2O3@ZnFe2O4 undergoes the evolution of cluster spin-glass state as evident from the critical slowing down law. Such interacting γ-Fe2O3@ZnFe2O4 with spin flipping of 1.2 × 10-8 s and energy barrier of 8.2 × 10-14 erg reflects enhanced MRI-contrast signal. Additionally, γ-Fe2O3@ZnFe2O4 is cell-viable to noncancerous HEK 293 cell-line and shows no pro-tumorigenic activity as observed in MDA-MB-231, an extremely aggressive triple-negative breast cancer cell line. As a result, γ-Fe2O3@ZnFe2O4 is a feasible option for an MRI-contrast agent having longitudinal relaxivity, r1, of 0.46 s-1mM-1 and transverse relaxivity, r2, of 15.94 s-1mM-1, together with r2/r1 of 34.65 at 1.41 T up to a modest metal concentration of 0.1 mM. Hence, this study addresses an interacting isotropic/anisotropic framework with faster water proton decay in MR-relaxivity resulting in phantom signal amplification.

Designing Pathway-Controlled Multicomponent Ultrashort Peptide Hydrogels with Diverse Functionalities at the Nanoscale for Directing Cellular Behavior.

Tuning self-assembling pathways by implementing different external stimuli has been extensively studied, owing to their effective control over structural and mechanical properties. Consequently, multicomponent peptide hydrogels with high structural tunability and stimuli responsiveness are crucial in dictating cellular behavior. Herein, we have implemented both coassembly approach and pathway-dependent self-assembly to design nonequilibrium nanostructures to understand the thermodynamic and kinetic aspects of peptide self-assembly toward controlling cellular response. Our system involved an ultrashort peptide gelator and a hydrophilic surfactant which coassembled through different pathways, i.e., heat-cool and sonication methods with variable energy input. Interestingly, it was possible to access diverse structural and mechanical properties at the nanoscale in a single coassembled system. Further, the hydrophilic surfactant provided additional surface functionalities, thus creating an efficient hydrophilic matrix for cellular interaction. Such diverse functionalities in a single coassembled system could lead to the development of advanced scaffolds, with applications in various biomedical fields.

16S rRNA metagenomic profiling of red amaranth grown organically with different composts and soils.

In recent years organic food is gaining popularity as it is believed to promote better human health and improve soil sustainability, but there are apprehensions about pathogens in organic produces. This study was designed to understand the effect of different composts and soils on the status of the microbiome present in organically grown leafy vegetables. 16S rRNA metagenomic profiling of the leaves was done, and data were analyzed. It was found that by adding composts, the OTU of the microbiome in the organic produce was higher than in the conventional produce. The beneficial genera identified across the samples included plant growth promoters (Achromobacter, Paenibacillus, Pseudomonas, Sphingobacterium) and probiotics (Lactobacillus), which were higher in the organic produce. Some pathogenic genera, viz., plant pathogenic bacteria (Cellvibrio, Georgenia) and human pathogenic bacteria (Corynebacterium, Acinetobacter, Streptococcus, Streptomyces) were also found but with relatively low counts in the organic produce. Thus, the present study highlights that organic produce has lesser pathogen contamination than the conventional produce. KEY POINTS: • 16S rRNA metagenomics profiling done for organic red amaranth cultivar • Microbial richness varied with respect to the soil and compost type used • The ratio of beneficial to pathogenic genera improves with the addition of compost.

Genotype-phenotype correlation and natural history study of dysferlinopathy: a single-centre experience from India.

Dysferlinopathies are a group of limb-girdle muscular dystrophies causing significant disability in the young population. There is a need for studies on large cohorts to describe the clinical, genotypic and natural history in our subcontinent. To describe and correlate the clinical, genetic profile and natural history of genetically confirmed dysferlinopathies. We analysed a retrospective cohort of patients with dysferlinopathy from a single quaternary care centre in India. A total of 124 patients with dysferlinopathy were included (40 females). Median age at onset and duration of illness were 21 years (range, 13-50) and 48 months (range, 8-288), respectively. The average follow-up period was 60 months (range, 12-288). Fifty-one percent had LGMD pattern of weakness at onset; 23.4% each had Miyoshi and proximo-distal type while isolated hyperCKemia was noted in 1.6%. About 60% were born to consanguineous parents and 26.6% had family history of similar illness. Twenty-three patients (18.6%) lost ambulation at follow-up; the median time to loss of independent ambulation was 120 months (range, 72-264). Single-nucleotide variants (SNVs) constituted 78.2% of patients; INDELs 14.5% and 7.3% had both SNVs and INDELs. Earlier age at onset was noted with SNVs. There was no correlation between the other clinical parameters and ambulatory status with the genotype. Thirty-seven (45.7%) novel pathogenic/likely pathogenic (P/LP) variants were identified out of a total of 81 variations. The c.3191G > A variant was the most recurrent mutation. Our cohort constitutes a clinically and genetically heterogeneous group of dysferlinopathies. There is no significant correlation between the clinico-genetic profile and the ambulatory status.

Vitamin D and genetic ancestry are associated with apoptosis rates in benign and malignant prostatic epithelium.

PURPOSE: Vitamin D metabolites may be protective against prostate cancer (PCa). We conducted a cross-sectional analysis to evaluate associations between in vivo vitamin D status, genetic ancestry, and degree of apoptosis using prostatic epithelial terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. EXPERIMENTAL DESIGN: Benign and tumor epithelial punch biopsies of participants with clinically localized PCa underwent indirect TUNEL staining. Serum levels of 25 hydroxyvitamin D [25(OH)D] and 1,25 dihydroxyvitamin D were assessed immediately before radical prostatectomy; levels of prostatic 25(OH)D were obtained from the specimen once the prostate was extracted. Ancestry informative markers were used to estimate the percentage of genetic West African, Native American, and European ancestry. RESULTS: One hundred twenty-one newly diagnosed men, age 40-79, were enrolled between 2013 and 2018. Serum 25(OH)D correlated positively with both tumor (ρ = 0.17, p = 0.03), and benign (ρ = 0.16, p = 0.04) prostatic epithelial TUNEL staining. Similarly, prostatic 25(OH)D correlated positively with both tumor (ρ = 0.31, p < 0.001) and benign (ρ = 0.20, p = 0.03) epithelial TUNEL staining. Only Native American ancestry was positively correlated with tumor (ρ = 0.22, p = 0.05) and benign (ρ = 0.27, p = 0.02) TUNEL staining. In multivariate regression models, increasing quartiles of prostatic 25(OH)D (ß = 0.25, p = 0.04) and Native American ancestry (ß = 0.327, p = 0.004) were independently associated with tumor TUNEL staining. CONCLUSIONS: Physiologic serum and prostatic 25(OH)D levels and Native American ancestry are positively associated with the degree of apoptosis in tumor and benign prostatic epithelium in clinically localized PCa. Vitamin D may have secondary chemoprevention benefits in preventing PCa progression in localized disease.

Synergetic anaerobic digestion of food waste for enhanced production of biogas and value-added products: strategies, challenges, and techno-economic analysis.

The generation of food waste (FW) is increasing at an alarming rate, contributing to a total of 32% of all the waste produced globally. Anaerobic digestion (AD) is an effective method for dealing with organic wastes of various compositions, like FW. Waste valorization into value-added products has increased due to the conversion of FW into biogas using AD technology. A variety of pathways are adopted by microbes to avoid unfavorable conditions in AD, including competition between sulfate-reducing bacteria and methane (CH4)-forming bacteria. Anaerobic bacteria decompose organic matter to produce biogas, a digester gas. The composition depends on the type of raw material and the method by which the digestion process is conducted. Studies have shown that the biogas produced by AD contains 65-75% CH4 and 35-45% carbon dioxide (CO2). Methanothrix soehngenii and Methanosaeta concilii are examples of species that convert acetate to CH4 and CO2. Methanobacterium bryantii, Methanobacterium thermoautotrophicum, and Methanobrevibacter arboriphilus are examples of species that produce CH4 from hydrogen and CO2. Methanobacterium formicicum, Methanobrevibacter smithii, and Methanococcus voltae are examples of species that consume formate, hydrogen, and CO2 and produce CH4. The popularity of AD has increased for the development of biorefinery because it is seen as a more environmentally acceptable alternative in comparison to physico-chemical techniques for resource and energy recovery. The review examines the possibility of using accessible FW to produce important value-added products such as organic acids (acetate/butyrate), biopolymers, and other essential value-added products.

HighlightsPopulation growth globally increases the generation of FW.FW generation, recycling, and reuse have been discussed.Biogas and bio-fertilizers can be recovered from FW through AD.

Designing Cardin-Motif Peptide and Heparin-Based Multicomponent Advanced Bioactive Hydrogel Scaffolds to Control Cellular Behavior.

Recently, peptide and sugar-based multicomponent systems have gained much interest in attaining the sophisticated structure and biofunctional complexity of the extracellular matrix (ECM). To this direction, we have designed for the first time a biologically relevant minimalist Cardin-motif peptide capable of binding ECM-derived glycosaminoglycans. Herein, we explored Cardin-motif peptide and heparin-based biomolecular matrix by employing simple noncovalent interactions at the molecular level. Interestingly, this peptide was inadequate to induce hydrogelation at ambient pH due to the presence of basic amino acids. However, addition of heparin successfully triggered its gelation at physiological pH following favorable electrostatic interactions with heparin. Importantly, the newly developed scaffolds displayed tunable nanofibrous morphology and superior mechanical properties as controlled simply by the differential mixing ratio of both biomolecular entities. Additionally, these composite scaffolds could closely mimic the complexity of ECM as they demonstrated superior biocompatibility and enhanced growth and proliferation of neural cells as compared to the peptide scaffold.

Diagnostic accuracy of pan-TRK immunohistochemistry in differentiating secretory carcinoma from acinic cell carcinoma of salivary gland-A systematic review.

BACKGROUND: Secretory carcinoma (SC) is a well-established salivary gland malignancy that has earned its popularity for its unique clinicopathological behavior. Although it is an indolent malignancy, few of them have been reported with high grade transformation making it mandatory to differentiate it from its prime histological mimicker, acinic cell carcinoma (AciCC). Recently, many studies have been directed toward validating the sensitivity and specificity of pan-TRK IHC for confirming ETV6::NTRK3 gene fusion in SCs involving salivary gland. AIM: The aim of the present systematic review was to establish the diagnostic utility of pan-TRK immunostaining in histological differentiation of SC from AciCC. MATERIAL AND METHODS: An electronic search was carried out using MEDLINE by PubMed, Scopus, Google scholar, Trip, Cochrane library and EMBASE databases. Articles in which SC assessed with pan-TRK immunohistochemical expressions were included for systematic review and their staining pattern (cytoplasmic, nuclear and/or combined), sensitivity, specificity, positive as well as negative predictive were gathered. Risk of bias was analyzed for each study using QUADAS-2 tool. RESULTS: Thirteen eligible articles were included for the quantitative analysis, which revealed positive immunostaining of pan-TRK by nearly all the ETV6::NTRK3 fusion prevalent SCs alongside negative expression in almost all the cases of AciCC with 100% of sensitivity as well as specificity. CONCLUSION: The evidence from the included studies supports that pan-TRK immunostaining could be used as a reliable preliminary screening tool for discerning SC from AciCC. PROSPERO No: CRD42022308913.

Clinicopathological and Molecular Characteristics of Intraosseous Rhabdomyosarcoma Involving Head and Neck Region: A Systematic Review and Meta-Analysis.

Rhabdomyosarcoma with TFCP2 rearrangement is a newly introduced spindle cell neoplasm showing predilection for craniofacial bones exhibiting highly aggressive nature and poor prognosis. Therefore, an attempt was made to delineate the entity for improved understanding and treatment outcomes through comprehensive analysis of the clinicopathological and molecular characteristics. An electronic search was carried out using MEDLINE by PubMed, Scopus, Google scholar, Cochrane library, and EMBASE databases. Original articles and case reports involving intraosseous rhabdomyosarcoma arising in head and neck region with TFCP2 fusion were included. Data were compiled and risk of bias was analyzed using JBI tool. Thirteen eligible articles were included for the quantitative analysis, which revealed 33 cases with TFCP2 fusion. Majority of the affected individuals were females (58%) with mandible being the common site. Most of the patients died within few months after diagnosis demonstrating a low mean survival rate (30 months). Odds ratio, overall survival and disease-free survival were calculated and analyzed statistically concluding that intraosseous rhabdomyosarcomas harboring TFCP2 fusion are found to be novel and dreadful neoplasms. The predilection for young age with poor prognosis exhibited by these lesions demand early diagnosis and specific treatment planning to curtail mortality.

CRY2 gene of rice (Oryza sativa subsp. indica) encodes a blue light sensory receptor involved in regulating flowering, plant height and partial photomorphogenesis in dark.

KEY MESSAGE: OsiCRY2 is involved in light-regulated plant development and plays a role in regulating photomorphogenesis, plant height, flowering and most strikingly partial photomorphogenesis in dark. Cryptochrome 2 (CRY2), the blue/UV-A light photoreceptor in plants, has been reported to regulate photoperiod-dependent flowering and seedling photomorphogenesis (under low-intensity light). Among monocots, CRY2 has been reported from japonica rice, wheat, sorghum and barley. The two sub-species of rice, indica and japonica, exhibit a high degree of genetic variation and morphological and physiological differences. This article describes the characterization of CRY2 of indica rice (OsiCRY2). While the transcript levels of OsiCRY2 did not change significantly under blue light, its protein levels were found to decline with increased time duration under blue light. For phenotypic characterization, OsiCRY2 over-expression (OX) transgenics were generated in Oryza sativa Pusa Sugandh 2 (PS2) cultivar, a highly scented Basmati cultivar. The OsiCRY2OX transgenics displayed shorter coleoptiles and dwarfism than wild-type under blue light, white, and far-red light. Interestingly, even the dark-grown transgenics were shorter, concomitant with higher OsiCRY2 protein levels in transgenics than wild-type. Histological analysis revealed that the decrease in the length of the seedlings was due to a decrease in the length of the epidermal cells. The fully mature rice transgenics were shorter than the untransformed plants but flowered at the same time as wild-type. However, the OsiCRY2 Arabidopsis over-expressors exhibited early flowering by 10-15 days, indicating the potential and conservation of function of OsiCRY2. The whole-genome transcriptome profiling of rice transgenics revealed the differential up-regulation of several light-regulated genes in dark-grown coleoptiles. These data provide evidence that OsiCRY2 regulates photomorphogenesis, plant height, and flowering in indica rice.

An Innovative Approach for Biocontrol of Meloidogyne incognita in Ginger Using Potential Bacteria Isolated from Indian Himalayas.

The prevalence of Meloidogyne incognita, a severe root-knot nematode, is alarmingly high in the production of ginger-a main cash crop of Himachal Pradesh, a Himalayan state of India. In order to control this through natural means, the nematicidal potential of plant growth-promoting rhizobacteria (PGPR) against M. incognita was analyzed. This is an effective alternative solution to manage nematode incidence as compared to hazardous chemicals under protected and field cultivation of ginger. In the present study an attempt has been made to isolate, characterize, and identify potential rhizobacteria associated with ginger rhizosphere and endosphere. In total, 169 bacterial isolates were isolated from ginger (Zingiber officinale) rhizosphere and endosphere of 4 different sites of Sirmaur district, screened out for multifarious PGP traits showing positive results. The combined cluster analysis and 16S rRNA genotypic analysis of selected bacterial isolates revealed that Serratia marcescens FS-23, Pseudochrobacter sp. GS-15, Stonotrophomonas pavanii HER-9, Pseudomonas brassicacearum HER-20 and Serratia marcescens IS-2 exhibited highest PGP traits. All tested bacterial isolates were capable of exerting a significant effect on mortality of juvenile M. incognita ranging upto 40-90% in laboratory experiments. Further a consortium of these screened isolates showed 86.67% reduction in gall formation by M. incognita in lab conditions. The remarkable increase to 93.24% with 138.73 q/ha with application of charcoal based bio-formulation of consortium without adding any chemical fertilizer was observed in field trials of Nohradhar of Sirmaur district. An alternative choice as a biocontrol agent as well as for PGP activities, the novel and most robust isolate Serratia marcescens IS-2 had revealed to have a variety of bioactive metabolic products with abilities against nematodes, bacteria, and fungi.

Oral formulation of Prussian blue with improved efficacy for prophylactic use against thallium.

OBJECTIVE: The present study is aimed to enhance the efficacy of Insoluble Prussian blue (PB) in the stomach. PB formulation was developed comprising of PB in combination with pH modifying agents particularly magnesium hydroxide, calcium carbonate, sodium carbonate, and sodium bicarbonate. pH profile and the binding efficacy of the final formulation was evaluated in simulated gastric fluid (SGF). METHODS: The capsule formulation was optimized with desired in vitro characteristics. The final formulations (FF1-FF4) were evaluated for drug release, pH profile, and binding efficacy for thallium (Tl). The stability studies were performed in terms of drug assay, Fourier-transformed infrared (FTIR) spectroscopy and Thermo-gravimetric analysis (TGA). The in vivo study was performed in rats to determine the removal efficacy of optimized formulation (FF4) for Tl. RESULTS: The PB formulation consisting of optimized PB granules and pH modifying agents showed a significant increase in the binding efficacy for Tl in SGF at an equilibrium time of 24 h. The Maximum Binding Capacity (MBC) of FF1-FF4 was found to be higher than commercially available Radiogardase®-Cs capsules and PB granules alone in SGF. The blood Tl level in rats treated with FF4 showed three-fold decreases in the level of Tl in the blood (Cmax) and Area under Curve (AUC) as compared to the control. CONCLUSION: The results revealed that the developed oral PB formulation has a significantly higher efficiency of binding Tl at the acidic pH of the stomach thereby reducing its absorption into the systemic circulation. Thus, the optimized formulation of PB with pH-modifying agents is a better drug for prophylactic use in thallium ingestion.

Effects of digestate-encapsulated biochar on plant growth, soil microbiome and nitrogen leaching.

The increasing amount of food waste and the excessive use of mineral fertilizers have caused detrimental impacts on soil, water, and air quality. Though digestate derived from food waste has been reported to partially replace fertilizer, its efficiency requires further improvement. In this study, the effects of digestate-encapsulated biochar were comprehensively investigated based on growth of an ornamental plant, soil characteristics, nutrient leaching and soil microbiome. Results showed that except for biochar, the tested fertilizers and soil additives, i.e., digestate, compost, commercial fertilizer, digestate-encapsulated biochar had positive effects on plants. Especially, the digestate-encapsulated biochar had the best effectiveness as evidenced by 9-25% increase in chlorophyll content index, fresh weight, leaf area and blossom frequency. For the effects of fertilizers or soil additives on soil characteristics and nutrient retention, the digestate-encapsulated biochar leached least N-nutrients (<8%), while the compost, digestate and mineral fertilizer leached up to 25% N-nutrients. All the treatments had minimal effects on the soil properties of pH and electrical conductivity. According to the microbial analysis, the digestate-encapsulated biochar has the comparable role with compost in improving the soil immune system against pathogen infection. The metagenomics coupling with qPCR analysis suggested that digestate-encapsulated biochar boosted the nitrification process and inhibited the denitrification process. This study provides an extensive understanding into the impacts of the digestate-encapsulated biochar on an ornamental plant and offers practical implications for the choice of sustainable fertilizers or soil additives and food-waste digestate management.