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immunophenotyping identifies distinct cellular signatures for systemic lupus erythematosus and lupus nephritis

Rheumatology & Autoimmunity 2023年第1期3卷 15-25页

作者： Yi Tong V.Aw Phillip J.Whiley Ayla May Lorenzo Tom Lea-Henry Somasundhari Shanmuganandam Maurice Stanley Sonia N.Babu Vicki Athanasopoulos Jean Cappello julia i.ellyard Matthew Cook Carola Vinuesa Giles Walters David A.Fulcher Simon H.Jiang Division of Medicine The Canberra HospitalGarranAustralian Capital TerritoryAustralia The Australian National University Medical School GarranAustralian Capital TerritoryAustralia Department of General Surgery The Canberra HospitalGarranAustralian Capital TerritoryAustralia Department of immunology and infectious Disease John Curtin School of Medical ResearchGarranAustralian Capital TerritoryAustralia Centre for Personalized immunology NHMRC Centre for Research ExcellenceCanberraAustralia Department of Renal Medicine The Canberra HospitalGarranAustralian Capital TerritoryAustralia Department of immunology The Canberra HospitalCanberraAustralian Capital TerritoryAustralia

Background:Systemic lupus erythematosus(SLE)is a complex systemic autoimmune disease characterized by development of autoantibodies and multiorgan *** involvement,termed lupus nephritis,has major impact on life *** is increasingly recognized that SLE is likely a common clinical manifestation of pathophysiologically diverse processes,and lupus nephritis has similarly been associated with several distinct immunological *** compared the immune cell phenotypes of individuals with SLE in the presence or absence of ***:Cryopreserved peripheral blood mononuclear cells from SLE patients with and without kidney involvement underwent flow cytometric analysis to identify major populations in T cells,B cells and myeloid ***:We compared the frequencies of lymphocyte populations in 69 SLE patients without nephritis,20 SLE patients with nephritis,and 92 healthy blood *** with SLE and lupus nephritis(LN)had reduced marginal zone B cells(Pin SLE;P=0.001 in LN),memory B cells(P=0.002 in SLE;P=0.001 in LN)and circulating T follicular helper(Tfh)memory cells(Pin SLE and LN)compared to healthy *** with lupus nephritis had increase Th2(Pients without nephritis and healthy ***:SLE patients with and without lupus nephritis have distinct immunologic differences that may reflect the unique pathophysiological processes contributing to disease manifestations.

关键词： immunoprofiling lupus nephritis systemic lupus erythematosus

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Woody plant taxonomic,functional,and phylogenetic diversity decrease along elevational gradients in Andean tropical montane forests:Environmental filtering and arrival of temperate taxa

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Plant Diversity 2024年第4期46卷 491-501页

作者： Guillermo Bañares-de-Dios Manuel J.Macía Gabriel Arellano Íñigo Granzow-de la Cerda julia Vega-álvarez itziar Arnelas Carlos i.Espinosa Norma Salinas Luis Cayuela Departamento de Biología y Geología Física y Química InorgánicaUniversidad Rey Juan CarlosCalle Tulipán s/nMóstolesMadridES-28933Spain Departamento de Biología Área de BotánicaUniversidad Autónoma de MadridCalle Darwin 2MadridES-28049Spain Centro de investigación en Biodiversidad y Cambio Global(CiBC-UAM) Universidad Autónoma de MadridCalle Darwin 2MadridES-28049Spain Ecology and Evolutionary Biology University of MichiganAnn ArborMI 48109USA Oikobit LLC ***AlbuquerqueNM87120USA Real Jardín Botánico–CSiC Plaza Murillo 2MadridES-28014Spain Departamento de Biología Animal EcologíaParasitologíaEdafología y Química AgrícolaUniversidad de SalamancaCalle Donantes de Sangre s/nSalamancaES-37007Spain Departamento de Biodiversidad Ecología y EvoluciónUniversidad Complutense de MadridCalle JoséAntonio Nováis 12Ciudad UniversitariaES-28040Spain Departamento de Ciencias Biológicas y Agropecuarias Universidad Técnica Particular de LojaA.P.11-01-608 LojaEcuador Sección Química Pontificia Universidad Católica del PerúA.P.Lima 32LimaPeru ECi School of Geography and EnvironmentUniversity of OxfordOX13QYOxfordshireUnited Kingdom instituto de investigación en Cambio Global(iiCG-URJC) Universidad Rey Juan CarlosCalle Tulipán s/nMóstolesMadridES-28933Spain

Mountains are paramount for exploring biodiversity patterns due to the mosaic of topographies and climates encompassed over short *** research has traditionally focused on taxonomic diversity when investigating changes along elevational gradients,but other facets should be *** first time,we simultaneously assessed elevational trends in taxonomic,functional,and phylogenetic diversity of woody plants in Andean tropical montane forests and explored their underlying ecological and evolutionary *** investigation covered four transects(traversing ca.2200 m a.s.l.) encompassing 114 plots of 0.1 ha across a broad latitudinal range(ca.10°).Using Hill numbers to quantify abundance-based diversity among 37,869 individuals we observed a consistent decrease in taxonomic,functional,and phylogenetic diversity as elevation increased,although the decrease was less pronounced for higher Hill *** exception was a slight increase in phylogenetic diversity when dominant species were *** decrease in taxonomic and functional diversity might be attributed to an environmental filtering process towards highlands,where the increasingly harsher conditions exclude species and functional ***,the differences in steepness decrease between Hill orders suggest that rare species disproportionately contribute to functional *** phylogenetic diversity the shifting elevational trend between Hill orders indicates a greater than previously considered influence in central Andean highlands of tropical lowlands originated species with strong niche conservatism relative to distantly related temperate *** could be explained by a decreasing presence and abundance of temperate,extratropical taxa towards the central Andes relative to northern or southern Andes,where they are more prevalent.

关键词： Altitudinal gradients Andes Environmentalﬁltering Out of the Tropical Lowlands Functional rarity Tropical Niche Conservatism

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Beyond wrecking a wall:revisiting the concept of blood–brain barrier breakdown in ischemic stroke

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Neural Regeneration Research 2025年第7期20卷 1944-1956页

作者： julia Castillo-González Elena González-Rey institute of Parasitology and Biomedicine Lopez-Neyra(iPBLN) CSICPT SaludGranadaSpain

The blood–brain barrier constitutes a dynamic and interactive boundary separating the central nervous system and the peripheral *** tightly modulates the ion transport and nutrient influx,while restricting the entry of harmful factors,and selectively limiting the migration of immune cells,thereby maintaining brain *** the well-established association between blood–brain barrier disruption and most neurodegenerative/neuroinflammatory diseases,much remains unknown about the factors influencing its physiology and the mechanisms underlying its ***,the role of blood–brain barrier breakdown in the translational failure underlying therapies for brain disorders is just starting to be *** review aims to revisit this concept of“blood–brain barrier breakdown,”delving into the most controversial aspects,prevalent challenges,and knowledge gaps concerning the lack of blood–brain barrier *** moving beyond the oversimplistic dichotomy of an“open”/“bad”or a“closed”/“good”barrier,our objective is to provide a more comprehensive insight into blood–brain barrier dynamics,to identify novel targets and/or therapeutic approaches aimed at mitigating blood–brain barrier ***,in this review,we advocate for considering the diverse time-and location-dependent alterations in the blood–brain barrier,which go beyond tight-junction disruption or brain endothelial cell breakdown,illustrated through the dynamics of ischemic stroke as a case *** this exploration,we seek to underscore the complexity of blood–brain barrier dysfunction and its implications for the pathogenesis and therapy of brain diseases.

关键词： blood–brain barrier disruption drug delivery ischemic stroke neuroinflammation tight-junctions

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Ca^(2+) binding to the C_(2)E domain of otoferlin is required for hair cell exocytosis and hearing

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Protein & Cell 2024年第4期15卷 305-312页

作者： Han Chen Mehar Monga Qinghua Fang Loujin Slitin Jakob Neef Shashank S.Chepurwar Regina Célia Mingroni Netto Karina Lezirovitz Alfredo Tabith,Jr. Fritz Benseler Nils Brose Kathrin Kusch Carolin Wichmann Nicola Strenzke Barbara Vona julia Preobraschenski Tobias Moser institute for Auditory Neuroscience and innerEarLab University Medical Center Göttingen37075 GöttingenGermany Collaborative Research Center 889 University of Göttingen37075 GöttingenGermany Auditory Neuroscience and Synaptic Nanophysiology Group Max Planck Institute for Multidisciplinary Sciences37075 GöttingenGermany Göttingen Graduate Center for Neurosciences Biophysics and Molecular BiosciencesUniversity of Göttingen37075 GöttingenGermany Biochemistry of Membrane Dynamics Group Institute for Auditory NeuroscienceUniversity Medical Center Göttingen37075 GöttingenGermany Molecular Architecture of Synapses Group Institute for Auditory Neuroscience and InnerEarLabUniversity Medical Center Göttingen37075 GöttingenGermany Center for Biostructural imaging of Neurodegeneration University Medical Center Göttingen37075 GöttingenGermany Auditory Systems Physiology Group Institute for Auditory Neuroscience and InnerEarLabUniversity Medical Center Göttingen37075 GöttingenGermany Departamento de Genética e Biologia Evolutiva Centro de Pesquisas sobre o Genoma Humano e Células-TroncoInstituto de BiociênciasUniversidade de São PauloSão Paulo 05508-220Brazil Laboratório de Otorrinolaringologia/LiM32 Faculdade de MedicinaHospital das ClínicasUniversidade de São PauloSão PauloSP 05508-220Brazil DERDiC Pontifícia Universidade Católica de São PauloSão Paulo 05508-220Brazil Department of Molecular Neurobiology Max Planck Institute for Multidisciplinary Sciences37075 GöttingenGermany Multiscale Bioimaging Cluster of Excellence(MBExC) University of Göttingen37075 GöttingenGermany Functional Auditory Genomics Group Auditory Neuroscience and Optogenetics LaboratoryGerman Primate Center37077 GöttingenGermany Hearing Genomics Group Institute for Auditory Neuroscience and InnerEarLabUniversity Medical Center Göttingen37075 GöttingenGermany institute of Human Genetics University Medical Center Göttingen37075 GöttingenGermany

Dear Editor,Afferent synapses of cochlear inner hair cells(iHCs)employ a unique molecular machinery(see extended background in Supplementary Materials).Otoferlin is a key player in this machinery and its defects cause human auditory synaptopathy(Moser and Starr,2016).Otoferlin,a tail-anchored(Vogl et al.,2016)multi-C_(2)-domain protein(Fig.1Ai)specific to hair cells(Roux et al.,2006),is a member of the ferlin protein family involved in membrane trafficking and repair that are of major disease relevance(Pangršičet al.,2012),also see Supplementary *** is distributed broadly within iHCs(Fig.2Ai-Aiii;Pangrsic et al.,2010;Roux et al.,2006).

关键词： auditory hair

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investigating approaches to improving rendering performance of 3D city models on mobile devices

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Geo-Spatial information Science 2014年第2期17卷 73-84页

作者： Claire ELLUL julia ALTENBUCHNER Department of Civil Environmental and Geomatic EngineeringUniversity College LondonLondonUK

Three-dimensional(3D)city models have uses including on-site validation of utility infrastructure,support for augmented reality,personalized tourist information,real estate sales,and 3D pedestrian ***,such applications are deployed on mobile devices,whose use is becoming more *** devices are used for more professional use requiring larger screens,mobile phones for more casual ***,many 3D city models contain hundreds of buildings,which in turn results in performance issues when attempting to visualize such models on these *** issues can be identified as contributory factors-the lower specification of the mobile device itself when compared with desktop machines and the lower bandwidth network between the device and the server(3G mobile or Wi-Fi).Both of these can be addressed by reducing the volume of data in the *** achieve this,we generalize a 2D data-set(using aggregation and simplification)and then extrude the generalized 2D maps to *** minimizes the number of buildings to be transmitted over the network and processed by the on-board graphics *** additionally address the bandwidth issue,we make use of topological data structuring to build and transmit a minimal description for each *** these approaches,we compare the results obtained for generalized and un-generalized data-sets,on a tablet and mobile device.A performance increase of between 7 and 9 times is observed.

关键词： 3D GiS generalization openGL ES mobile devices performance

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Associations of blood biomarkers with glomerular filtration rate in patients with TiA and stroke: population-based study

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Stroke & Vascular Neurology 2021年第1期6卷 48-56页

作者： Dearbhla M.Kelly Linxin Li Annette i Burgess Deborah L Poole julia M Duerden Peter M.Rothwell Wolfson Centre for the Prevention of Stroke and Dementia Nuffield Department of Clinical NeurosciencesOxford UniversityOxfordUK

Background and purpose Non-traditional risk factors such as chronic inflammation,oxidative stress and thrombogenic factors are believed to contribute to the excess stroke risk in chronic kidney disease(CKD)by triggering vascular injury and endothelial *** aimed to determine how well a panel of biomarkers representative of these factors would correlate with estimated glomerular filtration rate(eGFR)in patients with recent transient ischaemic attack(TiA)or *** also investigated whether eGFR would confound previously reported associations between biomarkers and *** We studied a panel of 16 blood biomarkers related to inflammation,thrombosis,atherogenesis and cardiac or neuronal cell damage in TiA or ischaemic stroke in a population-based study(Oxford Vascular Study).Biomarker levels were log-transformed and correlated with eGFR,adjusted for *** proportional hazard models were used for survival *** Among 1297 patients with TiA or stroke,52.7%(n=684)of patients had CKD(eGFRin/1.73 m^(2)).There was a moderate correlation between log-eGFR and the log-transformed soluble tumour necrosis factor receptor-1(R^(2)=0.21),attenuating with adjustment for age(R^(2)=0.12).There were moderate-to strong correlations with markers of cardiac injury,N-terminal pro-brain natriuretic peptide and heart-type fatty acid binding protein(hFABP,R2=0.14 and 0.34,respectively).The strongest correlation after adjustment for age was between hFABP and eGFR(R^(2)=0.20).Adjusting for eGFR did not impact any biomarker associations with *** Correlations between biomarkers related to inflammation and thrombosis with renal dysfunction in the setting of cerebrovascular events were generally modest after adjustment for age,suggesting that putative risk factors such as chronic inflammation or coagulopathy are unlikely to be important stroke mechanisms in patients with CKD.

关键词： inflammation patients mortality

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Adverse events related to physical restraint use in intensive care units: A review of the literature

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Journal of intensive Medicine 2024年第3期4卷 318-325页

作者： Sebastian Berger Pascale Grzonka Simon A.Amacher Sabina Hunziker Anja i.Frei Raoul Sutter Clinic for intensive Care Department of Acute MedicineUniversity Hospital BaselBaselSwitzerland Medical Communication and Psychosomatic Medicine University Hospital BaselBaselSwitzerland Medical faculty University of BaselBaselSwitzerland Department of Clinical Research University of BaselBaselSwitzerland

Physical restraints are widely used and accepted as protective measures during treatment in intensive care unit (iCU). This review of the literature summarizes the adverse events and outcomes associated with physical restraint use, and the risk factors associated with their use during treatment in the iCU. The PubMed, Scopus, and Google Scholar databases were screened using predefined search terms to identify studies pertaining to adverse events and/or outcomes associated with physical restraint use, and the factors associated with their use in adult patients admitted to the iCU. A total of 24 articles (including 6126 patients) that were published between 2006 and 2022 were identified. The described adverse events associated with physical restraint use included skin injuries, subsequent delirium, neurofunctional impairment, and a higher rate of post-traumatic stress disorder. Subsequent delirium was the most frequent adverse event to be reported. No alternative measures to physical restraints were discussed, and only one study reported a standardized protocol for their use. Although physical restraint use has been reported to be associated with adverse events (including neurofunctional impairment) in the literature, the available evidence is limited. Although causality cannot be confirmed, a definite association appears to exist. Our findings suggest that it is essential to improve awareness regarding their adverse impact and optimize approaches for their detection, management, and prevention using protocols or checklists.

关键词： Physical restraint intensive care unit Delirium Complication Adverse event

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Characterizing drug-metabolizing enzymes and transporters that are bona fide CAR-target genes in mouse intestine

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Acta Pharmaceutica Sinica B 2016年第5期6卷 475-491页

作者： Shinhee Park Sunny Lihua Cheng julia Yue Cui Department of Environmental and Occupational Health Sciences University of Washington

intestine is responsible for the biotransformation of many orally-exposed *** constitutive androstane receptor(CAR/Nr1i3) is known to up-regulate many genes encoding drugmetabolizing enzymes and transporters(drug-processing genes/DPGs) in liver,but less is known regarding its effect in ***-day-old wild-type and Car / mice were administered the CARligand TCPOBOP or vehicle once daily for 4 *** wild-type mice,Car m RNA was down-regulated by TCPOBOP in liver and *** / mice had altered basal intestinal expression of many DPGs in a section-specific *** with the liver data(Aleksunes and Klaassen,2012),TCPOBOP upregulated many DPGs(Cyp2b10,Cyp3a11,Aldh1a1,Aldh1a7,Gsta1,Gsta4,Gstm1-m4,Gstt1,Ugt1a1,Ugt2b34,Ugt2b36,and Mrp2–4) in specific sections of small intestine in a CAR-dependent ***,the m RNAs of Nqo1 and Papss2 were previously known to be up-regulated by TCPOBOP in liver but were not altered in ***,many known CAR-target genes were highest expressed in colon where CAR is minimally expressed,suggesting that additional regulators are involved in regulating their *** conclusion,CAR regulates the basal expression of many DPGs in intestine,and although many hepatic CAR-targeted DPGs were bona fide CAR-targets in intestine,pharmacological activation of CAR in liver and intestine are not identical.

关键词： Drug-processing genes intestine Mice CAR Drug-metabolizing enzymes Transporters

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Phylogenomic analyses shed light on the relationships of chiton superfamilies and shell‑eye evolution

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Marine Life Science & Technology 2023年第4期5卷 525-537页

作者： Xu Liu julia D.Sigwart Jin Sun Key Laboratory of Evolution&Marine Biodiversity(Ministry of Education)and institute of Evolution&Marine Biodiversity Ocean University of ChinaQingdao 266003China Laoshan Laboratory Qingdao 266237China Department of Marine Zoology Senckenberg Research Institute and Natural History Museum Frankfurt60325 Frankfurt Am MainGermany

Mollusca is the second-largest animal phylum with over 100,000 extant species representing eight *** 1000 extant species in the class Polyplacophora,chitons have a relatively constrained morphology but with some notable *** genera possess“shell eyes”,i.e.,true eyes with a lens and retina that are embedded within the dorsal *** phylogeny of the major chiton clades is mostly well established,in a set of superfamily-level and higher level taxa supported by various approaches,including morphological studies,multiple gene markers,mitogenome-phylogeny,and phylotranscriptomic ***,one critical lineage has remained unclear,namely Schizochiton which was controversially suggested as being the potential independent origin of chiton shell ***,with the draft genome sequencing of Schizochiton incisus(superfamily Schizochitonoidea)plus assemblies of transcriptome data from other polyplacophorans,we present phylogenetic reconstructions using both mitochondrial genomes and phylogenomic approaches with multiple *** found that phylogenetic trees from mitogenomic data are inconsistent,reﬂecting larger scale confounding factors in molluscan ***,a consistent and robust topology was generated with protein-coding genes using diﬀerent models and *** results support Schizochitonoidea as the sister group to other Chitonoidea in Chitonina,in agreement with the established classiﬁ*** with evidence from fossils,our phylogenetic results suggest that the earliest origin of shell eyes is in Schizochitonoidea,and that these structures were also gained secondarily in other genera in *** results have generated a holistic review of the internal relationship within Polyplacophora,and a better understanding of the evolution of Polyplacophora.

关键词： Chiton Mollusca Phylogenomics Polyplacophora Shell eyes

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Minor fibrillar collagens,variable regions alternative splicing,intrinsic disorder,and tyrosine sulfation

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Protein & Cell 2012年第6期3卷 419-433页

作者： Ming Fang Reed Jacob Owen McDougal julia Thom Oxford Department of Biological Sciences Boise State UniversityBoiseID 83725USA Department of Chemistry and Biochemistry Boise State UniversityBoiseID 83725USA Biomolecular Research Center Boise State UniversityBoiseID 83725USA

Minor fibrillar collagen types V and Xi,are those less abundant than the fibrillar collagen types i,ii and *** alpha chains share a high degree of similarity with respect to protein sequence in all domains except the variable *** variation and,in some cases,extensive alternative splicing contribute to the unique sequence characteristics of the variable *** unique expression patterns in tissues exist,the functions and biological relevance of the variable regions have not been *** this review,we summarize the existing knowledge about expression patterns and biological functions of the collagen types V and Xi alpha *** of biochemical similarities among the peptides encoded by each exon of the variable region suggests the potential for a shared *** alternative splicing,conservation of biochemical characteristics in light of low sequence conservation,and evidence for intrinsic disorder,suggest modulation of binding events between the surface of collagen fibrils and surrounding extracellular molecules as a shared function.

关键词： minor fibrillar collagens variable regions alternative splicing fibrillogenesis heparan sulfate binding sites intrinsic disorder tyrosine sulfation

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