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91.
This study aimed to assess the drinking water quality and human potential health risk in Peshawar, which is the most populous district of Khyber Pakhtunkhwa Province, Pakistan. Water was randomly collected throughout Peshawar District (urban = 45 samples and rural = 29 samples). These samples were analyzed for heavy metal (As, Cd, Co, Cu, Cr, Hg, Ni, Pb, and Zn) concentrations using the atomic absorption spectrometer (Perkin Elmer, AAS-PEA-700). Heavy metal concentrations in drinking water revealed the highest pollution index (PI) values—17.80, 11.92, 7.50, and 5.70 for the Pb, Cr, Cd, and Ni, respectively. The contaminations of Cd and Pb were significantly higher (p < .05) than their maximum allowable limits set by the World Health Organization. Heavy metal contaminations in drinking water were evaluated for health risk assessment: the chronic risk or hazard quotient (HQ) and cancer risk. Results revealed that HQ values were >1 for the Cd and Pb, suggesting that the exposed human beings could be at chronic risk. Therefore, serious measures such as drinking water treatments and contamination controlling policies are needed to avoid the hazardous effects of toxic heavy metals. 相似文献
92.
Determining the evolutionary potential of a gene 总被引:4,自引:0,他引:4
In addition to information for current functions, the sequence of a gene
includes potential information for the evolution of new functions. The
wild-type ebgA (evolved beta-galactosidase) gene of Escherichia coli
encodes a virtually inactive beta-galactosidase, but that gene has the
potential to evolve sufficient activity to replace the lacZ gene for growth
on the beta-galactoside sugars lactose and lactulose. Experimental
evidence, which has suggested that the evolutionary potential of Ebg enzyme
is limited o two specific amino acid replacements, is limited to examining
the consequences of single base- substitutions. Thirteen
beta-galactosidases homologous with the Ebg beta-galactosidase are widely
dispersed, being found in gram-negative and gram-positive eubacteria and in
a eukaryote. A comparison of Ebg beta-galactosidase with those 13
beta-galactosidases shows that Ebg is part of an ancient clade that
diverged from the paralogous lacZ beta- galactosidase over 2 billion years
ago. Ebg differs from other members of its clade at only 2 of the 15
active-site residues, and the two mutations required for full Ebg
beta-galactosidase activity bring Ebg into conformity with the other
members of its clade. We conclude that either these are the only acceptable
amino acids at those positions, or all of the single-base-substitution
replacements that must arise as intermediates on the way to other
acceptable amino acids are so deleterious that they constitute a deep
selective valley that has not been traversed in over 2 billion years. The
evolutionary potential of Ebg is thus limited to those two replacements.
相似文献
93.
We have investigated the effects of norepinephrine (NE) and acetylcholine (ACh) on prostaglandin (PGE2 and 6 keto-PGF1α) production by rabbit iris, measured by radioimmunoassay (RIA), and the type of phospholipase activated by NE in irides in which phosphatidylinositol (PI) was doubly prelabeled with [3H] myo-inositol and [1-14C] arachidonic acid (14C-AA), quantitated by radiometric and chromatographic methods. PGE2 output in 60 min (3.6 μg/g tissue) was 2.6 times greater than 6 keto-PGF1α. PG production is time-dependent and it is stimulated by NE and ACh in a dose-dependent manner. The Ne- and ACh-induced release of PGE2, measured by RIA, is mediated through α1-adrenergic and muscarinic cholinergic receptors, respectively, and it requeires Ca2+ for maximal stimulation. Studies on the mechanism of AA release PI in irides doubly prelabeled with 14C-AA and [3H] myo-inositol revelased the following: (a) Both Ne and ACh increased the breakdown of PI, and this was accompanied by a significant increase in the release of AA and consequently PGE2. The stimulatory effects of NE and ACh are mediated through α1-adrenergic and muscainic cholinergic receptors respectively. (b) The NE-induced formation of 3H-lyso PI and the NE-induced metabolism of 14C-1,2-diacyl-glycerol (DG) are time-dependent. Two pathways for AA release from PI are probably operaitve in the iris: (a) An indirect release by PI-specific phospholipase C which producers DG, followed by the actions of DG- and monoacylglycerol lipases on DG to release AA. (b) A direct release by phospholipase A2. Whether lyso PI is a product of the polypholipids such as prosphatidylcholine and phosphatidylethanolamine could also serve as a source for AA in PG synthesis. In conclusion, the data presented provide evidence that in the iris the neurotransmitter-stimulated release of PG and AA, from phosphoinositides, for PG synthesis is coupled to the activation of α1-adrenergic and muscarinic cholinergic receptors. 相似文献
94.
95.
Aquaporins (AQP) 1, 2, 3 and 4 belong to the aquaporin water channel family and play an important role in urine concentration by reabsorption of water from renal tubule fluid. Renal AQPs have not been reported in the yak (Bos grunniens), which resides in the Qinghai Tibetan Plateau. We investigated AQPs 1?4 expressions in the kidneys of Yak using immunohistochemical staining. AQP1 was expressed mainly in the basolateral and apical membranes of the proximal tubules and descending thin limb of the loop of Henle. AQP2 was detected in the apical plasma membranes of collecting ducts and distal convoluted tubules. AQP3 was located in the proximal tubule, distal tubule and collecting ducts. AQP4 was located in the collecting ducts, distal straight tubule, glomerular capillaries and peritubular capillaries. The expression pattern of AQPs 1?4 in kidney of yak was different from other species, which possibly is related to kidney function in a high altitude environment. 相似文献
96.
Molecular dynamics of synthetic leucine-serine ion channels in a phospholipid membrane 总被引:2,自引:0,他引:2
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Molecular dynamics calculations were carried out on models of two synthetic leucine-serine ion channels: a tetrameric bundle with sequence (LSLLLSL)(3)NH(2) and a hexameric bundle with sequence (LSSLLSL)(3)NH(2). Each protein bundle is inserted in a palmitoyloleoylphosphatidylcholine bilayer membrane and solvated by simple point charge water molecules inside the pore and at both mouths. Both systems appear to be stable in the absence of an electric field during the 4 ns of molecular dynamics simulation. The water motion in the narrow pore of the four-helix bundle is highly restricted and may provide suitable conditions for proton transfer via a water wire mechanism. In the wider hexameric pore, the water diffuses much more slowly than in bulk but is still mobile. This, along with the dimensions of the pore, supports the observation that this peptide is selective for monovalent cations. Reasonable agreement of predicted conductances with experimentally determined values lends support to the validity of the simulations. 相似文献
97.
Increased Concentrations of the Neurotoxin 3-Hydroxykynurenine in the Frontal Cortex of HIV-1-Positive Patients 总被引:5,自引:1,他引:4
Abstract: Human immunodeficiency virus (HIV)-1-associated dementia is a frequent consequence of HIV infection and is associated with neuronal deficits. Increased concentrations of the kynurenine pathway metabolites 3-hydroxykynurenine (3-HK) and quinolinic acid (QA) may contribute to this neuronal damage. We measured 3-HK concentrations and the activity of its catabolising enzyme, 3-hydroxykynureninase, in postmortem brain tissue from eight controls and 32 HIV-positive patients, including a group that exhibited dementia. 3-HK concentrations were significantly increased (over threefold) in the HIV-positive group when compared with controls. This increase was greater in those patients with dementia, but it was still apparent in the nondemented cases. 3-Hydroxykynureninase activity was significantly increased in the HIV-infected group compared with the control values. The effect was apparent in both nondementia and dementia cases, although the latter showed a slightly greater increase. The 3-HK content increase is thus unrelated to a reduction in activity of this enzyme and is likely to reflect an overall increase in the kynurenic metabolic pathway. Elevated levels of the neurotoxin 3-HK may contribute to the neuronal deficits underlying HIV-associated dementia. 相似文献
98.
Sardar E. Gasanov Indira H. Shrivastava Firuz S. Israilov Aleksandr A. Kim Kamila A. Rylova Boris Zhang Ruben K. Dagda 《PloS one》2015,10(6)
Cobra venom cytotoxins are basic three-fingered, amphipathic, non-enzymatic proteins that constitute a major fraction of cobra venom. While cytotoxins cause mitochondrial dysfunction in different cell types, the mechanisms by which cytotoxins bind to mitochondria remain unknown. We analyzed the abilities of CTI and CTII, S-type and P-type cytotoxins from Naja naja oxiana respectively, to associate with isolated mitochondrial fractions or with model membranes that simulate the mitochondrial lipid environment by using a myriad of biophysical techniques. Phosphorus-31 nuclear magnetic resonance (31P-NMR) spectroscopy data suggest that both cytotoxins bind to isolated mitochondrial fractions and promote the formation of aberrant non-bilayer structures. We then hypothesized that CTI and CTII bind to cardiolipin (CL) to disrupt mitochondrial membranes. Collectively, 31P-NMR, electron paramagnetic resonance (EPR), proton NMR (1H-NMR), deuterium NMR (2H-NMR) spectroscopy, differential scanning calorimetry, and erythrosine phosphorescence assays suggest that CTI and CTII bind to CL to generate non-bilayer structures and promote the permeabilization, dehydration and fusion of large unilamellar phosphatidylcholine (PC) liposomes enriched with CL. On the other hand, CTII but not CTI caused biophysical alterations of large unilamellar PC liposomes enriched with phosphatidylserine (PS). Mechanistically, single molecule docking simulations identified putative CL, PS and PC binding sites in CTI and CTII. While the predicted binding sites for PS and PC share a high number of interactive amino acid residues in CTI and CTII, the CL biding sites in CTII and CTI are more divergent as it contains additional interactive amino acid residues. Overall, our data suggest that cytotoxins physically associate with mitochondrial membranes by binding to CL to disrupt mitochondrial structural integrity. 相似文献
99.
100.