The SWI/SNF complex acts to constrain distribution of the centromeric histone variant Cse4

In order to gain insight into the function of the Saccharomyces cerevisiae SWI/SNF complex, we have identified DNA sequences to which it is bound genomewide. One surprising observation is that the complex is enriched at the centromeres of each chromosome. Deletion of the gene encoding the Snf2 subunit of the complex was found to cause partial redistribution of the centromeric histone variant Cse4 to sites on chromosome arms. Cultures of snf2Δ yeast were found to progress through mitosis slowly. This was dependent on the mitotic checkpoint protein Mad2. In the absence of Mad2, defects in chromosome segregation were observed. In the absence of Snf2, chromatin organisation at centromeres is less distinct. In particular, hypersensitive sites flanking the Cse4 containing nucleosomes are less pronounced. Furthermore, SWI/SNF complex was found to be especially effective in the dissociation of Cse4 containing chromatin in vitro. This suggests a role for Snf2 in the maintenance of point centromeres involving the removal of Cse4 from ectopic sites.     

Interaction Between Selenium and Mercury in Biological Samples of Pakistani Myocardial Infarction Patients at Different Stages as Related to Controls

It has been speculated that trace elements may a play role in the pathogenesis of heart diseases. In the present study, we aimed to assess the levels of selenium (Se) and mercury (Hg) in biological samples (whole blood, urine, and scalp hair) of myocardial infarction (MI) patients of both genders (age range 45–60 years) at the first, second, and third heart attack (n?=?130), hospitalized in a cardiac ward of a civil hospital of Hyderabad City (Pakistan). For comparison, healthy age-matched referent subjects (n?=?61) of both genders were also selected. Se and Hg in biological samples were measured by electrothermal atomic absorption spectrometry and cold vapor atomic absorption spectrometry, prior to microwave acid digestion, respectively. The validity of the methodology was checked by biological certified reference materials. During this study, 78 % of the 32 registered patients of third MI attack (aged >50 years) died. The concentration of Se was decreased in scalp hair and blood samples of MI patients, while Hg was higher in all biological samples as compared to referent subjects. Se concentration was inversely associated with the risk of MI attacks in both genders. These results add to an increasing body of evidence that Se is a protective element for cardiovascular health.     

Role of Bacillus licheniformis in Phytoremediation of Nickel Contaminated Soil Cultivated with Rice

Heavy metal contamination in soil is an important environmental problem and it has negative effect on agriculture. Bacteria play a major role in phytoremediation of heavy metals contaminated soil. In this study, the effect of Bacillus licheniformis NCCP-59, a halophilic bacterium isolated from salt mines near Karak, Pakistan, were determined on a three week old greenhouse grown seedling and germinating seeds of two rice varieties (Basmati-385 (B-385) and KSK-282) in soil contaminated with different concentrations (0, 100, 250, 500, and 1000 ppm) of Nickel. Nickel significantly reduced the germination rate and germination percentage mainly at 500 and 1000 ppm. Significant decrease in ion contents (Na, K, and Ca) was observed while Ni ion concentration in the plant tissues increases as the concentration of Ni applied increases. The photosynthetic pigments (chlorophyll a (chl a), chlorophyll b (chl b), and carotenoids) were also decreased by the application of different concentrations of Ni. Total protein and organic nitrogen were found to be reduced at higher concentrations of Nickel. Inoculation of Bacillus Licheniformis NCCP-59 improved seed germination and biochemical attribute of the plant under Ni stress. It is clear from the results that the Bacillus Licheniformis NCCP-59 strain has the ability to protect the plants from the toxic effects of nickel and can be used for the phytoremediation of Ni contaminated soil.     

Biocatalysts: Beautiful creatures

The chemical industry has come under increasing pressure to make chemical production more eco-friendly and independent to fossil resources. The development of industrial processes based on micro-organisms can especially help to eliminate the use or the generation of hazardous substances and can support the transition from dependence on fossil resources towards real sustainable and eco-safety industrial processes. The biocatalysts are the best solution given by nature that can be used to improve some biotechnological applications. In this research review, we report some peculiar properties of biocatalysts, implicated in a range of metabolic pathways and biotechnological tools.     

Recessive Mutations in COL25A1 Are a Cause of Congenital Cranial Dysinnervation Disorder

Abnormal ocular motility is a common clinical feature in congenital cranial dysinnervation disorder (CCDD). To date, eight genes related to neuronal development have been associated with different CCDD phenotypes. By using linkage analysis, candidate gene screening, and exome sequencing, we identified three mutations in collagen, type XXV, alpha 1 (COL25A1) in individuals with autosomal-recessive inheritance of CCDD ophthalmic phenotypes. These mutations affected either stability or levels of the protein. We further detected altered levels of sAPP (neuronal protein involved in axon guidance and synaptogenesis) and TUBB3 (encoded by TUBB3, which is mutated in CFEOM3) as a result of null mutations in COL25A1. Our data suggest that lack of COL25A1 might interfere with molecular pathways involved in oculomotor neuron development, leading to CCDD phenotypes.     

Pollutant fate and spatio-temporal variation and degree of sedimentation of industrial- and municipal wastes in Chakbandi drain and River Chenab

This study’s objective was to assess a seasonal impact of industrial and sewage waste disposal on water quality of the river upstream Trimu Head. Considering the significance of the river, drain wastewater was analyzed during the summer and the winter seasons from pre-determined locations. Water quality parameters were recorded higher than the maximum permissible limits prescribed by WHO for freshwater bodies. Level of these Physio-chemical variables was higher in the winter due to the least amount of water from domestic sewage. Although some of these parameters indicated sedimentation hitherto the water quality of River Chenab was found very poor due to the pollution bestowed by tributary waste water from drains. Findings of this investigation suggest the importance of continuous monitoring and assessment to improve the water quality of the river. This study provides a baseline data which may be compared to assess any further deterioration in the water quality and may also be used to plan future monitoring and required restoration of habitat for the safe supply of fish to the population of this region.     

Fish eco-genotoxicology: Comet and micronucleus assay in fish erythrocytes as in situ biomarker of freshwater pollution

Owing to white meat production Labeo rohita have vast economic importance, but its population has been reduced drastically in River Chenab due to pollution. Atomic absorption spectrophotometry showed a merciless toxicity level of Cd, Cu, Mn, Zn, Pb, Cr, Sn and Hg. Comet assay results indicated significant (p?<?.05) DNA fragmentation in Labeo rohita as 42.21?±?2.06%, 31.26?±?2.41% and 21.84?±?2.21% DNA in comet tail, tail moment as 17.71?±?1.79, 10.30?±?1.78 and 7.81?±?1.56, olive moment as 13.58?±?1.306, 8.10?±?1.04 and 5.88?±?0.06, respectively, from three different polluted sites on the river. Micronucleus assay showed similar findings of single micronucleus induction (MN) as 50.00?±?6.30‰, double MN 14.40?±?2.56‰, while nuclear abnormalities (NA) were found as 150.00?±?2.92‰. These higher frequencies of MN induction and NA were found to be the cause of reduction of 96% of the population of this fish species in an experimental area of the River Chenab. This fish species has been found near extinction through the length of the river Chenab and few specimens in rainy seasons if restored by flood, may die in sugarcane mill season. Due to sweeping extinction Labeo rohita showed the highest sensitivity for pollution and could be used as bioindicator and DNA fragmentation in this column feeder fish species as a biomarker of the pollution load in freshwater bodies.     

Dynamics of fluoroquinolones induced resistance in DNA gyrase of Mycobacterium tuberculosis

DNA gyrase is a validated target of fluoroquinolones which are key components of multidrug resistance tuberculosis (TB) treatment. Most frequent occurring mutations associated with high level of resistance to fluoroquinolone in clinical isolates of TB patients are A90V, D94G, and A90V–D94G (double mutant [DM]), present in the larger subunit of DNA Gyrase. In order to explicate the molecular mechanism of drug resistance corresponding to these mutations, molecular dynamics (MD) and mechanics approach was applied. Structure-based molecular docking of complex comprised of DNA bound with Gyrase A (large subunit) and Gyrase C (small subunit) with moxifloxacin (MFX) revealed high binding affinity to wild type with considerably high Glide XP docking score of ?7.88 kcal/mol. MFX affinity decreases toward single mutants and was minimum toward the DM with a docking score of ?3.82 kcal/mol. Docking studies were also performed against 8-Methyl-moxifloxacin which exhibited higher binding affinity against wild and mutants DNA gyrase when compared to MFX. Molecular Mechanics/Generalized Born Surface Area method predicted the binding free energy of the wild, A90V, D94G, and DM complexes to be ?55.81, ?25.87, ?20.45, and ?12.29 kcal/mol, respectively. These complexes were further subjected to 30 ns long MD simulations to examine significant interactions and conformational flexibilities in terms of root mean square deviation, root mean square fluctuation, and strength of hydrogen bond formed. This comparative drug interaction analysis provides systematic insights into the mechanism behind drug resistance and also paves way toward identifying potent lead compounds that could combat drug resistance of DNA gyrase due to mutations.