The p53Pro72Arg Polymorphism is Associated with Albuminuria among Aboriginal Australians

Albuminuria is a widely recognized marker of renal disease and cardiovascular risk. This is especially true in Aboriginal Australians living in remote communities who suffer high rates of end-stage renal disease and cardiovascular mortality. During a survey of risk factors for renal and cardiovascular disease in one such community, an association between a common polymorphism at codon 72 (Arg/Pro) of the p53 gene and markers of renal disease was sought. A cross-sectional community survey including 217 people was performed. Genotypes of the polymorphism were distributed in Hardy-Weinberg equilibrium, with p53Arg allele frequency of 0.45 (range, 0.41 to 0.50). Overall prevalence of albuminuria was high (31% microalbuminuria; 14% overt albuminuria). Urine albumin/creatinine ratio (ACR) was significantly associated with the number of p53Pro alleles (P = 0.01), and there was an interaction with tobacco smoking (P = 0.04). The p53 genotype was also associated with increasing HbA1c, but the relationship between p53 and ACR was independent of this. This is a previously unreported association. This study does not address the mechanism, but this finding, if confirmed, expands the described effects of p53 in cellular proliferation and apoptosis to include a role in the course of renal and possibly cardiovascular disease in this population

Pembuatan Briket Arang Daun Kelapa Sawit (Elaeis Guineensis Jacq.) Dengan Perekat Pati Sagu (Metroxylon Sago Rott.)

Increasing need of energy and decreasing of fuel supply requires human to discover alternative energy resources. Consequently, there should be a research to discover a new renewable energy source such as palm leaves waste. Oil palm\u27s leaves (Elaeis guineensis Jacq.) are mostly the least used waste from oil palm plantation as an alternative energy resources. This research aims to discover the precise adhesive consentration rate in sago\u27s starch (Metroxylon sago Rott.) to make oil palm\u27s kernel, which are 97%:3%, 96%:4%, 95%:5%, 94%:6%, and 93%:7%. Based on analitycal result of oil palm\u27s leaves charcoal briquet research, the best quality briquet is the P1 composition which composed rate is 97%:3%, has 3,21% water content, 30,18% ashes content, 0,0022 g/s combustion rate, 20,73% evaporated substance rate, 54,46% carbon rate, and 5.114 cal/g heat value

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Abstract Background: Elevated total homocysteine (tHcy) levels are associated with an increased risk of cerebrovascular disease. It is uncertain whether tHcy is also an independent risk factor for cognitive impairment. Methods: We examined 95 stroke subjects 3 months after their strokes, and 55 healthy comparison subjects, with a detailed neuropsychological assessment, and MRI brain scans in a proportion (n = 97). Baseline measurements of tHcy, serum folate and B 12 , creatinine and plasma fibrinogen levels were obtained. Results: tHcy levels were higher in the stroke subjects by a mean 34%. These levels were significantly correlated with the first factor of a principal component analysis of the neuropsychological data, after controlling for age, folate, B 12 and creatinine levels. The correlation of Hcy levels was particularly significant with frontal-executive functioning and attention. tHcy levels were significantly correlated with number of infarcts and total stroke volume in the stroke group, but not with T 2 -weighted deep white matter hyperintensity scores, after correction for age. In the control group, tHcy levels were significantly correlated with ventricle-tobrain ratios as measures of brain atrophy. Conclusion: This study provides evidence that high tHcy levels are associated with cognitive impairment, in particular that of frontal-executive function. The major component of this association is accounted for by small and large strokes, but non-vascular neurotoxic effects of tHcy also appear to play a role. tHcy must receive greater attention as a risk factor for cognitive impairment. Copyright © 2003 S. Karger AG, Basel Homocysteine (Hcy) is a sulfur-containing amino acid formed during the metabolism of the essential amino acid methionine. Elevated plasma homocysteine levels were first linked with vascular disease by McCully A high level of Hcy is both proatherogenic and prothrombotic If Hcy promotes cognitive impairment and is a risk factor for AD, it has important epidemiological implications. In this study, we examined plasma Hcy levels in a stroke sample to determine if there was an association between Hcy levels and cognition, and if this could be accounted for by infarct size or small vessel disease as detected by MRI. Methods Sample Subjects (n = 95) were consecutive patients admitted to two large teaching hospitals affiliated with the University of New South Wales who had recently suffered an ischemic stroke as diagnosed by two neurologists, and who met the diagnostic criteria for cerebral infarction Assessment Stroke subjects had a baseline assessment within 1 week of admission which included a detailed medical history and examination, history of risk factors for cerebrovascular disease and dementia, a functional assessment and the Mini-Mental State Examination Homocysteine Measurement Fasting blood was collected and centrifuged within 6 h, and the plasma stored at -20°C for later analysis. Total Hcy was measured using a fluorescence-based immunochemical technique with demonstrated high repeatability Neuropsychological Assessment Premorbid ability was estimated on the basis of performance on the National Adult Reading Test MRI Brain Scans MRI was performed on a proportion of subjects (n = 55 stroke; n = 42 controls) using a 1.5-T Signa GE magnet and the following protocol: a scout mid-sagittal cut (2D, TR 300 ms, TE 14 ms; 5 mm thick, number of excitations 1.5); 1.5-mm-thick T 1 -weighted contiguous coronal sections through whole brain using a FSPGR sequence and 3D acquisition (TR 14.3 ms, TE 5.4 ms); 4-mm-thick T 2 -weighted FLAIR coronal slices through whole brain (TR 8900, TE 145, TI 2200, FOV 25, 256 ! 192). Fifty-three subjects did not receive MRI scans because of claustrophobia or unwillingness to undergo the test. Analysis of Data Neuropsychological Tests. Raw scores were converted to agescaled scores using published norms [24-26, 28, 36, 38-41]. Composite z-scores were obtained for each domain. The raw scores from individual tests were also used in the exploratory analyses. MRI Scans. These were rated by a trained rater with good interrater (Î scores from 0.7 to 0.9 on various measures) and intra-rater (Î 0.8 to 0.9) reliability determined on five scans each. All ratings were carried out on a computer console using ANALYZE (Mayo Foundation) software. Brain infarctions were identified on T 1 -Homocysteine and Cognitive Impairment Dement Geriatr Cogn Disord 2003;15:155-162 15

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

Abstract: Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors

A Founder Mutation in PET100 Causes Isolated Complex IV Deficiency in Lebanese Individuals with Leigh Syndrome

Leigh syndrome (LS) is a severe neurodegenerative disorder with characteristic bilateral lesions, typically in the brainstem and basal ganglia. It usually presents in infancy and is genetically heterogeneous, but most individuals with mitochondrial complex IV (or cytochrome c oxidase) deficiency have mutations in the biogenesis factor SURF1. We studied eight complex IV-deficient LS individuals from six families of Lebanese origin. They differed from individuals with SURF1 mutations in having seizures as a prominent feature. Complementation analysis suggested they had mutation(s) in the same gene but targeted massively parallel sequencing (MPS) of 1,034 genes encoding known mitochondrial proteins failed to identify a likely candidate. Linkage and haplotype analyses mapped the location of the gene to chromosome 19 and targeted MPS of the linkage region identified a homozygous c.3G>C (p.Met1?) mutation in C19orf79. Abolishing the initiation codon could potentially still allow initiation at a downstream methionine residue but we showed that this would not result in a functional protein. We confirmed that mutation of this gene was causative by lentiviral-mediated phenotypic correction. C19orf79 was recently renamed PET100 and predicted to encode a complex IV biogenesis factor. We showed that it is located in the mitochondrial inner membrane and forms a ∼300 kDa subcomplex with complex IV subunits. Previous proteomic analyses of mitochondria had overlooked PET100 because its small size was below the cutoff for annotating bona fide proteins. The mutation was estimated to have arisen at least 520 years ago, explaining how the families could have different religions and different geographic origins within Lebanon