Genesis-DB: a database for autonomous laboratory systems

Artificial intelligence (AI)-driven laboratory automation - combining robotic labware and autonomous software agents - is a powerful trend in modern biology. We developed Genesis-DB, a database system designed to support AI-driven autonomous laboratories by providing software agents access to large quantities of structured domain information. In addition, we present a new ontology for modeling data and metadata from autonomously performed yeast microchemostat cultivations in the framework of the Genesis robot scientist system. We show an example of how Genesis-DB enables the research life cycle by modeling yeast gene regulation, guiding future hypotheses generation and design of experiments. Genesis-DB supports AI-driven discovery through automated reasoning and its design is portable, generic, and easily extensible to other AI-driven molecular biology laboratory data and beyond

Detection of Nail Oncometabolite SAICAR in Oral Cancer Patients and Its Molecular Interactions with PKM2 Enzyme

Oncometabolites are known to drive metabolic adaptations in oral cancer. Several oncometabolites are known to be shared between cancer cells and non-cancer cells including microbiotas to modulate the tumor microenvironment. Among potential oncometabolites, succinylaminoimidazolecarboxamide ribose5′-phosphate (SAICAR) supports the growth and invasiveness of cancer cells by pyruvate kinase M2 (PKM2) enzyme in a glucose starved tumor microenvironment. There is a significant gap that shows the detection of SAICAR in biological samples including nails of oral cancer patients. Metabolite identification of SAICAR was investigated in the nails of oral cancer patients using novel vertical tube gel electrophoresis (VTGE) and LC-HRMS. Further molecular docking and molecular dynamics simulations (MDS) were employed to determine the nature of molecular interactions of SAICAR (CHEBI ID:18319) with PKM2 (PDB ID: 4G1N). Molecular docking of SAICAR (CHEBI ID:18319) was performed against pyruvate kinase M2 (PDB ID: 4G1N). Data suggest the presence of oncometabolite SAICAR in nails of oral cancer. Molecular docking of SAICAR with PKM2 showed appreciable binding affinity (−8.0 kcal/mol) with residues including ASP407, THR405, GLU410, ARG443, GLY321, ARG436, HIS439, LYS266, and TYR466. Furthermore, MDS confirmed the specific binding of SAICAR within the activator site of PKM2 and the stability of SAICAR and PKM2 molecular interactions. In conclusion, SAICAR is a promising oncometabolite biomarker present in the nails of oral cancer patients. A significant activation potential of SAICAR exists with the PKM2 enzyme

Isolated PTH Renal Resistance Pseudo Hypo Parathyroidism 1b: A Rare Cause of Hypocalcemia

A case of Pseudohypoparathyroidism 1b is reported, who presented with signs and symptoms of hypocalcemia. Causes, diagnosis and management with new insight into genetic novel mutations in PHP are discussed. The objectives are to provide information regarding problems of Calcium balance, causes and making diagnosis of pseudohypoparathyroidism, learn complexities of PTH cellular interactions and calcium homeostasis and learn the genetic novel mutations of various types of PHP.  Keywords: Hyperphosphatemia, hypocalcemia Isolated PTH resistance, Pseudohypoparathyroidism, Secondary hyperparathyroidism. | PubMe

The role of polymorphism in various potential genes on polycystic ovary syndrome susceptibility and pathogenesis

Abstract Polycystic ovary syndrome (PCOS) is the most common endocrinopathies affecting the early reproductive age in women, whose pathophysiology perplexes many researchers till today. This syndrome is classically categorized by hyperandrogenism and/or hyperandrogenemia, menstrual and ovulatory dysfunction, bulky multi follicular ovaries on Ultrasonography (USG), and metabolic abnormalities such as hyperinsulinemia, dyslipidemia, obesity. The etiopathogenesis of PCOS is not fully elucidated, but it seems that the hypothalamus-pituitary-ovarian axis, ovarian, and/or adrenal androgen secretion may contribute to developing the syndrome. Infertility and poor reproductive health in women’s lives are highly associated with elevated levels of androgens. Studies with ovarian theca cells taken from PCOS women have demonstrated increased androgen production due to augmented ovarian steroidogenesis attributed to mainly altered expression of critical enzymes (Cytochrome P450 enzymes: CYP17, CYP21, CYP19, CYP11A) in the steroid hormone biosynthesis pathway. Despite the heterogeneity of PCOS, candidate gene studies are the widely used technique to delineate the genetic variants and analyze for the correlation of androgen biosynthesis pathway and those affecting the secretion or action of insulin with PCOS etiology. Linkage and association studies have predicted the relationship between genetic variants and PCOS risk among families or populations. Several genes have been proposed as playing a role in the etiopathogenesis of PCOS, and the presence of mutations and/or polymorphisms has been discovered, which suggests that PCOS has a vital heritable component. The following review summarizes the influence of polymorphisms in crucial genes of the steroidogenesis pathway leading to intraovarian hyperandrogenism which can result in PCOS

Assessment of gut microbial β-glucuronidase and β-glucosidase activity in women with polycystic ovary syndrome

Abstract PCOS is a prevalent endocrine disorder among women of reproductive age, characterized by hormonal imbalances and metabolic disturbances. This study explores the correlation between gut microbial β-glucuronidase and β-glucosidase and PCOS, focusing on their association with hormone levels and other clinical parameters. In this case-control study, fecal samples were collected from women of reproductive age, both with and without PCOS. The analysis of gut β-glucuronidase and β-glucosidase enzymes was conducted with the other clinical parameters, including body mass index, hormone levels, and hirsutism. These factors were then subjected to correlation analysis. PCOS women showed significantly higher levels of β-glucuronidase activity with a statistically significant P-value (0.05 ± 0.1 vs. 0.04 ± 0.1; P = 0.006) as well as β-glucosidase activity (0.13 ± 0.08 vs. 0.09 ± 0.05; P = 0.06) compared to the controls. This study also revealed intriguing connections between the selected enzymes and hormone levels, particularly testosterone and estradiol. Gut microbial enzymes β-glucuronidase and β-glucosidase may be used as biomarkers for early detection and monitoring of PCOS in women with metabolic challenges. It could lead to improved diagnostic tools and treatment options

A cross-sectional study of clinical, histopathological and direct immmunofluorescence diagnosis in autoimmune bullous diseases

Background: Immunobullous diseases are morphologically heterogeneous and the differentiation between various subtypes is essential for proper treatment and prognosis. Aim of our study was to analyze and correlate clinical, histopathological and immunofluorescence findings in autoimmune bullous diseases. Materials and Methods: A cross-sectional study was done over a period of two years (2010-2012) after approval of the ethics committee. Sixty patients, who met the inclusion criteria of immunobullous disease, were included in the study. Skin biopsy for histopathology and direct immunofluorescence (DIF) examination was taken. DIF using salt-split technique was done in few of the cases. The final diagnosis was based on clinical, histopathology and DIF findings. Pearson′s coefficient of correlation (r) was calculated. Statistical Analysis was done using Epi info version. 7.0. Results: Fifty-three cases with clinical diagnosis of autoimmune bullous diseases were evaluated. In 88.6% of cases, histopathology diagnosis was consistent with clinical diagnosis and in 75.5% of cases, DIF findings were consistent with clinical diagnosis. A positive relation was seen between clinical and DIF findings with r = 0.65 and between histopathology and DIF findings with r = 0.75. DIF positivity was seen in 100% cases of bullous pemphigoid (BP) and pemphigus foliaceous and 94.7% cases of pemphigus vulgaris, which was statistically significant with p < 0.05. In DIF salt-split test, deposition was seen on roof of blister in BP whereas on floor in epidermolysis bullosa acquisita. Conclusion: Our study provides evidence-based guidance for the diagnosis and classification of various immunobullous disorders. DIF test should be done in conjunction with histopathology for definitive diagnosis and to minimize both: False-positive and false-negative results

Evaluation of Antimicrobial Efficacy of Pudina (Menthaarvenis), Tulsi (Ocimumtenuiflorum) and Curry Leaves (Murrayakoenigii) on Streptococcus mutans by Modified Direct Contact Test- An In vitro Study

Introduction: Dental caries is a pandemic disease caused by Streptococcus mutans. Numerous preventive strategies have been developed to prevent dental caries with modern medicines. Recently, there has been a shift from use of modern medicines to herbal ayurvedic preparations which are easily available and cause least possible side effects but have not been tested against S. mutans. Aim: To evaluate antimicrobial value of Pudina, Tulsi and Curry leaves against S. mutans by modified direct contact test. Materials and Methods: This in vitro study used finely powdered form of Pudina, Tulsi and Curry leaves extracts (Hakim Chi Chi Pharmacy, Surat, India) without any added preservatives. The test microorganism S. mutans was isolated from human saliva using mitis salivarius agar. The Minimum Inhibition Concentration (MIC) was determined using agar well diffusion for Group 1 (Tulsi), Group 2 (Pudina), Group 3 (Curry leaves) and Group 4 (Chlorhexidine). Using this MIC, modified Direct Contact Test was performed for specific evaluation of the antimicrobial efficacy of each product. Chlorhexidine (0.2%) was used as a positive control for the comparison of each product. The results of modified direct contact test were subjected to ANOVA Test and Tukey’s Test using SPSS software version 23.0 which showed that when compared against chlorhexidine, the antimicrobial efficacy against S. mutans in decreasing order was of curry leaves, tulsi and pudina and the result of the study was significant. Results: Curry leaves showed higher antimicrobial efficacy than tulsi and pudina when compared against chlorhexidine (control) and the results were statistically significant (p<0.05). Conclusion: Curry leaf extract shows promising antimicrobial property against S. mutans and can be recommended for caries control with further investigations

Association of FTO gene variant rs9939609 with polycystic ovary syndrome from Gujarat, India

Abstract Background Polycystic ovary syndrome is a multifactorial endocrine disorder impacting women of reproductive age. Variations within the FTO gene have been linked to both obesity and type 2 diabetes mellitus. Given that PCOS is frequently associated with obesity and compromised glucose tolerance, we investigated the prevalence of the rs9939609 variant within the FTO gene among women diagnosed with PCOS and a control group. Our aim is to uncover potential correlations between this genetic variant, metabolic attributes, and endocrine markers within the Gujarat province of India. Method We enrolled a total of 114 participants, (62 individuals diagnosed with PCOS and 52 healthy controls). DNA extraction from venous blood was conducted for all participants. The rs9939609 polymorphism was investigated through tetra-primer amplification refractory mutation system-polymerase chain reaction. Furthermore, we performed biochemical assessments to quantify levels of estradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH), thyroid-stimulating hormone (TSH), total testosterone, prolactin (PRL), and Dehydroepiandrosterone sulfate (DHEAS). Statistical analyses were carried out utilizing SPSS version 21 (IBM, USA). Results The present study did not reveal any noteworthy association between cases and controls. The frequencies of genotypes and alleles within the cohorts displayed no statistically significant differences (p = 0.25, p = 0.68, and p = 0.78, respectively). The dominant model indicated a modest risk (OR:1.13, 95%CI: 0.55 to 2.38) toward PCOS development. There was a noticeable statistical difference observed in the levels of total testosterone, DHEAS, and BMI between the case and control groups (p < 0.002, p < 0.0002, p < 0.0008). However, no variations in clinical variables were observed among genotypes within the PCOS group. Conclusion This is the first study to investigate the association of FTO gene polymorphism and PCOS in Gujarati population. Our study findings indicate that the FTO gene variant is not directly linked to the onset of PCOS. However, it appears to exert an influence on metabolic factors such as obesity and insulin resistance. Notably, our results suggest that insulin resistance is more frequently observed among PCOS patients who are obese, as compared to those with non-obese PCOS patients

A parametric study and experimental investigations of microstructure and mechanical properties of multi-layered structure of metal core wire using wire arc additive manufacturing

In the present study, the Gas metal arc welding (GMAW) based Wire-arc additive manufacturing (WAAM) process was preferred for the fabrication of multi-layered structures and their investigations of mechanical properties on metal core wire. Based on literature work, preliminary trials, machine limits, travel speed (TS), voltage (V), and gas mixture ratio (GMR) were identified as machining parameters along with output factors of bead width (BW), bead height (BH), and depth-of-penetration (DOP). Experiments were conducted by following the Box-Behnken design. The feasibility of the generated non-linear regression models has been validated through the statistical analysis of variance and residual plots. The multi-layered structure has been successfully fabricated at the optimized parametric settings of TS at 24 mm/s; the voltage at 24 V, and GMR at 1 which was obtained through the heat transfer search (HTS) algorithm. The fabricated structure was observed to be uniform. The structure exhibited uniform bead-on-bead deposition for the deposited layers. The fabricated multi-layered structure underwent a detailed microstructural and mechanical examinations. Microstructural examination revealed dense needles at the bottom section of the structure as compared to the top section, as the bottom section undergoes multiple heating and cooling cycles. When comparing the multilayer structure to the metal core wire, all the properties exhibited favorable tensile characteristics. The obtained strength from the impact test results highlights the impressive ductility of the multi-layer deposition. Fractography of tensile and impact test specimens has shown the occurrences of larger dimples and suggested a ductile fracture. Lastly, the hardness value in all the sections of the built structure was observed to be uniform, suggesting uniform deposition across the built multi-layer structure. The authors consider the current work will be highly beneficial for users in fabricating multi-layer structures at optimized parametric settings and their investigations for mechanical properties for metal core wire.  CC BY 4.0</p