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DOCK8 regulates signal transduction events to control immunity

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Cellular & Molecular Immunology 2017年第5期14卷 406-411页

作者： Conor J kearney Katrina l Randall Jane Oliaro Immune Defence laboratory Cancer Immunology Division The Peter MacCallum Cancer Centre East Melbourne Victoria 3002 Australia Sir Peter MacCallum Department of Oncology The University of Melbourne Parkville Victoria 3052 Australia Department of Immunology and Infectious Disease The John Curtin School of Medical Research Australian National University Acton Australian Capital Territory 2601 Australia Australian National University Medical School Australian National University Acton Australian Capital Territory 2605 Australia

Genetic mutations in the gene encoding DOCK8 cause an autosomal recessive form of hyper immunoglobulin E syndrome （AR-HIES）, referred to as DOCK8 deficiency. DOCK8 deficiency in humans results in the onset of combined immunodeficiency disease （CID）, clinically associated with chronic infections with diverse microbial pathogens, and a predisposition to malignancy. It is now becoming clear that DOCK8 regulates the function of diverse immune cell sub-types, particularly lymphocytes, to drive both innate and adaptive immune responses. Early studies demonstrated that DOCK8 is required for lymphocyte survival, migration and immune synapse formation, which translates to poor pathogen control in the absence of DOCK8. However, more recent advances have pointed to a crucial role for DOCK8 in regulating the signal transduction events that control transcriptional activity, cytokine production and functional polarization of immune cells. Here, we summarize recent advances in our understanding of DOCK8 function, paying particular attention to an emerging role as a signaling intermediate to promote immune responses to diverse external stimuli.

关键词： DOCK8 immunodeficiency lymphocytes NK Cells signal transduction

Practical Application of Altitude/Hypoxic Training for Olympic Medal Performance:The Team USA Experience

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Journal of Science in Sport and Exercise 2022年第4期4卷 358-370页

作者： Randall l.Wilber United States Olympic&Paralympic Committee 1 Olympic PlazaColorado SpringsCO 80909USA

Although scientific conclusions remain equivocal,there is evidence-based research,as well as anecdotal support,suggesting that altitude training can enhance performance among Olympic level athletes,particularly in endurance *** appears to be due primarily to hypoxia-induced increases in total hemoglobin mass and subsequent improvements in maximal oxygen uptake and other factors contributing to aerobic *** less clear,it is possible that non-hematological adaptations may contribute secondarily to improvements in post-altitude *** physiological effects are most likely realized when the altitude exposure is of sufficient“hypoxic dose”to provide the necessary stimuli for performance-affecting changes to occur via hypoxia-inducible factor 1α(HIF-1α)and hypoxia-inducible factor 2α(HIF-2α)pathways and their downstream molecular *** USA has made a strong commitment over the past 20 years to utilizing altitude training for the enhancement of performance in elite athletes in preparation for the Olympic Games and World *** USA’s strongest medal-producing Olympic sports-USA Swimming and USA Track and Field-embraced altitude training several years ago,and they continue to be leaders within Team USA in the practical and successful application of altitude *** USA Swimming utilizes traditional“live high and train high”(lH+TH)altitude training,USA Track and Field tends more toward the use of the altitude training strategy whereby athletes live high(and potentially sleep higher,either naturally or via simulated altitude),while training high during moderate-intensity(lactate threshold 2)training sessions,and train low during high-intensity(>lactate threshold 2)training sessions(lH+TH_([lT])+Tl_([>lT])).Although USA Swim-ming and USA Track and Field have taken different approaches to altitude training,they have been equally successful at the Olympic Games and World Championships,both teams being ranked first

关键词： Hypoxia live high-train high live high-train low Intermittent hypoxic training Elite performance

瘦素是冠心病患者体内的一种非内皮依赖性血管舒张剂:瘦素抵抗组织特异性的证据

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世界核心医学期刊文摘（心脏病学分册） 2007年第3期3卷 47-48页

作者： Momin A.U. Melikian N. Shah A.M. M.T. kearney 韩瑞娟 Cardiovascular Division King's College School of Medicine at Guy'sKing's College London SE5 9PJUnited Kingdom

目的:本研究旨在探寻冠心病患者中瘦素血管活性的机制和相关因素。方法和结果:纳入131例患者(年龄65.7±0.7岁;x±sx),通过隐静脉(SV)环评估离体血管对瘦素(10-13M～10-7M)的反应性。

关键词：瘦素抵抗离体血管组织特异性隐静脉内皮依赖性内皮剥脱脂肪分布乳内动脉舒张反应指数和

linking microbial community analysis and ecosystem studies: A rapid lipid analysis protocol for high throughput

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Soil Ecology letters 2019年第1期1卷 22-32页

作者： Teri C.Balser Chao liang Jessica l.M.Gutknecht Department of Soil Science University of Wisconsin-Madison1525 Observatory DriveMadisonWI 53706USA Faculty of Science and Engineering Curtin UniversityPerthWestern Australia6845 Australia Institute of Applied Ecology Chinese Academy of SciencesShenyang 110016China Department of Soil Waterand ClimateUniversity of Minnesota439 Borlaug Hall1991 Upper Buford CircleSt.PaulMN 55108USA

During the past two decades interest in linking soil microbial community composition and activity with ecosystem scale field studies of nutrient cycling or plant community response to disturbances has *** its importance there are challenges in making this *** is the question of analytical *** general,microbiological community-level methodologies have not been readily adaptable to the large sample sizes necessary for ecosystem-scale *** a result,it has been difficult to generate compatible microbial and ecosystem data *** lipid analysis shows potential as a middle ground between simple biomass measures and molecular ***,the two protocols that have most often been followed are either rapid but indiscriminate(total lipid analysis or fatty acid methyl ester analysis;FAME),or precise but time consuming(phospholipid fatty acid analysis;PlFA).In this paper we report results from a standardized soil used test a modified extraction method(the‘hybrid’method)developed to balance the speed of FAME and the precision of PlFA in order to increase sample *** comparing the three methods,we find that FAME and PlFA are qualitatively and quantitatively *** FAME method yielded the highest fatty acid abundance,but also had high variance resulting in low *** PlFA method had precision,but low ***‘hybrid’method fell midway between FAME and PlFA for quantitative fatty acid *** addition,the hybrid extraction can be completed in a fraction of the time it takes for *** hybrid protocol appears to provide an optimal balance between effort and accuracy and therefore is a good choice for large-scale ecosystem studies.

关键词： Microbial community composition lipid analysis PlFA MIDI-FAME Ecosystem studies

Scientific case studies in land-use driven soil erosion in the central United States: Why soil potential and risk concepts should be included in the principles of soil health

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International Soil and Water Conservation Research 2018年第1期6卷 63-78页

作者： Benjamin l.Turner Jay Fuhrer Melissa Wuellner Hector M.Menendez Barry H.Dunn Roger Gates Texas A&M University-Kingsville Department of AgricultureAgribusinessand Environmental Science700 University Blvd.MSC 228KingsvilleTX 78363USA North Dakota Natural Resource Conservation Service 220 East Rosser AvenuePO Box 1458BismarckND 58502-1458USA University of Nebraska-kearney Department of BiologyBruner Hall of Science240111th AvenueKearneyNE 68849-1140USA South Dakota State University Department of Natural Resource ManagementBox 2140BBrookingsSD 57007USA South Dakota State University Box 2201BrookingsSD 57007USA University of Georgia 104 S.Thornton Ave.DaltonGA 30720USA

Despite recent improvements in overall soil health gained through conservation agriculture, which has become a global priority in agricultural systems, soil and water-related externalities (e.g., wind and water erosion) continue to persist or worsen. Using an inductive, systems approach, we tested the hypothesis that such externalities persist due to expansion of cultivation onto areas unsuitable for sustained production. To test this hypothesis, a variety of data sources and analyses were used to uncover the land and water resource dynamics underlying noteworthy cases of soil erosion (either wind or water) and hydrological effects (e.g., flooding, shifting hydrographs) throughout the central United States. Given the evidence, we failed to reject the hypothesis that cultivation expansion is contributing to increased soil and water externalities, since significant increases in cultivation on soils with severe erosion limitations were observed everywhere the externalities were documented. We discuss the case study results in terms of land use incentives (e.g., policy, economic, and biophysical), developing concepts of soil security, and ways to utilize case studies such as those presented to better communicate the value of soil and water resource conservation. Incorporating the tenets of soil potential and soil risk into soil health evaluations and cultivation decision-making is needed to better match the soil resource with land use and help avoid more extreme soil and water-related externalities.

关键词： Soil erosion Watershed runoff Soil potential Soil security Externality

Characterization of novel Brown midrib 6 mutations affecting lignin biosynthesis in sorghum

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Journal of Integrative Plant Biology 2016年第2期58卷 136-149页

作者： Erin D. Scully Tammy Gries Deanna l. Funnell-Harris Zhanguo Xin Frank A. Kovacs Wilfred Vermerris Scott E. Sattler Grain Forage and Bioenergy Research Unit USDA-ARS Lincoln NE 68583 USA Department of Agronomy and Horticulture University of Nebraska-Lincoln Lincoln NE 68583 USA Department of Plant Pathology University of Nebraska-Lincoln Lincoln NE 68583 USA Plant Stress and Germplasm Development Unit USDA-ARS Lubbock TX 79414 USA Department of Chemistry University of Nebraska-Kearney Kearney NE 68849 USA Department of Microbiology & Cell Science and UF Genetics Institute University of Florida Gainesville FL 32610 USA

The presence of lignin reduces the quality of lignocellulosic biomass for forage materials and feedstock for biofuels. In C4 grasses, the brown midrib phenotype has been linked to mutations to genes in the monolignol biosynthesis pathway. For example, the Bmr6 gene in sorghum （Sorghum bicolor） has been previously shown to encode cinnamyl alcohol dehydrogenase （CAD）, which catalyzes the final step of the monolignol biosynthesis pathway. Mutations in this gene have been shown to reduce the abundance of lignin, enhance digestibility, and improve saccharification efficiencies and ethanol yields. Nine sorghum lines harboring five different bmr6 alleles were identified in an EMS-mutagenized TIllING population. DNA sequencing of Bmr6 revealed that the majority of the mutations impacted evolutionarily conserved amino acids while three-dimensional structural modeling predicted that all of these alleles interfered with the enzyme＇s ability to bind with its NAPPH cofactor. All of the new alleles reduced in vitro CAD activity levels and enhanced glucose yields following saccharification. Further, many of these lines were associated with higher reductions in acid detergent lignin compared to lines harboring the previously characterized bmr6-ref allele. These bmr6 lines represent new breeding tools for manipulating biomass composition to enhance forage and feedstock quality.

关键词： Cinnamyl alcohol dehydrogenase (CAD) EMS mutagenesis biofuels C4 grass forage