Investigation of the Greek ancestry of populations from northern Pakistan

Three populations from northern Pakistan, the Burusho, Kalash, and Pathan, claim descent from soldiers left behind by Alexander the Great after his invasion of the Indo-Pak subcontinent. In order to investigate their genetic relationships, we analyzed nine Alu insertion polymorphisms and 113 autosomal microsatellites in the extant Pakistani and Greek populations. Principal component, phylogenetic, and structure analyses show that the Kalash are genetically distinct, and that the Burusho and Pathan populations are genetically close to each other and the Greek population. Admixture estimates suggest a small Greek contribution to the genetic pool of the Burusho and Pathan and demonstrate that these two northern Pakistani populations share a common Indo-European gene pool that probably predates Alexanders invasion. The genetically isolated Kalash population may represent the genetic pool of ancestral Eurasian populations of Central Asia or early Indo-European nomadic pastoral tribes that became sequestered in the valleys of the Hindu Kush Mountains.     

Immunohistochemical localization of orexin-B, orexin-1 receptor, ghrelin, GHS-R in the lacrimal gland of normal and diabetic rats

Orexin-B, ghrelin and their receptors play an important role in the regulation of feeding in mammals. The pattern of distribution of orexin-B, orexin-1-receptor (OX₁R), ghrelin and growth hormone secretagogue receptor (GHS-R) in the lacrimal gland of normal and diabetic rats has not been reported. Diabetes was induced by a single intraperitoneal injection of streptozotocin (STZ) at 60 mg kg⁻¹. Forty weeks after the induction of STZ-induced diabetes, normal, age-matched controls and diabetic rats were anesthetized with chloral hydrate (intraperitoneally) and their lacrimal glands removed and processed for immunofluorescence. Orexin-B was observed in the cells localized to the interacinar regions while OX₁R was discerned in the nerves innervating the wall of small blood vessels. Ghrelin was also present in a group of cells located in the periacinar regions of the lacrimal glands of normal and diabetic rats. In contrast, GHS-R was observed in the apical region of the ductal cells of the lacrimal glands of both normal and diabetic rats. The pattern of distribution of these orexigenic peptides and their receptors did not significantly change after the onset of diabetes. In conclusion, orexin-B, ghrelin and their receptors are present in the lacrimal glands of both normal and diabetic rats and may play a role in the regulation of lacrimal gland function.     

Effect of sigmaS on sigmaE-directed cell lysis in Escherichia coli early stationary phase

The sigmaE regulon has been shown to perform a novel function that causes dead-cell lysis specific to the early stationary phase in addition to its well-known role in the extracytoplasmic stress response in Escherichia coli. Here, the effect of sigmaS as a general stress-responsive sigma factor on sigmaE-directed cell lysis was investigated. The lysis phenomena were observed in both rpoS mutant and parental strains constitutively expressing active sigmaE, but the former lysis occurred at a relatively early stage compared to the latter. Based on these results and experiments with hydrogen peroxide, we propose that some stresses generate living but non-culturable cells, which are subject to sigmaE-directed cell lysis.     

Polyhydroxyalkanoates – what are the uses? Current challenges and perspectives

Over the past few decades, a considerable attention has been focused on the microbial polyhydroxyalkanoates (PHAs) owing to its multifaceted properties, i.e. biodegradability, biocompatibility, non-toxicity and thermo-plasticity. This article presents a critical review of the foregoing research, current trends and future perspectives on the value added applications of PHAs in the biomedical, environmental and industrial domains of life.     

Novel radio-chromic solution dosimeter for radiotherapy treatment planning

Nitro blue tetrazolium (NBT) solution dosimeters were prepared and investigated based on radiation-induced reduction of NBT²⁺. NBT solution dosimeters containing different concentrations of NBT dye from 1 to 5 mM were prepared in a solution of ethanol. The dosimeters were irradiated with 6 MV X-ray beam at doses up to 30 Gy. The dose sensitivity of NBT solution increases strongly with increase of concentrations of NBT dye. The dose response of NBT dosimeters increases remarkably by addition of various concentrations of sodium formate (0.5, 2.5 and 5 mM). It becomes more remarkable with increasing pH value of NBT-sodium formate dosimeters. The sensitivity of the solution increased fairly with increase of irradiation temperature, therefore, the response of the solutions has to be corrected under actual processing conditions. The stability of solution dosimeters after irradiation was very high up to 30 days.     

In silico characterization of a novel pathogenic deletion mutation identified in XPA gene in a Pakistani family with severe xeroderma pigmentosum

Background

Xeroderma Pigmentosum (XP) is a rare skin disorder characterized by skin hypersensitivity to sunlight and abnormal pigmentation. The aim of this study was to investigate the genetic cause of a severe XP phenotype in a consanguineous Pakistani family and in silico characterization of any identified disease-associated mutation.

Results

The XP complementation group was assigned by genotyping of family for known XP loci. Genotyping data mapped the family to complementation group A locus, involving XPA gene. Mutation analysis of the candidate XP gene by DNA sequencing revealed a novel deletion mutation (c.654del A) in exon 5 of XPA gene. The c.654del A, causes frameshift, which pre-maturely terminates protein and result into a truncated product of 222 amino acid (aa) residues instead of 273 (p.Lys218AsnfsX5). In silico tools were applied to study the likelihood of changes in structural motifs and thus interaction of mutated protein with binding partners. In silico analysis of mutant protein sequence, predicted to affect the aa residue which attains coiled coil structure. The coiled coil structure has an important role in key cellular interactions, especially with DNA damage-binding protein 2 (DDB2), which has important role in DDB-mediated nucleotide excision repair (NER) system.

Conclusions

Our findings support the fact of genetic and clinical heterogeneity in XP. The study also predicts the critical role of DDB2 binding region of XPA protein in NER pathway and opens an avenue for further research to study the functional role of the mutated protein domain.