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Converting lateral scanning into axial focusing to speed up three-dimensional microscopy

Light(Science & Applications) 2020年第1期9卷 429-440页

作者： Tonmoy Chakraborty Bingying Chen Stephan Daetwyler Bo-Jui Chang Oliver Vanderpoorten Etai Sapoznik Clemens F.Kaminski Tuomas P.J.Knowles kevin m.dean Reto Fiolka Department of Cell Biology UT Southwestern Medical CenterDallasTXUSA Department of Physics and Astronomy University of New MexicoAlbuquerqueNMUSA Department of Chemical Engineering and Biotechnology University of CambridgeCambridge CB30ASUK Department of Chemistry University of CambridgeLensfield RoadCambridge CB21EWUK Lyda Hill Department of Bioinformatics UT Southwestern Medical CenterDallasTXUSA

In optical microscopy,the slow axial scanning rate of the objective or the sample has traditionally limited the speed of volumetric ***,by conjugating either a movable mirror to the image plane in a remote-focusing geometry or an electrically tuneable lens(ETL)to the back focal plane,rapid axial scanning has been ***,mechanical actuation of a mirror limits the axial scanning rate(usually only 10–100 Hz for piezoelectric or voice coil-based actuators),while ETLs introduce spherical and higher-order aberrations that prevent high-resolution *** an effort to overcome these limitations,we introduce a novel optical design that transforms a lateral-scan motion into a spherical aberration-free axial scan that can be used for high-resolution *** a galvanometric mirror,we scan a laser beam laterally in a remote-focusing arm,which is then back-reflected from different heights of a mirror in the image *** characterize the optical performance of this remote-focusing technique and use it to accelerate axially swept light-sheet microscopy by an order of magnitude,allowing the quantification of rapid vesicular dynamics in three *** also demonstrate resonant remote focusing at 12 kHz with a two-photon raster-scanning microscope,which allows rapid imaging of brain tissues and zebrafish cardiac dynamics with diffraction-limited resolution.

关键词： mirror axial image

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Glia and hemichannels: key mediators of perinatal encephalopathy

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Neural Regeneration Research 2018年第2期13卷 181-189页

作者： Robert Galinsky Joanne O.Davidson Justin m.dean Colin R.Green Laura Bennet Alistair J.Gunn Department of Physiology University of Auckland The Ritchie Centre Hudson Institute of Medical Research Department of Ophthalmology University of Auckland

Perinatal encephalopathy remains a major cause of disability, such as cerebral palsy. Therapeutic hypo- thermia is now well established to partially reduce risk of disability in late preterm/term infants. However, new and complementary therapeutic targets are needed to further improve outcomes. There is increasing evidence that glia play a key role in neural damage after hypoxia-ischemia and infection/inflammation. In this review, we discuss the role of astrocytic gap junction （connexin） hemichannels in the spread of neural injury after hypoxia-ischemia and/or infection/inflammation. Potential mechanisms of hemichannel medi- ated injury likely involve impaired intraceUular calcium handling, loss of blood-brain barrier integrity and release of adenosine triphosphate （ATP） resulting in over-activation of purinergic receptors. We propose the hypothesis that inflammation-induced opening of connexin hemichannels is a key regulating event that initiates a vicious cycle of excessive ATP release, which in turn propagates activation of purinergic receptors on microglia and astrocytes. This suggests that developing new neuroprotective strategies for preterm infants will benefit from a detailed understanding of glial and connexin hemichannel responses.

关键词： hypoxia-ischemia connexin hemichannels spreading injury connexin 43 astrocytes hypoxicischemic encephalopathy

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Protein Phosphorylation Potentially Involved in an Ancient Adaption

Protein Phosphorylation Potentially Involved in an Ancient A...

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华东六省一市生物化学与分子生物学学会2006年学术交流会

作者： Antony m.dean BioTechnology Institute University of MinnesotaSaint Paul 55108USA

E. coli NADP-dependent isocitrate dehydrogenase (EcIDHNADP), encoded by icdA gene, locates at a crucial branch point in TCA cycle and is regulated by the reversible phosphorylation of IDH kinase/phosphatase (IDH K/P) to control isocitrate through the glyoxylate bypass during growth on poor carbon sources. The wild-type icdA gene was replaced with engineered icdA gene (encoding EcIDHNAD), native B. subtilis citC gene (encoding BsIDHNADP), or native *** icd gene (encoding SmIDHNAD) via chromosomal homologous recombination. When using acetate as a sole carbon source, the recombinant strains required much longer lag phase than wild-type E. coli and displayed decreased growth rate, especially BsIDH and SmIDH. It indicates the wild-type strain is advantaged for adjusting to the stressful environment. The affinity between EcIDHNAD and IDH K/P is decreased by -30%, and BsIDH is a highly poor substrate for IDH K/P although its structure is very similar to EcIDHNADP. There is no evidence that the genomes of B. subtilis and 5. mutans contain any sequence homologous with IDH K/P, and BsIDH and SmIDH are regulated by protein phosphorylation in vivo. Based on above reasons, the preliminary experiment results are supposed that protein phosphorylation is probably involved in an ancient adaptation that eubacterial IDHs evolved their coenzyme flavor from NAD-dependence to NADP-dependence on or around the time eukaryotes first appeared, about 3. 5 billions years ago.

关键词： isocitrate dehydrogenase homologous recombination coenzyme specificity adaptation

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Structural and functional roles of ether lipids

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Protein & Cell 2018年第2期9卷 196-206页

作者： John m. dean Irfan J. Lodhi Division of Endocrinology Metabolism and Lipid Research Department of Medicine Washington University School of Medicine Saint Louis MO 63110 USA

Ether lipids, such as plasmalogens, are peroxisome- derived glycerophospholipids in which the hydrocarbon chain at the sn-1 position of the glycerol backbone is attached by an ether bond, as opposed to an ester bond in the more common diacyl phospholipids. This seem- ingly simple biochemical change has profound structural and functional implications. Notably, the tendency of ether lipids to form non-lamellar inverted hexagonal structures in model membranes suggests that they have a role in facilitating membrane fusion processes. Ether lipids are also important for the organization and stability of lipid raft microdomains, cholesterol-rich membrane regions involved in cellular signaling. In addition to their structural roles, a subset of ether lipids are thought to function as endogenous antioxidants, and emerging studies suggest that they are involved in cell differentiation and signaling pathways. Here, we review the biology of ether lipids and their potential signifi- cance in human disorders, including neurological diseases, cancer, and metabolic disorders.

关键词： ether lipids plasmalogen phospholipid peroxisomes cancer metabolic disorders

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Assortative mating and self-fertilization differ in their contributions to reinforcement, cascade speciation, and diversification

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Current Zoology 2016年第2期62卷 169-181页

作者： dean m. CASTILLO Amanda K. GIBSON Leonie C. mOYLE Department of Biology 1001 East Third Street Indiana University Bloomington IN 47405 USA

Cascade speciation and reinforcement can evolve rapidly when traits are pleiotropic and act as both signal/cue in nonrandom mating. Here, we examine the contribution of two key traits-assortative mating and self-fertilization--to reinforcement and （by extension） cascade speciation. First, using a population genetic model of reinforcement we find that both assortative mating and self-fertilization can make independent contributions to increased reproductive isolation, consistent with reinforcement. Self-fertilization primarily evolves due to its 2-fold transmission advantage when inbreeding depression （d） is lower （d〈 0.45） but evolves as a function of the cost of hybridization under higher inbreeding depression （0.45 〈 d〈 0.48）. When both traits can evolve simultaneously, increased self-fertilization often prohibits the evolution of assortative mating. We infer that, under specific conditions, mating system transitions are more likely to lead to increased reproductive isolation and initiate cascade speciation, than assortative mating. Based on the results of our simulations, we hypothesized that transitions to self-fertilization could contribute to clade-wide diversification if reinforcement or cascade speciation is common. We tested this hypothesis with comparative data from two different groups. Consistent with our hypothesis, there was a trend towards uniparental reproduction being associated with increased diversification rate in the Nematode phylum. For the plant genus mimulus, however, self-fertilization was associated with reduced diversification. Reinforcement driving speciation via transitions to self-fertilization might be short lived or unsustainable across macroevolutionary scales in some systems （some plants）, but not others （such as nematodes）, potentially due to differences in susceptibility to inbreeding depression and/or the ability to transition between reproductive modes.

关键词： speciation pleiotropy self-fertilization.

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Glutamate transporters, EAAT1 and EAAT2, are potentially important in the pathophysiology and treatment of schizophrenia and affective disorders

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World Journal of Psychiatry 2018年第2期8卷 51-63页

作者： Georgia m Parkin madhara Udawela Andrew Gibbons Brian dean molecular Psychiatry Laboratory the Florey Institute of Neuroscience and Mental Health CRC for mental Health Research Centre for mental Health the Faculty of Health Arts and Design Swinburne University

Glutamate is the predominant excitatory neurotransmitter in the human brain and it has been shown that prolonged activation of the glutamatergic system leads to nerve damage and cell death. Following release from the pre-synaptic neuron and synaptic transmission, glutamate is either taken up into the presynaptic neuron or neighbouring glia by transmembrane glutamate transporters. Excitatory amino acid transporter(EAAT) 1 and EAAT2 are Na+-dependant glutamate transporters expressed predominantly in glia cells of the central nervous system. As the most abundant glutamate transporters, their primary role is to modulate levels of glutamatergic excitability and prevent spill over of glutamate beyond the synapse. This role is facilitated through the binding and transportation of glutamate into astrocytes and microglia. The function of EAAT1 and EAAT2 is heavily regulated at the levels of gene expression, post-transcriptional splicing, glycosylation states and cell-surface trafficking of the protein. Both glutamatergic dysfunction and glial dysfunction have been proposed to be involved in psychiatric disorder. This review will present an overview of the roles that EAAT1 and EAAT2 play in modulating glutamatergic activity in the human brain, and mount an argument that these two transporters could be involved in the aetiologies of schizophrenia and affective disorders as well as represent potential drug targets for novel therapies for those disorders.

关键词： Glia Excitatory amino acid transporter Psychiatry Affective disorders Glutamate transporter Glutamate Schizophrenia

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microstructure and mechanical properties of curved AZ31 magnesium alloy profiles produced by differential velocity sideways extrusion

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Journal of magnesium and Alloys 2023年第2期11卷 493-508页

作者： Wenbin Zhou Jianguo Lin Trevor A.dean Department of mechanical Engineering Imperial College LondonLondon SW72AZUK Department of mechanical Engineering University of BirminghamBirmingham B152TTUK School of Science and Engineering University of DundeeDundee DD14HNUK

Lightweight curved profiles are widely utilised in the transportation industry considering the increasing need for improving aerodynamic efficiency,aesthetics and cutting *** this paper,curved AZ31 mg alloy profiles were manufactured in one operation by a novel process,differential velocity sideways extrusion(DVSE),in which two opposed rams were *** of extrusion temperature and velocity(strain rate) on curvature,microstructure,and mechanical properties of the formed profiles were *** curvature was found to be more readily controlled by the velocity ratio of the bottom ram v2to the top ram v1,whereas extrusion temperature(T=250,300,350℃)and extrusion velocity(v_(1)=0.1,1 mm/s) slightly affect curvature for a given velocity ratio.A homogeneous microstructure with equiaxed grains(~4.5 μm) resulted from dynamic recrystallisation(DRX),was observed after DVSE(v_(2)/v_(1)=1/2) at 300 ℃ and v_(1)=0.1 mm/s,where the initial billet had an average grain size of ~25 *** extrusion temperature leads to grain growth(~5 μm) at 350 ℃ and v_(1)=0.1 mm/*** is incomplete at the relatively low temperature of 250℃(v_(1)=0.1 mm/s),and higher strain rate with v1=1mm/s(T=300℃),resulting in inhomogeneous bi-modal necklace pattern grains ranging in size around 1-25 μm for the former and 2-20μm for the *** refinement is attributed to DRX during the severe plastic deformation(SPD) arising in DVSE,and initiates at the prior boundaries of coarse grains in a necklace-like *** with the billet,micro-hardness and ultimate tensile strength of the profiles have been enhanced,which is compatible with grain ***,an obvious increase in tensile ductility was ***,yield strength slightly decreases except for the complete DRXed case(300℃,v_(1)=0.1 mm/s),where a slightly higher value was found,indicating strengthening by grain refinement is greater than softening caused by texture *** initial billet had a strong b

关键词： Extrusion magnesium alloy AZ31 Curved profiles/sections Bending Grain refinement Dynamic recrystallisation

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myokine Response to Blood-Flow Restricted Resistance Exercise in Younger and Older males in an Untrained and Resistance-Trained State:A Pilot Study

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Journal of Science in Sport and Exercise 2023年第3期5卷 203-217页

作者： dean m.Cordingley Judy E.Anderson Stephen m.Cornish Applied Health Sciences University of ManitobaWinnipegMB R3T 2N2Canada Pan Am Clinic Foundation 75 Poseidon BayWinnipegMB R3M 3E4Canada Faculty of Science University of ManitobaWinnipegMBCanada Faculty of Kinesiology and Recreation management University of Manitoba110 Frank Kennedy CentreWinnipegMB R3T 2N2Canada Centre for Aging University of ManitobaWinnipegMB R3T 2N2Canada

Purpose The purpose of this study was to examine the response of myokines to blood-flow restricted resistance-exercise(BFR-RE)in younger and older males before and after completing a 12-week resistance-training *** There were 8 younger(24.8±3.9 yrs)and 7 older(68.3±5.0 yrs)untrained male participants completed this *** and maximal strength(1Rm)measurements were collected before and after a 12-week,supervised,progres-sive full-body resistance-training *** well,an acute bout of full-body BFR-RE was performed with venipuncture blood samples collected before and immediately following the BFR-RE,followed by sampling at 3,6,24 and 48 *** The 12-week training program stimulated a 32.2%increase in average strength and 30%increase in strength per kg of fat free *** response of particular myokines to the acute bout of BFR-RE was influenced training status(IL-4,untrained=78.1±133.2 pg/mL ***=59.8±121.6 pg/mL,P=0.019;IL-7,untrained=3.46±1.8 pg/mL ***=2.66±1.3 pg/mL,P=0.047)or both training and age(irisin,P=0.04;leukemia inhibitory factor,Pmass were correlated with area under the curve for IL-4(r=0.537;P=0.039),IL-6(r=0.525;P=0.044)and LIF(r=−0.548;P=0.035)in the untrained *** This study identified that both age and training status influence the myokine response to an acute bout of BFR-RE with the release of IL-4,IL-6 and LIF in the untrained state being associated with changes in strength per kg of fat free mass.

关键词： Hypertrophy myokine Exercise immunology BFR Aging

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Prediction of the Residual Welding Stress in 2.25Cr-1mo Steel by Taking into Account the Effect of the Solid-State Phase Transformations

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Acta metallurgica Sinica(English Letters) 2013年第3期26卷 333-339页

作者： dean DENG Yangang TONG Ninshu mA Hidekazu mURAKAWA College of materials Science and Engineering Chongqing University State Key Laboratory of Advanced Welding and Joining Harbin Institute of Technology JWRI Osaka University11-1 MihogaokaIbaraki Osaka 567-0047 Japan

A computational approach based on the thermal elastic plastic finite element method was developed for predicting welding residual stress in low carbon alloyed steel welds by taking into account the effect of the solid-state phase transformations. The kinetics of phase transformations was described by Johnson mehl Avrami Kolmogrov （JmAK） equation for bainitic transition and by Koistinen-marburger （K-m） relationship for martensitic transition. moreover, an additive rule depending on volumetric phase fraction was adopted to represent the material property changes during heating and cooling. Consequently, the residual welding stresses in a 2.25Cr1mo steel TIG welded plate were computed. Early calculation results suggest that the bainitic and martensitic transformations took place in the weld the heat-affected zone drastically reduce the residual longitudinal tensile stress in the region.

关键词： Computational approach Numerical simulation Phase transformation Welding residual stress

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The influence of chemical composition on models of Type Ia supernovae

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Frontiers of physics 2013年第2期8卷 168-188页

作者： Alan C. Calder Brendan K. Krueger Aaron P. Jackson dean m. Townsley Department of Physics Astronomy The State University of New York - Stony Brook Stony BrookUSA NY 11794 New York Center for Computational Sciences The State University of New York - Stony Brook Stony BrookUSA NY 11794 National Research Council Research Associateship Program and Laboratories for Computational Physics and Fluid Dynamics Naval Research Laboratory WashingtonUSA DC 20375 Department of Physics and Astronomy The University of Alabama TuscaloosaUSA AL 35487

Type Ia supernovae are bright stellar explosions distinguished by standardizable light curves that allow for their use as distance indicators for cosmological studies. Despite the highly successful use of these events in this capacity, many fundamental questions remain. Contemporary research inves- tigates how properties of the progenitor system that follow from the host galaxy such as composition and age influence the brightness of an event with the goal of better understanding and assessing the intrinsic scatter in the brightness. We provide an overview of these supernovae and proposed progenitor systems, all of which involve one or more compact stars known as white dwarfs. We describe contemporary research investigating how the composition and structure of the progenitor white dwarf systematically influences the explosion outcome assuming the progenitor is a single white dwarf that has gained mass from a companion. We present results illustrating some of these systematic effects from our research.

关键词： hydrodynamics nuclear reactions nucleosynthesis abundances stars: supernovae:general stars: white dwarfs

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