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Adaptive pathways and emerging strategies overcoming treatment resistance in castration resistant prostate cancer

Asian Journal of Urology 2016年第4期3卷 185-194页

作者： cameron m.armstrong Allen C.Gao Department of Urology University of CaliforniaDavisSacramentoCAUSA Comprehensive Cancer Center University of CaliforniaDavisSacramentoCAUSA VA Northern California Health Care System SacramentoCAUSA

The therapies available for prostate cancer patients whom progress from hormonesensitive to castration resistant prostate cancer include both systemic drugs,including docetaxel and cabazitaxel,and drugs that inhibit androgen signaling such as enzalutamide and ***,it is estimated that up to 30%of patients have primary resistance to these treatments and over time even those who initially respond to therapy will eventually develop resistance and their disease will continue to progress regardless of the presence of the *** the mechanisms involved in the development of resistance to these therapies has been the area of intense study and several adaptive pathways have been *** receptor(AR)mutations,expression of AR-V7(or other constitutively active androgen receptor variants),intracrine androgen production and overexpression of androgen synthesis enzymes such as Aldo-Keto Reductase Family 1,member C3(AKR1C3)are among the many mechanisms associated with resistance to *** regards to the taxanes,one of the key contributors to drug resistance is increased drug efflux through ATP Binding Cassette Subfamily B member 1(ABCB1).Targeting these resistance mechanisms using different strategies has led to various levels of success in overcoming resistance to current *** instance,targeting AR-V7 with niclosamide or AKR1C3 with indomethacin can improve enzalutamide and abiraterone ***1 transport activity can be inhibited by the dietary constituent apigenin and antiandrogens such as bicalutamide which in turn improves response to docetaxel.A more thorough understanding of how drug resistance develops will lead to improved treatment *** review will cover the current knowledge of resistance mechanisms to castration resistant prostate cancer therapies and methods that have been identified which may improve treatment response.

关键词： Prostate cancer Castration resistant prostate cancer Enzalutamide Abiraterone Docetaxel Drug resistance

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Current strategies for targeting the activity of androgen receptor variants

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Asian Journal of Urology 2019年第1期6卷 42-49页

Current therapies for advanced prostate cancer,such as enzalutamide and abiraterone,focus on inhibiting androgen receptor(AR)activity and reducing downstream signaling pathways to inhibit tumor ***,cancer cells are very adaptable and,over time,these cells develop mechanisms by which they can circumvent *** of the many mechanisms that have been discovered is the generation of AR *** variants are generated through alternative splicing of the full length AR and often lack the ligand binding *** leads to forms of the AR that are constitutively active that continue to promote prostate cancer cell growth even in the absence of *** high prevalence of AR variants and their role in disease progression have prompted a number of studies investigating ways to inhibited AR variant expression and *** these are the antihelminthic drug,niclosamide,which selectively promotes degradation of AR variants over full length AR and re-sensitizes anti-androgen resistant prostate cancer cells to treatment with enzalutamide and *** AR variant targeting mechanisms include interfering with AR variant co-activators and the development of drugs that bind to the DNA or N-terminal AR domains,which are retained in most AR *** clinical efficacy of treating prostate cancer by targeting AR variants is under investigation in several clinical *** this review,we provide an overview of the most relevant AR variants and discuss current AR variant targeting strategies.

关键词： Prostate cancer Androgen receptor variants Drug resistance

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Planetary Homeostasis of Reactive Nitrogen Through Anaerobic Ammonium Oxidation

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Engineering 2024年第7期38卷 175-183页

作者： Guibing Zhu Bangrui Lan Shuci Liu cameron m.Callbeck Shanyun Wang Liping Jiang Asheesh Kumar Yadav Jan Vymazal mike S.m.Jetten Ganlin Zhang Yongguan Zhu Research Center for Eco-Environmental Sciences Chinese Academy of SciencesBeijing 100085China Department of Environment and Science Queensland GovernmentBrisbaneQLD 4102Australia Department of Environmental Sciences University of BaselBasel 4056Switzerland CSIR-Institute of minerals and materials Technology Bhubaneswar 751013India Faculty of Environmental Sciences Czech University of Life Sciences PraguePraha 16521Czech Republic Department of microbiology Radboud UniversityNijmegen 6525 XZThe Netherlands Key Laboratory of Watershed Geographic Sciences Nanjing Institute of Geography and LimnologyChinese Academy of SciencesNanjing 210008China State Key Laboratory of Soil and Sustainable Agriculture Institute of Soil ScienceChinese Academy of SciencesNanjing 210008China University of Chinese Academy of Sciences Beijing 100049China

The availability of nitrogen(N)is crucial for both the productivity of terrestrial and aquatic ecosystems ***,the overuse of artificial fertilizers and the energy required to fix nitrogen have pushed the global nitrogen cycle(N-cycle)past its safe operating limits,leading to severe nitrogen pollution and the production of significant amounts of greenhouse gas nitrous oxide(N2O).The anaerobic ammonium oxidation(anammox)mechanism can counteract the release of ammonium and N2O in many oxygenlimited situations,assisting in the restoration of the homeostasis of the Earth’s N *** this work,we looked into the characteristics of the anammox hotspots’distribution across various types of ecosystems *** hotspots are present at diverse oxic-anoxic interfaces in terrestrial systems,and they are most prevalent at the oxic-anoxic transition zone in aquatic *** on the discovery of an anammox hotspot capable of oxidizing ammonium anoxically into N2 without N2O by-product,we then designed an innovative concept and technical routes of nature-based anammox hotspot geoengineering for climate change,biodiversity loss,and efficient utilization of water *** 15 years of actual use,anammox hotspot geoengineering has proven to be effective in ensuring clean drinking water,regulating the climate,fostering plant and animal diversity,and enhancing longterm environmental *** sustainable biogeoengineering of anammox could be a workable natural remedy to resolve the conflicts between environmental pollution and food security connected to N management.

关键词： Biogeochemical N-cycle Oxic-anoxic interface Nature-based solution Biogeoengineering Nitrogen sustainable development

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An electropenetrography waveform library for the probing and ingestion behaviors of Culex tarsalis on human hands

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Insect Science 2024年第4期31卷 1165-1186页

作者： Anastasia m.W.Cooper Samuel B.Jameson Victoria Pickens cameron Osborne Elaine A.Backus Kristopher Silver Dana N.mitzel Department of Entomology Kansas State UniversityManhattanKansasUSA Department of Tropical medicine Tulane University School of Public Health and Tropical MedicineNew OrleansLos AngelesUSA USDA Agricultural Research Service San Joaquin Valley Agricultural Sciences CenterParlierCaliforniaUSA National Bio and Agro-Defense Facility USDA Agricultural Research ServiceManhattanKansasUSA

Culex tarsalis Coquillett(Diptera:Culicidae)mosquitoes are capable of vectoring numerous pathogens affecting public and animal ***,the probing behaviors of mosquitoes are poorly understood because they occur in opaque ***(EPG)has the potential to elucidate these behaviors by recording the electrical signals generated during *** used an AC–DC EPG with variable input resistors(Ri levels)to construct a waveform library for *** feeding on human *** events associated with mosquito probing were used to characterize waveforms at four Ri levels and with two electrical current *** optimal settings for EPG recordings of *** probing on human hands was an Ri level of 10^(7)Ohms using an applied signal of 150 millivolts alternating *** for *** included those previously observed and associated with probing behaviors in Aedes aegypti L.(Diptera:Culicidae):waveform families J(surface salivation),K(stylet penetration through the skin),L(types 1 and 2,search for a blood vessel/ingestion site),m(types 1 and 2,ingestion),N(type 1,an unknown behavior which may be a resting and digestion phase),and W(withdrawal).However,we also observed variations in the waveforms not described in ***,which we named types L3,m3,m4,and *** investigation enhances our understanding of mosquito probing *** also provides a new tool for the automated calculation of peak *** work will facilitate future pathogen acquisition and transmission studies and help identify new pest and disease management targets.

关键词： AC-DC blood feeders electrical penetration graph EPG human hands mosquitoes waveform library

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Outrunning the Red Queen： bystander activation as a means of outpacing innate immune subversion by intracellular pathogens

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Cellular & molecular Immunology 2017年第1期14卷 14-21页

作者： Alicia m Holmgren cameron A mcConkey Sunny Shin Depatment of microbiology Perelman School of Medicine University of Pennsylvania Philadelphia PA 19104-6060 USA Immunology Graduate Group Perelman School of Medicine University of Pennsylvania Philadelphia PA 19104-6060 USA

Originally described by the late evolutionary biologist Leigh Van Valen, the Red Queen hypothesis posits that the evolutionary arms race between hosts and their pathogens selects for discrete, genetically encoded events that lead to competitive advantages over the other species. Examples of immune evasion strategies are seen throughout the co-evolution of the mammalian immune system and pathogens, such as the enzymatic inactivation of nuclear factor-KB signaling or host translation by pathogen-encoded virulence factors. Such immunoevasive maneuvers would be expected to select for the evolution of innate immune counterstrategies. Recent advances in our understanding of host immunity and microbial pathogenesis have provided insight into a particular innate immune adaptation, termed bystander activation. Bystander activation occurs as a consequence of infected cells alerting and instructing neighboring uninfected cells to produce inflammatory mediators, either through direct cell contact or paracrine signals. Thus, bystander activation can allow the immune system to overcome the ability of pathogens to disarm immune signaling in directly infected cells. This review presents an overview of the general hallmarks of bystander activation and their emerging role in innate immunity to intraceUular pathogens, as well as examples of recent mechanistic discoveries relating to the bystander activation during infection with specific pathogens relevant to human health and disease.

关键词： cell-cell communication cGAS exosomes gap junctions inflammasomes innate immunity

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A longitudinal analysis of the U.S. Air Force Reserve Officers’ Training Corps physical fitness assessment

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military medical Research 2020年第2期7卷 166-173页

作者： cameron Smackey Jason mDe Freitas Applied Neuromuscular Physiology Laboratory Oklahoma State University192 CRCStillwaterOK 74078USA

Background:The *** Force physical fitness assessment(PFA)is used to determine the overall fitness of their *** is currently unknown to what extent the PFA scores of Reserve Officers’Training Corps(ROTC)cadets are affected by mandatory physical *** purpose of this investigation was to longitudinally examine the PFAs of ROTC cadets over a four-year period,evaluate the results across class ranks,and evaluate the sensitivity of the classification of the ***:Air Force ROTC cadets performed the PFAs(abdominal circumference,1-min pushups,1-min sit-ups,and a 1.5-mile run)in both the spring(n=26)and fall(n=22)*** were compiled over a four-year period(Spring 2014–Fall 2017)and were performed in accordance with Air Force Instruction 36–2905.A oneway repeated measures ANOVA was performed separately for the fall and spring groups for each dependent variable across the 4 ***,a one-way between groups ANOVA was performed for each dependent variable during the time point(fall 2015;n=46)with the most recorded cadets for each class ***:Longitudinal assessments revealed a main effect of time(P=0.010)on abdominal circumference;cadets had a smaller abdominal circumference in their freshman year than in their senior year.A main effect of time(P=0.006)was also observed on sit-up quantity;cadets performed more sit-ups in their junior year than in their freshman *** between class ranks during the same year(between-subjects ANOVA)revealed a main effect of class rank on sit-up quantity(P=0.003);the freshmen completed fewer repetitions than the sophomores(P=0.018)and the juniors did(P=0.001).Conclusions:The results indicated that only the sit-up component showed differences between class *** findings suggest that the Air Force PFA may not be sensitive enough to detect changes in physical fitness or distinguish between class ranks regarding physical performance,even after years of *** limitation may b

关键词： Class ranks Fitness assessment military Physical training ROTC

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Keratinized Nuptial Spines Are Used for male Combat in the Emei moustache Toad(Leptobrachium boringii)

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Asian Herpetological Research 2011年第3期2卷 142-148页

作者： cameron m. HUDSON Xianjin HE Jinzhong FU Department of Integrative Biology University of Guelph50 Stone Road East College of Life Science and Technology Southwest University for Nationalities

We describe the natural history and reproductive behaviour of the Emei moustache Toad(Leptobrachium boringii) with an emphasis on the development of keratinized nuptial spines in males and document combat behaviour for the first time in this species. Between February and march of 2011, 19 female and 43 male L. boringii from mount Emei UNESCO World Heritage Site, Sichuan, China were observed throughout the breeding season. This species exhibits male-biased sexual size dimorphism(SSD) with limited evidence of paternal care(nest guarding by males). Prior to the breeding season males grow 10 – 16 keratinized spines on their upper lip, which fall off once the season has ended. Throughout the breeding season males construct and defend aquatic nests where they produce advertisement calls to attract females. During this time we documented 14 cases involving a total of 22 males where males used their moustaches for aggressive interaction. Combat typically occurred at the beginning of the season when males would compete for a limited number of available nest sites. Neither male body size, nor body condition significantly affects the outcome of an aggressive interaction, suggesting that size may not be the only factor influencing an individual’s chance of victory. Our evidence for male competition and aggression, along with observed paternal care are potential mechanisms to explain the evolution of male-biased SSD observed in this species.

关键词： reproductive behaviour territoriality Leptobrachium boringii secondary sexual characters

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In vitro angiogenesis in response to biomaterial properties for bone tissue engineering:a review of the state of the art

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Regenerative Biomaterials 2023年第1期10卷 744-783页

作者： Else Ellermann Nima meyer Ruth E.cameron Serena m.Best Department of materials Science and metallurgy University of CambridgeCambridge CB30FSUK

Bone tissue engineering(BTE)aims to improve the healing of bone fractures using scaffolds that mimic the native extracellular *** successful bone regeneration,scaffolds should promote simultaneous bone tissue formation and blood vessel growth for nutrient and waste ***,a significant challenge in regenerative medicine remains the development of grafts that can be vascularized *** other things,optimization of physicochemical conditions of scaffolds is key to achieving appropriate angiogenesis in the period immediately following *** phosphates and collagen scaffolds are two of the most widely studied biomaterials for BTE,due to their close resemblance to inorganic and organic components of bone,respectively,and their bioactivity,tunable biodegradability and the ability to produce tailored *** various strategies exist to enhance vascularization of these scaffolds in vivo,further in vitro assessment is crucial to understand the relation between physicochemical properties of a biomaterial and its ability to induce *** mono-culture studies can provide evidence regarding cell-material interaction of a single cell type,a co-culture procedure is crucial for assessing the complex mechanisms involved in angiogenesis.A co-culture more closely resembles the natural tissue both physically and biologically by stimulating natural intercellular interactions and mimicking the organization of the in vivo ***,a co-culture is a complex system requiring optimization of various parameters including cell types,cell ratio,culture medium and seeding *** fundamental knowledge of the mechanism behind the bioactivity of biomaterials and understanding the contribution of surface and architectural features to the vascularization of scaffolds,and the biological response in general,can provide an invaluable basis for future optimization *** review gives an overview of the

关键词： angiogenesis collagen scaffolds hydroxyapatite co-culture architectural features physicochemical properties

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Immortalized Sertoli cell lines sk11 and sk9 and binding of spermatids in vitro

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Asian Journal of Andrology 2007年第3期9卷 312-320页

作者： Katja m. Wolski Caroline Feig Christiane Kirchhoff Don F. cameron Department of Pathology and Cell Biology School of Basic Biomedical Sciences University of South Florida Collegeof Medicine Tampa Florida 33612 USA Department of molecular Andrology University Clinics Eppendorf University of Hamburg Hamburg Germany

Aim： To determine the effectiveness of the ski 1, sk9 and ski 1 TNUA5 Sertoli cell lines in binding germ cells in vitro. methods： The immortalized Sertoli cell lines sk9, ski 1 and ski 1 TNUA5 were used in co-culture experiments with germ cells in media with or without reproductive hormones and incubated for 44 h at 32℃. The number of germ cells bound to Sertoli cells was then determined and statistically analyzed. Western blot analysis and reverse transcriptasepolymerase chain reaction （RT-PCR） studies were employed to investigate the presence of cell adhesion proteins and follicle stimulating hormone （FSH） receptor, respectively. Results： No statistical difference between the number of bound step-8 spermatids and bound pre-step 8 spermatids on Sertoli cells from any of the cell lines existed. After the addition of germ cells, Sertoli ceils showed more lipid accumulation in their cytoplasm, indicating active phagocytosis. Western blot analysis in the ski I TNUA5 line indicated the expression of N-cadherin. FSH-only and testosterone-only treatments increased N-cadherin expression, regardless of germ cell addition. The addition of germ cells to the ski l TNUA5 Sertoli cells increased the expression of espin, as did the addition of FSH with germ cells. RT-PCR studies of the ski I TNUA5 cells indicated that the mRNA for FSH receptor decreased with successive passages. Conclusion： In vitro binding between isolated germ cells and sk9, skll or skll TNUA5 Sertoli cells is not feasible, and therefore these cell lines are not useful for the in vitro investigation of Sertoli-germ cell interactions and primary Sertoli cell isolates must still be used.

关键词： sk Sertoli cells immortalized Sertoli cells Sertoli-germ cell binding Sertoli-germ cell co-culture Sertoli-spermatid junctionalcomplex in vitro cell-cell binding

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The omentum

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World Journal of Gastroenterology 2000年第2期6卷 169-176页

作者： cameron Platell Deborah Cooper John m.Papadimitriou John C.Hall Department of Surgery the University of Western Australia Departments of Pathology the University of Western Australia

INTRODUCTIONThe word omentum derives from the ancientEgyptians who,when embalming human bodies,used to assess their'omens'by looking at thevariations in what we recognise today as ***(128-199 AD)thought that therole of the omentum was to warm the *** was on the basis of a gladiator who had anomental resection after a stab injury and sufferedgreatly from cold for the rest of his life.A

关键词： omentum peritonitis macrophage neutrophil lymphocytes mesothelium adhesions omentectomy

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