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Family-based association analysis of alcohol dependence implicates KIAA0040 on Chromosome 1q in multiplex alcohol dependence families

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Open Journal of Genetics 2013年第4期3卷 243-252页

作者： Shirley Y. Hill Bobby l. Jones Nicholas Zezza scott Stiffler Department of Psychiatry University of Pittsburgh School of Medicine Pittsburgh USA

Background: A previous genome-wide linkage study of alcohol dependence in multiplex families found a suggestive linkage result for a region on Chromosome 1 near microsatellite markers D1S196 and D1S2878. The KIAA0040 gene has been mapped to this region (1q24-q25). A recent genome-wide association study using SAGE (the Study of Addiction: Genetics and Environment) and COGA (Collaborative Study on the Genetics of Alcoholism) found five SNPs within the KIAA0040 gene significantly associated with alcohol dependence. A meta-analysis using data from these sources also found the KIAA0040 gene significantly associated with alcohol dependence. Methods: Using family data consisting of 1000 individuals with phenotypic data (762 with both phenotype and DNA), finer mapping of a 0.3 cM region that included the KIAA0040 gene and a flanking gene was undertaken using SNPs with minor allele frequency (MAF) ≥ 0.15 and pair-wise linkage disequilibrium (lD) of r2 lation. Results: Significant FBAT p-values were observed for six SNPs, four within the KIAA0040 gene (rs2269650, rs2861158, rs1008459, rs2272785) and two adjacent to KIAA0040 (rs10912899 and rs3753555). Five haplotype blocks of varying size were identified using HAPlOVIEW. Analysis using the haplotype-based test function of FBAT revealed one two-SNP block (rs1008459rs2272785) associated with alcohol dependence. This block showed a pattern of transmission in which one haplotype, CT, with a frequency of 0.577 was found to be over-transmitted to affected offspring (p = 0.017) while another haplotype, AG, with a frequency of 0.238 was found to be under-transmitted to affected offspring (p = 0.006). A three-SNP block (rs1008459rs2272785-rs375355) showed an overall significant association (p = 0.011) with alcohol dependence with the haplotype ACT over-transmitted to affected offspring (p = 0.016) and the haplotype GAG undertransmitted (p = 0.002). Conclusions: Family-based association analysis shows the

关键词： KIAA0040 Alcohol Dependence Multiplex Families

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Enduring alterations in hippocampal astrocytesynaptic proximity following adolescent alcohol exposure: reversal by gabapentin

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Neural Regeneration Research 2020年第8期15卷 1496-1501页

作者： Kati l.Healey Sandra Kibble Sierra Hodges Kathryn J.Reissner Anze Testen Tiffany A.Wills Shawn K.Acheson Benjamin M.Siemsen John A.McFaddin Michael D.Scofield H.scott Swartzwelder Department of Psychiatry and Behavioral Sciences Duke University Medical CenterDurhamNCUSA Department of Psychology and Neuroscience University of North CarolinaChapel HillNCUSA Department of Cell Biology and Anatomy LSU School of MedicineNew OrleansLAUSA Department of Anesthesia and Perioperative Medicine Medical University of South CarolinaCharlestonSCUSA

Adolescent alcohol abuse is a substantive public health problem that has been the subject of intensive study in recent *** reports of a wide range of effects of adolescent intermittent ethanol(AIE)exposure on brain and behavior,little is known about the mechanisms that may underlie those effects,and even less about treatments that might reverse *** studies from our laboratory have indicated that AIE produced enduring changes in astrocyte function and synaptic activity in the hippocampal formation,suggesting the possibility of an alteration in astrocyte-neuronal connectivity and *** utilized astrocyte-specific,membrane restricted viral labeling paired with immunohistochemistry to perform confocal single cell astrocyte imaging,three-dimensional reconstruction,and quantification of astrocyte morphology in hippocampal area CA1 from adult rats after ***,we assessed the colocalization of astrocyte plasma membrane labeling with immunoreactivity for AMPA-(α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)glutamate receptor 1,an AMPA receptor subunit and established neuronal marker of excitatory synapses,as a metric of astrocyte-synapse *** significantly reduced the colocalization of the astrocyte plasma membrane with synaptic marker puncta in *** is striking in that it suggests not only an alteration of the physical association of astrocytes with synapses by AIE,but one that lasts into adulthood-well after the termination of alcohol *** even more notable,the AIE-induced reduction of astrocyte-synapse interaction was reversed by sub-chronic treatment with the clinically used agent,gabapentin(Neurontin),in *** suggests that a medication in common clinical use may have the potential to reverse some of the enduring effects of adolescent alcohol exposure on brain *** animal experiments conducted were approved by the Duke University Institutional Animal Care and Use Committee(Protocol

关键词： adolescent alcohol astrocyte astrocyte morphology astrocyte-neuronal colocalization CA1 gabapentin GluA1 hippocampus tripartite synapse

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Assessment of the 2006-2012 Climatological Fields and Mesoscale Features from Regional Downscaling of CESM Data by WRF-Chem over Southeast Alaska

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Atmospheric and Climate Sciences 2014年第4期4卷 589-613页

作者： Nicole Molders Cindy l.Bruyère scott Gende Michael A.Pirhalla Geophysical Institute Department of Atmospheric SciencesCollege of Natural Science and MathematicsUniversity of Alaska FairbanksFairbanksUSA National Center for Atmospheric Research BoulderUSA Environmental Sciences and Management North-West UniversityVanderbijlparkSouth Africa National Park Service Glacier Bay Field StationJuneauUSA

This case study examined how well downscaling of Community Earth System Model (CESM) data can reproduce climatological conditions relevant for summer (JJA) air quality in Glacier Bay National Park. Climatology was determined from the meteorological results obtained by the Weather Research and Forecasting model inline coupled with chemistry (WRF-chem) when driven with CESM data of 2006-2012. The climatology of this experiment (EXP) was evaluated by climatology from gridded blended sea-wind speeds, CRU data, and 42 surface meteorology sites. The quality relative to known performance was assessed by comparison to climatology determined from WRF-chem control simulations driven with FNl analysis data (CON) in forecast mode. Compared to observations, the thermodynamic and dynamic performances of EXP showed similar shortcomings (dampened diurnal temperature range, overestimation of wind speed over land) as CON. Over water EXP wind-speed climatology JJA bias (simulated minus observed) was -0.7 m/s. With respect to the CRU data EXP biases in JJA 2m temperature, diurnal temperature range, relative humidity and accumulated precipitation were -1.1 K, -4.9 K, 13%, and 110 mm, respectively. The slightly warmer atmosphere in EXP compensated for deficiencies in the cloud schemes leading to better results for the number of wet days and accumulated precipitation than in CON. Downscaling captured known mesoscale responses important for regional climate in a similar way as CON. When using CESM forcing, lateral boundary effects expanded spatially farther into the domain than known for forcing by analysis data. Overall, climatologies obtained from downscaling for Southeast Alaska had similar skill than those derived from forecasts driven by analysis data.

关键词： Evaluation Regional Climate Modeling Downscaling Southeast Alaska WRF-Chem CESM

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Accuracy of genomic selection in biparental populations of flax(linum usitatissimum l.)

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The Crop Journal 2016年第4期4卷 290-303页

作者： Frank M.You Helen M.Booker scott D.Duguid Gaofeng Jia Sylvie Cloutier Morden Research and Development Centre Agriculture and Agri-Food Canada Crop Development Centre Department of Plant Sciences University of Saskatchewan Ottawa Research and Development Centre Agriculture and Agri-Food Canada

Flax is an important economic crop for seed oil and stem fiber. Phenotyping of traits such as seed yield, seed quality, stem fiber yield, and quality characteristics is expensive and time consuming. Genomic selection(GS) refers to a breeding approach aimed at selecting preferred individuals based on genomic estimated breeding values predicted by a statistical model based on the relationship between phenotypes and genome-wide genetic markers. We evaluated the prediction accuracy of GS(rMP) and the efficiency of GS relative to phenotypic selection(RE) for three GS models: ridge regression best linear unbiased prediction(RR-BlUP),Bayesian lASSO(Bl), and Bayesian ridge regression(BRR), for seed yield, oil content, iodine value, linoleic, and linolenic acid content with a full and a common set of genome-wide simple sequence repeat markers in each of three biparental populations. The three GS models generated similar rMPand RE, while BRR displayed a higher coefficient of determination(R^2)of the fitted models than did RR-BlUP or Bl. The mean rMPand RE varied for traits with different heritabilities and was affected by the genetic variation of the traits in the *** for seed yield generated a mean RE of 1.52 across populations and marker sets, a value significantly superior to that for direct phenotypic selection. Our empirical results provide the first validation of GS in flax and demonstrate that GS could increase genetic gain per unit time for linseed breeding. Further studies for selection of training populations and markers are warranted.

关键词： Genomic selection SSR Flax linseed Seed yield Fatty acid composition

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Interaction of Seedling Germination, Planting Date, and Flumioxazin on Peanut Physiology under Irrigated Conditions

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American Journal of Plant Sciences 2020年第12期11卷 2012-2030页

作者： Nicholas l. Hurdle Timothy l. Grey Cristiane Pilon W. scott Monfort Donn G. Shilling Department of Crop and Soil Sciences University of Georgia Tifton GA USA

Diclosulam and flumioxazin applied preemergent (PRE) results in direct peanut exposure to these herbicides prior to seedling emergence. Flumioxazin has been reported to induce injury in adverse weather (i.e. cool-wet soil conditions) at crop emergence. Research at Ty Ty and Plains, Georgia evaluated the physiological effects of PRE herbicides to emerging peanut in 2018 and 2019. Peanut seed with variable germination and different planting dates were evaluated as additional factors. Peanut plant physiological measurements included electron transport (ETR), net assimilation rate (Anet), quantum yield of PSII (ΦPSII), and stomatal conductance to water vapor (GSW). Data were obtained from V3 to R1 peanut growth stages using a LiCOR 6800, along with stand counts and plant width measures. In 2018, diclosulam reduced peanut ETR when measured across multiple growing degree days (GDD) after planting, compared to the nontreated control (NTC). Flumioxazin reduced peanut ETR compared to the NTC, at several sample timings for each planting date. In 2018 and 2019 at both locations, flumioxazin impacted Anet less than ETR, but was consistently similar to/or greater than the NTC. Peanut ΦPSII responded similarly as Anet at each location and yr. GSW was variable in both years<

关键词： Diclosulam Flumioxazin Peanut Arachis hypogaea l. Photosynthesis Electron Transport

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Atypical osteochondroma of the lumbar spine associated with suprasellar pineal germinoma:A case report

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World Journal of Orthopedics 2021年第9期12卷 720-726页

作者： Patrik Suwak scott A Barnett Bryant M Song Michael J Heffernan Department of Orthopaedic Surgery Louisiana State University Health Sciences CenterNew OrleansLA 70112United States Department of Orthopaedic Surgery Children's Hospital New OrleansNew OrleansLA 70118United States

BACKGROUND Osteochondromas are the most common benign bone tumor,accounting for 36%of benign bone *** found within the appendicular skeleton,osteochondromas of the spine are rare,comprising 4%to 7%of primary benign spinal *** SUMMARY We report a case of a solitary lumbar osteochondroma in an 18-year-old male with a history of a suprasellar pineal germinoma treated with combined chemotherapy and *** underwent mass excision and partial laminectomy with the ultrasonic bone scalpel(Misonix,Farmingdale,NY,United States)at the l5 level without the use of *** patient returned to work and full activities without back pain at 3 mo *** Osteochondromas are common tumors of the appendicular skeleton but rarely occur within the *** case discussion supplements current osteochondroma literature by describing an unusual presentation of this tumor.

关键词： Spine osteochondroma lumbar osteochondroma laminectomy Radiationinduced osteochondroma Spine surgery Case report

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Cs_(3)Bi_(2)l_(9)-hydroxyapatite composite waste forms for cesium and iodine immobilization

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Journal of Advanced Ceramics 2022年第5期11卷 712-728页

作者： Kun YANG Yachun WANG Junhua SHEN Spencer M.scott Brian J.RIlEY John D.VIENNA Jie lIAN Department of Mechanical Aerospaceand Nuclear EngineeringRensselaer Polytechnic InstituteTroyUSA Department of Materials Science&Engineering Rensselaer Polytechnic InstituteTroyUSA Savannah River National laboratory AikenUSA Pacific Northwest National laboratory RichlandUSA

Perovskite-based ceramic composites were developed as potential waste form materials for immobilizing cesium(Cs)and iodine(I)with high waste loadings and chemical *** perovskite Cs_(3)Bi_(2)I_(9)has high Cs(22 wt%)and I(58 wt%)content,and thus can be used as a potential host phase to immobilize these critical *** this work,the perovskite Cs_(3)Bi_(2)I_(9)phase was synthesized by a cost effective solution-based approach,and was embedded into a highly durable hydroxyapatite matrix by spark plasma sintering to form dense ceramic composite waste *** chemical durabilities of the monolithic Cs_(3)Bi_(2)I_(9)and Cs_(3)Bi_(2)I_(9)-hydroxyapatite composite pellets were investigated by static and semi-dynamic leaching tests,*** and I are incongruently released from the matrix for both pure Cs_(3)Bi_(2)I_(9)and composite *** normalized Cs release rate is faster than that of I,which can be explained by the difference in the strengths between Cs-I and Bi-I bonds as well as the formation of insoluble micrometer-sized BiOI *** activation energies of elemental releases based on dissolution and diffusion-controlled mechanisms are determined with significantly higher energy barriers for dissolution from the composite versus that of the monolithic Cs_(3)Bi_(2)I_(9).The ceramic-based composite waste forms exhibit excellent chemical durabilities and waste loadings,commensurate with the state-of-the-art glass-bonded perovskite composites for I and Cs immobilization.

关键词： cesium(Cs) iodine(Ⅰ) perovskite nuclear waste hydroxyapatite

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Candidate genes underlying QTl for flowering time and their interactions in a wide spring barley(Hordeum vulgare l.) cross

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The Crop Journal 2021年第4期9卷 862-872页

作者： Ana M.Casas Carlota R.Gazulla Arantxa Monteagudo Carlos P.Cantalapiedra Marian Moralejo MPilar Gracia Francisco J.Ciudad William T.B.Thomas Jose l.Molina-Cano scott Boden Bruno Contreras-Moreira Ernesto Igartua Department of Genetics and Plant Production Aula Dei Experimental Station(EEAD-CSIC)Avda Montanana 1005E-50059 ZaragozaSpain University of lleida-AGROTECNIO Center Avda.Rovira Roure 19125198 LleidaSpain Instituto de Tecnologia Agraria Junta de Castilla y LeonITACyLP.O.Box 17247071 ValladolidSpain The James Hutton Institute InvergowrieDundee DD25DAUK Institut de Recerca i Tecnologia Agroalimentaries(Udl-IRTA) Avda Rovira Roure 19125198 LleidaSpain John Innes Centre Norwich Research ParkNorwich NR47UHUK Fundacion ARAID calle Maria de Luna 1150018 ZaragozaSpain Present address:Centro de Biotecnologia y Genomica de Plantas Universidad Politecnica de Madrid(UPM)and Instituto Nacional de Investigacion y Tecnologia Agraria y Alimentaria(INIA)Madrid 28223Spain Present address:School of Agriculture Food and WineWaite Research InstituteUniversity of AdelaideGlen OsmondSA 5064Australia Present address:The European Bioinformatics Institute(EMBl-EBI) Wellcome Trust Genome CampusHinxtonUK

Response to vernalization and photoperiod are the main determinants controlling the time to flowering in temperate cereals. While the individual genes that determine a plant's response to these environmental signals are well characterized, the combinatorial effect on flowering time of allelic variants for multiple genes remains unresolved. This study investigated the genetic control of flowering-time in a biparental population of spring barley, derived from a wide cross between a late-flowering European and an early-flowering North-American cultivar. While the major flowering time genes are not segregating in the Beka ×logan cross, large variation in flowering was observed. We identified five QTl, with both parents found to contribute early alleles. The catalog of QTl discovered aligns with several candidate genes affecting flowering time in barley. The combination of particular alleles at HvCEN, HvElF3 and HvFT1 in logan are responsible for the earliness of this cultivar. Interestingly, earliness for flowering could be further enhanced, with Beka found to contribute three early alleles, including a QTl colocating with a HvFD-like gene, suggesting that there are diverse aspects of the flowering-time pathway that have been manipulated in these two cultivars. Epistatic interactions between flowering-time QTl or candidate genes were observed in field data and confirmed under controlled conditions. The results of this study link photoperiod-dependent flowering-time genes with earliness per se genes into a single model, thus providing a unique framework that can be used by geneticists and breeders to optimize flowering time in barley.

关键词： Barley Flowering HvElF3 HvCEN HvFT1

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Genic C-Methylation in Soybean Is Associated with Gene Paralogs Relocated to Transposable Element-Rich Pericentromeres

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Molecular Plant 2018年第3期11卷 485-495页

作者： Moaine El Baidouri Kyung Do Kim Brian Abernathy Ying-Hui li li-Juan Qiu scott A. Jackson Center for Applied Genetic Technologies University of Georgia 111 Riverbend Road Athens GA 30602 USA Corporate R&D LG Chem LG Science Park 30 Magokjungang 10-ro Gangseo-gu Seoul 07796 Republic of Korea The National Key Facility for Crop Gene Resources and Genetic Improvement (NFCRI) Institute of Crop Science Chinese Academy of Agricultural SciencesBeijing China These authors contributed equally to this article.

Most plants are polyploid due to whole-genome duplications （WGD） and can thus have duplicated genes. Following a WGD, paralogs are often fractionated （lost） and few duplicate pairs remain. little attention has been paid to the role of DNA methylation in the functional divergence of paralogous genes. Using high- resolution methylation maps of accessions of domesticated and wild soybean, we show that in soybean, a recent paleopolyploid with many paralogs, DNA methylation likely contributed to the elimination of ge- netic redundancy of polyploidy-derived gene paralogs. Transcriptionally silenced paralogs exhibit partic- ular genomic features as they are often associated with proximal transposable elements （TEs） and are pref- erentially located in pericentromeres, likely due to gene movement during evolution. Additionally, we provide evidence that gene methylation associated with proximal TEs is implicated in the divergence of expression profiles between orthologous genes of wild and domesticated soybean, and within populations.

关键词： soybean paralog gene methylation proximal transposable element methylation spreading

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Pathophysiology of cerebral oedema in acute liver failure

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World Journal of Gastroenterology 2013年第48期19卷 9240-9255页

作者： Teresa R scott Victoria T Kronsten Robin D Hughes Debbie l Shawcross Institute of liver Studies King’s College London School of Medicine at King’s College Hospital King’s College Hospital London SE5 9RS United Kingdom

Cerebral oedema is a devastating consequence of acute liver failure(AlF)and may be associated with the development of intracranial hypertension and *** AlF,some patients may develop cerebral oedema and increased intracranial pressure but progression to lifethreatening intracranial hypertension is less frequent than previously described,complicating less than one third of cases who have proceeded to coma since the advent of improved clinical *** rapid onset of encephalopathy may be dramatic with the development of asterixis,delirium,seizures and *** and vasogenic oedema mechanisms have been implicated with a preponderance of experimental data favouring a cytotoxic *** swelling is the most consistent neuropathological finding in humans with AlF and ammonia plays a definitive role in the development of cytotoxic brain *** mechanism(s)by which ammonia induces astrocyte swelling remains unclear but glutamine accumulation within astrocytes has led to the osmolyte *** evidence also supports an alternate‘Trojan horse’hypothesis,with glutamine as a carrier of ammonia into mitochondria,where its accumulation results in oxidative stress,energy failure and ultimately astrocyte *** a complete breakdown of the blood-brain barrier is not evident in human AlF,increased permeation to water and other small molecules such as ammonia has been demonstrated resulting from subtle alterations in the protein composition of paracellular tight *** present,there is no fully efficacious therapy for cerebral oedema other than liver transplantation and this reflects our incomplete knowledge of the precise mechanisms underlying this process which remain largely unknown.

关键词： Cerebral oedema Acute liver failure Ammonia Hepatic encephalopathy Intracranial pressure Intracranial hypertension Cerebral blood flow

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