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Parkinson's disease: From genetics to molecular dysfunction and targeted therapeutic approaches

Genes & Diseases 2023年第3期10卷 786-798页

作者： Yue Huang jun Wei Antony Cooper Margaret j.morris China National Clinical Research Center for Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijing 100070China Department of Neurology Beijing Tiantan HospitalCapital Medical UniversityBeijing 100070China Department of Pharmacology School of Medical SciencesFaculty of Medicine&HealthUNSWSydneyNSW 2052Australia The Garvan Institute of Medical Research SydneyNSW 2010Australia St Vincent's Clinical School Faculty of Medicine&Healthand School of Biotechnology and Biomolecular SciencesFaculty of ScienceUNSWSydneyNSW 2052Australia

Parkinson's disease (PD) is the most common neurodegenerative movement disorder in the elderly. As the pathogenesis of PD is still not fully understood, medications with the capacity of halting the disease progression are currently unavailable. The discovery of genes that are causative for, or increase susceptibility to PD is pivotal for the development of novel therapeutic approaches, as they are critical for the onset of PD and the molecular pathways underlying its pathogenesis. By reviewing relevant data, we discuss causative genes, and those associated with PD susceptibility and quantitative traits. Through Gene Ontology database and STRING analysis, we emphasize the roles of inorganic cation transmembrane transport pathways and hypothalamic pituitary thyroid axis, in addition to the established roles of inflammation/oxidative stress and mitochondrial dysfunction in the pathogenesis of PD. It is hoped these insights 1) untangle the clinical complex presentations of PD, 2) reveal the interwoven molecular network leading to PD, and 3) identify critical molecular targets to facilitate novel PD drug discovery, with a view to providing improved consultation and personalized medicine for patients with PD in the future.

关键词： Drug discovery Genetics Molecular function Parkinson's disease Quantitative traits

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Fishing for Atlantic cod (Gadus morhua) with pots and gillnets: A catch comparison study along the southeast coast of Labrador

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Aquaculture and Fisheries 2022年第4期7卷 433-440页

作者： Khanh Q.Nguyen Corey j.morris Fisheries and Oceans Canada Northwest Atlantic Fisheries CentreSt.John’sNewfoundlandA1C5X1Canada

Gillnets are the primary fishing gear used to catch Atlantic cod(Gadus morhua)in coastal areas of Newfoundland and Labrador but are known to catch non-target species and produce lower quality fish than live-catch *** purpose of this study was to compare the catch efficiency of collapsible cod pots against gillnets near the Gilbert Bay Marine Protected Area(MPA),Labrador,where a reduction in by-catch is *** showed that one cod pot caught half as much Atlantic cod as a gillnet,and pots had a relatively stable catch rate throughout the sampling period,whereas gillnets caught relatively few fish later in the sampling ***,nearly all fish sampled with pots were caught alive undamaged,whereas most gillnet-caught fish experienced damage or *** a conservation measure pot-fishing would enable fishing within close proximity to the Gilbert Bay MPA and the live-release of visually distinguishable Gilbert Bay cod,thereby mitigating against the negative effects of commercial fishing on this protected Atlantic cod population.

关键词： Catch rates Cod pots Bycatch reduction Gillnets Conservation Atlantic cod fishery

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Metabolic reprogramming by Syntenin-1 directs RA FLS and endothelial cell-mediated inflammation and angiogenesis

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Cellular & Molecular Immunology 2024年第1期21卷 33-46页

作者： Anja Meyer Stephanie R.Zack Wes Nijim Adel Burgos Vishwa Patel brian Zanotti Michael V.Volin M.Asif Amin Myles j.Lewis Costantino Pitzalis Shiva Arami joseph A.Karam Nadera j.Sweiss Shiva Shahrara jesse Brown VA Medical Center ChicagoILUSA Department of Medicine Division of RheumatologyThe University of Illinois at ChicagoChicagoILUSA Department of Microbiology and Immunology Midwestern UniversityDowners GroveILUSA Division of Rheumatology and Clinical Autoimmunity Center of Excellence University of MichiganAnn ArborMIUSA Centre for Experimental Medicine and Rheumatology William Harvey Research InstituteBarts and The London School of Medicine and DentistryQueen Mary University of LondonLondonUnited Kingdom Centre for Experimental Medicine&Rheumatology William Harvey Research InstituteQueen Mary University of London and Barts NIHR BRC&NHS TrustLondonUK Department of Biomedical Sciences Humanitas Universityand Humanitas Research HospitalMilanItaly Department of Orthopedic Surgery the University of Illinois at ChicagoChicagoILUSA

A novel rheumatoid arthritis(RA)synovial fluid protein,Syntenin-1,and its receptor,Syndecan-1(SDC-1),are colocalized on RA synovial tissue endothelial cells and fibroblast-like synoviocytes(FLS).Syntenin-1 exacerbates the inflammatory landscape of endothelial cells and RA FLS by upregulating transcription of IRF1/5/7/9,IL-1β,IL-6,and CCL2 through SDC-1 ligation and HIF1α,or mTOR ***,Syntenin-1 orchestrates RA FLS and endothelial cell invasion via SDC-1 and/or mTOR *** Syntenin-1 reprogrammed endothelial cells,the dynamic expression of metabolic intermediates coincides with escalated glycolysis along with unchanged oxidative factors,AMPK,PGC-1α,citrate,and inactive oxidative ***,RA FLS rewired by Syntenin-1 displayed a modest glycolytic-ATP accompanied by a robust mitochondrial-ATP *** enriched mitochondrial-ATP detected in Syntenin-1 reprogrammed RA FLS was coupled with mitochondrial fusion and fission recapitulated by escalated Mitofusin-2 and DRP1 *** found that VEGFR1/2 and Notch1 networks are responsible for the crosstalk between Syntenin-1 rewired endothelial cells and RA FLS,which are also represented in RA *** to RA explants,morphological and transcriptome studies authenticated the importance of VEGFR1/2,Notch1,RAPTOR,and HIF1αpathways in Syntenin-1 arthritic mice and their obstruction in SDC-1 deficient ***,dysregulation of SDC-1,mTOR,and HIF1αnegated Syntenin-1 inflammatory phenotype in RA explants,while inhibition of HIF1αimpaired synovial angiogenic imprint amplified by *** conclusion,since the current therapies are ineffective on Syntenin-1 and SDC-1 expression in RA synovial tissue and blood,targeting this pathway and its interconnected metabolic intermediates may provide a novel therapeutic strategy.

关键词： Syntenin-1 Syndecan-1 RA FLS RA explants immunometabolism

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Fetal Head Compression: Its Possible Role in Neurologic Injury

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Open journal of Obstetrics and Gynecology 2024年第1期14卷 124-143页

作者： Barry S. Schifrin brian j. Koos Wayne R. Cohen Department of Obstetrics and Gynecology The Western University of Health Sciences Pomona USA The David Geffen School of Medicine at UCLA Los Angeles USA The University of Arizona College of Medicine Tucson USA

It is widely assumed that fetal ischemic brain injury during labor derives almost exclusively from severe, systemic hypoxemia with marked neonatal depression and acidemia. Severe asphyxia, however, is one of several causes of perinatal neurological injury and may not be the most common;most neonates diagnosed with hypoxic-ischemic encephalopathy do not have evidence of severe asphyxia. Sepsis, direct brain trauma, and drug or toxin exposure account for some cases, while mechanical forces of labor and delivery that increase fetal intracranial pressure sufficiently to impair brain perfusion may also contribute. Because of bony compliance and mobile suture lines, the fetal skull changes shape and redistributes cerebrospinal fluid during labor according to constraints imposed by contractions, and bony and soft tissue elements of the birth canal as the head descends. These accommodations, including the increase in intracranial pressure, are adaptive and necessary for efficient descent of the head while safeguarding cerebral blood flow. Autonomic reflexes mediated through central receptors normally provide ample protection of the brain from the considerable pressure exerted on the skull. On occasion, those forces, which are transmitted intracranially, may overcome the various adaptive anatomical, cardiovascular, metabolic, and neurological mechanisms that maintain cerebral perfusion and oxygen availability, resulting in ischemic brain injury. Accepting the notion of a potentially adverse impact of fetal head compression suggests that avoidance of excessive uterine activity and of relentless pushing without steady progress in descent may offer protection for the fetal brain during parturition. Excessive head compression should be considered in the differential diagnosis of ischemic encephalopathy.

关键词： Fetal Brain Injury Fetal Head Compression Ischemic Encephalopathy Neonatal Encephalopathy

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Circumcision reduces prostate cancer risk

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Asian journal of Andrology 2012年第5期14卷 661-662页

作者： brian j.morris lake H Waskett School of Medical Sciences University of SydneySydney NSW 2006 Australia CircumcisionIndependent Reference and Commentary Service Manchester M26 1JR UK

There is a strong negative correlation between prostate cancer and circumcision rate across 181 countries （P〈0.0001）. Adding to the large protective effect of cir- cumcision seen in small studies over the past six decades, a recent large study in Seattle has shown a smaller protective effect. If verified by other large studies else- where, the finding would add to the wide array of benefits conferred by this safe, sim- ple procedure that is best performed in infancy.

关键词： INFECTION

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Reply to Letter by Dr. Christoph Kupferschmid： Commentary on ＂Countries with high circumcision prevalence have lower prostate cancer mortality＂

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Asian journal of Andrology 2016年第6期18卷 950-951页

作者： Mitchell S Wachtel Shengping Yang brian j.morris Texas Tech University Health Sciences Center Lubbock Texas USA School of Medical Sciences University of Sydney Sydney New South Wales Australia

Dear Editor, We thank Dr. Kupferschmid for his interest in our study, which examined male circumcision （MC） and prostate cancer mortality〉2 Considerable strong evidence has been accumulated since 1951.3 Most of his references4-10 do not address MC and the risk of death from prostate cancer. That is a different question than MC and the risk of developing prostate cancer, which none of his references validly assess. One reference addressed bacterial colonization,6 not prostate cancer. Another7 concerned sexually transmitted infections and prostate cancer.

关键词： EPIDEMIOLOGY RISK

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Use of light-emitting diode(LED)lamps in combination with metal halide(MH)lamps reduce fuel consumption in the Vietnamese purse seine fishery

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Aquaculture and Fisheries 2021年第4期6卷 432-440页

作者： Khanh Q.Nguyen Phu D.Tran Luong T.Nguyen Phuong V.To Corey j.morris Nha Trang University 2 Nguyen Dinh ChieuNha TrangViet Nam Fisheries and Oceans Canada St.John’sNL A1C 5X1Canada

The use of high-power lights during night-time purse seining is common in ***,metal halide(MH)lamps are used in the commercial fishery to attract fish,however these lights require more energy,have a shorter lifespan,and lower chromatic performance than light emitting diode(LED)*** study examined catch efficiency and fuel consumption when using LED lamps in combination with reduced numbers of MH lamps(10.24 kW),compared to conventional lighting(28.6 kW),used during purse seining off the coast of Ninh Thuan province,*** economic performance associated with using LED lamps in this fishery was also *** found no significant differences in catch rates between the different light treatments,however fuel consumption was significantly *** consumption per nightly trip using LED with MH lamps was 70.8 l(11.1 l/h)compared to114 l(17.45 l/hr)using MH lamps alone,an estimated 37.9%reduction in fuel *** investment in LED lamps by a fishing enterprise will require additional initial costs,however our analysis revealed the financial break-event point can be reached after approximately 101 nightly trips when the fuel price is at the 2015 level of USD$0.74 per *** enterprises can increase their profitability,and reduce CO2 emissions,by using LED lamps in the Vietnamese purse seine fishery.

关键词： LED light Purse seine fishery Fuel consumption Catch comparison Economic efficiency

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论燕海扇和异海扇(英文)

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古生物学报 1999年第2期38卷 17-24页

作者：方宗杰,ＮｏｅｌＪ．Ｍｏrｒｉｓ中国科学院南京地质古生物研究所英国自然历史博物馆古生物部

燕海扇（Ａｖｉｃｕｌｏｐｅｃｔｅｎ）由ＭｃＣｏｙ（１８５１）创立，是燕海扇科和燕海扇超科的模式属，故地位十分重要。它是石炭二叠纪海扇类中最为常见的属名之一。由于它的模式种Ａｖｉｃｕｌｏｐｅｃｔｅｎｐｌａｎｏｒａｄｉ... 详细信息

燕海扇（Ａｖｉｃｕｌｏｐｅｃｔｅｎ）由ＭｃＣｏｙ（１８５１）创立，是燕海扇科和燕海扇超科的模式属，故地位十分重要。它是石炭二叠纪海扇类中最为常见的属名之一。由于它的模式种ＡｖｉｃｕｌｏｐｅｃｔｅｎｐｌａｎｏｒａｄｉａｔｕｓＭｃＣｏｙ只有左壳，而右壳和铰部构造的特征不明，在实际应用中，其含义被不适当地扩大，从而导致在燕海扇类研究中的混乱。１９８６年，笔者在大英博物馆发现４块燕海扇模式种Ａｖｉｃｕｌｏｐｅｃｔｅｎｐｌａｎｏｒａｄｉａｔｕｓ的右壳标本，其中包括一块双壳铰合在一起的标本，另有２块标本显示了铰合构造。这些标本的发现为系统修订燕海扇属的属征创造了条件。最近，Ｎｅｗｅｌ和Ｂｏｙｄ（１９９５）根据Ｐｅｃｔｅｎｆｌｅｘｕｏｓｕｓ（ＭｃＣｏｙ，１８４４，ｐ．９３，ｐｌ．１８，ｆｉｇ．１）和ＡｖｉｃｕｌｏｐｅｃｔｅｎａｍｅｒｉｃａｎｕｓＮｅｗｅｌｅｔＢｏｙｄ（１９９５，ｐ．６０，Ｆｉｇ．４４）的特征，推测燕海扇属的特征为两壳相等或几乎相等，这一推测显然与燕海扇模式种的特征不符，因此，他们对燕海扇和燕海扇科所作的定义不能成立。我们认为，对任何属征的修订都应基于对模式标本进行充分研究的基础之上，应避免建立在假设基

关键词：石炭-二叠纪海扇类,燕海扇,异海扇

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Aerosol jet printing of surface acoustic wave microfluidic devices

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Microsystems & Nanoengineering 2024年第1期10卷 231-242页

作者： joseph Rich brian Cole Teng Li Brandon Lu Hanyu Fu Brittany N.Smith jianping Xia Shujie Yang Ruoyu Zhong james L.Doherty Kanji Kaneko Hiroaki Suzuki Zhenhua Tian Aaron D.Franklin Tony jun Huang Department of Biomedical Engineering Duke UniversityDurhamNC 27708USA Department of Electrical and Computer Engineering Duke UniversityDurhamNC 27708USA Department of Mechanical Engineering Virginia Polytechnic Institute and State UniversityBlacksburgVA 24061USA Thomas Lord Department of Mechanical Engineering and Materials Science Duke UniversityDurhamNC 27708USA Deptartment of Precision Mechanics Faculty of Science and EngineeringChuo UniversityTokyo 112-8551Japan Department of Chemistry Duke UniversityDurhamNC 27708USA

The addition of surface acoustic wave(SAW)technologies to microfluidics has greatly advanced lab-on-a-chip applications due to their unique and powerful attributes,including high-precision manipulation,versatility,integrability,biocompatibility,contactless nature,and rapid ***,the development of SAW microfluidic devices is limited by complex and time-consuming micro/nanofabrication techniques and access to cleanroom facilities for multistep photolithography and vacuum-based *** simplify the fabrication of SAW microfluidic devices with customizable dimensions and functions,we utilized the additive manufacturing technique of aerosol jet *** successfully fabricated customized SAW microfluidic devices of varying materials,including silver nanowires,graphene,and poly(3,4-ethylenedioxythiophene)polystyrene sulfonate(PEDOT:PSS).To characterize and compare the acoustic actuation performance of these aerosol jet printed SAW microfluidic devices with their cleanroom-fabricated counterparts,the wave displacements and resonant frequencies of the different fabricated devices were directly measured through scanning laser Doppler ***,to exhibit the capability of the aerosol jet printed devices for lab-on-a-chip applications,we successfully conducted acoustic streaming and particle concentration ***,we demonstrated a novel solution-based,direct-write,single-step,cleanroom-free additive manufacturing technique to rapidly develop SAW microfluidic devices that shows viability for applications in the fields of biology,chemistry,engineering,and medicine.

关键词： printing wave fluid

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Comments by opponents on the British Medical Association’s guidance on non-therapeutic male circumcision of children seem one-sided and may undermine public health

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World journal of Clinical Pediatrics 2023年第5期12卷 244-262页

作者： Stephen Moreton Guy Cox Mark Sheldon Stefan A Bailis jeffrey D Klausner brian j.morris CircFacts Warrington WA51HYCheshireUnited Kingdom Australian Centre for Microscopy&Microanalysis and School of Aeronautical Mechanical and Mechatronic EngineeringUniversity of SydneySydney 2006New South WalesAustralia Medical Humanities and Bioethics Program Feinberg School of MedicineNorthwestern UniversityChicagoIL 60661United States Cornerstone Therapy&Recovery Center St.PaulMN 55101United States Department of Medicine Population and Public Health SciencesKeck School of MedicineUniversity of Southern CaliforniaLos AngelesCA 90089United States School of Medical Sciences University of SydneySydney 2006New South WalesAustralia

The British Medical Association(BMA)guidance on non-therapeutic circumcision(NTMC)of male children is limited to ethical,legal and religious *** we evaluate criticisms of the BMA’s guidance by Lempert et *** their arguments promoting autonomy and consent might be superficially appealing,their claim of high procedural risks and negligible benefits seem one-sided and contrast with high quality evidence of low risk and lifelong *** literature reviews by the American Academy of Pediatrics and the United States Centers for Disease Control and Prevention in developing evidence-based policies,as well as risk-benefit analyses,have found that the medical benefits of infant NTMC greatly exceed the risks,and there is no reduction in sexual function and *** BMA’s failure to consider the medical benefits of early childhood NTMC may partly explain why this prophylactic intervention is discouraged in the United *** consequence is higher prevalence of preventable infections,adverse medical conditions,suffering and net costs to the UK’s National Health Service for treatment of *** of the issues and contradictions in the BMA guidance identified by Lempert et al stem from the BMA’s guidance not being sufficiently ***,that document called for a review by others of the medical issues surrounding *** societal factors apply,ultimately,NTMC can only be justified rationally on scientific,evidence-based *** are entitled to an accurate presentation of the medical evidence so that they can make an informed *** decision either for or against NTMC should then be respected.

关键词： Circumcision,Male Child Infections Risk Policy Public health

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