Molecular basis of JAK2 activation in erythropoietin receptor and pathogenic JAK2 signaling.

Janus kinase 2 (JAK2) mediates type I/II cytokine receptor signaling, but JAK2 is also activated by somatic mutations that cause hematological malignancies by mechanisms that are still incompletely understood. Quantitative superresolution microscopy (qSMLM) showed that erythropoietin receptor (EpoR) exists as monomers and dimerizes upon Epo stimulation or through the predominant JAK2 pseudokinase domain mutations (V617F, K539L, and R683S). Crystallographic analysis complemented by kinase activity analysis and atomic-level simulations revealed distinct pseudokinase dimer interfaces and activation mechanisms for the mutants: JAK V617F activity is driven by dimerization, K539L involves both increased receptor dimerization and kinase activity, and R683S prevents autoinhibition and increases catalytic activity and drives JAK2 equilibrium toward activation state through a wild-type dimer interface. Artificial intelligence-guided modeling and simulations revealed that the pseudokinase mutations cause differences in the pathogenic full-length JAK2 dimers, particularly in the FERM-SH2 domains. A detailed molecular understanding of mutation-driven JAK2 hyperactivation may enable novel therapeutic approaches to selectively target pathogenic JAK2 signaling.

A powerful metric for expressive language lateralization in MEG.

Magnetoencephalography (MEG) has proven valuable for presurgical language lateralization. Investigators have established that low-beta (13-23 Hz) event-related desynchrony (ERD), a neuromagnetic signature for increased neuronal firing, maps to critical language centers for expressive language tasks in MEG. The distribution of low-beta ERD is relatively bilateral in early childhood, transitioning to left lateralized by adolescence or early adulthood. Recently, we showed that a complementary signal, low-beta event-related synchrony, thought to reflect neuronal inhibition, becomes increasingly right lateralized across development. Here, we introduce a hybrid laterality index for language derived from both low-beta ERD and ERS. We present findings from a large cohort of children performing verb generation in MEG, and show that inclusion of low-beta ERS provides relatively powerful estimation of language lateralization.

Role of Non-Coding RNAs in TGF-ß Signalling in Glioma.

Brain tumours and Gliomas, in particular, are among the primary causes of cancer mortality worldwide. Glioma diagnosis and therapy have not significantly improved despite decades of efforts. Autocrine TGF-ß signalling promotes glioma proliferation, invasion, epithelial-to-mesenchymal transition (EMT), and drug resistance. Non-coding RNAs such as miRNA, lncRNA, and circRNAs have emerged as critical transcriptional and post-transcriptional regulators of TGF-ß pathway components in glioma. Here, we summarize the complex regulatory network among regulatory ncRNAs and TGF-ß pathway during Glioma pathogenesis and discuss their role as potential therapeutic targets for Gliomas.

Assessment of Metal Ions Levels in Blood of Dental Implant Patients.

Background: Dental implants use has significantly increased and the concentration of metal ions into blood may have detrimental effect of human body. The present study aimed to determine metal ions levels in blood of dental implants patients. Materials and Methods: 48 patients scheduled for dental implant surgery was assessed for measurement of titanium and aluminum pre-operatively and post-operatively at 6 weeks, 3 months, 6 months, and 1 year. Results: Out of 48 patients, males were 22 (45.8%), and females were 26 (54.2%). The mean ± SD titanium metal levels in blood pre-operatively was 2.34 ± 0.47 mg/dl, at 6 weeks was 2.35 ± 0.48 mg/dl, at 3 months was 2.37 ± 0.52 mg/dl, at 6 months was 2.37 ± 0.42 mg/dl, and at 1 year was 2.38 ± 0.51 mg/dl. A non-significant difference was seen (P > 0.05). The mean ± SD aluminum metal levels in blood pre-operatively was 4.4 ± 0.12 mg/dl, at 6 weeks was 4.45 ± 0.14 mg/dl, at 3 months was 4.7 ± 0.13 mg/dl, at 6 months was 4.7 ± 0.21 mg/dl, and at 1 year was 4.8 ± 0.17 mg/dl. A non-significant difference was seen (P > 0.05). Conclusion: A non- significant increase in titanium and aluminum ions level in blood of patients receiving dental implants was observed.

Downregulation of ribosomal RNA (rRNA) genes in human head and neck squamous cell carcinoma (HNSCC) cells correlates with rDNA promoter hypermethylation.

Eukaryotes carry hundreds of ribosomal RNA (rRNA) genes as tandem arrays, which generate rRNA for protein synthesis. Humans carry âˆ¼ 400 rRNA gene copies and their expression is epigenetically regulated. Dysregulation of rRNA synthesis and ribosome biogenesis are characteristic features of cancers. Targeting aberrant rRNA expression for cancer therapy is being explored. Head and neck squamous cell carcinoma (HNSCC) is among the most prevalent cancers globally. Using quantitative PCR and bisulfite sequencing, we show that rRNA genes are downregulated and their promoters are hypermethylated in HNSCC cell lines. These findings may have relevance for prognosis and diagnosis of HNSCC.

Normal measurements of brainstem and related structures for all ages: An MRI-based morphometric study.

Background: Knowledge of the normal size of the brain stem and certain related structures play an important role in diagnosis of aging and neurodegenerative conditions affecting the brain. There is no well-established normative data for development and age-related changes pertaining to the brain stem and related structures in the Indian context. The objective of this study was to assess various linear and angle measurements of the brain stem, cerebral peduncles, middle cerebellar peduncles, and proximal cervical cord for all ages in patients who have undergone MRI brain for unrelated pathologies. Methods: A record-based retrospective cross-sectional and analytical study. T1WI axial and sagittal images were studied for the following variables: Cerebral peduncle transverse thickness, Interpeduncular angle, Middle cerebellar peduncle transverse thickness, Ventral midbrain anteroposterior thickness, Midbrain height, Mamillopontine distance (MPD), Pontomesencephalic angle (PMA), Pons anteroposterior thickness, Medulla anteroposterior thickness and Spinal cord anteroposterior diameter. Results: Significant differences (p = 0.001) were observed in nearly all the variables among various age groups. Males demonstrated significantly higher mean values (at 5% level of significance) for a majority of the variables. Most of the variables measured, e.g. Cerebral peduncle, Middle cerebellar peduncle, Ventral midbrain thickness, Midbrain height, Pons, Medulla, and Spinal Cord diameter, showed a steady and sharp increase in values from infancy and reached maximum values during the third decade, followed by a variable degree of decline in values. Conclusion: Magnetic Resonance Imaging (MRI) morphometry of brainstem and related structures is easily doable and is also reproducible. Present study lays down normative data for the brainstem and certain related structures for all ages, which can be referred to in day-to-day practice.

Tobacco Smoking among the Online Respondent Dental Students of a Dental College: A Descriptive Cross-sectional Study.

Introduction: Smoking tobacco is most common nowadays among dental students due to stress induced by practical workloads and exams. There is limited data regarding tobacco smoking among dental students. The aim of this study was to determine the prevalence of tobacco smoking among online respondent dental students of a dental college. Methods: This was a descriptive cross-sectional study conducted on dental students from 15 July 2021 to 15 August 2021. Ethical approval was obtained from the Institutional Review Committee of K.D. Dental College and Hospital (Reference number: KDDC/Admin/2021/9990A). Data was collected through a structured questionnaire and responses were gathered using an online Google form survey with informed consent. A convenience sampling method was used. Point estimate and 95% confidence interval were calculated. Results: Among 60 online respondents, the prevalence of tobacco smoking was found to be 11 (18.33%) (17.04-24.56, 95% Confidence Interval). The percentage of participants who wanted to stop smoking now was 11 (18.33%). Conclusions: The prevalence of tobacco smoking among the online dental respondents of a dental college was similar to the other studies done in similar settings. Keywords: dental students; smoking; tobacco cessation.

Biofortification of mungbean (Vigna radiata L. (Wilczek)) with boron, zinc and iron alters its grain yield and nutrition.

Mungbean [Vigna radiata L. (Wilczek)] is considered as an extremely nutritious crop possessing a high level of micronutrients, but their low bioavailability in the crop leads to micronutrient malnutrition in humans. Therefore, the present study was conducted to investigate the potential of nutrients viz. boron (B), zinc (Zn) and iron (Fe) biofortification on productivity, nutrient concentration and uptake as well as the economics of mungbean cultivation. In the experiment, the various combinations of RDF with ZnSO4.7H2O (0.5%), FeSO4.7H2O (0.5%) and borax (0.1%) were applied to mungbean variety ML 2056. The combined foliar application of Zn, Fe and B was highly efficient in increasing the yield of grain as well as straw in mungbean exhibiting maximum values i.e. 944 kg ha-1 and 6133 kg ha-1, respectively. Similar results for B, Zn and Fe concentration in grain (27.3 mg kg-1, 35.7 mg kg-1 and 187.1 mg kg-1, respectively) and straw (21.1 mg kg-1, 18.6 mg kg-1 and 376.1 mg kg-1, respectively) of mungbean were observed. Also, uptake of Zn and Fe by grain (31.3 g ha-1 and 164.4 g ha-1, respectively), as well as straw (113.7 g ha-1 and 2295.0 g ha-1, respectively), was maximum for the above treatment. Whereas, the B uptake was found to enhance significantly through the combined application of B, Zn and Fe, where the values 24.0 g ha-1 and 128.7 g ha-1 corresponded to grain and straw, respectively. Thus, combined use of ZnSO4.7H2O (0.5%) + FeSO4.7H2O (0.5%) and borax (0.1%) significantly improved the yield outcomes, the concentration of B, Zn and Fe, uptake and economic returns of mungbean cultivation to alleviate the B, Zn and Fe deficiency.

Role of regional diffusion tensor imaging (DTI)-derived tensor metrics in the evaluation of intracranial gliomas and its histopathological correlation.

Background: The imaging of brain tumours has significantly improved with the use of advanced magnetic resonance (MR) techniques like diffusion tensor imaging (DTI). This study was conducted to analyse the utility of DTI-derived tensor metrics in the evaluation of intracranial gliomas with histopathological correlation and further adoption of these image-data analyses in clinical setting. Methods: A total of 50 patients with suspected diagnosis of intracranial gliomas underwent DTI along with conventional MR examination. The study correlated various DTI parameters in the enhancing part of the tumour and the peritumoral region with the histopathological grades of the intracranial gliomas. Results: The study revealed higher values of Cl (linear anisotropy), Cp (planar anisotropy), AD (axial diffusivity), FA (fractional anisotropy) and RA (relative anisotropy) and lower values of Cs (spherical anisotropy), MD (mean diffusivity) and RD (radial diffusivity) in the enhancing part of the tumour in case of high-grade gliomas. However, in the peritumoral region, the values of Cl, Cp, AD, FA and RA were less whereas values of Cs, MD and RD were more in high-grade gliomas than in the low-grade gliomas. The various cutoff values of these DTI-derived tensor metrics were found to be statistically significant. Conclusion: DTI-derived tensor metrics can be a valuable tool in differentiation between high-grade and low-grade gliomas which might be accepted in clinical practice in near future.

Tetrahydrocannabinols: potential cannabimimetic agents for cancer therapy.

Tetrahydrocannabinols (THCs) antagonize the CB1 and CB2 cannabinoid receptors, whose signaling to the endocannabinoid system is essential for controlling cell survival and proliferation as well as psychoactive effects. Most tumor cells express a much higher level of CB1 and CB2; THCs have been investigated as potential cancer therapeutic due to their cannabimimetic properties. To date, THCs have been prescribed as palliative medicine to cancer patients but not as an anticancer modality. Growing evidence of preclinical research demonstrates that THCs reduce tumor progression by stimulating apoptosis and autophagy and inhibiting two significant hallmarks of cancer pathogenesis: metastasis and angiogenesis. However, the degree of their anticancer effects depends on the origin of the tumor site, the expression of cannabinoid receptors on tumor cells, and the dosages and types of THC. This review summarizes the current state of knowledge on the molecular processes that THCs target for their anticancer effects. It also emphasizes the substantial knowledge gaps that should be of concern in future studies. We also discuss the therapeutic effects of THCs and the problems that will need to be addressed in the future. Clarifying unanswered queries is a prerequisite to translating the THCs into an effective anticancer regime.

LINC01711 promotes transforming growth factor-beta (TGF-ß) induced invasion in glioblastoma multiforme (GBM) by acting as a competing endogenous RNA for miR-34a and promoting ZEB1 expression.

GBM is the central nervous system's most aggressive and malignant tumor. TGF-ß expression is elevated in GBM, and it promotes invasion and EMT. TGF-ß regulates the expression of several lncRNAs, which promote glioma pathogenesis. Here we characterize the role of TGF-ß-induced lncRNA- LINC01711 in glioma pathogenesis. We show that LINC01711 expression is significantly upregulated in GBM tissues and is associated with poor overall survival of GBM patients. Loss-of-function studies illustrate that LINC01711 promotes proliferation, migration, and invasion in GBM. In addition, LINC01711 depletion sensitizes glioma cells to Temozolomide (TMZ) induced apoptosis by inhibiting ZEB1 expression. LINC01711 functions as a competing endogenous RNA for miR-34a and promotes ZEB1 expression to regulate invasion. Our findings suggest that LINC01711 is an attractive therapeutic target for GBM.

Structural characterization of glutamyl-tRNA synthetase (GluRS) from Plasmodium falciparum.

Aminoacyl-tRNA synthetases (aaRSs) are essential enzymes in protein translation machinery that provide the charged tRNAs needed for protein synthesis. Over the past decades, aaRSs have been studied as anti-parasitic, anti-bacterial, and anti-fungal drug targets. This study focused on the cytoplasmic glutamyl-tRNA synthetase (GluRS) from Plasmodium falciparum, which belongs to class Ib in aaRSs. GluRS unlike most other aaRSs requires tRNA to activate its cognate amino acid substrate L-Glutamate (L-Glu), and fails to form an intermediate adenylate complex in the absence of tRNA. The crystal structures of the Apo, ATP, and ADP-bound forms of Plasmodium falciparum glutamyl-tRNA synthetase (PfGluRS) were solved at 2.1 Å, 2.2 Å, and 2.8 Å respectively. The structural comparison of the Apo- and ATP-bound holo-forms of PfGluRS showed considerable conformational changes in the loop regions around the ATP-binding pocket of the enzyme. Biophysical characterization of the PfGluRS showed binding of the enzyme substrates L-Gluand ATP.. The sequence and structural conservation were evident across GluRS compared to other species. The structural dissection of the PfGluRS gives insight into the critical residues involved in the binding of ATP substrate, which can be harvested to develop new antimalarial drugs.

Computed tomographic colonography for symptomatic patients: the diminutive polyp dilemma.

BACKGROUND: Computed tomographic colonography (CTC) is sensitive to polyp detection but is considered inaccurate for measuring diminutive polyps (<6 mm), with divergence between CTC and either colonoscopic or histopathological polyp measurements. Reporting diminutive polyps remains debatable. This study aims to compare outcomes of symptomatic patients with diminutive versus borderline polyps on CTC and to thereby examine the potential implication of reporting diminutive polyps. METHODS: A single-centre retrospective study of symptomatic patients who underwent CTC from October 2016 through September 2018 was performed. After excluding CTC demonstrating cancer, no polyps, or polyps >6 mm, cases were categorized as either 'diminutive' (largest polyp <6 mm), or 'borderline' (largest polyp = 6 mm). The outcome measures were progression to endoscopy, surgery, procedure-related morbidity, dysplasia and malignancy. RESULTS: A total of 308 cases (211 diminutive and 97 borderline) were analysed. The groups were similar (P > 0.05) in mean age (73 vs. 74 years), female proportion (57% vs. 49%), endoscopy-related morbidity (6% vs. 7%) and CTC-related morbidity (0 vs. 1%). Most patients (64%) underwent endoscopy, which was more common in the borderline vs. the diminutive group (76% vs. 59%; P = 0.003). Dysplasia was more common in the borderline vs. the diminutive group (69% vs. 48%; P = 0.003). No malignancies were diagnosed, and no patients proceeded to surgery. CONCLUSION: Reporting diminutive polyps on CTC for symptomatic patients frequently leads to endoscopy, which often reveals dysplasia but rarely malignancy. This raises the question of how referring clinicians can best counsel and manage symptomatic patients with diminutive polyps on CTC, by considering the balance between utilitarianism and deontology.

Emerging role of transforming growth factor-ß-regulated long non-coding RNAs in prostate cancer pathogenesis.

Prostate cancer (PCa) is the most common malignancy in men. Despite aggressive therapy involving surgery and hormonal treatments, the recurrence and emergence of metastatic castration-resistant prostate cancer (CRPCa) remain a major challenge. Dysregulation of the transforming growth factor-ß (TGF-ß) signaling pathway is crucial to PCa development and progression. This also contributes to androgen receptor activation and the emergence of CRPC. In addition, TGF-ß signaling regulates long non-coding RNA (lncRNA) expression in multiple cancers, including PCa. Here, we discuss the complex regulatory network of lncRNAs and TGF-ß signaling in PCa and their potential applications in diagnosing, prognosis, and treating PCa. Further investigations on the role of lncRNAs in the TGF-ß pathway will help to better understand PCa pathogenesis.

COVID-19-induced Stress in Health-care Workers: Effect of 8-week Common Yoga Protocol on Autonomic Function and Inflammatory and Oxidative Stress Markers.

Background: COVID-19 pandemic posed a huge stress on health-care givers affecting their physical and mental health. Wellness strategies like yoga can improve flexibility, resilience, and outlook. Aim: The present study explored the effect of 8-week standard common yoga protocol (CYP) intervention on autonomic functions, emotional stress, oxidative stress, and inflammation markers in the nurse group of health-care givers. Materials and Methods: It is a randomized controlled trial where 50 nurses underwent CYP and 50 participated as controls. Anthropometric parameters, cardiovascular parameters, autonomic function including time and frequency domain parameters, biochemical parameters, and psychological stress using the questionnaire were assessed before and after 8-week CYP. Results: Total 88 nurses completed the study with 42 and 46 participants, respectively, in the CYP and control groups. CYP intervention resulted in a significant reduction in cardiovascular parameters systolic blood pressure, diastolic blood pressure, mean arterial pressure, pulse pressure, and rate pressure product (P < 0.001, P < 0.001, P < 0.001, P < 0.001, and P = 0.002, respectively), perceived stress score and Depression, Anxiety, and Stress Scale psychological variables of depression, anxiety, and stress, and serum lipid parameters compared to the control group. CYP significantly increased total power, low frequency, high frequency, root mean square of successive differences between adjacent NN intervals, change in successive normal sinus (NN) intervals exceeds 50 ms, and pNN50% (P < 0.001, P = 0.006, P = 0.006, P = 0.039, P < 0.001, and P = 0.013, respectively) suggesting improved resting autonomic modulation and parasympathodominance due to higher vagal efferent activity. There were significant reductions in serum cortisol, tumor necrosis factor-alpha, interleukin (IL)-1, and IL-6 in both the groups. Serum telomerase significantly reduced (P = 0.024) and total antioxidant capacity (P = 0.036) increased in the CYP group post intervention. Conclusion: CYP intervention was beneficial in improving psychophysiological, autonomic, and biochemical profile of the nurse group of health-care workers.

Inhibition of Autotaxin Ameliorates LPA-Mediated Neuroinflammation and Alleviates Neurological Dysfunction in Acute Hepatic Encephalopathy.

Growing evidence suggests an essential role of neuroinflammation in behavioral abnormalities associated with hepatic encephalopathy (HE). Here, we report the involvement of autotaxin-lysophosphatidic acid (LPA) signaling in HE's pathogenesis. We demonstrate that the autotaxin (ATX) inhibitor PF-8380 attenuates neuroinflammation and improves neurological dysfunction in the mouse model of HE. In the thioacetamide (TAA)-induced model of HE, we found a twofold increase in the levels of ammonia in the brain and in plasma along with a significant change in HE-related behavioral parameters. Mice with HE show an increased brain weight, increased levels of tumor necrosis factor-α (TNF-α), IL-1ß (interleukin-1ß), interleukin-6 (IL-6), and LPA 18:0 in the cerebral cortex and hippocampus, and increased levels of LPA 18:0 in plasma. Treatment with the autotaxin inhibitor (ATXi) did not affect liver injury, as we observed no change in liver function markers including aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin (TBIL) and no change in ammonia levels in the brain and plasma. However, ATXi treatment significantly ameliorated the neuroinflammation, reduced the levels of LPA 18:0 in the cerebral cortex and hippocampus in the brain and plasma, and reduced brain edema and the levels of IL1ß, IL-6, and TNF-α. The neurobehavioral symptoms for HE such as the cognitive and motor function deficit and overall clinical grading score were significantly improved in ATXi-treated mice. Mouse astrocytes and microglia stimulated with NH4CL with or without ATXi showed significant attenuation of oxidative stress and the neuroinflammatory effect of NH4CL in ATXi-treated cells.

Analysis of Prediagnostic Circulating Levels of Gonadotropins and Androgens with Risk of Epithelial Ovarian Cancer.

Background Prevailing experimental and epidemiological evidence supports the role of circulating endogenous sex steroid hormones in the pathogenesis of ovarian carcinogenesis by dysregulation of cell differentiation, proliferation, and apoptosis but is scarce and inconclusive. Objectives This article evaluates the role of circulating levels of gonadotropins (follicle-stimulating hormone [FSH], luteinizing hormone [LH]) and androgens (testosterone, dehydroepiandrosterone-sulfate [DHEA-S]) for the risk of epithelial ovarian cancer in a case-control approach using samples collected in advance of clinical diagnosis. Materials and Methods A total of 100 epithelial ovarian cancer (EOC) patients and 100 healthy female controls were consequently enrolled in this hospital-based case-control study. Serum FSH, LH, testosterone, and DHEA-S were measured based on the principle of electrochemiluminescence immunoassay. Suitable descriptive statistics were used for different variables. Results Median values of FSH (58.9 vs. 45.5 IU/L, p = 0.02) and DHEA-S (163.43 vs. 142.2 ug/dL, p = 0.03) were significantly high in EOC patients compared with controls. Conditional logistic regression was used to estimate the odds ratio (OR) across increasing thirds of FSH and DHEA-S concentrations, and the results revealed that the highest third tertile of FSH (> 72.6 IU/L; OR = 3.0, confidence interval [CI] = 1.24-7.29, p trend = 0.04) and DHEA-S (> 194.2 ug/dL; OR = 3.8, CI = 1.26-11.61, p trend = 0.03) were significantly associated with increased risk of ovarian cancer in postmenopausal and premenopausal women, respectively. The statistically significant trend observed for FSH in postmenopausal women, remained only for the subgroup with menopause duration greater than 10 years (OR = 5.9, CI = 1.33-26.66, p trend = 0.04). FSH and DHEA-S concentrations and ovarian cancer risk were internally consistent with groups defined by oral contraceptive pill use, hormone replacement therapy, and smoking. However, no evidence was found for the association between serum LH and testosterone level with the occurrence of ovarian tumorigenesis. Conclusion Prediagnostic circulating concentration of FSH and DHEA-S unveiled a significant positive association with augmented risk of EOC, thus might serve as a predictive marker for the susceptibility to ovarian carcinogenesis and should be added in the screening profile of EOC for early recognition and scheduling necessary interventions/management strategies.

Phylogenetic and Structural Analysis of Bacterial Nitrilases for the Biodegradation of Nitrile Compounds.

BACKGROUND: Microbial nitrilases play a vital role in the biodegradation of nitrilecontaining pollutants, effluent treatments in chemical and textile industries, and the biosynthesis of Indole-3-acetic acid (IAA) from tryptophan in plants. However, the lack of structural information limits the correlation between its activity and substrate specificity. METHODS: The present study involves the genome mining of bacteria for the distribution and diversity of nitrilases, their phylogenetic analysis and structural characterization for motifs/ domains, followed by interaction with substrates. RESULTS: Here, we mined the bacterial genomes for nitrilases and correlated their functions to hypothetical, uncharacterized, or putative ones. The comparative genomics revealed four AcNit, As7Nit, Cn5Nit and Cn9Nit predicted nitrilases encoding genes as uncharacterized subgroups of the nitrilase superfamily. The annotation of these nitrilases encoding genes revealed relatedness with nitrilase hydratases and cyanoalanine hydratases. At the proteomics level, the motif analysis of these protein sequences predicted a single motif of 20-28 aa, with glutamate (E), lysine (K) and cysteine (C) residues as a part of catalytic triad along with several other residues at the active site. The structural analysis of the nitrilases revealed geometrical and close conformation in the form of α-helices and ß-sheets arranged in a sandwich structure. The catalytic residues constituted the substrate binding pocket and exhibited the broad nitrile substrate spectra for aromatic and aliphatic nitriles-containing compounds. The aromatic amino acid residues Y159 in the active site were predicted to be responsible for substrate specificity. The substitution of non-aromatic alanine residue in place of Y159 completely disrupted the catalytic activity for indole-3-acetonitrile (IAN). CONCLUSION: The present study reports genome mining and simulation of structure-function relationship for uncharacterized bacterial nitrilases and their role in the biodegradation of pollutants and xenobiotics, which could be of applications in different industrial sectors.

Biofortification of oil quality, yield, and nutrient uptake in Indian mustard (Brassica juncea L.) by foliar application of boron and nitrogen.

Indian mustard (Brassica juncea L.) is an essential oilseed crop that offers important nutrients to human beings. However, the concurrent micronutrient deficiencies including boron (B), sulfur (S), and nitrogen (N) could pose a significant threat to public health. Therefore, this study was conducted at the Punjab Agricultural University, Ludhiana, with nine treatments, i.e., T1-Control (recommended NPK only), T2- borax (0.5%) at flowering, T3-borax (1.0%) at flowering,T4- borax (0.5%) + urea (1.0%) at flowering,T5-borax (1.0%) + urea (1.0%) at flowering, T6-borax (0.5%) at flowering + capsule formation, T7-borax (1.0%) at flowering + capsule formation, T8-borax (0.5%) + urea (1.0%) at flowering + capsule formation, T9-borax (1.0%) + urea (1.0%) at flowering + Capsule formation, replicated three times in a randomized block design for 2 years (2020-2021 and 2021-2022). The foliar application of borax (1.0%) + urea (1.0%) at the flowering and capsule formation stage (treatment T9) was highly efficient in increasing food quality parameters such as crude fiber, total soluble solids (TSS), and protein content with maximum values of 3.77, 24.9, and 27.53%, respectively. Also, maximum yields of seed as well as stover for treatment T9 were 1.376 and 6.625 kg ha-1, respectively. Similarly, the results for B, S, and N concentrations in seed (27.71 mg kg-1, 17.69 mg kg-1, and 2.35%), as well as stover (25.92 mg kg-1, 17.31 mg kg-1, and 0.33%), were maximum in treatment T9. Also, B, S, and N uptake by seed (38.18 g ha-1, 24.40 g ha-1, and 32.05 Kg ha-1) and stover (172.55 g ha-1, 115.44 g ha-1, and 21.99 Kg ha-1) were maximum for the treatment T9 involving borax (1.0%) + urea (1.0%) at the flowering and capsule formation stage. Whereas, the concentration and uptake decreased in the treatments involving the sole application of borax and urea. Therefore, the application of borax (1.0%) and urea (1.0%) at the flowering and capsule formation stage significantly improved the quality parameters, seed and stover yield, nutrient concentration, and uptake over control and could be used to alleviate the B, S, and N deficiency in Indian mustard.

Genomics of prokaryotic extremophiles to unfold the mystery of survival in extreme environments.

The organisms surviving in extreme environments deploy system support including self-protection, and energy distribution to counter extreme environmental stresses. The biological adaptations provide clues about the metabolic networks and regulatory circuits involved in their success in survival to extreme environments of these organisms. Besides this, genes and proteins of these extremophiles have gained worldwide attention of researchers, due to their immense biotechnological importance including source of novel enzymes and biomolecules for applications in industrial processes. Therefore, obtaining an insight into genomic aspects is of vital importance for basic and applied research. Genome wide studies showed that the microbes living in extreme habitats reorganize their genome using insertion, expansion or reduction of genome size, gene reshuffling through displacements and genes reorganization, G+C skewness in the genome, horizontal transfer of genes, change in polyploidy level, and preference for codon in genes that assists during adaptations to environmental extremes. For example, the comparative genomics studies revealed a significant loss of genes in acidophiles than in alkaliphiles and smaller genome size of thermophiles in comparison to psychrophiles. The genomic adaptations in halotolerance include polyploidy, battery of genes for the biosynthesis of organic osmolytes, mechanism of inorganic osmolytes acquisition and role of inorganic osmolytes and transporter system. Furthermore, it is evident that local niche specific adaptations also play a key role during adaptations to extreme environments. All these adaptations maintain extremophiles as operational units and provide them a competitive advantage over their counterparts. The review article describes the genomic multifaceted adaptation at genomic and physiological levels of extremophiles that assists in reshaping the prokaryotic extremophiles during adaptations to extreme environments to obtain a competitive edge.