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Fluorine-thiol displacement probes for acetaminophen's hepatotoxicity

Acta Pharmaceutica Sinica B 2023年第1期13卷 204-212页

作者： Benjamin L.Prather Shuyue Ji Yue Zhao Femil Joseph Shajan Mi Zhao Zakey Yusuf Buuh robert Maloney Rui Zhang Carson Cohen Rongsheng e.Wang Department of Chemistry Temple UniversityPhiladelphiaPA 19122USA

Chemicals possessing reactive electrophiles can denature innate proteins leading to undesired toxicity,and the overdose-induced liver injury by drugs containing electrophiles has been one of the major causes of non-approval and withdraw by the US Food and Drug Administration(FDA).elucidating the associated proteins could guide the future development of therapeutics to circumvent these drugs’toxicities,but was largely limited by the current probing tools due to the steric hindrance of chemical tags including the common“click chemistry”*** the widely used non-steroidal anti-inflammatory drug acetaminophen(APAP)as an example,we hereby designed and synthesized an APAP analogue using fluorine as a steric-free *** toxicity studies indicated our analogue has similar activity to the parent *** analogue was applied to the mouse hepatocellular proteome together with the corresponding desthiobiotinSH probe for subsequent fluorine-thiol displacement reactions(FTDRs).This set of probes has enabled the labeling and pull-down of hepatocellular target proteins of the APAP metabolite as validated by Western *** preliminary validation results supported the interaction of APAP with the thioredoxin protein,which is an important redox protein for normal liver *** results demonstrated that our probes confer minimal steric perturbation and mimic the compounds of interest,allowing for global profiling of interacting *** fluorine-thiol displacement probing system could emerge as a powerful tool to enable the investigation of drug-protein interactions in complex biological environments.

关键词： Acetaminophen(APAP) Liver Hepatotoxicity Bioorthogonal Click chemistry Fluorinedisplacement Fluorinethiol displacementreaction FTDR

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Covering Your Bases： Inheritance of DNA Methylation in Plant Genomes

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Molecular Plant 2014年第3期7卷 472-480页

作者： Chad e. Niederhuth robert J. Schmitz Department of Genetics University of Georgia Athens GA 30602 USA

Cytosine methylation is an important base modification that is inherited across mitotic and meiotic cell divisions in plant genomes. Heritable methylation variants can contribute to within-species phenotypic variation. Few methylation variants were known until recently, making it possible to begin to address major unanswered questions： the extent of natural methylation variation within plant genomes, its effects on phenotypic variation, its degree of depend- ence on genotype, and how it fits into an evolutionary context. Techniques like whole-genome bisulfite sequencing （WGBS） make it possible to determine cytosine methylation states at single-base resolution across entire genomes and populations. Application of this method to natural and novel experimental populations is revealing answers to these long-standing questions about the role of DNA methylation in plant genomes.

关键词： DNA methylation epigenetics epiallele whole-genome bisulfite sequencing.

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evaluation of the Heat,entropy,and Rotational Changes Produced by Gravitational Segregation during Core Formation

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Journal of earth Science 2015年第1期26卷 124-133页

作者： Anne M.Hofmeister robert e.Criss Department of earth and Planetary Sciences Washington University

Core formation by gravitational segregation allegedly released sufficient interior heat to melt the earth. Analysis of the energetics, which compare gravitational potential energy （Ug） of a fictitious, homogeneous reference state to earth＇s current layered configuration, needs updating to correct errors and omissions, and to accommodate recent findings：（1） An erroneous positive sign was used for Ug while maintaining the reference value of 0 at infinity, which results in an incorrect sign fur AUg, which is crucial in determining whether a process is endothermic or exothermic. （2） The value of Ug for earth＇s initial state is uncertain. （3） Recent meteorite evidence indicates that core formation began before the earth was full-sized, which severely limits AUg. （4） Inhomogeneous accretion additionally reduced AUg. （5） The potentially large effect of differential rotation between the core and the mantle was not accounted for. （6） entropy changes associated with creating order were neglected. Accordingly, we revise values of Ug, evaluate uncertainties, and show that AUg was converted substantially to eonfigurational energy （TAS）. These considerations limit the large sources of primordial heat to impacts and radioactivity. Although these processes may play a role in core formation, their energies are independent of gravitational segregation, which produces order and rotational energy, not internal heat. Instead, gravitational segregation promotes planetary cooling mainly because it segregates lithophilic radioactive elements upward, increasing surface heat flux while shortening the distance over which radiogenic heat diffuses outwards.

关键词： core formation primordial heat configurational energy thermodynamics rotational energy.

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Long-Term Survival in Traumatic Brain Injury and Near-Death experience Increases Suicide Risks: A Personal experience and Related Literature

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Open Journal of Medical Psychology 2022年第3期11卷 112-124页

作者： robert e. Brandt Akihiro Takeuchi Hirotoshi Kamata Meded Japan 3-2-12 Eifuku Suginami Tokyo Japan Department of Medical Informatics Kitasato University School of Medicine Kanagawa Japan Department of Hematology Kitasato University School of Medicine Kanagawa Japan

Background: Traumatic brain injury (TBI) remains a cause of lifelong disability, death, and suicide worldwide. TBI-induced near-death experience (NDe) could increase suicide risks. Objective: We investigated TBI coupled with NDe and posttraumatic stress disorder (PTSD) as a possible indicator of suicide. Methods: A 17-year-old male who sustained an acute severe TBI in a traffic collision, was comatose 14 days, had an NDe awakening from the coma, and, years after rehabilitation, suffered PTSD, clinical depression, and survived a suicide attempt. This personal experience of a TBI-induced NDe and lingering PTSD was acquired directly from the patient by interview. We discuss his case while considering relevant literature. Results: Longitudinal data from 1961 to 2021 generated from the PubMed interface revealed 4056 TBI patients committed suicide. NDe was only reported in one of those cases and, although not a suicide, in the personal experience. Neuropsychological assessment at long-term follow-ups revealed few TBI patients exhibited normal mental/physical functions compared to the general population. Unfavorable GOS scores were risk predictors for neuropsychological/physical impairments later in life, with outcomes of depression, PTSD, poor QOL, and/or suicide. Conclusions: For TBI-NDe survivors, including those with PTSD, long-term periodic neuropsychological follow-ups and psychosocial support may help decrease suicide risks.

关键词： Traumatic Brain Injury Long-Term Outcome Posttraumatic Stress Disorder Near-Death experience Suicide

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Thinning and in-stream wood recruitment in riparian second growth forests in coastal Oregon and the use of buffers and tree tipping as mitigation

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Journal of Forestry Research 2016年第4期27卷 821-836页

作者： Lee e.Benda S.e.Litschert Gordon Reeves robert Pabst TerrainWorks Mt. Shasta CA 96067 USA BLM National Operations Center Denver CO 80225-0047USA Pacific Northwest Research Station U.S. Forest ServiceCorvallis OR 97331 USA Oregon State University Corvallis OR 97331 USA

Many aquatic habitats in coastal Oregon have been impacted by historic land use practices that led to losses of in-stream wood and associated degraded fish habitats. Many of these streams are now bordered by stands of dense second growth forests（30–80 years） that are incorporated into riparian buffer zones with low wood recruitment and storage. Thinning in riparian zones is one management option to increase the rate of large tree growth and eventually larger in-stream wood, however, it raises concern about impacts on current wood recruitment, among other issues. Using a forest growth simulation model coupled to a model of in-stream wood recruitment, we explore riparian management alternatives in a Douglas-fir plantation in coastal Oregon. Alternatives included：（1） no treatment,（2） single and double entry thinning, without and with a 10-m buffer, and（3） thinning combined with mechanical introduction of some portion of the thinned trees into the stream（tree tipping）. Compared to no treatment, single and double entry thinning on one side of a channel, without a 10-m buffer, reduce cumulative instream wood volume by 33 and 42 %, respectively, after100 years（includes decay）. Maintaining a 10-m buffer reduces the in-stream wood loss to 7 %（single entry thin）and 11 %（double entry）. To completely offset the losses of in-stream wood in a single entry thin（on one or both sides of the stream）, in the absence or presence of a 10-m buffer,requires a 12–14 % rate of tree tipping. Relative to the notreatment alternative, cumulative in-stream wood storage can be increased up to 24 % in a double-entry thin with no buffer by tipping 15–20 % of the thinned trees（increased to 48 % if thinning and tipping simultaneously on both sides of the stream）. The predicted increases in in-stream wood that can occur during a thin with tree tipping may be effective for restoring fish habitat, particularly in aquatic systems that have poor habitat conditions and low levels of in-stream wood due to h

关键词： thinning mitigation coastal Oregon forests habitat piece plantation stands cumulative

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Tripolye Mega-Sites:“Collective Computational Abilities”of Prehistoric Proto-Urban Societies?

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Journal of Social Computing 2022年第1期3卷 75-90页

作者： Johannes Müller robert Hofmann Mila Shatilo the Institute of Prehistoric and Protohistoric Archaeology Kiel UniversityKiel 24106Germany

In the east european region between Prut and Dnieper,proto-urban mega-sites developed ca.4100−3600 BCe with population agglomerations of around 10000 inhabitants per *** outline of complexity categories,based on *** et al.(2018),illustrates that“computational abilities”are first developed to make the shift from dispersed to agglomerated settlement *** development of an internal decision-making system for a polity that organizes communication via public buildings on different levels,together with a site-specific track system,may be responsible for this shift(or made it possible).However,after generations,this communication pattern was not developed into further collective communication abilities(e.g.,into a writing system),while at the same time a tendency toward centralizing decision processes probably destroyed the communication *** ultimately led to the collapse of Tripolye mega-sites.

关键词： non-state societies social constitution Chalcolithic mega-sites Tripolye

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Characterizing motor impulsivity of individuals classified as overweight to obese

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Sports Medicine and Health Science 2023年第4期5卷 314-318页

作者： Kyle D.Flack robert e.Anderson III Kylie F.McFee Bridgette T.Day Department of Dietetics and Human Nutrition College of AgricultureUniversity of KentuckyLexingtonKYUSA

Deficits in the impulse control system are an important predictor of energy intake and body *** classified as overweight to obese may possess these deficits as a general behavioral trait or they may be food*** present study assessed motor impulsivity(ability to suppress a pre-potent response)when presented with food and neutral(non-food)cues,testing if deficits in motor impulsivity is specific to food cues or a general trait among participants classified as overweight to *** proportion of inhibitory failures to no-go targets following food cues(10.8%)was significantly greater than the proportion of inhibitory failures to no-go targets following neutral cues(1.9%,pese differences remained when covering for sex and *** indicates deficits in food-specific impulse control(as opposed to general impulse control)are present in those classified as overweight to *** the specific aspect of impulse control that is present in this population is needed for the development of future impulse control training interventions that seek to change eating behaviors as a means for weight control.

关键词： Impulsivity Inhibitory control Impulse control Response inhibition Food cues Obesity Go/NoGo task

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FORCeD SOLITARY WAVeS IN A PARAMeTRICALLY eXCITeD CIRCULAR TANK

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Science China Mathematics 1992年第5期35卷 570-575页

作者：王本仁 robert.e.APFeL Institute of Acoustics Nanjing University Nanjing 210008 PRC Yale University Connecticut 06520 U.S.A.

A new mode of nonpropagating solitary waves in circular tank, which are forcedly ex-cited in tbe vertical direction, is described. The waveform is measured and the data accordwell with the hyperbolic secant *** of the vibration modes of the wave showthat the mode is not a pure mode of circular container. A wax cone was inserted in themiddle of tank in order to keep down the plateau. The hysteresis phenomenon of excitation ofsolitary wave has been observed as well.

关键词： solitary wave water waves nonpropagating solitary wave parametrically excited vibration.

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electroanalysis overview:Addressing the green credentials in the use of electroanalytical sensors

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Green Carbon 2023年第1期1卷 85-93页

作者： robert D.Crapnel Craig e.Banks Faculty of Science and engineering Manchester Metropolitan UniversityChester StreetM15GD ManchesterUnited Kingdom

electrochemical methodologies provide a wide arsenal of options for analytical sensors,providing a high sensitivity,short analysis time,low-cost,possibility for miniaturization,and are readily portable *** common theme within the literature is the use of the word“green”.The use of this terminology is intended to demonstrate the development of electroanalytical sensing platforms utilizing biodegradable and sustainable *** many cases,the claims of“green”electroanalytical platforms is *** minireview looks to address the green credentials that are utilized in the pursuit of electroanalytical sensors,offering insights into future research opportunities.

关键词： electroanalysis Biodegradable Sensors Green chemistry Circular economy Recycling Sustainability

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Developmental ecology of the American horseshoe crab Limulus polyphemus

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Current Zoology 2010年第5期56卷 550-562页

作者： Mark L.BOTTON Richard A.TANKeRSLeY robert e.LOVeLAND Department of Natural Sciences Fordham University Department of Biological Sciences Florida Institute of Technology Department of ecology Evolution and Natural Resources Rutgers University

During spawning events,horseshoe crab eggs are released from the female's oviducts,and fertilized by one or *** are shaped by the female into discrete clutches deposited in nests at depths of 10-20 cm on intertidal *** between fresh eggs and the early developmental stages is obfuscated by the large amount of dense,opaque *** first unambiguous confirmation of development is the formation of the rudimentary prosomatic appendages atthe 'limb bud' *** days thereafter,the outer chorion is shed and the developing embryo expands and undergoes a seriesof molts within the clear inner egg *** trilobite (first instar) stage thus attained may remain within the beach sedimentsfor several more weeks,until hatching is facilitated by environmental factors such as hydration,agitation,and osmoticshock that accompany the infiltration of seawater into the *** exhibit endogenous circatidal swimming rhythms thatare entrained by mechanical agitation,suggesting that peaks in larval swimming are timed to coincide with periods of high waterand the inundation of the *** swimming is limited and does not appear to result in long-distance *** limiteddispersal of the larvae has important implications for the population dynamics of relatively isolated *** rate of larvaldevelopment is highly plastic and is influenced by temperature,salinity,dissolved oxygen,and the presence of *** environmental tolerances of horseshoe crab embryos and larvae are important in understanding their current geographicdistribution and their evolutionary

关键词：水环境因素美国生态早期发育阶段胚胎发育种群动态模糊处理机械搅拌

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