Padmanaban S. Suresh

Factors associated with 2009 pandemic influenza A (H1N1) vaccination acceptance among university students from India during the post-pandemic phase

BackgroundThere was a low adherence to influenza A (H1N1) vaccination program among university students and health care workers during the pandemic influenza in many parts of the world. Vaccination of high risk individuals is one of the recommendations of World Health Organization during the post-pandemic period. It is not documented about the students knowledge, attitude and willingness to accept H1N1 vaccination during the post-pandemic period. We aimed to analyze the students knowledge, attitude and willingness to accept H1N1 vaccination during the post-pandemic period in India.MethodsVaccine against H1N1 was made available to the students of Vellore Institute of Technology, India from September 2010. The data are based on a cross-sectional study conducted during October 2010 to January 2011 using a self-administered questionnaire with a representative sample of the student population (N = 802).ResultsOf the 802 respondents, only 102/802 (12.7%) had been vaccinated and 105/802 (13%) planned to do so in the future, while 595/802 (74%) would probably or definitely not get vaccinated in the future. The highest coverage was among the female (65/102, 63.7%) and non-compliance was higher among men in the group (384/595; 64.5%) (p < 0.0001). The representation of students from school of Bio-sciences and Bio-technology among vaccinees is significantly higher than that of other schools. Majority of the study population from the three groups perceived vaccine against H1N1 as the effective preventive measure when compared to other preventive measures. 250/595 (42%) of the responders argued of not being in the risk group. The risk perception was significantly higher among female (p < 0.0001). With in the study group, 453/802 (56.4%) said that they got the information, mostly from media.ConclusionsOur study shows that the vaccination coverage among university students remains very low in the post-pandemic period and doubts about the safety and effectiveness of the vaccine are key elements in their rejection. Our results indicate a need to provide accessible information about the vaccine safety by scientific authorities and fill gaps and confusions in this regard.

New insights into the genetic basis of infertility

Infertility is a disease of the reproductive system characterized by inability to achieve pregnancy after 12 or more months of regular unprotected sexual intercourse. A variety of factors, including ovulation defects, spermatogenic failure, parental age, obesity, and infections have been linked with infertility, in addition to specific karyotypes and genotypes. The study of genes associated with infertility in rodent models has expanded the field of translational genetics in identifying the underlying cause of human infertility problems. Many intriguing aspects of the molecular basis of infertility in humans remain poorly understood; however, application of genetic knowledge in this field looks promising. The growing literature on the genetics of human infertility disorders deserves attention and a critical concise summary is required. This paper provides information obtained from a systematic analysis of the literature related to current research into the genetics of infertility affecting both sexes.

Emerging roles of MCPH1: expedition from primary microcephaly to cancer.

Genetic mutations in microcephalin1 (MCPH1) cause primary autosomal recessive microcephaly which is characterized by a marked reduction in brain size. MCPH1 encodes a centrosomal protein with three BRCT (BRCA1 C-terminal) domains. Also, it is a key regulator of DNA repair pathway and cell cycle checkpoints. Interestingly, in the past few years, many research studies have explored the role of MCPH1, a neurodevelopmental gene in several cancers and its tumor suppressor functions have been elucidated. Given the diverse new emerging roles, it becomes critical to review and summarize the multiple roles of MCPH1 that is currently lacking in the literature. In this review after systematic analysis of literature, we summarise the multiple functional roles of MCPH1 in centrosomal, DNA repair and apoptotic pathways. Additionally, we discuss the considerable efforts taken to understand the implications of MCPH1 in diseases such as primary microcephaly and its other emerging association with cancer and otitis media. The promising view is that MCPH1 has distinct roles and its clinical associations in various diseases makes it an attractive therapeutic target.

Exploration of deleterious single nucleotide polymorphisms in the components of human P bodies: an in silico approach.

P bodies are 100-300 nm sized organelles involved in mRNA silencing and degradation. A total of 60 human proteins have been reported to localize to P bodies. Several human SNPs contribute to complex diseases by altering the structure and function of the proteins. Also, SNPs alter various transcription factors binding, splicing and miRNA regulatory sites. Owing to the essential functions of P bodies in mRNA regulation, we explored computationally the functional significance of SNPs in 7 P body components such as XRN1, DCP2, EDC3, CPEB1, GEMIN5, STAU1 and TRIM71. Computational analyses of non-synonymous SNPs of these components was initiated using well utilized publicly available software programs such as the SIFT, followed by PolyPhen, PANTHER, MutPred, I-Mutant-2.0 and PhosSNP 1.0. Functional significance of noncoding SNPs in the regulatory regions were analysed using FastSNP. Utilizing miRSNP database, we explored the role of SNPs in the context that alters the miRNA binding sites in the above mentioned genes. Our in silico studies have identified various deleterious SNPs and this cataloguing is essential and gives first hand information for further analysis by in vitro and in vivo methods for a better understanding of maintenance, assembly and functional aspects of P bodies in both health and disease.

Single nucleotide polymorphisms in genes that are common targets of luteotropin and luteolysin in primate corpus luteum: Computational exploration

Luteal insufficiency affects fertility and hence study of mechanisms that regulate corpus luteum (CL) function is of prime importance to overcome infertility problems. Exploration of human genome sequence has helped to study the frequency of single nucleotide polymorphisms (SNPs). Clinical benefits of screening SNPs in infertility are being recognized well in recent times. Examining SNPs in genes associated with maintenance and regression of CL may help to understand unexplained luteal insufficiency and related infertility. Publicly available microarray gene expression databases reveal the global gene expression patterns in primate CL during the different functional state. We intend to explore computationally the deleterious SNPs of human genes reported to be common targets of luteolysin and luteotropin in primate CL. Different computational algorithms were used to dissect out the functional significance of SNPs in the luteinizing hormone sensitive genes. The results raise the possibility that screening for SNPs might be integrated to evaluate luteal insufficiency associated with human female infertility for future studies.

In silico analysis of polymorphisms in microRNAs that target genes affecting aerobic glycolysis

BACKGROUND Cancer cells preferentially metabolize glucose through aerobic glycolysis, an observation known as the Warburg effect. Recently, studies have deciphered the role of oncogenes and tumor suppressor genes in regulating the Warburg effect. Furthermore, mutations in glycolytic enzymes identified in various cancers highlight the importance of the Warburg effect at the molecular and cellular level. MicroRNAs (miRNAs) are non-coding RNAs that posttranscriptionally regulate gene expression and are dysregulated in the pathogenesis of various types of human cancers. Single nucleotide polymorphisms (SNPs) in miRNA genes may affect miRNA biogenesis, processing, function, and stability and provide additional complexity in the pathogenesis of cancer. Moreover, mutations in miRNA target sequences in target mRNAs can affect expression. METHODS In silico analysis and cataloguing polymorphisms in miRNA genes that target genes directly or indirectly controlling aerobic glycolysis was carried out using different publically available databases. RESULTS miRNA SNP2.0 database revealed several SNPs in miR-126 and miR-25 in the upstream and downstream pre-miRNA flanking regions respectively should be inserted after flanking regions and miR-504 and miR-451 had the fewest. These miRNAs target genes that control aerobic glycolysis indirectly. SNPs in premiRNA genes were found in miR-96, miR-155, miR-25 and miR34a by miRNASNP. Dragon database of polymorphic regulation of miRNA genes (dPORE-miRNA) database revealed several SNPs that modify transcription factor binding sites (TFBS) or creating new TFBS in promoter regions of selected miRNA genes as analyzed by dPORE-miRNA. CONCLUSIONS Our results raise the possibility that integration of SNP analysis in miRNA genes with studies of metabolic adaptations in cancer cells could provide greater understanding of oncogenic mechanisms.

Computational interrogation of cis-regulatory elements of genes that are common targets of luteotropin and luteolysin in the primate corpus luteum

The rapid recent increase in microarray-based gene expression studies in the corpus luteum (CL) utilizing macaque models gathered increasing volume of data in publically accessible microarray expression databases. Examining gene pathways in different functional states of CL may help to understand the factors that control luteal function and hence human fertility. Co-regulation of genes in microarray experiments may imply common transcriptional regulation by sequence-specific DNA-binding transcriptional factors. We have computationally analyzed the transcription factor binding sites (TFBS) in a previously reported macaque luteal microarray gene set (n=15) that are common targets of luteotropin (luteinizing hormone (LH) and human chorionic gonadotropin (hCG)) and luteolysin (prostaglandin (PG) F(2)α). This in silico approach can reveal transcriptional networks that control these important genes which are representative of the interplay between luteotropic and luteolytic factors in the control of luteal function. Our computational analyses revealed 6 matrix families whose binding sites are significantly over-represented in promoters of these genes. The roles of these factors are discussed, which might help to understand the transcriptional regulatory network in the control of luteal function. These factors might be promising experimental targets for investigation of human luteal insufficiency.

Next-generation sequencing for endocrine cancers: Recent advances and challenges

Contemporary molecular biology research tools have enriched numerous areas of biomedical research that address challenging diseases, including endocrine cancers (pituitary, thyroid, parathyroid, adrenal, testicular, ovarian, and neuroendocrine cancers). These tools have placed several intriguing clues before the scientific community. Endocrine cancers pose a major challenge in health care and research despite considerable attempts by researchers to understand their etiology. Microarray analyses have provided gene signatures from many cells, tissues, and organs that can differentiate healthy states from diseased ones, and even show patterns that correlate with stages of a disease. Microarray data can also elucidate the responses of endocrine tumors to therapeutic treatments. The rapid progress in next-generation sequencing methods has overcome many of the initial challenges of these technologies, and their advantages over microarray techniques have enabled them to emerge as valuable aids for clinical research applications (prognosis, identification of drug targets, etc.). A comprehensive review describing the recent advances in next-generation sequencing methods and their application in the evaluation of endocrine and endocrine-related cancers is lacking. The main purpose of this review is to illustrate the concepts that collectively constitute our current view of the possibilities offered by next-generation sequencing technological platforms, challenges to relevant applications, and perspectives on the future of clinical genetic testing of patients with endocrine tumors. We focus on recent discoveries in the use of next-generation sequencing methods for clinical diagnosis of endocrine tumors in patients and conclude with a discussion on persisting challenges and future objectives.

Effect of acute and chronic stress on leucocyte count: modulation by chlordiazepoxide

Total and differential leucocyte count (TLC and DLC) in blood circulation influence humoral immune response and stress alters TLC and DLC by leucocyte misdistribution. Chlordiazepoxide, a widely used benzodiazepine anti-stress agent, is reported to reverse suppression of antibody response induced by acute stress but not by chronic stress. The effect of chlordiazepoxide on the changes in leucocyte count by acute and chronic stress has not been clearly defined. We examined the effect of restraint stress (1 h/day) for 6, 10, 14 and 21 days on TLC and DLC and their modulation by chlordiazepoxide pretreatment (10 mg/kg/day) 1 h before exposure to stress in albino rats. Acute stress, i.e. restraint stress (1 h/day) for 6 and 10 days with or with out chlordiazepoxide pretreatment did not alter TLC and DLC. Chronic stress, i.e. restraint stress (1 h/day) for 14 and 21 days significantly decreased TLC and the percentage of lymphocytes in comparison to control. Pretreatment with chlordiazepoxide reversed these changes. We conclude that chlordiazepoxide, a benzodiazepine, reverses changes in TLC and DLC probably by improving chronic stress-induced leucocytes misdistribution.

Mining of single nucleotide polymorphisms in the 3' untranslated region of liver cancer-implicated miR-122 target genes

Currently there has been a lot of focus on the microRNA (miR)-122 to understand the genetics of hepatocellular carcinoma (HCC), pathology of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, hepatic insulin resistance, and lipid metabolism (1-4). Interestingly, miR-122 expression levels were significantly reduced than the normal levels in HBV-associated liver cancer, but not in HCV related liver cancer (5). Also, there is an overwhelming amount of data suggesting the role of single nucleotide polymorphisms (SNPs) in hepatic genes and its association with the altered risk/development of hepatic cancer and its progression. Polymorphisms in the miRNA-binding sites of the target genes are more frequent than SNPs in miRNA genes and therefore, it is considered that polymorphisms in the cytokines and other genes have correlations with chronic HBV or HCV infections. These SNPs in the miRNA binding sites of the target genes can potentially enhance or weaken the interaction between the miRNAs and the target transcripts. Therefore, it is important to study the SNPs in miR-122 binding sites of the target genes to understand the genetic basis of HCC.