Retrieval guide to thermophysical properties research literature.

Second ed. published in 1967 under title: Thermophysical properties research literature retrieval guide.Mode of access: Internet

Allele-specific Characterization of Alanine: Glyoxylate Aminotransferase Variants Associated with Primary Hyperoxaluria

Primary Hyperoxaluria Type 1 (PH1) is a rare autosomal recessive kidney stone disease caused by deficiency of the peroxisomal enzyme alanine: glyoxylate aminotransferase (AGT), which is involved in glyoxylate detoxification. Over 75 different missense mutations in AGT have been found associated with PH1. While some of the mutations have been found to affect enzyme activity, stability, and/or localization, approximately half of these mutations are completely uncharacterized. In this study, we sought to systematically characterize AGT missense mutations associated with PH1. To facilitate analysis, we used two high-throughput yeast-based assays: one that assesses AGT specific activity, and one that assesses protein stability. Approximately 30% of PH1-associated missense mutations are found in conjunction with a minor allele polymorphic variant, which can interact to elicit complex effects on protein stability and trafficking. To better understand this allele interaction, we functionally characterized each of 34 mutants on both the major (wild-type) and minor allele backgrounds, identifying mutations that synergize with the minor allele. We classify these mutants into four distinct categories depending on activity/stability results in the different alleles. Twelve mutants were found to display reduced activity in combination with the minor allele, compared with the major allele background. When mapped on the AGT dimer structure, these mutants reveal localized regions of the protein that appear particularly sensitive to interactions with the minor allele variant. While the majority of the deleterious effects on activity in the minor allele can be attributed to synergistic interaction affecting protein stability, we identify one mutation, E274D, that appears to specifically affect activity when in combination with the minor allele

An Iron Age ceramic sequence from the Bayt Bin Ati, al‐Ain, UAE

© 2019 John Wiley & Sons Ltd Rescue excavations associated with the adaptive reuse of a historic building in the Qattara Oasis revealed a 5 m stratigraphic sequence spanning the past 3000 years. The main period of occupation—roughly half the sequence—belongs to the Iron Age II and III periods (c.1100–300 BC). Evidence of agriculture and industry was found which complements our understanding of the well-known Iron Age settlements of al-Ain. The present paper sets out the stratigraphic sequence and presents the phased ceramic assemblage, before considering the broader implications for the archaeology of Iron Age south-east Arabia

Genetic variation in the vitamin d pathway in relation to risk of prostate cancer--results from the breast and prostate cancer cohort consortium.

BACKGROUND: Studies suggest that vitamin D status may be associated with prostate cancer risk although the direction and strength of this association differs between experimental and observational studies. Genome-wide association studies have identified genetic variants associated with 25-hydroxyvitamin D [25(OH)D] status. We examined prostate cancer risk in relation to single-nucleotide polymorphisms (SNP) in four genes shown to predict circulating levels of 25(OH)D. METHODS: SNP markers localized to each of four genes (GC, CYP24A1, CYP2R1, and DHCR7) previously associated with 25(OH)D were genotyped in 10,018 cases and 11,052 controls from the National Cancer Institute (NCI) Breast and Prostate Cancer Cohort Consortium. Logistic regression was used to estimate the individual and cumulative association between genetic variants and risk of overall and aggressive prostate cancer. RESULTS: We observed a decreased risk of aggressive prostate cancer among men with the allele in rs6013897 near CYP24A1 associated with lower serum 25(OH)D [per A allele, OR, 0.86; 95% confidence interval (CI), 0.80-0.93; Ptrend = 0.0002) but an increased risk for nonaggressive disease (per A allele: OR, 1.10; 95% CI, 1.04-1.17; Ptrend = 0.002). Examination of a polygenic score of the four SNPs revealed statistically significantly lower risk of aggressive prostate cancer among men with a greater number of low vitamin D alleles (OR for 6-8 vs. 0-1 alleles, 0.66; 95% CI, 0.44-0.98; Ptrend = 0.003). CONCLUSIONS: In this large, pooled analysis, genetic variants related to lower 25(OH)D levels were associated with a decreased risk of aggressive prostate cancer. IMPACT: Our genetic findings do not support a protective association between loci known to influence vitamin D levels and prostate cancer risk

Genetic variation in the vitamin d pathway in relation to risk of prostate cancer--results from the breast and prostate cancer cohort consortium.

Background: Studies suggest that vitamin Dstatus may be associated with prostate cancer risk although the direction and strength of this association differs between experimental and observational studies. Genomewide association studies have identified genetic variants associated with 25-hydroxyvitamin D [25(OH)D] status. We examined prostate cancer risk in relation to single-nucleotide polymorphisms (SNP) in four genes shown to predict circulating levels of 25(OH)D. Methods: SNP markers localized to each of four genes (GC, CYP24A1, CYP2R1, and DHCR7) previously associated with 25(OH)D were genotyped in 10,018 cases and 11,052 controls from the National Cancer Institute (NCI) Breast and Prostate Cancer Cohort Consortium. Logistic regression was used to estimate the individual and cumulative association between genetic variants and risk of overall and aggressive prostate cancer. Results: We observed a decreased risk of aggressive prostate cancer among men with the allele in rs6013897 near CYP24A1 associated with lower serum 25(OH)D [perAallele, OR, 0.86; 95% confidence interval (CI), 0.80- 0.93; Ptrend 0.0002) but an increased risk for nonaggressive disease (per A allele: OR, 1.10; 95% CI, 1.04-1.17; Ptrend 0.002). Examination of a polygenic score of the four SNPs revealed statistically significantly lower risk of aggressive prostate cancer among men with a greater number of low vitamin D alleles (OR for 6-8 vs. 0-1 alleles, 0.66; 95% CI, 0.44-0.98; Ptrend 0.003). Conclusions: In this large, pooled analysis, genetic variants related to lower 25(OH)D levels were associated with a decreased risk of aggressive prostate cancer. Impact: Our genetic findings do not support a protective association between loci known to influence vitamin D levels and prostate cancer risk

Folding defects leading to primary hyperoxaluria

Protein misfolding is becoming one of the main mechanisms underlying inherited enzymatic deficits. This review is focused on primary hyperoxalurias, a group of disorders of glyoxylate detoxification associated with massive calcium oxalate deposition mainly in the kidneys. The most common and severe form, primary hyperoxaluria Type I, is due to the deficit of liver peroxisomal alanine/glyoxylate aminotransferase (AGT). Various studies performed in the last decade clearly evidence that many pathogenic missense mutations prevent the AGT correct folding, leading to various downstream effects including aggregation, increased degradation or mistargeting to mitochondria. Primary hyperoxaluria Type II and primary hyperoxaluria Type III are due to the deficit of glyoxylate reductase/hydroxypyruvate reductase (GRHPR) and 4-hydroxy-2-oxoglutarate aldolase (HOGA1), respectively. Although the molecular features of pathogenic variants of GRHPR and HOGA1 have not been investigated in detail, the data available suggest that some of them display folding defects. Thus, primary hyperoxalurias can be ranked among protein misfolding disorders, because in most cases the enzymatic deficit is due to the inability of each enzyme to reach its native and functional conformation. It follows that molecules able to improve the folding yield of the enzymes involved in each disease form could represent new therapeutic strategies