Integration of text mining and biological network analysis: Identification of essential genes in sulfate-reducing bacteria

The growth and survival of an organism in a particular environment is highly depends on the certain indispensable genes, termed as essential genes. Sulfate-reducing bacteria (SRB) are obligate anaerobes which thrives on sulfate reduction for its energy requirements. The present study used Oleidesulfovibrio alaskensis G20 (OA G20) as a model SRB to categorize the essential genes based on their key metabolic pathways. Herein, we reported a feedback loop framework for gene of interest discovery, from bio-problem to gene set of interest, leveraging expert annotation with computational prediction. Defined bio-problem was applied to retrieve the genes of SRB from literature databases (PubMed, and PubMed Central) and annotated them to the genome of OA G20. Retrieved gene list was further used to enrich protein–protein interaction and was corroborated to the pangenome analysis, to categorize the enriched gene sets and the respective pathways under essential and non-essential. Interestingly, the sat gene (dde_2265) from the sulfur metabolism was the bridging gene between all the enriched pathways. Gene clusters involved in essential pathways were linked with the genes from seleno-compound metabolism, amino acid metabolism, secondary metabolite synthesis, and cofactor biosynthesis. Furthermore, pangenome analysis demonstrated the gene distribution, where 69.83% of the 116 enriched genes were mapped under “persistent,” inferring the essentiality of these genes. Likewise, 21.55% of the enriched genes, which involves specially the formate dehydrogenases and metallic hydrogenases, appeared under “shell.” Our methodology suggested that semi-automated text mining and network analysis may play a crucial role in deciphering the previously unexplored genes and key mechanisms which can help to generate a baseline prior to perform any experimental studies

Copy number variants as modifiers of breast cancer risk for BRCA1/BRCA2 pathogenic variant carriers

The risk of germline copy number variants (CNVs) in BRCA1 and BRCA2 pathogenic variant carriers in breast cancer is assessed, with CNVs overlapping SULT1A1 decreasing breast cancer risk in BRCA1 carriers.The contribution of germline copy number variants (CNVs) to risk of developing cancer in individuals with pathogenic BRCA1 or BRCA2 variants remains relatively unknown. We conducted the largest genome-wide analysis of CNVs in 15,342 BRCA1 and 10,740 BRCA2 pathogenic variant carriers. We used these results to prioritise a candidate breast cancer risk-modifier gene for laboratory analysis and biological validation. Notably, the HR for deletions in BRCA1 suggested an elevated breast cancer risk estimate (hazard ratio (HR) = 1.21), 95% confidence interval (95% CI = 1.09-1.35) compared with non-CNV pathogenic variants. In contrast, deletions overlapping SULT1A1 suggested a decreased breast cancer risk (HR = 0.73, 95% CI 0.59-0.91) in BRCA1 pathogenic variant carriers. Functional analyses of SULT1A1 showed that reduced mRNA expression in pathogenic BRCA1 variant cells was associated with reduced cellular proliferation and reduced DNA damage after treatment with DNA damaging agents. These data provide evidence that deleterious variants in BRCA1 plus SULT1A1 deletions contribute to variable breast cancer risk in BRCA1 carriers.Peer reviewe

Breast and Prostate Cancer Risks for Male BRCA1 and BRCA2 Pathogenic Variant Carriers Using Polygenic Risk Scores

Background: Recent population-based female breast cancer and prostate cancer polygenic risk scores (PRS) have been developed. We assessed the associations of these PRS with breast and prostate cancer risks for male BRCA1 and BRCA2 pathogenic variant carriers. Methods: 483 BRCA1 and 1318 BRCA2 European ancestry male carriers were available from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). A 147-single nucleotide polymorphism (SNP) prostate cancer PRS (PRSPC) and a 313-SNP breast cancer PRS were evaluated. There were 3 versions of the breast cancer PRS, optimized to predict overall (PRSBC), estrogen receptor (ER)-negative (PRSER-), or ER-positive (PRSER+) breast cancer risk. Results: PRSER+ yielded the strongest association with breast cancer risk. The odds ratios (ORs) per PRSER+ standard deviation estimates were 1.40 (95% confidence interval [CI] =1.07 to 1.83) for BRCA1 and 1.33 (95% CI = 1.16 to 1.52) for BRCA2 carriers. PRSPC was associated with prostate cancer risk for BRCA1 (OR = 1.73, 95% CI = 1.28 to 2.33) and BRCA2 (OR = 1.60, 95% CI = 1.34 to 1.91) carriers. The estimated breast cancer odds ratios were larger after adjusting for female relative breast cancer family history. By age 85 years, for BRCA2 carriers, the breast cancer risk varied from 7.7% to 18.4% and prostate cancer risk from 34.1% to 87.6% between the 5th and 95th percentiles of the PRS distributions. Conclusions: Population-based prostate and female breast cancer PRS are associated with a wide range of absolute breast and prostate cancer risks for male BRCA1 and BRCA2 carriers. These findings warrant further investigation aimed at providing personalized cancer risks for male carriers and informing clinical management.Peer reviewe

Shaping the Future of Antimicrobial Therapy: Harnessing the Power of Antimicrobial Peptides in Biomedical Applications

Antimicrobial peptides (AMPs) have emerged as a promising class of bioactive molecules with the potential to combat infections associated with medical implants and biomaterials. This review article aims to provide a comprehensive analysis of the role of antimicrobial peptides in medical implants and biomaterials, along with their diverse clinical applications. The incorporation of AMPs into various medical implants and biomaterials has shown immense potential in mitigating biofilm formation and preventing implant-related infections. We review the latest advancements in biomedical sciences and discuss the AMPs that were immobilized successfully to enhance their efficacy and stability within the implant environment. We also highlight successful examples of AMP coatings for the treatment of surgical site infections (SSIs), contact lenses, dental applications, AMP-incorporated bone grafts, urinary tract infections (UTIs), medical implants, etc. Additionally, we discuss the potential challenges and prospects of AMPs in medical implants, such as effectiveness, instability and implant-related complications. We also discuss strategies that can be employed to overcome the limitations of AMP-coated biomaterials for prolonged longevity in clinical settings

Studies on biomarkers for oxidative stress in patients with chronic myeloid leukemia

BACKGROUND: Chronic myeloid leukemia (CML) is a myeloproliferative disorder with a unique genetic rearrangement, the Philadelphia chromosome. High reactive oxygen species (ROS) levels favor oxidative stress, which could play a vital role in normal processes and various pathophysiologies including neoplasm. Biomarkers of oxidative stress are measured as products of oxidized proteins and lipids. Plasma levels of protein carbonyl (PC), thiobarbituric acid reactive substances (TBARS) and total lipid hydroperoxide (LOOH) were used as biomarkers of oxidative stress in the past. The aim of this study was to evaluate the products of protein oxidation and lipid peroxidation in plasma as biomarkers of oxidative stress in CML patients. PATIENTS AND METHODS: The study included 40 CML patients and 20 age- and sex-matched healthy volunteers. Of 40 CML patients, 28 were in chronic phase (CML-CP) and 12 in accelerated phase (CML-AP). Plasma levels of PC, TBARS and LOOH as biomarkers of oxidative stress were evaluated by spectrophotometric methods. RESULTS: There were significant differences (P<.05) in plasma levels of PC, TBARS and LOOH in CML, CML-CP and CML-AP patients as compared to controls. CONCLUSION: PC, TBARS and LOOH might reflect oxidative stress in CML patients and might be used as biomarkers in such patients

Determinants of School Enrolment of Children in Slums of Varanasi

Introduction: Education plays a vital role to developing a nation. In India, urban slums constituting about 22.6% of the urban population are the poor and socially disadvantaged. This slum community is least concerned for school enrolment of their children inspite of the fact that primary education is compulsory and is free in public schools. In urban areas schools available are mostly of private sector that are not free and beyond affordability to slums; government and corporation schools are few, but beyond reach. Motive of the parents is to involve children in income generating activities and the girls are more deprived of school enrolment in poorer society.&nbsp;Objectives:&nbsp;1) assess the enrolment status of slum children and 2) determine the factors influencing school enrolment. Methodology:&nbsp;The data was collected during 2011-12 from 15 randomly selected slums out of 227 in which a total of 893 families were contacted and mothers with children aged 5-15 years interrogated. In addition to child history on age, sex and school enrolment, the family background characteristics were e.g. religion, caste, and family size as well as age, education and occupation of both mother &amp; father were recorded. Results:&nbsp;Out of 1145 children, male and female equal represented; mostly (90.9%) were Hindus and half were SC/ST class. About 30% father and 57.2% mothers were illiterate; about half fathers were unskilled-worker and 96.0% mother’s house wife. Overall 31.3% children were not enrolled and were decreasing from 49.2% to 24.3% to 21.4% in the age groups 5-6, 7-9 and 10-15 years respectively. Enrolment was poor in Muslims (50.0%) compared to Hindus (29.4%); enrolment was similar irrespective of child sex among Hindus, but in Muslims 62.5% male and 35.4% female children were only enrolled. Similar was the situation as one move from SC/ST (67.6%) to OBC (73.4%) and general caste (77.9%). Education of father and mother had significant role to enrolment but not the age and occupation of father and mother. Female child enrolment was poor if father was in business and mother was aged. Logistic regression analysis indicated that school enrolment of children aged 5-7 years was associated with age of mother and educational combination of father and mother, while of children 8-15 years caste/religion, family size, sex of child and educational combination of father and mother were found associated. Conclusion: Findings suggest that slum community as a whole is the pocket constituted by habitats of socially disadvantaged class has to be promoted with attitudinal change to schooling of their children without discriminating child sex

S-phase fraction as a useful marker for prognosis and therapeutic response in patients with aplastic anemia

BACKGROUND: The functional definition of aplastic anemia (AA) is the failure of hematopoietic stem cells to proliferate. The aim of the present study was to analyze the S-phase fraction (SPF) (proliferative activity) in patients with AA at diagnosis to explore its relationship with disease characteristics and its value in discriminating among patients with different prognoses. We also investigated whether the SPF value influenced the response to immunosuppressive therapy in AA patients. PATIENTS AND METHODS: The analysis of SPF at the time of diagnosis was carried out by flow cytometry on peripheral blood samples from 53 consecutive patients with AA and 30 age- and sex-matched controls. All patients were given cyclosporine and followed up periodically to determine response to therapy. RESULTS: Based on the median SPF, AA patients were divided into two groups: patients with SPF ≤0.59% (n=27) and patients with SPF >0.59% (n=26). An SPF >0.59% was associated with advanced age (P=.02) and elevated serum LDH level (P=.01). Patients with an SPF >0.59% also had a higher incidence of paroxysmal nocturnal hemoglobinuria and cytogenetic abnormalities. During a median follow-up of 18 months, 3.7% of patients with SPF ≤0.59 and 11.5% of patients with SPF >0.59% developed dysplasia and one patient with SPF >0.59% converted into AML. A significantly higher (P=.018) overall response rate of 53.9% was found in patients with SPF >0.59% versus 22.2% of patients with SPF ≤0.59% at 6 months. CONCLUSIONS: Independently of the peripheral blood count, the SPF at diagnosis may provide information on the expected response to immunosuppressive therapy and the propensity for disease to evolve into MDS/AML. Hence, SPF may serve as an early indicator for the evolution of MDS/AML in patients with AA and thus contribute to therapeutic decisions

Age and Sex Specific Reference Intervals for Modifiable Risk Factors of Cardiovascular Diseases for Gujarati Asian Indians

Objective. We aimed to establish age and sex specific percentile reference data for cardiovascular risk factors such as lipids, sugar, blood pressure, and BMI in apparently healthy and disease-free Gujarati population. Methods. In this cross-sectional study, we enrolled 3265 apparently healthy and disease-free individuals of both genders residing in Gujarat state. Fasting samples of blood were used for biochemical estimations of lipids and sugar. The measurement of BMI and blood pressure was also done according to the standard guidelines. Age and gender specific 5th, 25th, 50th, 75th, 90th, and 95th percentiles were obtained. Results. The mean values of lipids, sugar, blood pressure, and BMI were significantly ( &lt; 0.001) higher in males as compared to female population. Age-wise distribution trends showed increase in the risk factors from the 2nd decade until the 5th to 6th decade in most of the cases, where loss of premenopausal protection in females was also observed. Specific trends according to gender and age were observed in percentile values of various parameters. Conclusion. The outcome of current study will contribute significantly to proposing clinically important reference values of various lipids, sugar, blood pressure, and BMI that could be used to screen the asymptomatic Gujarati Indian population with a propensity of developing dyslipidemia, diabetes, blood pressure, and obesity