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  • 1
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    Systematic Functional Characterization of Human 21st Chromosome Orthologs in Caenorhabditis elegans (2018)
    Genetics Society of America (GSA)
    Details
    Publication Date: 2018-03-06
    Description: Individuals with Down syndrome have neurological and muscle impairments due to an additional copy of the human 21st chromosome (HSA21). Only a few of ~200 HSA21 genes encoding proteins have been linked to specific Down syndrome phenotypes, while the remainder are understudied. To identify poorly characterized HSA21 genes required for nervous system function, we studied behavioral phenotypes caused by loss-of-function mutations in conserved HSA21 orthologs in the nematode Caenorhabditis elegans . We identified 10 HSA21 orthologs that are required for neuromuscular behaviors: cle-1 ( COL18A1 ), cysl-2 ( CBS ), dnsn-1 ( DONSON ), eva-1 ( EVA1C ), mtq-2 ( N6ATM1 ), ncam-1 ( NCAM2 ), pad-2 ( POFUT2 ), pdxk-1 ( PDXK ), rnt-1 ( RUNX1 ), and unc-26 ( SYNJ1 ). We also found that three of these genes are required for normal release of the neurotransmitter acetylcholine. This includes a known synaptic gene unc-26 ( SYNJ1 ), as well as uncharacterized genes pdxk-1 ( PDXK ) and mtq-2 ( N6ATM1 ). As the first systematic functional analysis of HSA21 orthologs, this study may serve as a platform to understand genes that underlie phenotypes associated with Down syndrome.
    Electronic ISSN: 2160-1836
    Topics: Biology
    Published by Genetics Society of America (GSA)
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  • 2
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    Genetic associations with expression for genes implicated in GWAS studies for atherosclerotic cardiovascular disease and blood phenotypes (2014)
    Oxford University Press
    Details
    Publication Date: 2014-01-11
    Description: Genome-wide association studies (GWAS) have uncovered many genetic associations for cardiovascular disease (CVD). However, data are limited regarding causal genetic variants within implicated loci. We sought to identify regulatory variants ( cis- and trans -eQTLs) affecting expression levels of 93 genes selected by their proximity to SNPs with significant associations in prior GWAS for CVD traits. Expression levels were measured by qRT–PCR in leukocytes from 1846 Framingham Heart Study participants. An additive genetic model was applied to 2.5 million imputed SNPs for each gene. Approximately 45% of genes ( N = 38) harbored at least one cis -eSNP after a regional multiple-test adjustment. Applying a more rigorous significance threshold ( P 〈 5 x 10 –8 ), we found the expression level of 10 genes was significantly associated with more than one cis -eSNP. The top cis -eSNPs for 7 of these 10 genes exhibited moderate-to-strong association with ≥1 CVD clinical phenotypes. Several eSNPs or proxy SNPs ( r 2 = 1) were replicated by other eQTL studies. After adjusting for the lead GWAS SNPs for the 10 genes, expression variances explained by top cis -eSNPs were attenuated markedly for LPL , FADS2 and C6orf184 , suggesting a shared genetic basis for the GWAS and expression trait . A significant association between cis -eSNPs, gene expression and lipid levels was discovered for LPL and C6orf184 . In conclusion, strong cis -acting variants are localized within nearly half of the GWAS loci studied, with particularly strong evidence for a regulatory role of the top GWAS SNP for expression of LPL , FADS2 and C6orf184 .
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 3
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    Crystal structure of Argonaute and its implications for RISC slicer activity (2004)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2004-07-31
    Description: Argonaute proteins and small interfering RNAs (siRNAs) are the known signature components of the RNA interference effector complex RNA-induced silencing complex (RISC). However, the identity of "Slicer," the enzyme that cleaves the messenger RNA (mRNA) as directed by the siRNA, has not been resolved. Here, we report the crystal structure of the Argonaute protein from Pyrococcus furiosus at 2.25 angstrom resolution. The structure reveals a crescent-shaped base made up of the amino-terminal, middle, and PIWI domains. The Piwi Argonaute Zwille (PAZ) domain is held above the base by a "stalk"-like region. The PIWI domain (named for the protein piwi) is similar to ribonuclease H, with a conserved active site aspartate-aspartate-glutamate motif, strongly implicating Argonaute as "Slicer." The architecture of the molecule and the placement of the PAZ and PIWI domains define a groove for substrate binding and suggest a mechanism for siRNA-guided mRNA cleavage.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Song, Ji-Joon -- Smith, Stephanie K -- Hannon, Gregory J -- Joshua-Tor, Leemor -- New York, N.Y. -- Science. 2004 Sep 3;305(5689):1434-7. Epub 2004 Jul 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Watson School of Biological Sciences, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15284453" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Archaeal Proteins/*chemistry/metabolism ; Binding Sites ; Catalytic Domain ; Crystallography, X-Ray ; Models, Molecular ; Molecular Sequence Data ; Protein Conformation ; Protein Folding ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Pyrococcus furiosus/*chemistry ; *RNA Interference ; RNA, Messenger/*metabolism ; RNA, Small Interfering/*metabolism ; RNA-Induced Silencing Complex/*metabolism ; Ribonuclease H/chemistry
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 4
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    Unexpected DNA context-dependence identifies a new determinant of Chi recombination hotspots (2016)
    Oxford University Press
    Details
    Publication Date: 2016-10-08
    Description: Homologous recombination occurs especially frequently near special chromosomal sites called hotspots. In Escherichia coli , Chi hotspots control RecBCD enzyme, a protein machine essential for the major pathway of DNA break-repair and recombination. RecBCD generates recombinogenic single-stranded DNA ends by unwinding DNA and cutting it a few nucleotides to the 3' side of 5' GCTGGTGG 3', the sequence historically equated with Chi. To test if sequence context affects Chi activity, we deep-sequenced the products of a DNA library containing 10 random base-pairs on each side of the Chi sequence and cut by purified RecBCD. We found strongly enhanced cutting at Chi with certain preferred sequences, such as A or G at nucleotides 4–7, on the 3' flank of the Chi octamer. These sequences also strongly increased Chi hotspot activity in E. coli cells. Our combined enzymatic and genetic results redefine the Chi hotspot sequence, implicate the nuclease domain in Chi recognition, indicate that nicking of one strand at Chi is RecBCD's biologically important reaction in living cells, and enable more precise analysis of Chi's role in recombination and genome evolution.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 5
    Electronic Resource
    Electronic Resource
    Routine direct determination of oxygen in organic and inorganic compounds via inert gas fusion (1968)
    s.l. : American Chemical Society
    Analytical chemistry 40 (1968), S. 2034-2035 
    Details
    ISSN: 1520-6882
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1021/ac60269a032
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  • 6
    Electronic Resource
    Electronic Resource
    Stochastic characterization and seismic response of upper and middle crustal rocks based on the Lewisian gneiss complex, Scotland (1994)
    Oxford, UK : Blackwell Publishing Ltd
    Geophysical journal international 119 (1994), S. 0 
    Details
    ISSN: 1365-246X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Geosciences
    Notes: We have developed statistical models of upper and middle crustal seismic velocity heterogeneity based on geologic maps and petrophysical data from the Lewisian gneiss complex, Scotland. the level of heterogeneity we have measured is relevant to seismic exploration of the crystalline crust using conventional reflection and refraction techniques. We digitized two 1:10560 geologic maps of Laxfordian (Archean) age Lewisian rocks on a 26.8m grid. Both maps are believed to be representative of the upper and middle crust in north-western Scotland, and both are believed to provide cross-sectional views of parts of the crust. the digital maps were characterized by the statistics of their lithologic populations and by their 2-D spatial autocorrelation functions. Different lithologies were assigned seismic velocities appropriate for the mid-crust using petrophysical data. Three lithologies are dominant: silicic gneisses (Vp∼6.2 km s−1), mafic amphibolites (Vp— 6.75 kms−1), and intermediate composition schists (Vp—6.5kms−1). Both maps have self-affine spatial fabrics.The first map covers the core of a syncline. Its autocorrelation function defines a medium with a fractal dimension of 2.78, a horizontal characteristic length of about 244m and a vertical correlation of about 133m (aspect ratio is 2:1). It has an essentially trimodal velocity (lithology) population consisting of 37 per cent silicicgneiss, 43 per cent mafic amphibolites, and 20 per cent schists. This map is representative of 30-40 per cent of Laxfordian rocks. the second map is a plan view which can be rotated 90° about an axis perpendicular to strike to give a cross-section. This map is characterized by a fractal dimension of 2.55, with a horizontal correlation length of about 111m and a vertical correlation of about 38m (aspect ratio 3:1). It has a nearly bimodal population consisting of 77 per cent silicic gneisses and 22 per cent mafic amphibotites. It is representative of 60-70 per cent of Laxfordian rocks.Lastly we examine the seismic response of an upper to middle crust based on our statistical models using acoustic and elastic 2-D finite-difference synthetic seismograms. Short-offset shot records demonstrate that a Lewisian upper crust produces scattered waves which significantly disrupt signals reflecting from deeper levels. Measurements of transmission scattering Q, and coda decay rates confirm that seismic scattering in Lewisian-type crust is strong. the migrated CMP response of a Lewisian crustal model shows the characteristic ‘salt and pepper’ pattern often observed in the upper crust, and described, incorrectly, as ‘transparent'. We suggest that ‘translucent’ is a more appropriate descriptor.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-246X.1994.tb00925.x
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  • 7
    Electronic Resource
    Electronic Resource
    Neutron and X-ray diffraction study of magnesium phosphite hexahydrate, [Mg(H2O)6]2+[PHO3]2– (1994)
    Oxford [u.a.] : International Union of Crystallography (IUCr)
    Acta crystallographica 50 (1994), S. 342-346 
    Details
    ISSN: 1600-5759
    Source: Crystallography Journals Online : IUCR Backfile Archive 1948-2001
    Topics: Chemistry and Pharmacology , Geosciences , Physics
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1107/S0108270193008169
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  • 8
    Electronic Resource
    Electronic Resource
    Alkali treatment and fermentation of straw for animal feedContribution of the Agricultural Research Service, U.S. Dept. of Agriculture, in cooperation with the Department of Microbiology. Technical Paper No. 4589, Oregon Agricultural Experiment Station. (1978)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 20 (1978), S. 1015-1026 
    Details
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: The feed value of annual ryegrass straw was improved by treatment with various concentrations of NaOH or NH3 followed by fermentation of the treated straw with a mixed culture of Cellulomonas sp. and Alcaligenes faecalis. Laboratory feeding trials with voles showed that NaOH or NH3 treatment considerably increased the feed efficiency of straw, but apparently gave a poorly palatable product. Fermentation tended to decrease the in vitro rumen digestibility (IVRD) of alkali-treated straw. The fermentations were carried out aerobically on a semisolid straw matrix having 11-86% moisture. Treatment by both NaOH and NH3 increased the IVRD of straw. NH3 also increased the nitrogen content in straw. The optimum condition for alkaline treatment of the straw was 4-6% NaOH for 1 hr or with 3% NH3 for four weeks at room temperature. A minimum of 63% moisture was needed for significant fermentation of the straw. The combined effects of NaOH treatment and fermentation more than doubled crude protein, doubled crude fat, and increased IVRD by 75%. The NH3 plus fermentation treatment tripled crude protein, doubled crude fat, and increased IVRD by 60%. Acetic acid was the main volatile fatty acid in the fermented straw.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bit.260200704
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  • 9
    Electronic Resource
    Electronic Resource
    Platelet-activating factor stimulates phospholipase C activity in human endometrium (1992)
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 152 (1992), S. 207-214 
    Details
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Human preimplantation embryos secrete platelet-activating factor (PAF), which stimulates prostaglandin E2 synthesis from secretory endometrium. This study investigated the action of PAF on phosphatidylinositol 4,5-bisphosphate (Ptdlns(4,5)P2)-specific phospholipase C activity in human endometrium. Slices of normal endometrium were incubated with 5 μCi/ml myo-[2-3H] inositol for 3 h at 37°C in 95% O2 and 5% CO2 to label tissue phosphoinositides. Inositol phosphates were extracted using trichloroacetic acid precipitation and diethylether neutralization and production was measured using Dowex 1-X8 anion-exchange column chromatography. PAF induced rapid and concentration-dependent accumulation of inositol phosphates (IP) from secretory endometrium, but had no effect on endometrium removed in the proliferative phase of the menstrual cycle. The IP3 fraction was significantly elevated from a median value of 14.0 c.p.m. mg-1 dry wt [range: 8-41 c.p.m. mg-1 dry wt] to 28.0 c.p.m. mg-1 dry wt [range: 11-87 c.p.m. mg-1 dry wt, P 〈 0.002] following 1 min exposure of secretory endometrium to PAF-acether, in the presence of 10 mM LiCl. PAF-induced hydrolysis of Ptdlns(4,5)P2 was inhibited by the specific PAF receptor antagonist WEB 2086, in a dose-dependent manner (P 〈 0.02), indicating that in human endometrium Ptdlns(4,5)P2 hydrolysis is mediated via a PAF receptor. These results indicate that PAF receptor coupling activates endometrial Ptdlns(4,5)P2-specific phospholipase C only in the secretory phase of the menstrual cycle, suggesting that the PAF response may be under ovarian steroid regulation. It is proposed that the ability of the endometrium to respond to PAF appears to be a feature of the preparation of this tissue for implantation and that the second messengers generated may play a role in cellular processes involved in the maternal recognition of very early human pregnancy. © 1992 Wiley-Liss, Inc.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jcp.1041520126
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  • 10
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    Inhibition of Stat3 activation in the endometrium prevents implantation: A nonsteroidal approach to contraception (2005)
    National Academy of Sciences
    Details
    Publication Date: 2005-06-03
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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