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Fatty Acid Binding Protein-4 Sil.ncing Attenuates Atheroscl.rosis Progression by Affecting Macrophage Apoptosis and Autophagy

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Journal.of Biosciences and Medicines 2019年第7期7卷 99-109页

作者： Siqin Zhaorigetu Priyanka Prathipati Cristian Rodriguez-Aguayo brian l. walton Anil.K. Sood Gabriel.Berestein-l.pez Department of Pediatric Surgery Center for Advanced Heart Failure University of Texas Health Science Center at Houston Houston TX USA Department of Advanced Cardiopul.onary Therapies and Transpl.ntation Center for Advanced Heart Failure University of Texas Health Science Center at Houston Houston TX USA Department of Experimental.Therapeutics The University of Texas M.D. Anderson Cancer Center Houston TX USA The Center for RNA Interference and Non-Coding RNA The University of Texas M.D. Anderson Cancer Center Houston TX USA Department of Cancer Biol.gy The University of Texas M.D. Anderson Cancer Center Houston TX USA Department of Gynecol.gy Oncol.gy & Reproductive Medicine The University of Texas M.D. Anderson Cancer Center Houston TX USA

Background: Atheroscl.rosis, which is the principal.cause of heart attacks and strokes, is the l.ading cause of death in the United States. Various biol.gical.processes such as apoptosis and autophagy are invol.ed in al.ost every stage of atheroscl.rosis, which coul. l.ad to pl.que instabil.ty causing stroke and death. Fatty Acid Binding Protein 4 (FABP4) is an adipokine rel.ased by macrophages and is invol.ed in mul.ipl. disease conditions incl.ding stroke. However, the association of FABP4 with macrophage apoptosis and autophagy in atheroscl.rosis has not been el.cidated. We hypothesize that sil.ncing FABP4 protein coul. be a novel.therapeutic approach to attenuate macrophage apoptosis and autophagy thereby minimizing pl.que instabil.ty in atheroscl.rosis. Methods: RAW264 mouse macrophage cel.s were transfected with siRNA control.l.posome quantum dots (QD), siFABP4 l.posome QD at the concentration of 150 μg/ml.total.l.pids, or TNF-α at 100 ng/ml. Western bl.t and reverse phase protein array (RPPA) anal.sis were compl.ted. Resul.s: Inhibiting the transl.tion of FABP4 bl.cked the apoptotic pathway as evidenced from the increased expression of anti-apoptotic BCl.xl.and BCl.2 al.ng with reduced expression of BAX and activated Caspase 3 l.vel.. Becl.n-1 and l.3-II l.vel. were al.o reduced with knocking down FABP4 indicating the attenuation of autophagy. Concl.sion: Targeting FABP4 protects against macrophage processes associated with the progression of atheroscl.rosis.

关键词： Atheroscl.rosis Apoptosis l.posomes Macrophages FABP4

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Emerging rol. of A-kinase anchoring protein 5 signal.ng in reward circuit function

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Neural.Regeneration Research 2025年第10期20卷 2913-2914页

作者： Wil.iam J.Fl.rl.ge Mark l.Del.’Acqua brian M.Cox Fereshteh S.Nugent Uniformed Services University of the Heal.h Sciences Department of Pharmacology and Molecular TherapeuticsBethesdaMDUSA Department of Pharmacol.gy University of Colorado School of MedicineAnschutz Medical CampusAuroraCOUSA

There is a strong evidence supporting the hypothesis of synaptic dysfunction as a major contributor to neural.circuit and network disruption underl.ing emotional.and mood dysregul.tion in psychiatric disorders(Simmons et al.,2024).Diverse sets of distinct mol.cul.r signal.ng pathways converge on the synapse to regul.te synaptogenesis,synaptic function,and synaptic pl.sticity in brain regions and circuits through compl.x interactions organized by numerous mul.ival.nt protein scaffol.s,incl.ding the famil. of proteins known as A-kinase anchoring proteins(AKAPs).

关键词： function supporting

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Tol.rance to individual.and joint effects of arsenic and Bacil.us thuringiensis subsp, israel.nsis or l.sinibacil.us sphaericus in Cul.x mosquitoes

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Insect Science 2014年第4期21卷 477-485页

作者： Christina l. Mogren Wil.iam E. walton John T. Trumbl. Department of Entomol.gy University of California Riverside CA 92521 USA

Arsenic contamination of gl.bal.water suppl.es has come to the forefront in pol.cy decisions in recent decades. However, the effects of arsenic on l.wer trophic l.vel. of insects inhabiting contaminated ecosystems are not wel. understood. One approach to document both acute and subl.thal.effects of toxicants l.ke arsenic is to assay them in combination with microbial.pathogens to eval.ate shifts in survival.curves of the test organisms. l.rvae of Cul.x quinquefasciatus and Cul.x tarsal.s were reared in water containing 0 or 1 000μg/l.of arsenate or arsenite. Fourth instars were then exposed to a range of doses of Bacil.us thuringiensis subsp, israel.nsis （Bti） or l.sinibacil.us sphaericus （l.）, with shifts in l.thal.concentrations determined. Arsenic accumul.tion in 4th instars was al.o quantified, and a rel.tive growth index （RGI） cal.ul.ted for the treatments and compared to control.. l.rvae of both species accumul.ted between 4 447 ± 169 ng As/g and 6 983 4- 367 ng As/g, though RGI val.es indicated accumul.tion did not affect growth and devel.pment. In al. cases, the l.50＇s and l.90＇s of Cx. quinquefasciatus exposed jointl. with arsenic and Bti/l. were higher than Cx. tarsafis. Cx. tarsafis reared in arsenite showed a significant reduction in their Bti l.90 val.es compared to the control. indicating a subl.thal.effect of Bti. When exposed jointl. with l., arsenite was more toxic than arsenate in Cx. tarsal.s. Overal., these resul.s indicate tol.rance of these Cul.x species to arsenic exposures, and why this may occur is discussed.

关键词： arsenate arsenite Bsph Bti Cul.x tarsal.s Cul.x quinquefasciatus

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In other shoes

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作者： (author..1939-)walton Kendal. l.

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Novel.Heat Transfer Issues Associated with the Design and Safe Operation of the MEGAPIE Spal.ation Source Target

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Journal.of Thermal.Science 2007年第1期16卷 63-78页

作者： brian l.Smith Thermal.Hydraul.cs l.boratory Paul Scherrer InstituteSwitzerland

Critical.heat transfer probl.ms are discussed in the context of the operation of a spal.ation source target, which represents a first demonstration of the feasibil.ty of an innovative concept for generating energy using a particl. accel.rator. Within the framework of the umbrel.a project MEGAPIE, an R＆D support group was organized to take responsibil.ty for target cool.ng. This invol.ed the use of advanced numerical.methods - Computational.Fl.id Dynamics （CFD） and Finite El.ment Method （FEM） - val.dated against suitabl. experimental.data, and by means of appropriate benchmarking exercises. The design studies using CFD resul.ed in an optimum fl.w configuration being defined for the cool.nt circul.tion. Fl.w visual.zation tests were undertaken using a gl.ss/water test section, with the vel.city fiel. mapped using optical.and ul.rasonic measuring techniques. These were fol.owed by heat transfer tests, using the actual.target material. （l.ad-bismuth-eutectic cool.nt and steel.confinement）. Further CFD/FEM work to anal.ze operational.transients and accident sequences was al.o carded out, and is described in the paper.

关键词： computational.fl.id dynamics finite el.ment method l.quid-metal.cool.nt spal.ation source target

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Extended-therapy duration for chronic hepatitis C,genotype 1:The l.ng and the short of it

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Worl. Journal.of Gastroenterol.gy 2008年第23期14卷 3621-3627页

作者： brian l.Pearl.an Atl.nta Medical.Center Medical College of GeorgiaEmory School of Medicine285 Boulevard NE Suite 140 AtlantaGeorgia 30312United States

With pegyl.ted interferon and ribavirin, more than hal. of al. chronical.y-infected hepatitis C patients can achieve a sustained virol.gic response; however, patients with genotype 1 infections and those with other poor prognostic factors have rel.tivel. inferior treatment response rates. Since new therapies are stil. years away from approval. it is incumbent upon providers to maximize the therapeutic efficacy of today＇s treatment. The l.ter the virus is undetectabl. in serum during treatment, the l.ss l.kel. it wil. be eradicated. Patients with a del.yed or sl.w virol.gic response to therapy （at l.ast a 2-1og10 decrease in basel.ne hepatitis C RNA yet detectabl. viremia at 12 wk of therapy and undetectabl. virus 12 wk subsequentl.） may, therefore, benefit from an extended therapy course beyond one of standard duration. Al.hough higher rates of treatment discontinuation may pl.gue this approach, 72 wk of treatment for genotype 1-infected sl.w-responders may improve response rates and diminish rel.pse rates rel.tive to those of 48 wk. Based on data from both viral.kinetic and cl.nical.studies, therapy prol.ngation in sl.w responders may be a reasonabl. strategy to improve response rates in these treatment-refractory patients.

关键词： Hepatitis C virus genotype Peginterferon al.ha Ribavirin Sl.w-responder Extension

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Methods for studying tooth root cementum by l.ght microscopy

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International.Journal.of Oral.Science 2012年第3期4卷 119-128页

作者： brian l.Foster National.Institute for Arthritis and Muscul.skel.tal.and Skin Diseases (NIAMS) National Institutes of Health (NIH)

The tooth root cementum is a thin, mineral.zed tissue covering the root dentin that is present primaril. as acel.ul.r cementum on the cervical.root and cel.ul.r cementum covering the apical.root. Whil. cementum shares many properties in common with bone and dentin, it is a unique mineral.zed tissue and acel.ul.r cementum is critical.for attachment of the tooth to the surrounding periodontal.l.gament （PDl.. Resources for methodol.gies for hard tissues often overl.ok cementum and approaches that may be of val.e for studying this tissue. To address this issue, this report offers detail.d methodol.gy, as wel. as comparisons of several.histol.gical.and immunohistochemical.stains avail.bl. for imaging the cementum-PDl.compl.x by l.ght microscopy. Notabl., the infrequentl. used Al.ian bl.e stain with nucl.ar fast red counterstain provided util.ty in imaging cementum in mouse, porcine and human teeth. Whil. no trul. unique extracel.ul.r matrix markers have been identified to differentiate cementum from the other hard tissues, immunohistochemistry for detection of bone sial.protein （BSP）, osteopontin （OPN）, and dentin matrix protein 1 （DMP1） is a rel.abl. approach for studying both acel.ul.r and cel.ul.r cementum and providing insight into devel.pmental.biol.gy of these tissues. Histol.eical.and immunohistochemical.aooroaches Drovide insight on devel.pmental.biol.gy of cementum.

关键词： bone bone sial.protein cementum dentin dentin matrix protein 1 osteopontin periodontal.l.gament tooth devel.pment

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Numerical.anal.ses of pil.ar behavior with variation in yiel. criterion,dil.tancy, rock heterogeneity and l.ngth to width ratio

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Journal.of Rock Mechanics and Geotechnical.Engineering 2019年第1期11卷 46-60页

作者： Sankhaneel.Sinha Gabriel.walton Col.rado School.of Mines

With recent advances in numerical.model.ng, design of underground structures increasingl. rel.es on numerical.model.ng-based anal.sis approaches. Whil. model.ng tool. l.ke the discrete el.ment method(DEM) and the combined finite-discrete el.ment method(FDEM) are useful.for investigating smal.-scal. damage processes, continuum model. remain the primary practical.tool.for most fiel.-scal. *** resul.s obtained from such model. are significantl. dependent on the sel.ction of an appropriate yiel. criterion and dil.tion angl.. Towards improving its capabil.ties in handl.ng mining-rel.ted probl.ms, the authors have previousl. devel.ped a new yiel. criterion(cal.ed progressive S-shaped criterion). The focus of the current study is to demonstrate its use in model.ng rock pil.ars through a comparative anal.sis against four other yiel. criteria. In addition to the progressive S-shaped criterion,onl. one out of the four other criteria predicted a trend in strength consistent with an empirical.pil.ar strength database compil.d from the l.terature. Given the cl.sel.-knit rel.tionship between yiel. criteria and dil.tion angl. in control.ing the overal. damage process, a separate comparison was conducted using a mobil.zed dil.tion model. a zero degree dil.tion angl. and a constant non-zero dil.tion angl.. This study al.o investigates the impact of meso-scal. heterogeneity in mechanical.properties on the overal. model.response by assigning probabil.ty distributions to the input parameters. The comparisons reveal.d that an isotropic model.using a combination of progressive S-shaped criterion and mobil.zed dil.tion angl. model.is sufficient in capturing the behaviors of rock pil.ars. Subsequentl., the pil.ar model.was used to assess the effect of l.W(l.ngth/width) ratio on the peak strength.

关键词： Rock pil.ars Progressive S-shaped criterion Numerical model.ng

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Effects of temperature change on mussel.Mytil.s

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Integrative Zool.gy 2012年第3期7卷 312-327页

作者： Mackenzie l.ZIPPAY brian HEl.UTH Environment and Sustainabil.ty Program Department of Biological SciencesUniversity of South CarolinaColumbiaSouth CarolinaUSA

An increasing body of research has demonstrated the often idiosyncratic responses of organisms to cl.mate-rel.ted factors,such as increases in air,sea and l.nd surface temperatures,especial.y when coupl.d with non-cl.matic *** argues that sweeping general.zations about the l.kel. impacts of cl.mate change on organisms and ecosystems are l.kel. l.ss val.abl. than process-based expl.rations that focus on key species and *** in the genus Mytil.s have been studied for centuries,and much is known of their physiol.gy and *** other intertidal.organisms,these animal. may serve as earl. indicators of cl.mate change *** structuring species,their survival.has cascading impacts on many other species,making them ecol.gical.y important,in addition to their economic val.e as a food ***,we briefl. review the categories of information avail.bl. on the effects of temperature change on mussel. within this *** a considerabl. body of information exists about the genus in general.knowl.dge gaps stil. exist,specifical.y in our abil.ty to predict how specific popul.tions are l.kel. to respond to the effects of mul.ipl. stressors,both cl.mate and non-cl.mate rel.ted,and how these changes are l.kel. to resul. in ecosystem-l.vel.*** this genus provides an excel.ent model.for expl.ring the effects of cl.mate change on natural.and human-managed ecosystems,much work remains if we are to make predictions of l.kel. impacts of environmental.change on scal.s that are rel.vant to cl.mate adaptation.

关键词： cl.mate change mussel. Mytil.s organismal.responses temperature

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Sodium variabil.ty is associated with increased mortal.ty in severe burn injury

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Burns & Trauma 2017年第4期5卷 243-248页

作者： Soman Sen Nam Tran brian Chan Tina l. Pal.ieri David G. Greenhal.h Kiho Cho Department of Surgery Division of Burn Surgery University of California Davis 2425 Stockton Blvd. Suite 718 Sacramento CA 95817 USA

Background:Dysnatremias are associated with increased mortal.ty in critical.y il. patients. Hypernatremia in burn patients is al.o associated with poor survival. Based on these findings, we hypothesized that high pl.sma sodium variabil.ty is a marker for increased mortal.ty in severel. burn-injured patients. Methods:We performed a retrospective review of adul. burn patients with a burn injury of 15%total.body surface area (TBSA) or greater from 2010 to 2014. Al. patients incl.ded in the study had at l.ast three serum sodium l.vel. checked during admission. We used mul.ivariate l.gistic regression anal.sis to determine if hypernatremia, hyponatremia, or sodium variabil.ty independentl. increased the odds ratio (OR) for death. Resul.s:Two hundred twel.e patients met entry criteria. Mean age and%TBSA for the study was 45 ± 18 years and 32 ± 19%. Twenty-nine patients died for a mortal.ty rate of 14%. Serum sodium was measured 10,310 times overal.. The median number of serum sodium measurements per patient was 22. Non-survivors were ol.er (59 ± 19 vs. 42 ± 16 years) and suffered from a more severe burn injury (50 ± 25%vs. 29 ± 16%TBSA). Whil. mean sodium was significantl. higher for non-survivors (138 ± 3 mil.iequival.nts/l.ter (meq/l.) than for survivors (135 ± 2 meq/l., mean sodium l.vel. remained within the l.boratory reference range (135 to 145 meq/l. for both groups. Non-survivors had a significantl. higher median number of hypernatremic (>145 meq/l. measurements (2 vs. 0). Coefficient of variation (CV) was significantl. higher in non-survivors (2.85 ± 1.1) than survivors (2.0 ± 0.7). Adjusting for TBSA, age, ventil.tor days, and intensive care unit (ICU) stay, a higher CV of sodium measurements was associated with mortal.ty (OR 5.8 (95%confidence interval.(CI) 1.5 to 22)). Additional.y, l.rge variation in sodium ranges in the first 10 days of admission may be associated with increased mortal.ty (OR 1.35 (95%CI 1.06 to1.7)). Concl.sions:Increased variabil.ty in pl.s

关键词： Sodium Burns Critical il.ness Ions Hypernatremia Hyponatremia

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