Comprehensive Analysis of Damage Associated SNPs of Luteinizing Hormone and Its Receptor: A Computational Approach.

PROBLEM: The luteinizing hormone (LH), produced by gonadal and nongonadal cells in the anterior pituitary gland play a critical role in human sexual development and reproduction. It is required for the induction of ovulation in females and sex steroid hormone production in both males and females. It is also an important player in early pregnancy events in oviducts and in absence of LH signalling, the uterus cannot initiate pregnancy. LH works through its receptor LHCGR. Therefore, it is quite important to figure out those mutations that have the potential to affect the structure and function of both LH and LHR. MATERIALS AND METHODS: Various in silico tools were employed in the study for the data mining of SNPs and predicting their possible impact on the structure and function of the protein. ConSurf analysis predicted V454I and I161K are exposed residues in the 2D structure of protein and highly conserved in protein structure. PSIPRED and Swiss Modeller were employed to predict the 2D and 3D structure of mutated receptor protein. FT site server predicted both substitutions were involved in the ligand-binding site RESULTS: By present analysis, we have found that R59G in LHα, Q74R and T78N in LHß and V454I and I161K in LHCGR are the most deleterious nsSNPs affecting the structure and function of the protein. CONCLUSION: These SNPs are still uncharacterised; hence providing a baseline for validation of their association with the susceptibility of diseases and develop personalised therapeutics.

Comparative Genomic and Functional Analyses for Insights into Pantoea agglomerans Strains Adaptability in Diverse Ecological Niches.

Pantoea agglomerans inhabit diverse ecological niches, ranging from epiphytes and endophytes in plants, body of animals, and occasionally in the human system. This multifaceted bacterium contributes substantially to plant growth promotion, stress resilience, and biocontrol but can also act as a pathogen to its host. The genetic determinants underlying these diverse functions remain largely unfathomed and to uncover this phenomenon, nineteen strains of Pantoea agglomerans were selected and analyzed. Genome-to-Genome Distance Calculator (GGDC) which uses the Genome Blast Distance Phylogeny (GBDP) technique to calculate digital DDH values. Phylogenetic analysis via Genome-to-Genome distance, Average Nucleotide Identity, and Amino Acid Identity calculation revealed that all strains belonged to the genus Pantoea. However, strain 33.1 had a lower value than the threshold for the same species delineation. Bacterial Pan Genome Analysis (BPGA) Pipeline and MinPath analysis revealed genetic traits associated with environmental resilience, such as oxidative stress, UV radiation, temperature extremes, and metabolism of distinct host-specific carbohydrates. Protein-protein interactome analysis illustrated osmotic stress proteins closely linked with core proteins, while heavy metal tolerance, nitrogen metabolism, and Type III and VI secretion systems proteins generally associated with pathogenicity formed a separate network, indicating strain-specific characteristics. These findings shed new light on the intricate genetic architecture of Pantoea agglomerans, revealing its adaptability to inhabit diverse niches and thrive in varied environments.

Understanding the Genetic Basis of Celiac Disease: A Comprehensive Review.

Celiac disease is an immune-mediated enteropathy with typical symptoms of weight loss, abdominal bloating, diarrhea, vomiting, or constipation. Many shreds of evidence show that CeD is hereditary in origin and various biochemical pathways have been connected to its etiology. Numerous genes from different physiological pathways have been investigated in the last few decades, however a comprehensive analysis is required to address the gaps and provide a more integrated understanding of how these genetic factors contribute to the pathogenesis of disease. Present study attempts to summarize the historical and up-to-date findings to understand the role of genetics in Celiac disease. The literature was searched from sources such as PubMed and Google Scholar to analyze studies conducted on celiac disease from the years 1995 to 2024. Term maps were created to examine the frequency of studies related to various terms to understand the major focus of the studies till date. The study also concise the different genetic polymorphisms studied in a table to understand the role of genetics in celiac diseases. Early studies on celiac disease primarily focused on its pathophysiology, prevalence, and general aspects, with limited attention to genetics. However, recent studies have increasingly emphasized the genetic basis of the disease and highlighting the involvement of various pathways like inflammation, T-cell differentiation and activation, epithelial barrier function, stress and apoptosis pathways. However, present study indicate that most current research predominantly focus on cytokines, specifically the TNF alpha gene. Consequently, there is a need for additional research to gain a more comprehensive understanding of the genetics of celiac disease.

Draft genome sequence of halotolerant plant growth-promoting Bacillus paralicheniformis MHN12.

Bacillus paralicheniformis MHN12 possesses a 4,245,453-base pair genome with 45.9% G + C content, including 1 CRISPR, 80 tRNA, 8 rRNA genes, and 4,418 predicted coding sequences . MHN12 exhibits high salinity tolerance and plant growth-promoting abilities, making it a promising bioinoculant for enhancing plant growth in saline soils.

Whole genome analysis for plant growth promotion profiling of Pantoea agglomerans CPHN2, a non-rhizobial nodule endophyte.

Reduced agricultural production as well as issues like nutrient-depleted soils, eutrophication, and groundwater contamination have drawn attention to the use of endophyte-based bioformulations to restore soil fertility. Pantoea agglomerans CPHN2, a non-rhizobial nodule endophyte isolated from Cicer arietinum, exhibited a variety of plant growth-promoting traits. In this study, we used NextSeq500 technology to analyze whole-genome sequence information of this plant growth-promoting endophytic bacteria. The genome of P. agglomerans CPHN2 has a length of 4,839,532 bp and a G + C content of 55.2%. The whole genome comprises three different genomic fractions, comprising one circular chromosome and two circular plasmids. A comparative analysis between P. agglomerans CPHN2 and 10 genetically similar strains was performed using a bacterial pan-genome pipeline. All the predicted and annotated gene sequences for plant growth promotions (PGPs), such as phosphate solubilization, siderophore synthesis, nitrogen metabolism, and indole-3-acetic acid (IAA) of P. agglomerans CPHN2, were identified. The whole-genome analysis of P. agglomerans CPHN2 provides an insight into the mechanisms underlying PGP by endophytes and its potential applications as a biofertilizer.

Characterization of halo-tolerant plant growth promoting endophytic Bacillus licheniformis MHN 12.

BACKGROUND: Endophytic bacteria overlay significant role in plant growth promotion, eliminating phyto-pathogens and combating stress-conditions. In the present study, we aimed to screen high salt tolerant bacteria and study their adaptive response to elevated salt concentrations. A total of 46 endophytic bacterial isolates from Vigna radiata were screened for salt tolerance. The high salt tolerant endophytic isolate was characterized for alteration in morphology, growth rate, protein profiling, and compatible solute concentrations. RESULTS: The isolate MHN12, based upon biochemical characterization and partial 16S rDNA sequencing identified as B. licheniformis (accession number MG273753) was able to tolerate up to 15% NaCl (Sodium Chloride) (2.6 M) concentration. The isolate possessed 1-aminocyclopropane-1-carboxylic acid deaminase (ACCD) activity along with indole acetic acid (IAA), siderophore, ammonia, organic acid and hydrogen cyanide (HCN) production. Accumulation of proline was apparent up to 7.5% NaCl concentration and declined afterwards. Ultrastructure analysis using TEM (transmission electron microscopy) revealed the morphological alteration from rods to filaments. CONCLUSION: Acclimatization to salt stress and plant growth promoting activities could contribute to utilization of this bacterium as bioinoculant to enhance the crop yield and discourage the application of chemical fertilizers.

Draft Genome Sequence of Pantoea agglomerans CPHN2, a Potential Plant-Growth-Promoting Endophyte.

Here, we report the draft genome sequence of Pantoea agglomerans CPHN2, an endophyte isolated from nodules of Cicer arietinum (Chickpea) from Hisar, Haryana, India. The genome was 4,839,532 bp and exhibited a GC content of 55.2% and 4,508 genes with 4,468 coding sequences, 1 rRNA, 71 tRNAs, and 1 CRISPR.

Biogenic Synthesis of Zinc Nanoparticles, Their Applications, and Toxicity Prospects.

Nanofertilizers effectively deliver the micronutrients besides reducing the phytotoxicity and environmental damage associated with chemical fertilizers. Zinc, an essential micronutrient, is significant for chloroplast development, activation of certain enzymes, and primary metabolism. Nano zinc oxide (ZnO) is the most widely used zinc nanoparticle. Concerns regarding the toxicity of conventional physical and chemical methods of synthesizing the nanoparticles have generated the need for a green approach. It involves the biogenic synthesis of metallic nanoparticles using plants and microorganisms. Microbe-mediated biogenic synthesis of metallic nanoparticles is a bottom-up approach in which the functional biomolecules of microbial supernatant reduce the metal ions into its nanoparticles. This review discusses the biological synthesis of nano-ZnO from microorganisms and related aspects such as the mechanism of synthesis, factors affecting the same, methods of application, along with their role in conferring drought stress tolerance to the plants and challenges involved in their large-scale synthesis and applications.

Interplay between PCOS and microbiome: The road less travelled.

Polycystic ovarian syndrome (PCOS) is a complicated neuro-endocrinal, reproductive, and metabolic condition. It encompasses patterns such as hyperandrogenism, recurrent cysts triggered by steroidogenic functional aberrations in the ovaries, overweight, chronic inflammation, and more. The underlying cause of this heterogeneous illness is obscure, although it is suspected to be driven by a blend of environmental and hereditary factors. In recent years, the connection between the microbiome and PCOS has been acknowledged and is thought to be involved in the genesis of the syndrome's emergence. Microbiota vary in different pathological features of PCOS, and fundamental pathways linked to their involvement in the commencement of diverse clinical presentations in PCOS open up a new avenue for its management. Prebiotic, probiotic, synbiotic, and fecal-microbiota-transplant, by promoting eubiosis and nullifying the effect caused by the altered microbial profile in PCOS women, can aid in management of diverse phenotypes associated with the syndrome. These microbiota-mediated treatments improve PCOS women's metabolic, inflammatory, and hormonal profiles. However, more studies are needed to elucidate the mechanisms that drive this positive effect.

Endophytism: A Multidimensional Approach to Plant-Prokaryotic Microbe Interaction.

Plant growth and development are positively regulated by the endophytic microbiome via both direct and indirect perspectives. Endophytes use phytohormone production to promote plant health along with other added benefits such as nutrient acquisition, nitrogen fixation, and survival under abiotic and biotic stress conditions. The ability of endophytes to penetrate the plant tissues, reside and interact with the host in multiple ways makes them unique. The common assumption that these endophytes interact with plants in a similar manner as the rhizospheric bacteria is a deterring factor to go deeper into their study, and more focus was on symbiotic associations and plant-pathogen reactions. The current focus has shifted on the complexity of relationships between host plants and their endophytic counterparts. It would be gripping to inspect how endophytes influence host gene expression and can be utilized to climb the ladder of "Sustainable agriculture." Advancements in various molecular techniques have provided an impetus to elucidate the complexity of endophytic microbiome. The present review is focused on canvassing different aspects concerned with the multidimensional interaction of endophytes with plants along with their application.

Dissecting the role of micro-RNAs as a diagnostic marker for polycystic ovary syndrome: a systematic review and meta-analysis.

OBJECTIVE: To investigate the clinical diagnostic value and role of micro-RNAs (miRNAs) in the pathogenesis of polycystic ovary syndrome (PCOS). DESIGN: Systematic review and meta-analysis. SETTING: Not applicable. PATIENT(S): Patients were women of reproductive age with PCOS and controls. INTERVENTION(S): Summary odds ratio was calculated using a random effects model. MAIN OUTCOME MEASURE(S): Association of micro-RNAs with PCOS. METHOD(S): An electronic literature search was conducted using PubMed, Scopus, and Google Scholar databases to identify all relevant studies up to May 2019. A random effects model was used to conduct a meta-analysis. Fold change and P values were used to pool effect size. A funnel plot was used to assess publication bias. Quality score was calculated using the QUADAS scale. Subgroup analysis was based on tissue type. Odds ratios, 95% confidence intervals, and P values were estimated using meta-analysis. Metaregression was performed for correlating covariates with effect size. Area under the curve and receiver operating characteristic analysis was done to assess diagnostic performance accuracy of miRNAs in PCOS. RESULT(S): Twenty-one studies with a total of 79 miRNAs were included initially. Only three miRNAs (miR-29a-5p, miR-320, miR-93) are reported in more than three studies as of December 2018, so 12 studies were finally included in the quantitative analysis of meta-analysis and 21 studies were involved in the systematic review. The micro-RNAs miR-29a-5p and miR-320 were found to be significantly associated with PCOS. Funnel plot revealed an absence of publication bias for miR-29a-5p and miR-320. Receiver operating characteristic analysis with an area under the curve value of 0.95 proved miR-29a-5p to be the better diagnostic marker of PCOS. CONCLUSION(S): Aberrant expression of various miRNAs plays an important role in PCOS pathogenesis. Micro-RNAs hold potential diagnostic value for PCOS. These findings may offer new insights for PCOS pathogenesis research. PROSPERO REGISTRATION NUMBER: CRD42018106198.

Single nucleotide polymorphisms in treatment of polycystic ovary syndrome: a systematic review.

As 15-20% of reproductive aged females are suffering from polycystic ovary syndrome (PCOS), a large number of pharmacological preparations are frequently available in the market for the treatment of PCOS; however, they seem to be ineffective and cause undesirable side effects. This has emphasized the need to optimize dosage regimens for individualized treatment. The objective of this systematic review is to review single nucleotide polymorphisms (SNPs) associated with drugs used for the treatment of PCOS to understand pharmacogenetics variability of patients to drug response there by helping clinicians in designing tailored treatments and possibly reducing adverse drug reactions. A comprehensive electronic literature search was conducted to highlight some clinically relevant SNPs that act to influence PCOS and associated co-morbidities. A total of 16 studies were included in this review. These genetic variations can be used as a potential target for pharmacotherapy and pharmacogenetic clinical trials for better diagnosis, management, and treatment planning.

Association of Luteinizing hormone and LH receptor gene polymorphism with susceptibility of Polycystic ovary syndrome.

Altered folliculogenesis and reproductive anomalies in polycystic ovary syndrome (PCOS) suggest that variations of genes involved in folliculogenesis might influence etiopathogenesis of this syndrome. The objective of this study was to assess the association of LHß (rs1056917) and lutropin receptor (LHR) (rs61996318) polymorphism with polycystic ovarian syndrome and to interrelate the levels of luteinizing hormone (LH) with severity of clinical manifestations of PCOS. Three hundred women of reproductive age were enrolled in this retrospective case-control study. Rotterdam Criteria was used to diagnose PCOS patients. Nucleotide mutations of LH and LHR gene was analyzed using polymerase chain reaction-restriction fragment length polymorphism. High LH levels were found in 88% of PCOS patients. LHß TC and CC genotypes were significantly associated with PCOS risk (OR [odds ratio] 13.95, CI [confidence interval] 6.30-30.86, p < 0.0001 and OR 3.31, CI 1.30-8.41, p = 0.01). The frequency of the C allele was 0.31 in PCOS and 0.02 in controls (OR 18.80, CI 8.54-41.37, p < 0.0001). LHR CA and AA genotype conferred a significant risk in development of PCOS (OR 5.07, CI 2.50-10.31, p < 0.0001). The frequency of the A allele was 0.51 in PCOS and 0.03 in controls (OR 26.62, CI 13.99-50.65, p < 0.0001). The results show an association between polymorphism of LHß, LHR and PCOS, indicating that variants of these genes may affect the metabolic pathways involved in this syndrome. Majority of the affected women were found to have elevated LH levels. This study sheds new light in the diagnosis, treatment and management of PCOS syndrome. Abbreviations: AUC: area under curve; BMI: body mass index; C: cholesterol; CI: confidence interval; DBP: diastolic blood pressure; DHEAS: dehydroepiandrosterone sulfate; FG: Ferriman-Gallway; FSH: follicle stimulating hormone; GHQ: general health questionnaire; HA: hyperandrogenism; HDL-C: high-density lipoprotein cholesterol; HOMA-IR: homeostatic model assessment for insulin resistance; HWR: hip waist ratio; LDL-C: low-density lipoprotein cholesterol; LH: luteinizing hormone; LH: luteinizing hormone; LHR: lutropin receptor; O: oligomenorrhea; OR: odds ratio; PCO: polycystic ovaries; PCO: polycystic ovary; PCOS: polycystic ovary syndrome; PCR: polymerase chain reaction; ROC: receiver operating curve; SBP: systolic blood pressure; SE: standard error of coefficient; SNP: single nucleotide polymorphism; TG: triglycerides; TSH: thyroid stimulating hormone; VD: vitamin D.

Sex hormone binding globulin - an important biomarker for predicting PCOS risk: A systematic review and meta-analysis.

Sex hormone-binding globulin (SHBG) is a glycoprotein which regulates bioavailability of sex steroid hormones. Interest in SHBG has escalated in recent years because of its inverse association with polycystic ovary syndrome (PCOS), obesity, insulin resistance, metabolic syndrome, and diabetes type II. This meta-analysis was performed to examine the associations of SHBG with PCOS and to correlate serum SHBG levels with various PCOS associated endocrine and metabolic dysregulation as well as to determine the effects of various therapeutic agents on serum SHBG levels in PCOS patients in order to assess the true accuracy of SHBG in the prediction of PCOS. A literature search was performed using Pub-Med, Science direct, google scholar, EMBASE, and Cochrane library. A total of 675 relevant records were identified, of which 62 articles were included. Meta-analysis using a random-effects model was performed using STATA version 13 to calculate standardized mean difference (SMD) with 95% confidence intervals (95 % CIs). SHBG levels in controls were significantly higher than that of PCOS patients (SMD= -0.83, 95%CI = -1.01, -0.64), with significant heterogeneity across studies (I2= 93.9% and p=0.000). Our results suggest that the lower serum SHBG levels are associated with the risk of PCOS. SHBG may also play an important role in various metabolic disturbances in PCOS patients. Therapeutic interventions improved SHBG levels in PCOS women which further reduced PCOS associated complications. Therefore, SHBG levels may prove to be a useful biomarker for the diagnosis and treatment of PCOS. Systematic review registration: PROSPERO CRD42017057972 Abbreviations: PCOS: polycystic ovary syndrome; SHBG: sex hormone-binding globulin.

Unveiling the association between Vitamin D Receptor and Poly Cystic Ovary Syndrome - a systematic review and meta-analysis.

Background: Low Vitamin D status observed in the populations globally and its associations with diverse systems have kindled the interest for Vitamin D in medical literature in last two decades. Accumulating evidence manifest that deficiency of Vitamin D might be a causal factor in the pathogenesis of various features of Poly Cystic Ovary Syndrome (PCOS). This notion is supported by the fact that > 3 % of the human genome is regulated by vitamin D receptor (VDR). Therefore, this meta-analysis was carried out to quantify the magnitude of risk associated with VDR polymorphisms (BsmI, TaqI, FokI and ApaI) and PCOS susceptibility. Methods: Pub-med, EMBASE, Cochrane database, Science direct, Scirus, ISI web of knowledge and Google scholar were searched for all years until July 2016. The case control studies related to VDR polymorphism and PCOS risk were selected according to inclusion and exclusion criteria. Nine studies of the initial 553 hits reporting VDR polymorphism in PCOS were included. All statistical analysis was performed using the STATA 11.0 software and odd ratio with 95 % confidence intervals was used as effect size to assess the strength of associations. Results: Nine studies comprising 1558 cases and 1033 controls were included in this meta-analysis. Significant association between VDR Fok1 polymorphisms and PCOS risk was observed. In further stratified analysis, an increased risks were observed among Asian and African populations for Taq1 polymorphism. Apa1 and Bsm1 polymorphism was found not to be a risk factor for PCOS susceptibility. Conclusion: The FokI polymorphism is found to be a significant risk factor for PCOS.