Pakistan Origin Research Articles

Role of HGF polymorphisms in the development of keratoconus in South Asian population

<b>Background</b>: Hepatocyte growth factor (HGF) has been previously reported to be causative of keratoconus (KC) in different populations.<br /> <b>Aims</b>: The current study was conducted to investigate the role of HGF single nucleotide polymorphisms (SNPs) in sporadic KC cases from South Asian population of Pakistani origin.<br /> <b>Methodology</b>: A total of 100 sporadic cases were screened KC associated reported polymorphisms in HGF (rs17501108 and rs3735520) using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.<br /> <b>Results</b>:<b> </b>No significant association of the HGF SNPs were observed in the sporadic cases of KC and possibility of involvement of another gene in the pathogenesis of KC exist.<b> </b><br /> <b>Conclusion: </b>Present study came with the findings that although globally an association exit between HGF and KC but genotyping data of Asian population of Pakistan origin does not show any association between HGF and pathogenesis of KC.

Analysis of Fuel Alternative Products Obtained by the Pyrolysis of Diverse Types of Plastic Materials Isolated from a Dumpsite Origin in Pakistan.

The current energy crisis and waste management problems have compelled people to find alternatives to conventional non-renewable fuels and utilize waste to recover energy. Pyrolysis of plastics, which make up a considerable portion of municipal and industrial waste, has emerged as a feasible resolution to both satisfy our energy needs and mitigate the issue of plastic waste. This study was therefore conducted to find a solution for plastic waste management problems, as well as to find an alternative to mitigate the current energy crisis. Pyrolysis of five of the most commonly used plastics, polyethylene terephthalate (PET), high- and low-density polyethylene (HDPE, LDPE), polypropylene (PP), and polystyrene (PS), was executed in a pyrolytic reactor designed utilizing a cylindrical shaped stainless steel container with pressure and temperature gauges and a condenser to cool down the hydrocarbons produced. The liquid products collected were highly flammable and their chemical properties revealed them as fuel alternatives. Among them, the highest yield of fuel conversion (82%) was observed for HDPE followed by PP, PS, LDPE, PS, and PET (61.8%, 58.0%, 50.0%, and 11.0%, respectively). The calorific values of the products, 46.2, 46.2, 45.9, 42.8 and 42.4 MJ/kg for LPDE, PP, HPDE, PS, and PET, respectively, were comparable to those of diesel and gasoline. Spectroscopic and chromatographic analysis proved the presence of alkanes and alkenes with carbon number ranges of C9-C15, C9-C24, C10-C21, C10-C28, and C9-C17 for PP, PET, HDPE, LDPE, and PS, respectively. If implemented, the study will prove to be beneficial and contribute to mitigating the major energy and environmental issues of developing countries, as well as enhance entrepreneurship opportunities by replicating the process at small-scale and industrial levels.

Identification of radiation processing of different plant foods of Pakistan origin using the rapid technique of Electron Spin Resonance (ESR) spectrometry

Electron Spin Resonance (ESR) spectrometry is a potential technique for detection of irradiated foods like plant foods, which contain cellulosic materials as well as low molecular weight sugars and like the meat and fish, which contain bones. This study is focused on identification of irradiated foods such as tree nuts (pine nuts and walnuts), beans and pulses (red grams, white beans, pinto beans and green peas), and food containing low molecular weight sugars (pan masala and dried dates). The food samples were obtained from Pakistan and exposed to different permissible doses of radiation using electron beam linear accelerator. The control and irradiated samples were kept at room temperature in the laboratory for the record of ESR spectra. For post-irradiation stabilities the food samples were analysed at different intervals of time (15, 90 and 300 days). The controlled samples in case of cellulosic foods showed ESR signal at g0 = 2.004 and irradiated samples were shown with triplet signal indicative of the presence of radiation-induced cellulose radicals. Similarly, in case of Pan Masala and dried dates, a straight signal at zero level was observed for un-irradiated samples and a complex ESR signal was appeared for irradiated samples. The observed radiation-induced signals were dose-dependent and showed an increasing trend with an increase in radiation dose. The comparison of intensities of ESR signals was also carried out along with the study of post-irradiation stabilities of the ESR signals and method proved to be valid for differentiation of controlled and irradiated samples of food.

Clinical and genetic characterization of patients segregating variants in KPTN, MINPP1, NGLY1, AP4B1, and SON underlying neurodevelopmental disorders: Genetic and phenotypic expansion.

Neurodevelopmental disorders (NDDs) are heterogeneous genetic conditions of the central nervous system (CNS). Primary phenotypes of NDDs include epilepsy, loss of developmental skills, abnormal movements, muscle weakness, ocular anomalies, hearing problems, and macro- or microcephaly. NDDs occur due to variants in genes encoding proteins involved in the structure and function of CNS, thus interrupting its normal physiological role. In the study presented here, four consanguineous families (A-D), with members showing neurodevelopmental symptoms, were recruited for clinical and genetic characterization of the phenotypes. Clinical examinations, including Seguin Form Board Test (SFBT), Vineland Social Maturity Scale (VSMS), brain Magnetic Resonance Imaging (MRI), Electroencephalogram (EEG), Electromyography (EMG), Nerve Conduction Velocity (NCV), and Magnetic Resonance Spectroscopy, were employed to characterize the disease phenotypes. Whole exome sequencing (WES) followed by Sanger sequencing was employed to search for the genetic basis of the neurological symptoms observed in four families (A-D). Two of these families (A, B) were of Saudi Arabian origin, and two others (C, D) were of Pakistan origin. Two homozygous missense (KPTN: NM_007059.4:c.301T>G: NP_008990.2; p.(Phe101Val) and MINPP1:NM_001178118.2:c.1202G>A: NP_001171588.1; p.(Arg401Gln)) variants in families A and B, respectively, and two homozygous nonsense (NGLY1:NM_018297.3:c.1534_1541dup: NP_060767.2; p.(Ser515LysfsTer51) and AP4B1:NM_001253852:c.1668G>A: NP_001240781.1; p.(Trp556X)) variants in families C and D, respectively, were identified. Interestingly, additional heterozygous nonsense variant in SON: NM_138927.2: c.5753_5756del: NP_620305.3; p.(Val1918GlufsTer87) and a homozygous variant in FLG (FLG: NM_002016.2:c.7339C>T: NP_002007.1; p.(Arg2447X) were detected in families A and D, respectively. Further, we determined the deleteriousness of each variant through computational approaches. The present study expands the phenotypic and genetic spectrum of NDD-associated genes (KPTN, MINPP1, NGLY1, and AP4B1). Moreover, additional nonsense variants (SON: c.5753_5756del and FLG: c.7339C>T) identified in two families segregating with the phenotype might explain the phenotypic variability and severity in our patients.

Optimization and characterization of alkaliphilic lipase from a novel Bacillus cereus NC7401 strain isolated from diesel fuel polluted soil.

Five Bacillus cereus strains including B. cereus AVP12, B. cereus NC7401, B. cereus BDBCO1, B. cereus JF70 and B. specie JL47 isolated from the diesel fuel polluted soil adhered to the roots of Tagetes minuta were screened for lipase production with phenol red agar method. B. cereus NC7401 strain successfully expressing and secreting lipase with maximal lipolytic activity was subjected to a submerged fermentation process with five different carbon (starch, glucose, maltose, fructose, and lactose) and five different nitrogen (tryptone, ammonium nitrate, peptone, urea, yeast extract) sources to produce lipase enzyme. Maximum enzyme activity was found with starch (30.6 UmL-1), maltose (40 UmL-1), and tryptone (38.6 UmL-1), and the lipases produced using these sources were named lipase A, B, and C respectively. The total protein content of 8.56, 8.86, and 2.75 μg mL-1 were obtained from B. cereus NC7401 cultured using starch, maltose, and tryptone respectively. Lipase was stable between temperature range 30-80°C and pH 5-10 whereas optimally active at 55°C and pH 8.0. The enzyme was relatively stable for 10 days at 4°C and its optimum reaction time with the substrate was 30 minutes. It was tolerant to 1.5% (v/v) methanol as an organic solvent, 1.5% (v/v) Triton X-100 as a media additive and 1.5% (w/v) Ni2+ as a metal ion. SDS, n-hexane, and Ag+ inhibited lipolytic activity. Oil stains were removed from cotton fabric which showed oil removal efficiency enhancement in the presence of a lipase. Fat hydrolysis of 20, 24, and 30% was achieved following 6 hours of incubation of the fat particles with lipase A, B, and C respectively at a concentration of 20 mg mL-1. To as best of our knowledge, this study on lipases extracted from bacteria of Azad Kashmir, Pakistan origin has never been reported before.

Widespread prevalence and molecular epidemiology of tet(X4) and mcr-1 harboring Escherichia coli isolated from chickens in Pakistan

The emergence and spread of plasmid-mediated tigecycline resistance gene tet(X4) and colistin resistance gene mcr-1 in Escherichia coli (E. coli) pose a potential threat to public health, due to the importance of colistin and tigecycline for treating serious clinical infections. However, the characterization of bacteria coharboring both genes was few reported. Here, we described the molecular epidemiology of tet(X4) and mcr-1 harboring E. coli strains of chicken origin in Pakistan, with methods including PCR, antimicrobial susceptibility testing, DNA transfer assays, plasmid replicon typing, whole-genome sequencing and bioinformatics analysis. The tet(X4) gene was identified in 36 isolates exhibiting high levels of tigecycline resistance (MICs, 16–128 mg/L). Worryingly, 24 of the 36 tet(X4)-bearing isolates were confirmed as colistin resistance, positive for plasmid-borne mcr-1. We observed the prevalence of tet(X4)-bearing IncFII plasmid with mcr-1-bearing IncI2 plasmid in 12 E. coli isolates, with a high co-transfer frequency except for one strain PK8233, in which tet(X4)- and mcr-1-bearing plasmids were non-transferable. Coexistence of tet(X4)-bearing IncFII plasmid with mcr-1-carrying multidrug-resistant (MDR) IncHI2 plasmid was also identified in 10 E. coli isolates, and a relatively low co-transfer frequency was obtained except PK8575, in which mcr-1 was non-transferable. The transferability of pPK8275-tetX in PK8275 and pPK8233-tetX in PK8233, that could transfer from E. coli J53 to C600 by conjugation, was interfered by certain factors in PK8275 and PK8233. This may provide new insights to prevent and control the spread of antibiotic resistance genes. Two strains were reported to co-carry tet(X4)-positive IncQ1 plasmid and mcr-1-positive IncI2 plasmid. Convergence of tet(X4) and mcr-1 genes in E. coli by conjugative or mobilizable plasmids may lead to potentially widespread transmission of such resistance genes, which may incur antibiotic-resistance crisis globally.

Evaluation of Antioxidant Prospective of Diospyros malabarica Methanolic Extract for Improving Oxidative Stability of Mustard Oil

Antioxidants are substances which inhibit auto-oxidation of oils and fats by donating an atom of hydrogen to free radicals produced in the initial stages of autooxidation. In the course of the past two decades, a lot of work is done on application of natural plants extracts as preservative in edible oils due to the drift towards reducing the use of synthetic food additives. The aim of this research project was to estimate antioxidant efficacy of pharmaceutical plant species of Pakistan origin famous as �Gaab tree� (Diospyros malabarica), in local language and its use as a stabilizing agent for mustard oil. To carry out this study, its fruit and leaves methanolic extracts were prepared and their antioxidant efficiencies were analyzed by means of various tests like: TPC, TFC, TAC. They were found to be enriched with potential antioxidants. For finding antioxidant potential, DPPH, ABTS, FRAP analysis and a-carotene bleaching tests were also carried out. Results indicated their oxidative potentials were similar to synthetic antioxidants, like: BHA and BHT. So these extracts can be used as natural stabilizers, like synthetic one, for minimizing the use of synthetic chemicals for food storage.

Impressions and Glimpses of the Socio-Economic History of Migrant Settlement in Glasgow

Accounts of the history of migrant and refugee settlement in Glasgow from mid nineteenth century onwards have been lacking in two aspects. Firstly, their arrival and settlement as well as their economic participation profile has not been placed in the context of the socio-economic evolution of the city. Secondly, a broader overview of the history of the arrival of a range of diverse migrant and settlement groups, their integration against a changing economic backdrop as well as ecological factors they encountered, and the implications of these for community relations, has not been constructed. In addition, there appears to have been little attempt to focus on this period with a view to identify if there are any patterns of community economic identities which evolved based on enterprise development as well as the challenges the entrepreneurial or commercial sections of the community may have faced. In this first of the two-part series of working papers we explore mainly the experience and challenges of the invisible minority’s settlement patterns in these respects and attempt to develop an impressionistic socio-economic picture. We attempt to do the same for the post World War II Asian (mostly Panjabi’s of Indian and Pakistan origin) communities’ arrival and settlement in a subsequent working paper to be published soon.

Draft genome sequence of an extended-spectrum β-lactamase-producing Escherichia coli ST58 isolate from cattle in Pakistan

ObjectivesFood animals have been recognised as an important reservoir of extended-spectrum β-lactamase-producing Escherichia coli (ESBL-Ec). This study reports the draft genome sequence of a bovine ESBL-Ec from Pakistan. MethodsGenomic DNA from a bovine E. coli (PK-1421) was extracted and whole-genome sequencing was performed using an Illumina HiSeq 2500 platform. De novo genome assembly was performed using SPAdes v.3.9 and annotation of the assembled genome was performed using the DDBJ Fast Annotation and Submission Tool (DFAST). In silico tools from the Center for Genomic Epidemiology were used to find out for analysis of antimicrobial resistance genes, sequence type (ST), plasmid replicon type, serotype and phylogenetics. ResultsEscherichia coli strain PK-1421 showed multiple drug resistance. The draft genome was calculated at 4 869 610 bp, comprising a total of 131 contigs with a G + C content of 50.6% and 4487 protein-coding sequences. Escherichia coli PK-1412 belongs to ST58 and serotype O75:H9. A large number of antimicrobial resistance genes associated with resistance to β-lactams (blaCTX-M-15, blaTEM-1B), trimethoprim (dfrA14), aminoglycosides [aph(3ʹ)-lb, aph(6)-ld], sulfonamides (sul2), tetracycline (tetA), macrolides (mdfA) and quinolones (qnrS1) were detected. A conjugation experiment showed successful transfer of the blaCTX-M-15 gene to an E. coli J53 recipient strain. The phylogenetic tree indicated that ST58 E. coli PK-1421 was distant from other strains. ConclusionThis is the first draft genome of an E. coli of bovine origin in Pakistan. The genome sequence presented here may be helpful to understand the genomic diversity and antimicrobial resistance potential of E. coli from large ruminants.

The Phytochemical and Comparative Anticancer Study of Methanolic and Chloroform Extracts of Psidium guajava L. Leaves of Pakistani Origin

The chief focus of our study is to evaluate the phytochemical and anti-cancer activity of methanol (PGM) and chloroform extracts (PGC) of the leaves of Psidium guajava (guava) collected from local area of district Sialkot, Pakistan. Shade dried milled leaves was subjected to extraction (maceration) with methanol and chloroform. Quantitative and qualitative screenings by GC-MS and phytochemical techniques were performed. Then different secondary metabolites and phytochemical compounds were identified which are typically associated with the existence of therapeutic characteristics. Psidium guajava has been extensively used as herbal remedies like, anti-diarrheal, antihypertensive, antibacterial, antifungal as well as to control obesity, ulcer, diabetes. In this study, both extracts of P. guajava were evaluated for their anticancer activities against HeLa cell-lines (cancerous cells). The healthiest anticancer response in the form of cell-line suppression was perceived with 200µg/mL of both extracts, PGM showed 81% and PGC exhibited 91% while the standard drug doxorubicin presented around 76% inhibition. The comparative better result was seen with chloroform extract than methanolic abstract. In conclusion, the chloroform and methanol extracts of our nominated plant from Pakistan origin has a good source of phytochemicals that revealed an outstanding anti-cancer potential.
 Keywords: Psidium guajava, anticancer, phytochemicals, methanol extracts, secondary metabolites.

Phylovenomics of Daboia russelii across the Indian subcontinent. Bioactivities and comparative in vivo neutralization and in vitro third-generation antivenomics of antivenoms against venoms from India, Bangladesh and Sri Lanka

Russell's viper (Daboia russelii) is, together with Naja naja, Bungarus caeruleus and Echis carinatus, a member of the medically important ‘Big Four’ species responsible for causing a large number of morbidity and mortality cases across the Indian subcontinent. Despite the wide distribution of Russell's viper and the well-documented ubiquity of the phenomenon of geographic variability of intraspecific snake venom composition, Indian polyvalent antivenoms against the “Big Four” venoms are raised against venoms sourced mainly from Chennai in the southeastern Indian state of Tamil Nadu. Biochemical and venomics investigations have consistently revealed notable compositional, functional, and immunological differences among geographic variants of Russell's viper venoms across the Indian subcontinent. However, these studies, carried out by different laboratories using different protocols and involving venoms from a single geographical region, make the comparison of the different venoms difficult. To bridge this gap, we have conducted bioactivities and proteomic analyses of D. russelii venoms from the three corners of the Indian subcontinent, Pakistan, Bangladesh, and Tamil Nandu (India) and Sri Lanka, along with comparative in vivo neutralization and in vitro third-generation antivenomics of antivenoms used in India, Bangladesh and Sri Lanka. These analyses let us to propose two alternative routes of radiation for Russell's viper in the Indian subcontinent. Both radiations, towards the northeast of India and Bangladesh and towards south India and Sri Lanka, have a common origin in Pakistan, and provide a phylovenomics ground for rationalizing the geographic variability in venom composition and their distinct immunoreactivity against available antivenoms. Biological significanceRussell's viper (Daboia russelii), the Indian cobra (Naja naja), the common krait (Bungarus caeruleus), and the saw-scaled viper (Echis carinatus) constitute the ‘Big Four’ snake species responsible for most snakebite envenomings and deaths in the Indian subcontinent. Despite the medical relevance of Daboia russelii, and the well documented variations in the clinical manifestations of envenomings by this wide distributed species, which are doubtless functionally related to differences in venom composition of its geographic variants, antivenoms for the clinical treatment of envenomings by D. russelii across the Indian subcontinent are invariably raised using venom sourced mainly from the southeastern Indian state of Tamil Nadu. We have applied a phylovenomics approach to compare the venom proteomes of Russell's vipers from the three corners of the Indian subcontinent, Pakistan, Bangladesh, and South India/Sri Lanka, and have assessed the in vitro (third-generation antivenomics) and in vivo preclinical efficacy of a panel of homologous antivenoms. The identification of two dispersal routes of ancestral D. russelii into the Indian subcontinent provides the ground for rationalizing the variability in composition and immunoreactivity of the venoms of extant geographic variants of Russell's viper. Such knowledge is relevant for envisioning strategies to improve the clinical coverage of anti- D. russelii antivenoms.

Building Usage Attitude for Mobile Shopping Applications: an Emerging Market Perspective

Mobile commerce has gained pace in recent years, providingan extended interaction channel between consumers and online retailers. Regardless of a significant increase in mobile internet usage, the adoption of mobile e-commerce (MC) services has not been as far-reached in the growing economies of the world. Recently, research in the e-commerce applied Technology Acceptance Model (TAM) indicated contradicting results.Some research studies found perceived usefulness has a significant effect on online purchase attitude, whereas in another study it was insignificant. We understand this, among many other factors, to be a consequence of the different levels of internet usage and its penetration in the region. We performed this study in Pakistan origin, a growing economy, where internet usage has significantly increased in the last decade or so. The e-commerce industry reviews pointed out that low consumer trust and poor logistics might be the key constraints in B2C mobile e-commerce adoption in Pakistan. Based on these grounds we adapted TAM by including consumer trust belief in mobile e-commerce and excluding perceived ease of use, as many research studies reported it insignificant for online shopping context. The proposition developed that trust in online shopping has an impact on improved perceptions about the usefulness of this interaction channel between online buyers and sellers. This positive usage attitude facilitates favorable online purchase intentions. The research conducted based on empirical evidence from Pakistan, and the model was developed on the bases of TAM, consumer trust in MC, and perceived usefulness and trust in mobile e-commerce. An online questionnaire survey was distributed to gather responses. Data analysis was performed with the partial least square technique or structured equation modeling. The research findings show that belief in trustworthiness of e-commerce has a more significant impact on usage attitude for mobile e-commerce as compared to PU. This implicates that online retailers in Pakistan should focus more on developing trust of their prospects by providing trust cues and other trust-building mechanisms. The research model empirically studied on evidence from Pakistan was first of its kind . In the future, the research can be conducted on specific categories of items (such as apparel fashion, technology base products) or services (such as traveling, hotels) developing effective strategies for retailers in B2C mobile e-commerce.

Investigation of transmigrated mandibular canines.

ABSTRACTIntroduction: Canine transmigration is a rare orthodontic condition and it is relevant to perform the proper diagnose at an early age. Objective: The aim of the current study was to find out the frequency of transmigrated mandibular canines (TRC) in orthodontic patients obtained from South Asian population of Pakistan origin. Methods: Panoramic radiographs of 2,550 untreated orthodontic patients (1,248 males; 1,302 females) were included, to investigate the presence, site, and type of TRC. Any permanent mandibular canine that was found to be crossing the midline in panoramic radiographs was considered as TRC. Results: The frequency of TRC was found to be 0.98%. TRC were only found unilaterally. No significance regarding gender and side was found. Nineteen TRC displayed a type 1 transmigratory pattern, while type 2 and type 5 transmigratory patterns were encountered in three patients.Conclusion: Frequency of transmigrated mandibular canines in the studied sample was 0.98%.

Primary hyperoxaluria in populations of Pakistan origin: results from a literature review and two major registries.

Primary hyperoxalurias (PH) are devastating, autosomal recessive diseases causing renal stones. Undifferentiated hyperoxaluria is seen in up to 43% of Pakistani paediatric stone patients. High rates of consanguinity in Pakistan suggest significant local prevalence. There is no detailed information regarding number of cases, clinical features, and genetics in Pakistan-origin (P-o) patients. We reviewed available information on P-o PH patients recorded in the literature as well as from two major PH registries (the Rare Kidney Stone Consortium PH Registry (RKSCPHR) and the OxalEurope PH Registry (OxER); and the Aga Khan University Hospital in Pakistan. After excluding overlaps, we noted 217 P-o PH subjects (42 in OxER and 4 in RKSCPHR). Presentations were protean. Details of mutations were available for 94 patients of 201 who had genetic analyses. Unique mutations were noted. Mutation [c.508G>A (p. Gly170Arg)] (present in up to 25% in the West) was reported in only one case. In one series, only 30% had mutations on exons 1,4,7 of AGXT. Of 42 P-o patients in OxER, 52.4% were PH1, 45.2% PH2, and 2.4% PH3. Of concern is that diagnosis was made after renal transplant rejection (four cases) and on bone-marrow aspiration (in five). Lack of consideration of PH as a diagnosis, late diagnosis, and loss of transplanted kidneys mandates that PH be searched for diligently. Mutation analysis will need to extend to all exons and include PH 1,2,3. There is a need to spread awareness and identify patients through a scoring or screening system that alerts physicians to consider a diagnosis of PH.

Long Range Transport and Wet Deposition Fluxes of Major Chemical Species in Snow at Gulmarg in North Western Himalayas (India)

ABSTRACTThe study reports snow chemistry and long range transport of pollutants at Gulmarg in north-western Himalayan region of India during winters of 2012–2013. The pH of snowmelt varied between 5.16 and 7.68 with an average of 5.90. The frequency distribution of pH of snowmelt showed that the maximum number of samples (31%) had pH between 6.81 and 7.20. However, 12% samples were observed to be acidic (below 5.6). Scavenging ratios (SR) values suggested that crustal components (Ca2+, Mg2+) are efficiently removed by snow. The study site has significant influence of non-marine sources. Wet deposition contributed 34, 27, 45, 71, 8 and 13 meq m–2 fluxes of nssSO42–, NO3–, NH4+, nssCa2+, nssMg2+ and nssK+ respectively. Both local emissions as well as long range transport (LRT) of pollutants were found to be the sources of these ionic species. Backward airmass trajectory calculations showed that this site received airmasses from six major sectors i.e., i) North Atlantic Ocean origin (NAO), ii) African origin (Af), iii) Middle East origin (ME), iv) European origin (Eu), v) Western India origin (InW), vi) Pakistan origin (Pk). The highest average pH (7.58) of the snowfall was noticed during InW airmasses which had the lowest ratios of nssSO42–/nssCa2+ and NO3–/nssCa2+. Very high pH has been observed in precipitation samples at Indian sites due to buffering of acidic components by atmospheric dust rich in CaCO3. The lowest pH (4.94) was noticed for ME airmasses which had the highest nssSO42–/nssCa2+ and NO3–/nssCa2+ ratios. Data of present study was compared with a study reported almost three decades ago. We noticed a drastic increase in the concentrations of anthropogenic components such as nssSO42– (114%), NO3– (109%) and NH4+ (90%). This is probably due to increase in LRT of pollutants as well as local activities during past three decades.

Novel Mutation in the AAAS Gene in a Severely Affected Triple-A Syndrome Patient

Triple-A syndrome known as Allgroves syndrome classically present with: achalasia, alacrimia and adrenal insufficiency. Ataxia and autonomic dysfunction is additionally described in many cases. We present a case report of a young man of Pakistan origin with achalasia, alacrimia, adrenal insufficiency, ataxia and autonomic dysfunction. Genetic screening identified a novel mutation in the AAAS gene resulting in a homozygous point-mutation

Two new triterpenes from Alstonia scholaris flowers

In the context of our previous communication on phytochemical studies of the ethanolic extract of flowers of Alstonia scholaris of Pakistan origin, these have resulted in the isolation of two new triterpenoids. One is of the oleanane type, alstoprenyol, 3-β-hydroxy-28-β-acetoxy-5-olea triterpene (1), the other is of ursane type, alstoprenylene 3β-acetate-24-nor-urs-4,12,2′-triene ester triterpene (2) and together with four known triterpenes, α-amyrin acetate (3), α-amyrin (4), lupeol acetate (5) and 3β-hydroxy-24-nor-urs-4,12,28-triene triterpene (6) were isolated. The structures of 1–6 were elucidated with the aid of extensive NMR spectroscopic studies.

Promiscuous prediction and conservancy analysis of CTL binding epitopes of HCV 3a viral proteome from Punjab Pakistan: an In Silico Approach

BackgroundHCV is a positive sense RNA virus affecting approximately 180 million people world wide and about 10 million Pakistani populations. HCV genotype 3a is the major cause of infection in Pakistani population. One of the major problems of HCV infection especially in the developing countries that limits the limits the antiviral therapy is the long term treatment, high dosage and side effects. Studies of antigenic epitopes of viral sequences of a specific origin can provide an effective way to overcome the mutation rate and to determine the promiscuous binders to be used for epitope based subunit vaccine design. An in silico approach was applied for the analysis of entire HCV proteome of Pakistani origin, aimed to identify the viral epitopes and their conservancy in HCV genotypes 1, 2 and 3 of diverse origin.ResultsImmunoinformatic tools were applied for the predictive analysis of HCV 3a antigenic epitopes of Pakistani origin. All the predicted epitopes were then subjected for their conservancy analysis in HCV genotypes 1, 2 and 3 of diverse origin (worldwide). Using freely available web servers, 150 MHC II epitopes were predicted as promiscuous binders against 51 subjected alleles. E2 protein represented the 20% of all the predicted MHC II epitopes. 75.33% of the predicted MHC II epitopes were (77-100%) conserve in genotype 3; 47.33% and 40.66% in genotype 1 and 2 respectively. 69 MHC I epitopes were predicted as promiscuous binders against 47 subjected alleles. NS4b represented 26% of all the MHC I predicted epitopes. Significantly higher epitope conservancy was represented by genotype 3 i.e. 78.26% and 21.05% for genotype 1 and 2.ConclusionsThe study revealed comprehensive catalogue of potential HCV derived CTL epitopes from viral proteome of Pakistan origin. A considerable number of predicted epitopes were found to be conserved in different HCV genotype. However, the number of conserved epitopes in HCV genotype 3 was significantly higher in contrast to its conservancy in HCV genotype 1 and 2. Despite of the lower conservancy in genotype 1 and 2, all the predicted epitopes have important implications in diagnostics as well as CTL-based rational vaccine design, effective for most population of the world and especially the Pakistani Population.

Phytochemical Studies on Alstonia scholaris

Reinvestigation of the flowers of Alstonia scholaris of Pakistan origin have resulted in the isolation of three new triterpenoids, two of the ursane type, 3β -acetate-24-nor-urs-4,12-diene ester triterpene (1) and 3β -hydroxy-24-nor-urs-4,12,28-triene triterpene (2), and one of the oleanane type, 3,28-β - diacetoxy-5-olea-triterpene (3), together with two known triterpenes,α-amyrin acetate (4) and ursolic acid (5). This is the first report of the isolation of 4 and 5 from the flower part of this species. The structures of 1 - 5 were elucidated with the aid of extensive NMR-spectroscopic studies.

Runs in the Outfield: The Pakistani Diaspora and Cricket in England

In an age of heightened global flows and disjunctures the transnational appeal of the idea of Pakistan has grown. The socio-political context of diaspora marginalization in England, along with stronger transnational linkages between migrants and their regions of origin in Pakistan, has led to the development of other Pakistani identities that subvert the authoritarian political discourse of officialdom in Islamabad. This article will analyse the emergence of disparate British-Pakistani cricket cultures and their relevance to discussions on Pakistani national consciousness and identity. It will be argued that these discourses from diaspora communities in England provide crucial insights into the construction of political and cultural identities. Their disposition to be pluralistic, heterogeneous and composed of numerous cultural and political influences reflects the reality of historical human interchange. As such, they are rebuttals of simplistic modernist constructions of identity, particularly of the type emanating from the discourses of authoritarian political leaders like those in Pakistan.