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The Effect of Retinoic Acid on Neutrophil Innate Immune Interactions With Cutaneous Bacterial Pathogens

Infectious Microbes & diseases 2024年第2期6卷 65-73页

作者： Alexandra Stream Ross Corriden Simon döhrmann richard L.Gallo Victor Nizet Ericka L.Anderson division of Host-Microbe Systems and Therapeutics Department of PediatricsUniversity of California San Diego School of MedicineLa JollaCaliforniaUSA department of dermatology University of California San Diego School of MedicineLa JollaCaliforniaUSA Skaggs School of Pharmacy and Pharmaceutical Sciences University of California San DiegoLa JollaCaliforniaUSA

Vitamin A and its biologically active derivative,retinoic acid(RA),are important for many immune ***,in particular,is essential for the development of immune cells,including neutrophils,which serve as a front-line defense against *** vitamin A deficiency has been linked to higher susceptibility to infections,the precise role of vitamin A/RA in host-pathogen interactions remains poorly ***,we provided evidence that RA boosts neutrophil killing of methicillin-resistant Staphylococcus aureus(MRSA).RA treatment stimulated primary human neutrophils to produce reactive oxygen species,neutrophil extracellular traps and the antimicrobial peptide cathelicidin(LL-37).Because RA treatment was insufficient to reduce MRSA burden in an in vivo murine model of skin infection,we expanded our analysis to other infectious *** did not affect the growth of a number of common bacterial pathogens,including MRSA,Escherichia coli K1 and Pseudomonas aeruginosa;however,RA directly inhibited the growth of group A Streptococcus(GAS).This antimicrobial effect,likely in combination with RA-mediated neutrophil boosting,resulted in substantial GAS killing in neutrophil killing assays conducted in the presence of ***,in a murine model of GAS skin infection,topical RA treatment showed therapeutic potential by reducing both skin lesion size and bacterial *** findings suggest that RA may hold promise as a therapeutic agent against GAS and perhaps other clinically significant human pathogens.

关键词： retinoic acid neutrophil bacterial infection Staphylococcus aureus group A Streptococcus neutrophil extracellular traps antimicrobial peptide cathelicidin

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Hepatitis C virus infection and apoptosis

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World Journal of Gastroenterology 2007年第36期13卷 4865-4872页

作者： richard Fischer Thomas Baumert Hubert E Blum department of InternalMedicine II University of Freiburg Germany Inserm U748 Service d’Hépatogastro-entérologie Hpitaux Universitaires de Strasbourg Strasbourg France

Apoptosis is central for the control and elimination of viral infections. In chronic hepatitis C virus (HCV) infection, enhanced hepatocyte apoptosis and upregulation of the death inducing ligands Cd95/Fas, TRAIL and TNFα occur. Nevertheless, HCV infection persists in the majority of patients. The impact of apoptosis in chronic HCV infection is not well understood. It may be harmful by triggering liver fibrosis, or essential in interferon (IFN) induced HCV elimination. For virtually all HCV proteins, pro- and anti-apoptotic effects have been described, especially for the core and NS5A protein. To date, it is not known which HCV protein affects apoptosis in vivo and whether the infectious virions act pro- or anti- apoptotic. With the availability of an infectious tissue culture system, we now can address pathophysiologically relevant issues. This review focuses on the effect of HCV infection and different HCV proteins on apoptosis and of the corresponding signaling cascades.

关键词： Hepatitis C Spoptosis TRAIL Cd95/Fas TNFα Perforin

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Palaeogeographic reconstruction of Minchin palaeolake system,South America: The influence of astronomical forcing

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Geoscience Frontiers 2014年第2期5卷 249-259页

作者： Andrea Sánchez-Saldías richard A.Faria Universidad de la República Facultad de Ciencias Departamento de Astronomía Universidad de la República Facultad de Ciencias Laboratorio de Paleobiología

Current palaeoclimatic reconstructions for the R＆#237;o de la Plata region during the latest Pleistocene （30,000 e10,000 yr BP） propose dry conditions, with rainfall at the Last Glacial Maximum amounting to one-third of today＇s precipitation. despite the consequential low primary productivity inferred, an impressive megafauna existed in the area at that time. Here we explore the influence of the flooding from a huge extinct system of water bodies in the Andean Altiplano as a likely source for wet regimes that might have increased the primary productivity and, hence, the vast number of megaherbivores. The system was reconstructed using specifically combined software resources, including Insola, Global Mapper v13, Surfer and Matlab. Changes in water volume and area covered were related to climatic change, assessed through a model of astronomical forcing that describes the changes in insolation at the top of the at-mosphere in the last 50,000 yr BP. The model was validated by comparing its results with several proxies （CH4, CO2, d, 18O） from dated cores taken from the ice covering Antarctic lakes Vostok and EPICA dome C. It is concluded that the Altiplano Lake system drained towards the southeast in the rainy seasons and that it must have been a major source of water for the Paran＆#225;-Plata Basin, consequently enhancing primary productivity within it.

关键词： Planetary science Climate science Quaternary Palaeoecology Megafauna Parana Basin

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Nonlinear terahertz devices utilizing semiconducting plasmonic metamaterials

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Light(Science & Applications) 2016年第1期5卷 760-766页

作者： Huseyin R Seren Jingdi Zhang George R Keiser Scott J Maddox Xiaoguang Zhao Kebin Fan Seth R Bank Xin Zhang richard d Averitt Laboratory for Microsystems Technology Department of Mechanical EngineeringBoston UniversityBostonMA 02215USA department of Physics Boston UniversityBostonMA 02215USA department of Physics UC San DiegoLa JollaCA 92093USA School of Engineering Brown UniversityProvidenceRI 02912USA Microelectronics Research Center The University of Texas at AustinAustinTX 78758USA

The development of responsive metamaterials has enabled the realization of compact tunable photonic devices capable of manipulating the amplitude,polarization,wave vector and frequency of *** of semiconductors into the active regions of metallic resonators is a proven approach for creating nonlinear metamaterials through optoelectronic control of the semiconductor carrier ***-free subwavelength resonant semiconductor structures offer an alternative approach to create dynamic *** present InAs plasmonic disk arrays as a viable resonant metamaterial at terahertz ***,InAs plasmonic disks exhibit a strong nonlinear response arising from electric field-induced intervalley scattering,resulting in a reduced carrier mobility thereby damping the plasmonic *** demonstrate nonlinear perfect absorbers configured as either optical limiters or saturable absorbers,including flexible nonlinear absorbers achieved by transferring the disks to polyimide *** plasmonic metamaterials show potential for use in ultrafast terahertz(THz)optics and for passive protection of sensitive electromagnetic devices.

关键词： nonlinear absorbers nonlinear metamaterials plasmonic semiconductor metamaterials terahertz metamaterials transfer printing

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Molecular phylogeny of Solms-laubachia(Brassicaceae) s.l.,based on multiple nuclear and plastid dNA sequences,and its biogeographic implications

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Journal of Systematics and Evolution 2009年第5期47卷 402-415页

作者： david A.BAUM Ihsan A.AL-SHEHBAZ richard REE department of Botany University of Wisconsin Missouri Botanical Garden PO Box 299St LouisMO 63166-0299USA 3. Department of BotanyThe Field Museum1400 S.Lake Shore DriveChicagoIL 60605USA

The Hengduan Mountains region of south-west China is a noted biodiversity hotspot,but the geographic origins and historical assembly of its rich endemic flora,including the sky-island species of Solms-laubachia Muschl.(Brassicaceae),have been little *** molecular studies on the phylogeny of Solms-laubachia showed it to be paraphyletic,leading to considerable expansion not only of its taxonomic limits,but also its geographic range,with the inclusion of taxa from outside the Hengduan ***,these studies provided little resolution of interspecific relationships,preventing inferences about historical biogeography within the *** the present study,new sequence data from two nuclear genes(LEAFY and G3pdh) and two chloroplast intergenic spacers(petN-psbM and psbM-trnd) were combined with existing markers to increase phylogenetic *** villosum(Maxim.) Al-Shehbaz was found to be nested within Solms-laubachia *** general,phylogenetic relationships appear to be a good predictor of geography,with the Hengduan Mountain endemics embedded in a paraphyletic grade of species from the western Himalayas and central Asia,but they also imply morphological *** was detected between the nuclear and chloroplast gene trees,perhaps resulting from incomplete lineage sorting of ancestral *** crown age of Solms-laubachia *** estimated to be approximately 1.42-3.68 mya,using Bayesian relaxed molecular clock *** biogeographic analysis using a parametric dispersal-extinction-cladogenesis model inferred central Asia and the western Himalayas as most probable ancestral range of Solms-laubachia s.l.,and estimated higher rates of eastward expansion than westward during the diversification of descendant *** summary,our results suggest that Solms-laubachia *** during the Pliocene in central Asia,and subsequently migrated eastward into the Hengduan Mountains,colonizing sky-island,alpine scr

关键词： biogeography Brassicaceae Hengduan Mountains phylogeny Solms-laubachia s.l.

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Persistent EGFR/K-RAS/SIAH pathway activation drives chemo-resistance and early tumor relapse in triple-negative breast cancer

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Cancer drug Resistance 2022年第3期5卷 691-702页

作者： Amy H.Tang richard A.Hoefer Mary L.Guye Harry d.Bear department of Microbiology and Molecular Cell Biology Leroy T.Canoles Jr.Cancer Research CenterEastern Virginia Medical SchoolNorfolkVA 23507USA School of Systems Biology George Mason UniversityManassasVA 20110USA Sentara Cancer Network Sentara HealthcareNorfolkVA 23507USA Sentara Surgery Specialists Surgical OncologySentara CarePlex HospitalNewport NewsVA 23606USA division of Surgical Oncology Departments of Surgery and Microbiology and ImmunologyMassey Cancer CenterVirginia Commonwealth UniversityRichmondVA 23298-0011USA

Triple-negative breast cancer(TNBC)is the most aggressive breast cancer *** disproportionately affects BRCA mutation carriers and young women,especially African American(AA)*** TNBC is a heterogeneous and molecularly unstable disease that challenges our ability to apply personalized *** the approval of immune checkpoint blockade(ICB)for TNBC,the addition of pembrolizumab to systemic chemotherapy has become standard of care(SOC)in neoadjuvant systemic therapy(NST)for high-risk early-stage *** plus chemotherapy significantly increased the pathologic complete response(pCR)and improved event-free survival in ***,clinical uncertainties remain because similarly treated TNBC partial responders with comparable tumor responses to neoadjuvant therapy often experience disparate clinical *** methods fall short in accurately predicting which high-risk patients will develop chemo-resistance and tumor ***,novel treatment strategies and innovative new research initiatives are *** propose that the EGFR-K-RAS-SIAH pathway activation is a major tumor driver in chemoresistant *** high expression of SIAH in residual tumors following NACT/NST reflects that the EGFR/K-RAS pathway remains activated(ON),indicating an ineffective response to *** chemoresistant tumor clones persist in expressing SIAH(SIAH^(High/ON))and are linked to early tumor relapse and poorer ***,the loss of SIAH expression(SIAH^(Low/OFF))in residual tumors post-NACT/NST reflects EGFR/K-RAS pathway inactivation(OFF),indicating effective therapy and chemo-sensitive tumor ***^(Low/OFF) signal is linked to tumor remission and better prognosis post-NACT/***,SIAH is well-positioned to become a novel tumor-specific,therapy-responsive,and prognostic ***,this new biomarker(SIAH^(High/ON))could be used to quantify therapy response,predict chemo-resistance,and identi

关键词： Triple-negative breast cancer(TNBC) chemo-resistance seven in absentia(SINA)and human homologs of SINA(SIAH)E3 ligase ubiquitin-mediated proteolysis EGFR/K-RAS/SIAH pathway activation in TNBC neoadjuvant chemotherapy prognosis patient risk stratification detection of chemo-resistance precision quantification of therapy efficacy and treatment optimization

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Laboratory characterization of temperature induced reflection cracks

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Journal of Traffic and Transportation Engineering(English Edition) 2020年第5期7卷 668-677页

作者： richard Y.Ji Tirupan Mandal Hao Yin William J.Hughes Technical Center Airport Technology R&D BranchFederal Aviation AdministrationAtlantic CityNJ 08234USA Gemini Technologies Inc.Atlantic CityNJ 08234USA

A hot-mix asphalt(HMA) overlay is one of the primary strategy for rehabilitating existing HMA pavements and Portland cement concrete(PCC) pavements. The current design program, FAARFIELd, does not address reflective cracking for asphalt-overlaid concrete pavements due to its mechanism complexity. The bending, shearing, and thermal are three crucial factors to successfully model reflective cracking. To implement this failure mode in flexible over rigid design procedure, a series of full-scale test pavements were constructed, instrumented, and tested in the condition of extreme cooling temperature at the FAA National Airport Pavement Test Facility. The purpose was to assess cooling effects on the propagation of reflection cracks for airport AC over PCC pavements. In preparation for reflective cracking phase VI test, the FAA is conducting laboratory experiment on field extracted hot mix asphalt(HMA) cores. In order to test these field HMA cores, the Texas Overlay Tester(OT) was customized to get data similar to the full-scale tests. This paper discusses finite element analysis on the full-scale testing, development of the customized Texas OT, and a laboratory testing suite using the customized Texas OT, including preliminary tests, instrumentation, experiment design, and test results. data obtained from this research effort will be used to develop a rational testing procedure to simulate extreme cooling cycles through full-scale testing.

关键词： Reflection cracks Customized Texas overlay tester Overlay Strain properties Fracture properties

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Elucidating the genetic basis of antioxidant status in lettuce (Lactuca sativa)

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Horticulture Research 2015年第1期2卷 47-59页

作者： Annabelle damerum Stacey L Selmes Gaia F Biggi Graham JJ Clarkson Steve d Rothwell Maria JoséTruco richard W Michelmore Robert d Hancock Connie Shellcock Mark A Chapman Gail Taylor Centre for Biological Sciences University of SouthamptonLife SciencesUniversity RoadSouthamptonSO171BJUK Vitacress Limited Lower Link FarmSt Mary BourneAndoverSP116DBHampshireUK The Genome Centre and the department of Plant Sciences University of CaliforniaDavis95616CAUSA The James Hutton Institute InvergowrieDD25DADundeeUK

A diet rich in phytonutrients from fruit and vegetables has been acknowledged to afford protection against a range of human diseases,but many of the most popular vegetables are low in *** relatives of crops may contain allelic variation for genes determining the concentrations of these beneficial phytonutrients,and therefore understanding the genetic basis of this variation is important for breeding efforts to enhance nutritional *** this study,lettuce recombinant inbred lines,generated from a cross between wild and cultivated lettuce(Lactuca serriola and Lactuca sativa,respectively),were analysed for antioxidant(AO)potential and important phytonutrients including carotenoids,chlorophyll and phenolic *** grown in two environments,96 quantitative trait loci(QTL)were identified for these nutritional traits:4 for AO potential,2 for carotenoid content,3 for total chlorophyll content and 87 for individual phenolic compounds(two per compound on average).Most often,the *** alleles conferred an increase in total AOs and *** genes underlying these QTL were identified by BLASTn searches;in several cases,these had functions suggesting involvement in phytonutrient biosynthetic *** of a QTL on linkage group 3,which accounted for>30%of the variation in AO potential,revealed several candidate genes encoding multiple MYB transcription factors which regulate flavonoid biosynthesis and flavanone 3-hydroxylase,an enzyme involved in the biosynthesis of the flavonoids quercetin and kaempferol,which are known to have powerful AO ***-up quantitative RT-PCR of these candidates revealed that 5 out of 10 genes investigated were significantly differentially expressed between the wild and cultivated parents,providing further evidence of their potential involvement in determining the contrasting *** results offer exciting opportunities to improve the nutritional content and health benefits of lettu

关键词： breeding crops Lactuca

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decreasing recurrent bowel obstructions,improving quality of life with physiotherapy:Controlled study

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World Journal of Gastroenterology 2018年第19期24卷 2108-2119页

作者： Amanda d Rice Kimberley Patterson Evette d Reed Belinda F Wurn Kristen Robles Bernhard Klingenberg Leonard B Weinstock Janey SA Pratt C richard King III Lawrence J Wurn department of Internal Medicine College of Medicine-PhoenixUniversity of ArizonaPhoenixAZ 85004United States Clear Passage Therapies GainesvilleFL 32606United States department of Mathematics and Statistics Williams CollegeWilliamstownMA 01267United States Clinical Medicine and Surgery Washington University School of MedicineSpecialists in GastroenterologyLLCSt.LouisMO 63141United States department of Surgery Stanford University School of MedicinePalo AltoCA 94035United States College of Medicine University of FloridaGainesvilleFL 32607United States

AIM To compare(1) quality of life and(2) rate of recurrent small bowel obstructions(SBO) for patients treated with novel manual physiotherapy vs no treatment. METHOdS One hundred and three subjects(age 19-89) with a history of recurrent adhesive SBO were treated with a manual physiotherapy called the Clear Passage Approach(CPA) which focused on decreasing adhesive crosslinking in abdominopelvic viscera. Pre-and post-therapy data measured recurring obstructions and quality of life, using a validated test sent 90 d after therapy. Results were compared to 136 untreated control subjects who underwent the same measurements for subjects who did not receive any therapy, which is the normal course for patients with recurring SBO. Comparison of the groups allowed us to assess changes when the physiotherapy was added as an adjunct treatment for patients with recurring *** despite histories of more prior hospitalizations, obstructions, surgeries, and years impacted by bowel issues, the 103 CPA-treated subjects reported a significantly lower rate of repeat SBO than 136 untreated controls(total obstructions P = 0.0003; partial obstructions P = 0.0076). Subjects treated with the therapy demonstrated significant improvements in five of six total domains in the validated Small Bowel Obstruction Questionnaire(SBO-Q). domains of diet, pain, gastrointestinal symptoms, quality of life(QOL) and pain severity when compared to post CPA treatment were significantly improved(P dication domain was not changed in the CPA treated group(P = 0.176).CONCLUSION CPA physical therapy was effective for patients with adhesive SBO with significantly lower recurrence rate, improvement in reported symptoms and overall quality of life of subjects.

关键词： Clear passage approach Manual therapy Physical therapy Small bowel obstructions Adhesions Physiotherapy Alternative therapy

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Polyethylene glycol restores axonal conduction after corpus callosum transection

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Neural Regeneration Research 2017年第5期12卷 757-760页

作者： Ravinder Bamba d.Colton Riley richard B.Boyer Alonda C.Pollins R.Bruce Shack Wesley P.Thayer department of Plastic Surgery Vanderbilt University Medical Center Nashville TN USA department of Surgery Georgetown University Washington DC USA Georgetown University School of Medicine Washington DC USA

Polyethylene glycol（PEG） has been shown to restore axonal continuity after peripheral nerve transection in animal models. We hypothesized that PEG can also restore axonal continuity in the central nervous system. In this current experiment, coronal sectioning of the brains of Sprague-dawley rats was performed after animal sacrifice. 3Brain high-resolution microelectrode arrays（MEA） were used to measure mean firing rate（MFR） and peak amplitude across the corpus callosum of the ex-vivo brain slices. The corpus callosum was subsequently transected and repeated measurements were performed. The cut ends of the corpus callosum were still apposite at this time. A PEG solution was applied to the injury site and repeated measurements were performed. MEA measurements showed that PEG was capable of restoring electrophysiology signaling after transection of central nerves. Before injury, the average MFRs at the ipsilateral, midline, and contralateral corpus callosum were 0.76, 0.66, and 0.65 spikes/second, respectively, and the average peak amplitudes were 69.79, 58.68, and 49.60 μV, respectively. After injury, the average MFRs were 0.71, 0.14, and 0.25 spikes/second, respectively and peak amplitudes were 52.11, 8.98, and 16.09 μV, respectively. After application of PEG, there were spikes in MFR and peak amplitude at the injury site and contralaterally. The average MFRs were 0.75, 0.55, and 0.47 spikes/second at the ipsilateral, midline, and contralateral corpus callosum, respectively and peak amplitudes were 59.44, 45.33, 40.02 μV, respectively. There were statistically differences in the average MFRs and peak amplitudes between the midline and non-midline corpus callosum groups（P 〈 0.01, P 〈 0.05）. These findings suggest that PEG restores axonal conduction between severed central nerves, potentially representing axonal fusion.

关键词： nerve regeneration polyethylene glycol nerve repair axonal fusion central nerve injury axonal conduction corpus callosum neural regeneration

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