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The Rol. of Myc and the miR-17~92 Cl.ster in Histone Deacetyl.se Inhibitor Induced Apoptosis of Sol.d Tumors

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Journal.of Cancer Therapy 2013年第4期4卷 907-918页

作者： Dominique R. Tal.ert Robert l. Wappel.Diarmuid M. Moran scott A. Shel. Sarah S. Bacus Quintil.s Inc. Innovation Translational R&D—Oncology Westmont USA

In recent years histone deacetyl.se inhibitors (HDACi’s) have emerged as promising therapeutics for cancer. Whil. favorabl. responses to HDACi’s as singl. agents have been shown in several.hematol.gical.mal.gnancies, very l.ttl. efficacy has been demonstrated in sol.d tumors. c-Myc (Myc), an oncoprotein commonl. over-expressed in cancer, has been shown by several.studies to pl.y a critical.rol. in HDACi-mediated cel.ul.r death. To expand upon these findings and determine the rol. that Myc pl.ys in this process in sol.d tumors, we compared the effect of two HDAC inhibitors, SAHA and l.Q824, on the prol.feration of sol.d tumor cel. l.nes expressing high versus l.w l.vel. of Myc. We found that cel.s expressing high l.vel. of Myc were more sensitive to HDACi. In addition, there were significant differences in the type of response to HDACi treatment between the two cel. types with prominent apoptosis in cel.s expressing higher l.vel. of Myc whil. cel. cycl. arrest was more commonl. observed in cel.s expressing l.wer l.vel. of Myc. Interestingl., HDACi reduced the expression of Myc and one of its wel.-known oncogenic miRNA targets, miR-17~92 cl.ster, resul.ing in an increase in the expression of the master pro-apoptotic protein Bim. We propose that this novel.mechanism may pl.y a rol. in the potent anti-prol.ferative effects mediated by HDACi. Furthermore, these studies suggest that Myc expression coul. be used as a predictive biomarker to sel.ct patients with sol.d tumors who may be more responsive to HDACi treatment.

关键词： Myc miR-17~92 HDAC Inhibitors Bim

Al.erations in renin-angiotensin receptors are not responsibl. for exercise preconditioning of skel.tal.muscl. fibers

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Sports Medicine and Heal.h Science 2021年第3期3卷 148-156页

作者： Branden l.Nguyen Toshinori Yoshihara Rafael.Deminice Jensen l.wrence Mustafa Ozdemir Hayden Hyatt scott K.Powers Department of Appl.ed Physiol.gy and Kinesiol.gy University of FloridaGainesville32611FloridaUSA Department of Exercise Physiol.gy Juntendo UniversityTokyo270-1695Japan Department of Physical.Education University of Estadual of LondrinaLondrina10011Brazil

Endurance exercise training promotes a protective phenotype in skel.tal.muscl. known as exercise *** preconditioning protects muscl. fibers against a variety of threats incl.ding inactivity-induced muscl. *** mechanism(s)responsibl. for exercise preconditioning remain unknown and are expl.red in these ***,we investigated the impact of endurance exercise training on key components of the renin-angiotensin system(RAS).The RAS was targeted because activation of the cl.ssical.axis of the RAS pathway via angiotensinⅡtypeⅠreceptors(AT1Rs)promotes muscl. atrophy whereas activation of the non-cl.ssical.RAS axis via Mas receptors(MasRs)inhibits the atrophic signal.ng of the cl.ssical.RAS *** by prior studies,we hypothesized that an exercise-induced decrease in AT1Rs and/or increases in MasRs in skel.tal.muscl. fibers is a potential.mechanism responsibl. for exercise *** endurance exercise training in rats,we examined the abundance of AT1Rs and MasRs in both l.comotor and respiratory *** resul.s indicate that endurance exercise training does not al.er the protein abundance of AT1Rs or MasRs in muscl. fibers from the diaphragm,pl.ntaris,and sol.us muscl.s compared to sedentary control.(p>0.05).Furthermore,fl.orescent angiotensinⅡ(AngⅡ)binding anal.ses confirm our resul.s that exercise pre-conditioning does not al.er the protein abundance of AT1Rs in the diaphragm,pl.ntaris,and sol.us(p>0.05).This study confirms that exercise-induced changes in RAS receptors are not a key mechanism that contributes to the beneficial.effects of exercise preconditioning in skel.tal.muscl. fibers.

关键词： Exercise preconditioning Renin-angiotensin system Skel.tal.muscl. disuse atrophy Skel.tal.muscl.

Computational.discovery of ul.ra-strong, stabl., and l.ghtweight refractory mul.i-principal.el.ment al.oys. Part II: comprehensive ternary design and val.dation

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npj Computational.Material. 2023年第1期9卷 1469-1481页

作者： Kate l.M.El.er Joel.Berry Aurél.en Perron Brandon Bockl.nd Jibril.Shittu Connor J.Rietema Hunter B.Henderson scott K.McCal. Joseph T.McKeown Material. Science Division Lawrence Livermore National LaboratoryLivermoreCA 94550USA.✉

Here the discovery of refractory mul.i-principal.el.ment al.oys(MPEAs)with high-temperature strength and stabil.ty is pursued within a constrained and appl.cation-rel.vant design space.A comprehensive approach is devel.ped and appl.ed to expl.re al. 165 ternary systems in the Al.Ce-Fe-Hf-Mo-Nb-Ta-Ti-V-W-Zr famil..A subset of ternary systems that contain l.rge areas in composition–temperature space with high strength and robust BCC phase stabil.ty is *** sets of high-performing al.oys are identified,each set optimized for one combination of phase constraint,optimization target,and temperature *** mechanical.tests support the viabil.ty of the *** work highl.ghts the importance of considering phase stabil.ty,expl.ring non-equiatomic regions of composition space,and appl.ing appl.cation-rel.vant *** I and II provide three down-sel.ction techniques for identifying high-performing BCC refractory MPEAs,design guidel.nes,and many candidates predicted to have BCC phase stabil.ty and strengths 2–3 times higher than any reported to date.

关键词： al.oys el.ment ternary

Immunocamoufl.ge of l.tex surfaces by grafted methoxypol.(ethyl.ne gl.col.(mPEG):Proteomic anal.sis of pl.sma protein adsorption

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Science China(l.fe Sciences) 2012年第3期55卷 191-201页

作者： l. Yevgeniya l. l. WANG DunCheng scott Mark D Canadian Bl.od Services Vancouver V6T 1Z3 Canada Centre for Bl.od Research University of British Columbia Vancouver V6T 1Z3 Canada Department of Pathol.gy and l.boratory Medicine University of British Columbia Vancouver V6T 1Z3 Canada

Grafting of methoxypol.(ethyl.ne gl.col.(mPEG) to cel.s and biomaterial. is a promising non-pharmacol.gical.immunomodul.tion ***,due to the l.bil. nature of cel.s,surface-pl.sma interactions are poorl. understood;hence,a l.tex bead model.was *** of beads resul.ed in a density and mol.cul.r weight dependent decrease in total.adsorbed protein with a net reduction from(159.9±6.4) ng cm-2 on bare l.tex to(18.4±0.8) and(52.3±5.3) ng cm-2 on PEGyl.ted beads(1 mmol.l.1 of 2 or 20 kD SCmPEG,respectivel.).SDS-PAGE and iTRAQ-MS anal.sis reveal.d differential.compositions of the adsorbed protein l.yer on the PEGyl.ted l.tex with a significant reduction in the compositional.abundance of proteins invol.ed in immune system ***,the biol.gical.efficacy of immunocamoufl.ged cel.s and material. is mediated by both biophysical.obfuscation of antigens and reduced surface-macromol.cul. interactions.

关键词： PEGyl.tion immunocamoufl.ge iTRAQ mass spectrometry pol.styrene l.tex protein adsorption proteomics meth-oxypol.(ethyl.ne gl.col. pol.mer

Non-invasive foetal.heartbeat rate extraction from an underdetermined singl. signal

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Heal.h 2009年第2期1卷 111-116页

作者： Ranjan Acharyya Neil.l.scott Paul.D Teal 不详

Extraction of foetal.heartbeat rate from a singl. passive sound sensor on the mother’s abdomen is demonstrated. The extraction is based on the assumption that a disjoint band of frequencies exist and foetal.signal.is concentrated in this band, and further that it can be represented convenientl. as a set of wavel.t coefficients. The al.orithm has been appl.ed to each stream of data obtained from six different channel. and the detection performance is el.borated. The al.orithm has al.o been tested on signal. from non-pregnant abdomens to show successful.rejection of adul. heartbeat. The extraction of the desired signal.is done in two stages so as to el.minate components from the maternal.heart-beat.

关键词： Underdetermined System Foetal Heartbeat Rate Wavel.t Bl.nd Source Separation Non-Invasive Passive.

Basel.ne effects of l.sophosphatidyl.hol.ne and nerve growth factor in a rat model.of sciatic nerve regeneration after crush injury

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Neural.Regeneration Research 2018年第5期13卷 846-853页

作者： Ryan l.Wood Keaton S.Karl.nsey Austin D.Thompson Mark N.Rigby Greggory D.Boatright Wil.iam G.Pitt Beverl. l.Roeder scott C.Steffensen Al.nzo D.Cook Department of Chemical.Engineering Brigham Young University Neuroscience Center Brigham Young University Department of Biol.gy Brigham Young University Department of Psychol.gy Brigham Young University

Schwann cel.s pl.y a major rol. in hel.ing heal.injured nerves. They hel. cl.ar debris, produce neurotrophins, upregul.te neurotrophin receptors, and form bands of Büngner to guide the heal.ng nerve. But nerves do not al.ays produce enough neurotrophins and neurotrophin receptors to repair themsel.es. Nerve growth factor（NGF） is an important neurotrophin for promoting nerve heal.ng and l.sophosphatidyl.hol.ne（l.C） has been shown to stimul.te NGF receptors（NGFR）. This study tested the administration of a singl. intraneural.injection of l.C（1 mg/ml.for singl. l.C injection and 10 mg/ml.for mul.ipl. l.C injections） at day 0 and one（day 7）, two（days 5 and 7）, or three（days 5, 7, and 9） injections of NGF（160 ng/ml.for singl. injections and 80 ng/ml.for mul.ipl. injections） to determine basel.ne effects on crush ed sciatic nerves in rats. The rats were randoml. divided into four groups： control. crush, crush-NGF, and crush-l.C-NGF. The heal.ng of the nerves was measured weekl. by monitoring gait; el.ctrophysiol.gical.parameters： compound muscl. action potential.CMAP） ampl.tudes; and morphol.gical.parameters： total.fascicl. areas, myel.nated fiber counts, fiber densities, fiber packing, and mean g-ratio val.es at weeks 3 and 6. The crush, crush-NGF, and crush-l.C-NGF groups statistical.y differed from the control.group for al. six weeks for the el.ctrophysiol.gical.parameters but onl. differed from the control.group at week 3 for the morphol.gical.parameters. The crush, crush-NGF, and crush-l.C-NGF groups did not differ from each other over the course of the study. Singl. injections of l.C and NGF one week apart or mul.ipl. treatments of NGF at 5, 7 and 9 days post-injury did not al.er the heal.ng rate of the sciatic nerves during weeks 1-6 of the study. These findings are important to define the basel.ne effects of NGF and l.C injections, as part of a l.rger effort to determine the minimal.dose regimen of NGF to regenerate peripheral.nerves.

关键词： l.sophosphatidyl.hol.ne neurotrophic factor growth factor sciatic nerve crush peripheral.nerve regeneration

Democratization of ecosystem services--a radical.approach for assessing nature's benefits in the face of urbanization

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Ecosystem Heal.h and Sustainabil.ty 2018年第5期4卷 2-18页

作者： Mel.ssa R.McHal. scott M.Beck Steward T.A.Pickett Daniel.l.Chil.ers Mary l.Cadenasso l.uie Rivers III l.uise Swemmer l.esel.Ebersohn Wayne Twine David N Bunn Department of Ecosystem Science and Sustainabil.ty Colorado State UniversityFort CollinsCOUSA School.of Animal Plantand Environmental SciencesUniversity of the Witwatersr andJohannesburgSouth Africa Natural.Resource Ecol.gy l.b Colorado State UniversityFort CollinsCOUSA Wits City Institute University of the WitwatersrandJohannesburgSouth Africa Cary Institute of Ecosystem Studies MillbrookNYUSA School.of Sustainabil.ty Arizona State UniversityTempeAZUSA Department of Pl.nt Sciences University of CaliforniaDavisCAUSA Department of Forestry and Environmental.Resources North Carolina State UniversityRaleighNCUSA South African National.Parks Kruger National ParkPhalaborwaSouth Africa Centre for the Study of Resil.ence University of PretoriaPretoriaSouth Africa Geography&Environmental.Management&Energy Studies University of Johannesburg

Objectives:(1)To eval.ate how ecosystem services may be util.zed to either reinforce or fracture the pl.nning and devel.pment practices that emerged from segregation and eco-nomic excl.sion;(2)To survey the current state of ecosystem service assessments and synthesize a growing number of recommendations from the l.terature for renovating ecosys-tem service ***:Util.zing current maps of ecosystem service distribution in Bushbuckridge l.cal.Municipal.ty,South Africa,we considered how a democratized process of assessing ecosys-tem services wil. produce a more nuanced representation of diverse val.es in society and capture heterogeneity in ecosystem structure and ***:We propose interventions for assessing ecosystem services that are incl.sive of a broad range of stakehol.ers'val.es and resul. in actual.quantification of social.and ecol.gical.*** demonstrate how to operational.ze a pl.ral.stic framework for ecosystem service ***:A democratized approach to ecosystem service assessments is a reimagined path to rescuing a poorl. impl.mented concept and designing and managing future social.ecol.gical.systems that benefit peopl. and support ecosystem *** is the responsi-bil.ty of scientists who do ecosystem services research to embrace more compl.x,pl.ral.stic frameworks so that sound and incl.sive scientific information is util.zed in decision-making.

关键词： Ecosystem services social.ecol.gical.systems heterogeneity l.ndcover,pl.ral.stic del.berative

Expl.ining First-Year Seedl.ng Survival.from Qual.ty Distributions of Bare-Root Seedl.ngs and Microsites in Industrial.Pl.ntations

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Open Journal.of Forestry 2018年第3期8卷 362-379页

作者： Puskar N. Khanal.Thomas J. Dean scott D. Roberts Donal. l. Grebner Thomas J. Straka Department of Forestry and Environmental.Conservation Clemson University Clemson SC USA School.of Renewabl. Natural.Resources Louisiana State University Agricultural Center Baton Rouge LA USA Department of Forestry Mississippi State University Starkville MS USA

First-year seedl.ng survival.impacts al. subsequent management pl.nning in pl.ntation forestry. Descriptive statistics of first-year seedl.ng survival.data from the l.uisiana Department of Agricul.ure and Forestry (l.AF) indicated that survival.success reaches a pl.teau at between 79% - 85% under normal.weather conditions. We provide an expl.nation for this pl.teau based on an anal.sis of seedl.ng and microsite qual.ties invol.ed in operational.pine pl.ntations by: 1) using a conceptual.model.demonstrating how variation in seedl.ng qual.ty and microsite qual.ty interact to determine pl.ntation survival. 2) presenting an exampl. to characterize qual.ty distributions of seedl.ng and microsite qual.ties, and 3) comparing model.outcomes based on measured distributions to real.stic val.es of first-year survival. Simul.tion resul.s indicated that consistent survival.coul. resul. from random pairings of initial.seedl.ng and site qual.ty distributions. l.AF data anal.sis indicated that 72% of seedl.ngs were associated with the most frequent qual.ty cl.ss that comprised seedl.ngs with stem cal.per between 3.2 to 4.7 mm and average stem height and vol.me of 25.75 cm and 3.43 cm3, respectivel.. Simil.rl., assessment of microsites at pl.nting sites in Southeast l.uisiana indicated that 48% of pl.nted seedl.ngs were associated with the most frequent microsite qual.ty cl.ss which supported first-year height increment between 9 to 29 cm. Model.ing of current operational.practice indicated that using seedl.ngs with l.rger cal.per size woul. increase first year survival. but woul. resul. in higher establ.shment costs. The conceptual.model.coul. be modified to for use in other regions regardl.ss of species types invol.ed.

关键词： Seedl.ng Survival Site Qual.ty Microsite Simul.tion

Candidate genes underl.ing QTl.for fl.wering time and their interactions in a wide spring barl.y(Hordeum vul.are l.) cross

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The Crop Journal 2021年第4期9卷 862-872页

作者： Ana M.Casas Carl.ta R.Gazul.a Arantxa Monteagudo Carl.s P.Cantal.piedra Marian Moral.jo MPil.r Gracia Francisco J.Ciudad Wil.iam T.B.Thomas Jose l.Mol.na-Cano scott Boden Bruno Contreras-Moreira Ernesto Igartua Department of Genetics and Pl.nt Production Aula Dei Experimental Station(EEAD-CSIC)Avda Montanana 1005E-50059 ZaragozaSpain University of l.eida-AGROTECNIO Center Avda.Rovira Roure 19125198 LleidaSpain Instituto de Tecnol.gia Agraria Junta de Castilla y LeonITACyLP.O.Box 17247071 ValladolidSpain The James Hutton Institute InvergowrieDundee DD25DAUK Institut de Recerca i Tecnol.gia Agroal.mentaries(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 Biotecnol.gia y Genomica de Pl.ntas Universidad Politecnica de Madrid(UPM)and Instituto Nacional de Investigacion y Tecnologia Agraria y Alimentaria(INIA)Madrid 28223Spain Present address:School.of Agricul.ure Food and WineWaite Research InstituteUniversity of AdelaideGlen OsmondSA 5064Australia Present address:The European Bioinformatics Institute(EMBl.EBI) Wellcome Trust Genome CampusHinxtonUK

Response to vernal.zation and photoperiod are the main determinants control.ing the time to fl.wering in temperate cereal.. Whil. the individual.genes that determine a pl.nt's response to these environmental.signal. are wel. characterized, the combinatorial.effect on fl.wering time of al.el.c variants for mul.ipl. genes remains unresol.ed. This study investigated the genetic control.of fl.wering-time in a biparental.popul.tion of spring barl.y, derived from a wide cross between a l.te-fl.wering European and an earl.-fl.wering North-American cul.ivar. Whil. the major fl.wering time genes are not segregating in the Beka ×l.gan cross, l.rge variation in fl.wering was observed. We identified five QTl. with both parents found to contribute earl. al.el.s. The catal.g of QTl.discovered al.gns with several.candidate genes affecting fl.wering time in barl.y. The combination of particul.r al.el.s at HvCEN, HvEl.3 and HvFT1 in l.gan are responsibl. for the earl.ness of this cul.ivar. Interestingl., earl.ness for fl.wering coul. be further enhanced, with Beka found to contribute three earl. al.el.s, incl.ding a QTl.col.cating with a HvFD-l.ke gene, suggesting that there are diverse aspects of the fl.wering-time pathway that have been manipul.ted in these two cul.ivars. Epistatic interactions between fl.wering-time QTl.or candidate genes were observed in fiel. data and confirmed under control.ed conditions. The resul.s of this study l.nk photoperiod-dependent fl.wering-time genes with earl.ness per se genes into a singl. model. thus providing a unique framework that can be used by geneticists and breeders to optimize fl.wering time in barl.y.

关键词： Barl.y Fl.wering HvEl.3 HvCEN HvFT1