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  • Oxford University Press  (5)
  • American Association for the Advancement of Science (AAAS)  (4)
  • 1
    Publication Date: 2012-05-11
    Description: Vitamin B12 (VitB12 or cobalamin) is an essential cofactor in several metabolic pathways. Clinically, VitB12 deficiency is associated with pernicious anemia, neurodegenerative disorder, cardiovascular disease and gastrointestinal disease. Although previous genome-wide association studies (GWAS) identified several genes, including FUT2 , CUBN , TCN1 and MUT , that may influence VitB12 levels in European populations, common genetic determinants of VitB12 remain largely unknown, especially in Asian populations. Here we performed a GWAS in 1999 healthy Chinese men and replicated the top findings in an independent Chinese sample with 1496 subjects. We identified four novel genomic loci that were significantly associated with serum level of VitB12 at a genome-wide significance level of 5.00 x 10 –8 . These four loci were MS4A3 (11q12.1; rs2298585; P = 2.64 x 10 –15 ), CLYBL (13q32; rs41281112; P = 9.23 x 10 –10 ), FUT6 (19p13.3; rs3760776; P = 3.68 x 10 –13 ) and 5q32 region (rs10515552; P = 3.94 x 10 –8 ). In addition, we also confirmed the association with the serum level of VitB12 for the previously reported FUT2 gene and identified one novel non-synonymous single-nucleotide polymorphism in FUT2 gene in this Chinese population (19q13.33; rs1047781; P = 3.62 x 10 –36 ). The new loci identified offer new insights into the biochemical pathways involved in determining the serum level of VitB12 and provide opportunities to better delineate the role of VitB12 in health and disease.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
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  • 2
    Publication Date: 2014-05-01
    Description: Messenger RNA (mRNA) secondary structure decreases the elongation rate, as ribosomes must unwind every structure they encounter during translation. Therefore, the strength of mRNA secondary structure is assumed to be reduced in highly translated mRNAs. However, previous studies in vitro reported a positive correlation between mRNA folding strength and protein abundance. The counterintuitive finding suggests that mRNA secondary structure affects translation efficiency in an undetermined manner. Here, we analyzed the folding behavior of mRNA during translation and its effect on translation efficiency. We simulated translation process based on a novel computational model, taking into account the interactions among ribosomes, codon usage and mRNA secondary structures. We showed that mRNA secondary structure shortens ribosomal distance through the dynamics of folding strength. Notably, when adjacent ribosomes are close, mRNA secondary structures between them disappear, and codon usage determines the elongation rate. More importantly, our results showed that the combined effect of mRNA secondary structure and codon usage in highly translated mRNAs causes a short ribosomal distance in structural regions, which in turn eliminates the structures during translation, leading to a high elongation rate. Together, these findings reveal how the dynamics of mRNA secondary structure coupling with codon usage affect translation efficiency.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 3
    Publication Date: 2017-07-20
    Description: Direct residential and transportation energy consumption (RTC) contributes significantly to ambient fine particulate matter with a diameter smaller than 2.5 μm (PM 2.5 ) in China. During massive rural-urban migration, population and pollutant emissions from RTC have evolved in terms of magnitude and geographic distribution, which was thought to worsen PM 2.5 levels in cities but has not been quantitatively addressed. We quantify the temporal trends and spatial patterns of migration to cities and evaluate their associated pollutant emissions from RTC and subsequent health impact from 1980 to 2030. We show that, despite increased urban RTC emissions due to migration, the net effect of migration in China has been a reduction of PM 2.5 exposure, primarily because of an unequal distribution of RTC energy mixes between urban and rural areas. After migration, people have switched to cleaner fuel types, which considerably lessened regional emissions. Consequently, the national average PM 2.5 exposure concentration in 2010 was reduced by 3.9 μg/m 3 (90% confidence interval, 3.0 to 5.4 μg/m 3 ) due to migration, corresponding to an annual reduction of 36,000 (19,000 to 47,000) premature deaths. This reduction was the result of an increase in deaths by 142,000 (78,000 to 181,000) due to migrants swarming into cities and decreases in deaths by 148,000 (76,000 to 194,000) and 29,000 (15,000 to 39,000) due to transitions to a cleaner energy mix and lower urban population densities, respectively. Locally, however, megacities such as Beijing and Shanghai experienced increases in PM 2.5 exposure associated with migration because these cities received massive immigration, which has driven a large increase in local emissions.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
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  • 4
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2016-08-19
    Description: In previous reports, flowing CO 2 at the cathode is essential for either conventional molten carbonate fuel cells (MCFCs) based on molten carbonate/LiAlO 2 electrolytes or matrix-free MCFCs. For the first time, we demonstrate a high-performance matrix-free MCFC without CO 2 recirculation. At 800°C, power densities of 430 and 410 mW/cm 2 are achieved when biomass—bamboo charcoal and wood, respectively–is used as fuel. At 600°C, a stable performance is observed during the measured 90 hours after the initial degradation. In this MCFC, CO 2 is produced at the anode when carbon-containing fuels are used. The produced CO 2 then dissolves and diffuses to the cathode to react with oxygen in open air, forming the required CO32– or CO42– ions for continuous operation. The dissolved O2– ions may also take part in the cell reactions. This provides a simple new fuel cell technology to directly convert carbon-containing fuels such as carbon and biomass into electricity with high efficiency.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
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  • 5
    Publication Date: 2012-11-07
    Description: Circulating androgen levels are often used as indicators of physiological or pathological conditions. More than half of the variance for circulating androgen levels is thought to be genetically influenced. A genome-wide association study (GWAS) has identified two loci, SHBG at 17p13 and FAM9B at Xp22, for serum testosterone (T) levels; however, these explain only a small fraction of inter-individual variability. To identify additional genetic determinants of androgen levels, a GWAS of baseline serum T and dihydrotestosterone (DHT) levels was conducted in 3225 men of European ancestry from the REduction by DUtasteride of Prostate Cancer Events (REDUCE) study. Cross-validation was used to confirm the observed associations between the drug ( n = 1581) and placebo ( n = 1644) groups of REDUCE. In addition to confirming the associations of two known loci with serum T levels (rs727428 in SHBG : P = 1.26 x 10 –12 ; rs5934505 in FAM9B : P = 1.61 x 10 –8 ), we identified a new locus, JMJD1C at 10q21 that was associated with serum T levels at a genome-wide significance level (rs10822184: P = 1.12 x 10 –8 ). We also observed that the SHBG locus was associated with serum DHT levels (rs727428: P = 1.47 x 10 –11 ). Moreover, two additional variants in SHBG [rs72829446, in strong linkage equilibrium with the missense variant D356N (rs6259), and rs1799941] were also independently associated with circulating androgen levels in a statistical scale. These three loci ( JMJD1C , SHBG and FAM9B ) were estimated to account for ~5.3 and 4.1% of the variance of serum T and DHT levels. Our findings may provide new insights into the regulation of circulating androgens and potential targets for androgen-based therapy.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
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  • 6
    Publication Date: 2013-03-14
    Description: Various regulatory elements in messenger RNAs (mRNAs) carrying the secondary structure play important roles in a wide range of expression processes. Numerous recent works have focused on the discovery of these functional elements that contain the conserved mRNA structures. However, to date, regions with high structural stability have been largely overlooked. In this study, we defined high stability regions (HSRs) in the coding sequences (CDSs) in bacteria based on the normalized folding free energy. We found that CDSs had high number of HSRs, and these HSRs showed high structural context robustness compared with random sequences, indicating a direct selective constraint imposed on HSRs. A reduced ribosome speed was detected near the start position of HSR, implying a possibility that HSR acted as obstacle to drive translational pausing that coordinated protein synthesis. Interestingly, we found that genes with high HSR density were enriched in the processes of translation, protein folding, and cell division. In addition, essential genes exhibited higher HSR density than nonessential genes. Overall, our study presented the previously unappreciated correlation between the number variation of HSRs and cellular processes.
    Electronic ISSN: 1759-6653
    Topics: Biology
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  • 7
    Publication Date: 2019
    Description: 〈p〉Botsyun 〈i〉et al〈/i〉. (Research Articles, 1 March 2019, eaaq1436) have suggested that the Tibetan Plateau was low (substantially less than 3000 meters) during the Eocene, based on a comparison of oxygen isotope proxy data with isotope-enabled climate model simulations. However, we contend that their conclusions are flawed as the result of a number of failings of both the modeling and the data comparison.〈/p〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 8
    Publication Date: 2019
    Description: 〈p〉The characteristics of DNA methylation changes that occur during neurogenesis in vivo remain unknown. We used whole-genome bisulfite sequencing to quantitate DNA cytosine modifications in differentiating neurons and their progenitors isolated from mouse brain at the peak of embryonic neurogenesis. Localized DNA hypomethylation was much more common than hypermethylation and often occurred at putative enhancers within genes that were upregulated in neurons and encoded proteins crucial for neuronal differentiation. The hypomethylated regions strongly overlapped with mapped binding sites of the key neuronal transcription factor NEUROD2. The 5-methylcytosine oxidase ten-eleven translocation 2 (TET2) interacted with NEUROD2, and its reaction product 5-hydroxymethylcytosine accumulated at the demethylated regions. NEUROD2-targeted differentially methylated regions retained higher methylation levels in 〈i〉Neurod2〈/i〉 knockout mice, and inducible expression of NEUROD2 caused TET2-associated demethylation at its in vivo binding sites. The data suggest that the reorganization of DNA methylation in developing neurons involves NEUROD2 and TET2-mediated DNA demethylation. 〈/p〉
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
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  • 9
    Publication Date: 2010-08-19
    Print ISSN: 0737-4038
    Electronic ISSN: 1537-1719
    Topics: Biology
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