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CUX2, BRAP and ALDH2 are associated with metabolic traits in people with excessive alcohol consumption

SCIENTIFIC REPORTS 2020年第1期10卷 1-11页

作者： Chen, I-Chun Kuo, Po-Hsiu Yang, Albert C. Tsai, Shih-Jen Liu, Tung-Hsia Liu, Hung-Jen Lan, Tsuo-Hung Chen, Hong-Ming Huang, Huang-Nan Chung, Ren-Hua Liu, Yu-Li Taichung Vet Gen Hosp Dept Psychiat Taichung Taiwan Natl Chung Hsing Univ PhD Program Translat Med Taichung Taiwan Natl Chung Hsing Univ Rong Hsing Res Ctr Translat Med Taichung Taiwan Natl Taiwan Univ Inst Epidemiol & Prevent Med Coll Publ Hlth Taipei Taiwan Natl Taiwan Univ Dept Publ Hlth Coll Publ Hlth Taipei Taiwan Harvard Med Sch Div Interdisciplinary Med & Biotechnol Beth Israel Deaconess Med Ctr Boston MA 02115 USA Natl Yang Ming Univ Inst Brain Sci Taipei Taiwan Natl Yang Ming Univ Div Psychiat Taipei Taiwan Taipei Vet Gen Hosp Dept Psychiat Taipei Taiwan Natl Hlth Res Inst Ctr Neuropsychiat Res 35 Keyan Rd Zhunan Town 35053 Miaoli County Taiwan Natl Chung Hsing Univ Inst Mol Biol 145 Xingda Rd Taichung 402 Taiwan Natl Yang Ming Univ Fac Med Taipei Taiwan Tunghai Univ Dept Appl Math Taichung Taiwan Natl Hlth Res Inst Inst Populat Hlth Sci Div Biostat & Bioinformat Taipei Taiwan China Med Univ Grad Inst Clin Med Sci Taichung Taiwan

Molecular mechanisms that prompt or mitigate excessive alcohol consumption could be partly explained by metabolic shifts. This genome-wide association study aims to identify the susceptibility gene loci for excessive alcohol consumption by jointly measuring weekly alcohol consumption and gamma-GT levels. We analysed the Taiwan Biobank data of 18,363 Taiwanese people, including 1945 with excessive alcohol use. We found that one or two copies of the G allele in rs671 (ALDH2) increased the risk of excessive alcohol consumption, while one or two copies of the C allele in rs3782886 (BRAP) reduced the risk of excessive alcohol consumption. To minimize the influence of extensive regional linkage disequilibrium, we used the ridge regression. The ridge coefficients of rs7398833, rs671 and rs3782886 were unchanged across different values of the shrinkage parameter. The three variants corresponded to posttranscriptional activity, including cut-like homeobox 2 (a protein coded by CUX2), Glu504Lys of acetaldehyde dehydrogenase 2 (a protein encoded by ALDH2) and Glu4Gly of BRCA1-associated protein (a protein encoded by BRAP). We found that Glu504Lys of ALDH2 and Glu4Gly of BRAP are involved in the negative regulation of excessive alcohol consumption. The mechanism underlying the gamma-GT-catalytic metabolic reaction in excessive alcohol consumption is associated with ALDH2, BRAP and CUX2. Further study is needed to clarify the roles of ALDH2, BRAP and CUX2 in the liver-brain endocrine axis connecting metabolic shifts with excessive alcohol consumption.

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Gramicidin Increases Lipid Flip-Flop in Symmetric and Asymmetric Lipid Vesicles

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BIOPHYSICAL JOURNAL 2019年第5期116卷 860-873页

作者： Doktorova, Milka Heberle, Frederick A. Marquardt, Drew Rusinova, Radda Sanford, R. Lea Peyear, Thasin A. Katsaras, John Feigenson, Gerald W. Weinstein, Harel Andersen, Olaf S. Weill Cornell Med Coll Tri Inst PhD Program Computat Biol & Med New York NY 10065 USA Univ Texas Hlth Sci Ctr Houston Dept Integrat Biol & Pharmacol Houston TX 77030 USA Univ Tennessee Bredesen Ctr Interdisciplinary Res & Grad Educ Knoxville TN USA Univ Windsor Windsor ON Canada Weill Cornell Med Coll Dept Physiol & Biophys New York NY USA Oak Ridge Natl Lab Large Scale Struct Grp Oak Ridge TN USA Oak Ridge Natl Lab Shull Wollan Ctr Oak Ridge TN USA Cornell Univ Dept Mol Biol & Genet Ithaca NY USA Weill Greenberg Ctr HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsau New York NY USA

Unlike most transmembrane proteins, phospholipids can migrate from one leaflet of the membrane to the other. Because this spontaneous lipid translocation (flip-flop) tends to be very slow, cells facilitate the process with enzymes that catalyze the transmembrane movement and thereby regulate the transbilayer lipid distribution. Nonenzymatic membrane-spanning proteins with unrelated primary functions have also been found to accelerate lipid flip-flop in a nonspecific manner and by various hypothesized mechanisms. Using deuterated phospholipids, we examined the acceleration of flip-flop by gramicidin channels, which have well-defined structures and known functions, features that make them ideal candidates for probing the protein-membrane interactions underlying lipid flip-flop. To study compositionally and isotopically asymmetric proteoliposomes containing gramicidin, we expanded a recently developed protocol for the preparation and characterization of lipid-only asymmetric vesicles. Channel incorporation, conformation, and function were examined with small angle x-ray scattering, circular dichroism, and a stopped-flow spectrofluorometric assay, respectively. As a measure of lipid scrambling, we used differential scanning calorimetry to monitor the effect of gramicidin on the melting transition temperatures of the two bilayer leaflets. The two calorimetric peaks of the individual leaflets merged into a single peak over time, suggestive of scrambling, and the effect of the channel on the transbilayer lipid distribution in both symmetric 1-palmitoy1-2-oleoyl-sn-glycero-3-phosphocholine and asymmetric 1-palmitoy1-2-oleoyl-sn-glycero-3-phosphocholine/1,2-dimyristoyl-sn-glycero-3-phosphocholine vesicles was quantified from proton NM R measurements. Our results show that gramicidin increases lipid flip-flop in a complex, concentration-dependent manner. To determine the molecular mechanism of the process, we used molecular dynamics simulations and further computational analy

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Neuro-Inspired Reinforcement Learning to Improve Trajectory Prediction in Reward-Guided Behavior

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INTERNATIONAL JOURNAL OF NEURAL SYSTEMS 2022年第9期32卷 2250038-2250038页

作者： Chen, Bo-Wei Yang, Shih-Hung Kuo, Chao-Hung Chen, Jia-Wei Lo, Yu-Chun Kuo, Yun-Ting Lin, Yi-Chen Chang, Hao-Cheng Lin, Sheng-Huang Yu, Xiao Qu, Boyi Ro, Shuan-Chu Vina Lai, Hsin-Yi Chen, You-Yin Natl Yang Ming Chiao Tung Univ Dept Biomed Engn 155 Sec 2Linong St Taipei 11221 Taiwan Natl Cheng Kung Univ Dept Mech Engn 1 Univ Rd Tainan 70101 Taiwan Taipei Vet Gen Hosp Neurol Inst Dept Neurosurg 201Sec 2Shipai Rd Taipei 11217 Taiwan Univ Washington Dept Neurol Surg 1959 NE Pacific St Seattle WA 98195 USA Taipei Med Univ Coll Med Sci & Technol PhD Program Neural Regenerat Med 250 Wu Xing St Taipei 11031 Taiwan Buddhist Tzu Chi Med Fdn Hualien Tzu Chi Hosp Dept Neurol 707Sec 3 Zhongyang Rd Hualien 97002 Taiwan Tzu Chi Univ Sch Med Dept Neurol 701Sec 3Zhongyang Rd Hualien 97004 Taiwan Zhejiang Univ Affiliated Hosp 2 Interdisciplinary Inst Neurosci & TechnolSch Med Dept NeurolKey Lab Med Neurobiol Zhejiang Prov Hangzhou 310029 Peoples R China Zhejiang Univ Coll Biomed Engn & Instrument Key Lab Biomed Engn Hangzhou 310027 Peoples R China Zhejiang Univ Sch Brain Sci & Brain Med MOE Frontier Sci Ctr Brain Sci & Brain Machine In Hangzhou 310012 Peoples R China Johns Hopkins Sch Med Dept Biomed Engn 720 Rutland Ave Baltimore MD 21205 USA

Hippocampal pyramidal cells and interneurons play a key role in spatial navigation. In goal-directed behavior associated with rewards, the spatial firing pattern of pyramidal cells is modulated by the animal's moving direction toward a reward, with a dependence on auditory, olfactory, and somatosensory stimuli for head orientation. Additionally, interneurons in the CA1 region of the hippocampus monosynaptically connected to CA1 pyramidal cells are modulated by a complex set of interacting brain regions related to reward and recall. The computational method of reinforcement learning (RL) has been widely used to investigate spatial navigation, which in turn has been increasingly used to study rodent learning associated with the reward. The rewards in RL are used for discovering a desired behavior through the integration of two streams of neural activity: trial-and-error interactions with the external environment to achieve a goal, and the intrinsic motivation primarily driven by brain reward system to accelerate learning. Recognizing the potential benefit of the neural representation of this reward design for novel RL architectures, we propose a RL algorithm based on Q-learning with a perspective on biomimetics (neuro-inspired RL) to decode rodent movement trajectories. The reward function, inspired by the neuronal information processing uncovered in the hippocampus, combines the preferred direction of pyramidal cell firing as the extrinsic reward signal with the coupling between pyramidal cell-interneuron pairs as the intrinsic reward signal. Our experimental results demonstrate that the neuro-inspired RL, with a combined use of extrinsic and intrinsic rewards, outperforms other spatial decoding algorithms, including RL methods that use a single reward function. The new RL algorithm could help accelerate learning convergence rates and improve the prediction accuracy for moving trajectories.

关键词： Hippocampus goal-directed behaviors spatial navigation neuro-inspired reinforcement learning reward function neural decoding

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Can deception be desirable?

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SOCIAL SCIENCE INFORMATION SUR LES SCIENCES SOCIALES 2017年第1期56卷 98-106页

作者： Uz, Irem Kemmelmeier, Markus TOBB Univ Econ & Technol Ankara Turkey Univ Nevada Interdisciplinary Social Psychol PhD Program Reno NV 89557 USA

Critics of deception in research allege harm to society, the discipline of psychology, the researchers and participants. However, neither empirical findings nor a reasonable-person' test seem to support those allegations. By and large, researchers who use deception consider its costs and benefits, and the kind and degree of deceit that is typically used in psychology is of a benevolent type. Moreover, participants prefer to participate in deception research rather than its non-deceptive alternatives. In the light of these premises, we argue that deception can be desirable, especially when considering cost and benefits to research participants.

关键词： deception harm and benefits psychology experiments research ethics research participants

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Soil physical quality associated with tillage practices during sugarcane planting in south-central Brazil

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SOIL & TILLAGE RESEARCH 2019年 195卷 104383-000页

作者： Barbosa, Leandro Carneiro Graziano Magalhaes, Paulo Sergio Bordonal, Ricardo Oliveira Cherubin, Mauricio Roberto Ferreira Castioni, Guilherme Adalberto Tenelli, Sarah Junqueira Franco, Henrique Coutinho Nunes Carvalho, Joao Luis Univ Estadual Campinas FEAGRI UNICAMP Fac Agr Engn BR-13083875 Campinas SP Brazil LNBR CNPEM Brazilian Biorenewables Natl Lab Brazilian Ctr Res Energy & Mat Giuseppe Maximo Scolfaro St 10000 BR-13083100 Campinas SP Brazil NIPE UNICAMP Interdisciplinary Ctr Energy Planning Campinas SP Brazil Univ Sao Paulo Luiz de Queiroz Coll Agr Dept Soil Sci ESALQ BR-13418900 Piracicaba SP Brazil Univ Campinas UNICAMP Interdisciplinary PhD Program Bioenergy Rua Monteiro Lobato 80Cidade Univ BR-13083862 Campinas SP Brazil

Soil tillage operations had been carried out during the sugarcane planting to improve soil's physical quality, thus providing proper conditions for sugarcane growth. Long-term field experiments were designed to assess the implications of tillage operations during sugarcane planting on soil physical quality and the associated effects on sugarcane yields under two soil types in south-central Brazil. In 2013, two treatments were arranged in a randomized block design with four repetitions: (i) conventional tillage (CT) and ii) no-tillage (NT). Undisturbed soil samples were collected representing the row and inter-row positions to a 0.40-m depth (0-0.10, 0.10-0.20 and 0.20-0.40 m) over four crop cycles (from 2014 to 2017). In the laboratory, bulk density (BD), soil resistance to penetration (SRP), snacroporosity (MaP) and microporosity (MiP) were evaluated. Additionally, sugarcane yields were measured annually using an instrumented truck equipped with load cells. CT management alleviated soil compaction only in the plant cane cycle, indicating that the intensive machinery traffic performed in sugarcane harvesting nullify the effects of tillage practices. The opening of planting furrow in both tillage systems reduced soil physical limitations, thus favoring the crop development in the row position. The changes in soil physical attributes were observed mostly in the inter-row position. In clayey soil, BD increased by 24 and 16%, and the SRP by 63 and 55% in the 0-0.10 m layer from plant cane to 3rd ratoon for CT and NT, respectively. Similarly, in sandy loam soil, the SRP increased over time in the 0-0.10 m layer for CT and NT, reaching values higher than 2 MPa. Likewise, MaP decreased for values lower than 0.10 m(3) m(-3) after four years for both soils and tillage systems. Regardless of soil type, tillage management did not show differences in sugarcane yields over the assessed period. Our findings suggest that NT could be a feasible strategy to reduce soil mobilization

关键词： Soil quality Conservationist agriculture No-tillage Conventional tillage Soil compaction Sugarcane yields Saccharum spp.

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Facilitating interdisciplinary Graduate Education: Barriers, Solutions, and Needed Innovations

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Change: The Magazine of Higher Learning 2018年第5期50卷 53-59页

作者： Meredith Welch-Devine Alana Shaw Julie Coffield Nik Heynen Meredith Welch-Devine is the Director of Interdisciplinary and Innovative Initiatives for the University of Georgia Graduate School. In addition to helping develop and administer interdisciplinary programs for the university she has a research interest in interdisciplinary team science and interdisciplinary training.http://***/0000-0001-8519-4585 Alana Shaw received her PhD from the University of Georgia in 2016 and is now the Environmental Coordinator for the Village of Wainwright. Shaw was a student in the interdisciplinary Integrative Conservation program. Julie Coffield recently returned to the faculty after serving as Associate Dean of the Graduate School. She also formerly directed the Interdisciplinary Toxicology Program at UGA. Nik Heynen is the immediate past director of the interdisciplinary Integrative Conservation program.

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关键词： interdisciplinary education GRADUATE education HUMAN resources departments STUDENTS TRAINING

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Gender differences in the evaluation of aggravating and mitigating circumstances: the mediating role of attributional complexity

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PSYCHOLOGY CRIME & LAW 2018年第8期24卷 761-789页

作者： West, Matthew P. Yelderman, Logan A. Miller, Monica K. Univ Nevada Dept Criminal Justice 4505 S Maryland Pkwy Las Vegas NV 89154 USA Prairie View A&M Univ Dept Psychol Prairie View TX USA Univ Nevada Criminal Justice Dept Reno NV 89557 USA Univ Nevada Interdisciplinary Social Psychol PhD Program Reno NV 89557 USA

At the penalty phase of a capital trial, jurors endorse and weigh aggravators and mitigators. The purpose of the current studies was to examine how gender differences in attributional complexity relate to endorsements of aggravators and mitigators. In Study 1, undergraduate participants read definitions of aggravators and mitigators and rated the extent to which circumstances were aggravating or mitigating. In Study 2, a death qualified community sample read a trial summary, rated the extent to which aggravators and mitigators were present in the case, reported whether mitigators outweighed aggravators, and rendered a sentence. Results indicated that gender differences in mitigator endorsement were mediated by attributional complexity, and that gender differences in sentencing decisions were serially mediated by attributional complexity, mitigator endorsement, and aggravator and mitigator weighing.

关键词： Attributional complexity gender differences death penalty juror decision-making aggravating and mitigating evidence

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Microbial communities and diazotrophic activity differ in the root-zone of Alamo and Dacotah switchgrass feedstocks

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GLOBAL CHANGE BIOLOGY BIOENERGY 2017年第6期9卷 1057-1070页

作者： Rodrigues, Richard R. Moon, Jinyoung Zhao, Bingyu Williams, Mark A. Virginia Tech Interdisciplinary PhD Program Genet Bioinformat & 1015 Life Sci Circle Blacksburg VA 24061 USA Virginia Tech Dept Hort 220 Ag Quad Lane Blacksburg VA 24061 USA

Nitrogen (N) bioavailability is a primary limiting nutrient for crop and feedstock productivity. Associative nitrogen fixation (ANF) by diazotrophic bacteria in root-zone soil microbial communities have been shown to provide significant amounts of N to some tropical grasses, but this potential in switchgrass, a warm-season, temperate, US native, perennial tallgrass has not been widely studied. 'Alamo' and 'Dacotah' are cultivars of switchgrass, adapted to the southern and northern regions of the United States, respectively, and offer an opportunity to better describe this plant-bacterial association. The nitrogenase enzyme activity, microbial communities, and amino acid profiles in the root-zones of the two ecotypes were studied at three different plant growth stages. Differences in the nitrogenase enzyme activity and free soluble amino acid profiles indicated the potential for greater nitrogen fixation in the high productivity Alamo compared with the lower productivity Dacotah. Changes in the amino acid profiles and microbial community structure (rRNA genes) of the root-zone suggest different plant-bacterial interactions can help to explain differences in nitrogenase activity. PICRUSt analysis revealed functional differences, especially nitrogen metabolism, that supported ecotype differences in root-zone nitrogenase enzyme activity. It is thought that the greater productivity of Alamo increased the belowground flow of carbon into roots and root-zone habitats, which in turn support the high energy demands needed to support nitrogen fixation. Further research is thus needed to understand plant ecotype and cultivar trait differences that can be used to breed or genetically modify crop plants to support root-zone associations with diazotrophs.

关键词： 16s rRNA Alamo and Dacotah diazotrophs function interactions ITS microbial communities root-zone structure switchgrass

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Microbial Exposure Enhances Immunity to Pathogens Recognized by TLR2 but Increases Susceptibility to Cytokine Storm through TLR4 Sensitization

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CELL REPORTS 2019年第7期28卷 1729-+页

作者： Huggins, Matthew A. Sjaastad, Frances V. Pierson, Mark Kucaba, Tamara A. Swanson, Whitney Staley, Christopher Weingarden, Alexa R. Jensen, Isaac J. Danahy, Derek B. Badovinac, Vladimir P. Jameson, Stephen C. Vezys, Vaiva Masopust, David Khoruts, Alexander Griffith, Thomas S. Hamilton, Sara E. Univ Minnesota Dept Lab Med & Pathol Minneapolis MN 55455 USA Univ Minnesota Microbiol Immunol & Canc Biol PhD Program Minneapolis MN 55455 USA Univ Minnesota Dept Urol Minneapolis MN 55455 USA Univ Minnesota Dept Surg Box 242 UMHC Minneapolis MN 55455 USA Univ Minnesota Dept Soil Water & Climate St Paul MN 55108 USA Univ Minnesota BioTechnol Inst St Paul MN 55108 USA Univ Iowa Interdisciplinary Grad Program Immunol Iowa City IA USA Univ Iowa Dept Pathol Iowa City IA 52242 USA Univ Iowa Dept Microbiol & Immunol Iowa City IA USA Univ Minnesota Ctr Immunol Minneapolis MN 55455 USA Univ Minnesota Masonic Canc Ctr Minneapolis MN 55455 USA Univ Minnesota Dept Microbiol & Immunol Minneapolis MN USA Univ Minnesota Dept Med Box 736 UMHC Minneapolis MN 55455 USA Minneapolis VA Hlth Care Syst Minneapolis MN 55417 USA

Microbial exposures can define an individual's basal immune state. Cohousing specific pathogen-free (SPF) mice with pet store mice, which harbor numerous infectious microbes, results in global changes to the immune system, including increased circulating phagocytes and elevated inflammatory cytokines. How these differences in the basal immune state influence the acute response to systemic infection is unclear. Cohoused mice exhibit enhanced protection from virulent Listeria monocytogenes (LM) infection, but increased morbidity and mortality to polymicrobial sepsis. Cohoused mice have more TLR2(+) and TLR4(+) phagocytes, enhancing recognition of microbes through pattern-recognition receptors. However, the response to a TLR2 ligand is muted in cohoused mice, whereas the response to a TLR4 ligand is greatly amplified, suggesting a basis for the distinct response to Listeria monocytogenes and sepsis. Our data illustrate how microbial exposure can enhance the immune response to unrelated challenges but also increase the risk of immunopathology from a severe cytokine storm.

关键词： infection Listeria monocytogenes polymicrobial sepsis Toll-like receptors physiological microbial exposure microbiome

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Human perceptions of an avian predator in an urban ecosystem: close proximity to nests increases fondness among local residents

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URBAN ECOSYSTEMS 2018年第2期21卷 271-280页

作者： White, Justin Kemmelmeier, Markus Bassett, Scott Smith, Jeremy Univ Wisconsin Dept Geog & Anthropol 900 Wood Rd Kenosha WI 53141 USA Univ Nevada Interdisciplinary Social Psychol PhD Program 1664 N Virginia StMS 1300 Reno NV 89557 USA Univ Nevada Dept Geog 1664 N Virginia StMS 154 Reno NV 89557 USA Truckee Meadows Reg Planning Agcy 1105 Terminal Way 316 Reno NV 89502 USA

How humans view their local birds influences the habitat quality for the birds. Humans that enjoy birds will often consider them when altering landscapes or may enhance their own property to benefit the birds (e.g. maintaining birdfeeders, keeping cats indoors). Human perceptions of hawks are unique as hawks predatory and much larger than most other urban birds. From June-July 2016, we surveyed 280 homes near Red-tailed Hawk's (Buteo jamaicensis) nests in Reno-Sparks, NV about their perceptions of and experiences with hawks. Seventy percent of residents viewed hawks positively, 3% negatively, and 27% indifferently. Results from generalized linear mixed models indicated that whether residents had domestic animals threatened by hawks, or raised chickens, did not impact the residents' perceptions of hawks (p = 0.52, p = 0.57, respectively). Age was also a nonsignificant indicator of residents' perceptions of hawks (p = 0.34), though the residents that viewed hawks negatively were concentrated between 40 and 70 years of age. Mediation analysis revealed that human experiences with hawks (e.g. observing hawks) fully mediated the relationship between resident proximity to a nest and whether they viewed hawks positively (p < 0.001). This human-hawk relationship lies within the broader topic of nature-society interactions and based on our findings we suggest that residents' experiences with hawks can lead to the residents obtaining some of the benefits of nature-society interactions. Though unquantified in our study, these benefits can include increased positive emotions and life satisfaction, which lead to healthier residents that are more likely to engage in conservation activities.

关键词： Human-environment interactions Red-tailed hawks Urban ecosystems

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