Role of 677C→T polymorphism a single substitution in methylenetetrahydrofolate reductase (MTHFR) gene in North Indian infertile men

Failure or severe difficulty in conceiving a child is surprisingly common, worldwide problem. Half of these cases are due to male factors with defects in sperm (1 in 15 men) being the single most common cause. Also about 60–75 % of male infertility cases are idiopathic, since the molecular mechanisms underlying the defects remain unknown. DNA methylation is crucial for spermatogenesis and high methylenetetrahydrofolate reductase (MTHFR) activity in adult testis than other organs in mouse, signifies its critical role in spermatogenesis. According to recent findings there is a correlation of epigenetic regulation of several imprinted genes with disturbed spermatogenesis and fertility. Consequently any change in the MTHFR gene sequence can modify the spermatogenesis including transmission of infertility to the carriers. The aim of the study is to analyze the distribution of the single nucleotide polymorphism C677T in the MTHFR gene in 637 North Indian infertile patients and 364 fertile North Indian men as controls by using PCR–RFLP technique and Chi Square test for statistical analysis. The average MTHFR 677CC, 677CT, 677TT genotype frequencies of total infertile men were 70.17, 24.17, 5.65 % in infertile men and 75.27, 21.7, 2.74 % in controls, respectively. The average frequency of the MTHFR 677T allele was 17.73 % in infertile men as compared to 13.59 % in controls. The statistical difference was significant. Disease risk was found 2.27-folds increased in patients who were carrying T allele. We found an association of C677T polymorphism with male infertility and that it may be a genetic risk factor for male infertility in North Indian population.     

Modelling and simulation of mutant alleles of breast cancer metastasis suppressor 1 (BRMS1) gene

Computational tools occupy the prime position in the analysis of large volume of post-genomic data. These tools have advantage over the wet lab experiments in terms of high coverage, cost and time. Breast cancer is the most common cancer in females worldwide. It is a genetically heterogeneous disorder and many genes are involved in the pathway of the disease. Mutations in metastasis suppressor gene are the major cause of the disease. In this study, the effects of mutations in breast cancer metastasis suppressor 1gene upon protein structure and function were examined by means of computational tools and information from databases.This study can be useful to predict the potential effect of every allelic variant, devise new biological experiments and to interpret and predict the patho-physiological impact of new mutations or non-synonymous polymorphisms.     

Prevalence of Hypertension in Indian Tribes: A Systematic Review and Meta-Analysis of Observational Studies

Introduction

In India there is an increasing trend in hypertension prevalence among the general population. Studies have shown that tribal populations in India are also experiencing this burden.

Objective

The aim was to estimate the pooled prevalence of primary hypertension among adult tribal populations of India.

Methods

A systematic search was conducted in MEDLINE, IndMed, Web of Science, Google Scholar and major journals for studies published between 1981 and 2011. Two authors independently reviewed the studies, did quality assessment and extracted data in pre-coded spread-sheets. Pooled estimates of prevalence of hypertension were calculated using DerSimonian-Laird random effects model. Subgroup and sensitivity analyses and meta-regression were performed.

Results

Twenty studies or 53 subpopulations with 64 674 subjects were included in final review. The pooled estimate of hypertension prevalence was 16.1% (95% CI: 13.5, 19.2). There was significant heterogeneity among the studies (I² = 99% and Q = 4624.0, df  = 53, p<0.001). Subgroup analyses showed that year of study, acculturation status, special features, and BP measurement techniques significantly influenced prevalence, but after meta-regression analyses, ‘decade of study’ remained the only covariate that significantly and independently influenced prevalence (R² = 0.57, Q = 119.2, df  = 49, p value <0.001).

Conclusion

An increasing trend was found in the prevalence of hypertension in adult tribal populations across three decades. Although acculturation was probably the underlying agent that caused this increase, other unmeasured factors that need further research were also important. Concerned policy makers should focus on the changing health needs of tribal communities.     

Probing the intermolecular interactions into serum albumin and anthraquinone systems: a spectroscopic and docking approach

Intermolecular interaction study of human serum albumin (HSA) with two anthraquinones i.e. danthron and quinizarin has been performed through fluorescence, UV-vis and CD spectroscopy along with docking analysis. The titration of drugs into HSA solution brought about the quenching of fluorescence emission by way of complex formation. The binding constants were found to be 1.51 × 10⁴ L mol^?1 and 1.70 × 10⁴ L mol^?1 at λ_exc = 280 nm while at λ_exc = 295 nm, the values of binding constants were 1.81 × 10⁴ L mol^?1 and 1.90 × 10⁴ L mol^?1 which hinted toward binding of both the drugs in the vicinity of subdomain IIA. Different temperature study revealed the presence of static quenching mechanism. Moreover, more effective quenching of the fluorescence emission was observed at λ_exc = 295 nm which also suggested that both the drug molecule bind nearer to Trp-214. Thermodynamic parameters showed that hydrophobic interaction was the major force behind the binding of drugs. The UV-vis spectroscopy testified the formation of complex in both the systems and primary quenching mechanism as static one. The changes in secondary structure and α-helicity in both the systems were observed by circular dichroism spectroscopy. Furthermore, molecular docking analysis predicted the probable binding site of drugs in subdomain IIA of HSA molecule. The types of amino acid residues surrounding the drug molecule advocated that van der Waals forces, hydrophobic forces and electrostatic forces played a vital role in the stabilization of drug-protein complex formed.     

More stable structure of wheat germ lipase at low pH than its native state

Wheat germ lipase is a cereal lipase which is a monomeric protein. In the present study we sought to structurally characterize this protein along with equilibrium unfolding in solution. Conformational changes occurring in the protein with varying pH, were monitored by circular dichroism (CD) spectroscopy, fluorescence emission spectroscopy, binding of hydrophobic dye, 1-anilino 8-naphthalenesulfonic acid (ANS) and dynamic light scattering (DLS). Our study showed that acid denaturation of lipase lead to characterization of multiple monomeric intermediates. Native protein at pH 7.0 showed far-UV spectrum indicating mixed structure with both alpha and beta-type of characteristics. Activity of lipase was found to fall on either sides of pH 7.0–8.0. Acid-unfolded state was characterized at pH 4.0 with residual secondary structure, disrupted tertiary spectrum and red-shifted fluorescence spectrum with decreased intensity. Further decrease in pH lead to formation of secondary structure and acid-induced molten globule state was found to be stabilized at pH 1.4, with exposed tryptophan residues and hydrophobic patches. Notably, interesting finding of this study was characterization of acid-induced state at pH 0.8 with higher secondary structure content than native lipase, regain in tertiary spectrum and induction of compact conformation. Although enzymatically inactive, acid-induced state at pH 0.8 was found to be structurally more stable than native lipase, as shown by chemical and thermal denaturation profiles.     

Approximation of ground water quality for microbial and chemical contamination

Present study was designed to obtain estimation about ground water quality of Bhimber, Azad Jammu and Kashmir (AJK), Pakistan. A total of 12 water samples were collected from different localities of study area to analyze for various physicochemical and biological parameters i.e. namely temperature, pH, turbidity, color, odor, taste, electric conductivity (EC), total dissolved solids (TDS), total hardness (Calcium + Magnesium), chloride, arsenic, phosphate, lead, ammonium ion, nitrite, Fecal coliform and Escherichia coli. Results exposed that all ground water samples of study area were grossly contaminated with pathogenic microorganisms like E. coli and Fecal coliform except one water sample that was obtained from community filter plant Samahni Chowk site. Besides it, values of some physicochemical water quality determining parameters also deviated from recommended limits of World Health Organization (WHO). Chloride ion concentration was little below the prescribed limits in almost all water samples. It has been proven that consumption of un-safe drinking water is one of the major cause of prevalence of water borne diseases like diarrhea, gastroenteritis, typhoid fever and malaria etc. in study area. Community water supply and sanitation projects should be encouraged; government should provide filter plants in all regions of the country so that people could have easy approach to safe drinking water.     

Zur m?glichen Funktion und Konvergenz wippender K?rperbewegungen bei V?geln

Summary Many species of wagging birds — e.g. tail-wagging Common and Spotted Sandpiper (Actitis hypoleucos, A. macularia), some Wagtails (Motacillidae), Forktails (Enicuridae) or body-bobbing Dippers (Cinclidae) — inhabit fast-running streams and it appears that the behaviour is a convergent adaption to this habitat. Possible functions are discussed; the hypothesis is given that birds of fast-running streams benefit due to wagging as an optical intraspecific signal (e. g. in territorial or sexual behaviour). Owing to the unfavourable acoustical situation (noise of the running water) and the linear habitat, vocal signals are presumed to be generally less effective than optical signals. Predictions concerning the European species based on this hypothesis are in agreement with the available evidence in literature.     

Measurements of auto‐antibodies to α‐synuclein in the serum and cerebral spinal fluids of patients with Parkinson's disease

Biomarkers for α‐synuclein are needed for diagnosis and prognosis in Parkinson's disease (PD ). Endogenous auto‐antibodies to α‐synuclein could serve as biomarkers for underlying synucleinopathy, but previous assessments of auto‐antibodies have shown variability and inconsistent clinical correlations. We hypothesized that auto‐antibodies to α‐synuclein could be diagnostic for PD and explain its clinical heterogeneity. To test this hypothesis, we developed an enzyme‐linked immunosorbent assay for measuring α‐synuclein auto‐antibodies in human samples. We evaluated 69 serum samples (16 healthy controls (HC ) and 53 PD patients) and 145 CSF samples (52 HC and 93 PD patients) from our Institution. Both serum and CSF were available for 24 participants. Males had higher auto‐antibody levels than females in both fluids. CSF auto‐antibody levels were significantly higher in PD patients as compared with HC , whereas serum levels were not significantly different. CSF auto‐antibody levels did not associate with amyloid‐β_1–42, total tau, or phosphorylated tau. CSF auto‐antibody levels correlated with performance on the Montreal Cognitive Assessment, even when controlled for CSF amyloidβ_1–42. CSF hemoglobin levels, as a proxy for contamination of CSF by blood during lumbar puncture, did not influence these observations. Using recombinant α‐synuclein with N‐ and C‐terminal truncations, we found that CSF auto‐antibodies target amino acids 100 through 120 of α‐synuclein. We conclude that endogenous CSF auto‐antibodies are significantly higher in PD patients as compared with HC , suggesting that they could indicate the presence of underlying synucleinopathy. These auto‐antibodies associate with poor cognition, independently of CSF amyloidβ_1–42, and target a select C‐terminal region of α‐synuclein.

Read the Editorial Highlight for this article on page 433 .