MOLECULAR ANALYSIS OF THE CAMP- RESPONSE ELEMENT [CRE] ELEMENTS IN THE PROMOTER REGION AND EXON 1 OF THE SURVIVAL OF MOTOR NEURON 2 [SMN2] GENE IN MALAYSIAN SPINAL MUSCULAR ATROPHY PATIENTS; TO ELUCIDATE THEIR ROLE IN CIRCUMSCRIBING THE CLINICAL SEVERITY

Objective: In the Spinal muscular atrophy [SMA] genes [SMN1 and SMN2 genes]; the CRE-II elements at -400 bp in the promoter region of the SMN genes and CRE-I element at +108 bp in the exon 1 of the SMN genes, are reported to have a role in c-AMP induce expression of the SMN genes through its binding affinity to CREB-1. This study was designed to determine the role of CRE sites in the circumscribing the clinical severity of SMA. Methods: Direct sequencing was performed for the PCR products of the promoter regions of the SMA patients with homozygous deletion of SMN1, different copy number of SMN2 and NAIP non deletion. Results: No variation among the CRE-I and CRE-II sites was found in all the clinical types as compare to normal healthy control showing no role of CRE sites in circumscribing the clinical severity of SMA. Conclusion: There was no sequence variation found in the CRE binding sites in the three different clinical types of SMA reflecting no role of CRE binding sites in circumscribing the clinical severity of SMA

Biological production of hydrogen from glucose by natural anaerobic microflora

Palm oil mill effluent (POME) sludge, sludge compost from Malaysia and CREST compost from Philippines were collected for the study. The capability of these microflora to produce hydrogen was examined with 500 ml artificial wastewater containing 1% glucose, 0.2% yeast extract and 0.018% magnesium chloride hexahydrate under anaerobic fermentation in a batch culture. The microflora in POME sludge, sludge compost and CREST compost were found to produce significant amounts of hydrogen. The maximum production yield of hydrogen per decomposed glucose was 2.1 mol/mol-glucose at a conversion rate of 0.137 L/(L-medh) at 50°C obtained by sludge compost. All fermentations were carried out without pH control. It was also found that the addition of nitrogen source in the medium caused a change in hydrogen produced. There was no methane gas in the evolved gas

Free-standing graphene films embedded in epoxy resin with enhanced thermal properties

The poor thermal conductivity of polymer composites has long been a deterrent to their increased use in high-end aerospace or defence applications. This study describes a new approach for the incorporation of graphene in an epoxy resin, through the addition of graphene as free-standing film in the polymeric matrix. The electrical and thermal conductivity of composites embedding two different free-standing graphene films was compared to composites with embedded carbon nanotube buckypapers (CNT-BP). Considerably higher thermal conductivity values than those achieved with conventional dispersing methods of graphene or CNTs in epoxy resins were obtained. The characterisation was complemented with a study of the structure at the microscale by cross-sectional scanning electron microscopy (SEM) images and a thermogravimetric analysis (TGA). The films are preconditioned in order to incorporate them into the composites, and the complete manufacturing process proposed allows the production and processing of these materials in large batches. The high thermal conductivity obtained for the composites opens the way for their use in demanding thermal management applications, such as electronic enclosures or platforms facing critical temperature loads.European Defence Agency tender No 17.ESI.OP.066. Study on the Impact of Graphene on Defence Application

Molecular analysis of promoter region of the SMN2 gene in the patients of spinal musculatr atrophy.

Spinal muscular atrophy (SMA) is a neurodegenerative disorder caused by the absence of the full length SMN protein (FL-SMN) as a result of mutation or deletion of SMN1 gene. The isoform to this gene, SMN2 gene, with mutation in 1 base pair, encodes for 10% of FL-SMN protein and is reported to decrease the severity of the disease when there is an increase gene dosage. There are 3 clinical types of SMA; type I, type II and type III. Type I SMA is the most severe type and only a small amount of FL-SMN protein is present in these individuals. We postulated that the difference in the promoter region of SMN2 gene produces the different level of FL-SMN protein. To verify this hypothesis, the DNA samples of 69 SMA patients who were referred to the Human Genome Center, USM were extracted from their blood. The SMN1 deletion analysis was performed, followed by the SMN2 copy no. analysis and NAIP deletion analysis to remove any clinical bias as NAIP gene deletion and SMN2 copy number have been reported to be associated with SMA disease severity. Only 10 SMA patients from different clinical types (type I=2, type II=3, type III=5) with homozygous deletion of the SMN1 and 2 copies of the SMN2 and deletion in NAIP were finally recruited. Primers were designed for the amplification of the SMN2 promoter region. Bioinformatics analysis was performed to identify the crucial transcription factor binding sites within the reported ~4.6 kb promoter region. As the core promoter region is still unknown (unreported), we analyzed 15 ORFs and 24 nested ORFs with 15 TATA boxes reflecting the diverse functional integrity of this region. The promoter prediction and core promoter prediction was also performed. Based on the bioinformatics analysis and the designed primers, PCR amplification was done for different regions in the promoter and the PCR products were subjected to direct DNA sequencing. The results were analyzed by Vector NTI suite 9, ClustalX and Gene Doc softwares. The molecular analysis confirmed the absence of any mutation in the promoter region of the SMN2 gene between normal healthy individuals (total 2) and SMA patients. In 4 patients and 1 normal healthy individual the CA repeats were found to be increased which we think cause no effect in disease progression and severity. In conclusion, there was no mutation found in the promoter region of the SMN2 gene among the SMA patients of different clinical types and normal controls. Further analysis involving the cloning of the promoter regions with highest probability of involvement in expression of the SMN2 gene using luciferase assay is ongoing. The results will be useful for the subsequent phase of the study involving the transcription initiation of the SMN2 gene

GALLSTONES IN PATIENTS WITH INHERITED HEMOLYTIC DISEASES

The purpose is to provide an overview on the incidence of gallstone disease in patients with various types of inherited (chronic) hemolytic diseases at risk of cholelithiasis/choledocholithiasis with particular emphasis on its pathogenesis, genetic, risk factors and management. A detailed electronic literature search to determine the source of materials for this review article was done. The reported incidences of gallstones and choledocholithiasis vary according to the different types of inherited hemolytic diseases and the ethnicity of the studied populations. To date, no review article summarises the incidences of cholelithiasis in patients with various inherited haemolytic diseases was published. Regular ultrasound examination for the presence of gallstones recommended in patients with inherited haemolytic anaemias, particularly those with additional risk factors recommended. Further studies for evaluating the reasons for the higher incidence of cholelithiasis in thalassemia major and sickle cell anemia compared to hereditary spherocytosis; the effect of co inheritance of alpha thalassaemia on decreasing bilirubin level in patients with sickle cell disease and beta thalassaemia; the effect of the co inheritance of UGT1A1 and ABCG8 gene mutation on the incidence of gallstones in other blood diseases such as Hb-H disease, autoimmune haemolytic anaemias, congenital dyserythropoietic anaemia, hereditary elliptocytosis, Southeast Asian Ovalocytosis, glucose-6-phosphate and pyruvate kinase deficiency are recommended. Evaluation of the potential role of the solubility of the mutant proteins and haemoglobin subunit in the red blood cells as an additional mechanism for the development of gallstones in patients with inherited haemolytic anaemias recommended

Risk factors associated with typhoid fever in children aged 2-16 years in Karachi, Pakistan

We analysed the data from the control group in a typhoid vaccine trial in Karachi to assess the differences in individual-, household-and cluster-level characteristics for developing typhoid fever. The annual incidence of typhoid in children aged 2-16 years in the control arm of the vaccine trial was 151/100 000 population. After adjustment, the risk of typhoid was lower with increasing age [risk ratio (RR) 0.89, 95% confidence interval (CI) 0.83-0.95], was higher with an increase in population density (RR 1.13, 95% CI 1.05-1.21) and was lower in the households using a safe drinking-water source (RR 0.63, 95% CI 0.41-0.99). Typhoid fever affects younger children living in areas of high population density and lack of access to safe water in Pakistan. A combination of environmental and biological interventions is required to prevent the continued epidemiological and economic impact of typhoid fever in high-risk areas of Pakistan

Hot Property in New Zealand: Empirical Evidence of Housing Bubbles in the Metropolitan

Using recently developed statistical methods for testing and dating exhuberant behavior in asset prices we document evidence of episodic bubbles in the New Zealand property market over the past two decades. The results show clear evidence of a broad-based New Zealand housing bubble that began in 2003 and collapsed over mid 2007 to early 2008 with the onset of the worldwide recession and the financial crisis. New methods of analyzing market contagion are also developed and are used to examine spillovers from the Auckland property market to the other metropolitan centres. Evidence from the latest data reveals that the greater Auckland metropolitan area is currently experiencing a new property bubble that began in 2013. But there is no evidence yet of any contagion effect of this bubble on the other centres, in contrast to the earlier bubble over 2003-2008 for which there is evidence of transmission of the housing bubble from Auckland to the other centres. One of our primary conclusions is that the expensive nature of New Zealand real estate relative to potential earnings in rents is partly due to the sustained market exuberance that produced the broad based bubble in house prices during the last decade and that has continued through the most recent bubble experienced in the Auckland region since 2013

Pitching non-English language research: a dual-language application of the Pitching Research Framework

YesThe global language of scholarly research is English and so the obstacle of getting noticed is montainous when the article is not written in the English language. Indeed, despite rapid advances in technology, the “tyranny of language” creates a segmentation inhibiting scholarly research and innovation generally. Mass translation of non-English language articles is neither feasible nor desirable. Our paper proposes a strategy for remedying this segmentation – such that, the work of non-English language scholars become more discoverable. The core piece of this strategy is a “reverse-engineering” [RE] application of Faff’s (2015, 2017a) “pitching research” template. More specifically, we provide access to translated versions of the “cued” template across thirty-three different languages, and most notably for this journal, including the Romanian and French languages. Further, we showcase an illustrative dual language French-English example