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Secretory IgA in complex with Lactobacillus rhamnosus potentiates mucosal dendritic cell-mediated Treg cell differentiation via TLR regulatory proteins, RALDH2 and secretion of IL-IO and TGF-β

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Cellular & Molecular Immunology 2017年第6期14卷 546-556页

作者： Josip Mikulic stephanie Longet Laurent Favre Jalil Benyacoub Blaise Corthesy R&D Laboratory Division of Immunology and Allergy CHUV Centre des Laboratoires d'Epalinges 1066 Epalinges Switzerl Nutrition and Health Nestle Research Center 1000 Lausanne 26 Switzerland

The importance of secretory IgA in controlling the microbiota is well known, yet how the antibody affects the perception of the commensals by the local immune system is still poorly defined. We have previously shown that the transport of secretory IgA in complex with bacteria across intestinal micmfold cells results in an association with dendritic cells in Peyer＇s patches. However, the consequences of such an interaction on dendritic cell conditioning have not been elucidated. In this study, we analyzed the impact of the commensal Lactobacillus rhamnosus, alone or associated with secretory IgA, on the responsiveness of dendritic cells freshly recovered from mouse Peyer＇s patches, mesenteric lymph nodes, and spleen. Lactobacillus rhamnosus-conditioned mucosal dendritic cells are characterized by increased expression of Toll-like receptor regulatory proteins lincluding single immunoglobulin interleukin-1 receptor-related molecule, suppressor of cytokine signaling 1, and Toll-interacting moleculel and retinaldehyde dehydrogenase 2, low surface expression of co-stimulatory markers, high anti- versus pro-inflammatory cytokine production ratios, and induction of T regulatory cells with suppressive function. Association with secretory IgA enhanced the anti-inflammatory/regulatory Lactobacillus rhamnosus-induced conditioning of mucosal dendritic cells, particularly in Peyer＇s patches. At the systemic level, activation of splenic dendritic cells exposed to Lactobacillus rhamnosus was partially dampened upon association with secretory IgA. These data suggest that secretory IgA, through coating of commensal bacteria, contributes to the conditioning of mucosal dendritic cells toward tolerogenic profiles essential for the maintenance of intestinal homeostasis.

关键词： commensal bacteria dendritic cells secretory IgA TLR regulatory proteins T regulatory cells

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Osmotic Stress Modulates the Balance between Exocytosis and Clathrin-Mediated Endocytosis in Arabidopsis thaliana

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Molecular Plant 2015年第8期8卷 1175-1187页

作者： Marta Zwiewka Tomasz Nodzynski stephanie Robert Steffen Vanneste Jiri Friml Mendel Centre for Plant Genomics and Proteomics Central European Institute of Technology (CEITEC) Masaryk University Kamenice 5 CZ-625 00 BrnoCzech Republic Department of Plant Systems Biology VlB and Department of Plant Biotechnology and Bioinformatics Ghent University Technologiepark 927 9052 Gent Belgium Institute of Science and Technology (IST) Austria Am Campus 1 3400 Klosterneuburg Austria Present address: Department of Forest Genetics and Plant Physiology Swedish University of Agricultural Sciences/Ume~. Plant Science Center 901 83 UmeaSweden

The sessile life style of plants creates the need to deal with an often adverse environment, in which water availability can change on a daily basis, challenging the cellular physiology and integrity. Changes in os- motic conditions disrupt the equilibrium of the plasma membrane： hypoosmotic conditions increase and hyperosmotic environment decrease the cell volume. Here, we show that short-term extracellular osmotic treatments are closely followed by a shift in the balance between endocytosis and exocytosis in root mer- istem cells. Acute hyperosmotic treatments （ionic and nonionic） enhance clathrin-mediated endocytosis simultaneously attenuating exocytosis, whereas hypoosmotic treatments have the opposite effects. In addition to clathrin recruitment to the plasma membrane, components of early endocytic trafficking are essential during hyperosmotic stress responses. Consequently, growth of seedlings defective in elements of clathrin or early endocytic machinery is more sensitive to hyperosmotic treatments. We also found that the endocytotic response to a change of osmotic status in the environment is dominant over the presum- ably evolutionary more recent regulatory effect of plant hormones, such as auxin. These results imply that osmotic perturbation influences the balance between endocytosis and exocytosis acting through clathrin- mediated endocytosis. We propose that tension on the plasma membrane determines the addition or removal of membranes at the cell surface, thus preserving cell integrity.

关键词： osmotic stress protein trafficking clathrin-mediated endocytosis auxin

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Biogreen Synthesis of Carbon Dots for Biotechnology and Nanomedicine Applications

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Nano-Micro Letters 2018年第4期10卷 268-313页

作者： Kok Ken Chan stephanie Hui Kit Yap Ken-Tye Yong School of Electrical and Electronic Engineering Nanyang Technological University

Over the past decade, carbon dots have ignited a burst of interest in many different fields, including nanomedicine, solar energy, optoelectronics, energy storage,and sensing applications, owing to their excellent photoluminescence properties and the easiness to modify their optical properties through doping and functionalization. In this review, the synthesis, structural and optical properties,as well as photoluminescence mechanisms of carbon dots are first reviewed and summarized. Then, we describe a series of designs for carbon dot-based sensors and the different sensing mechanisms associated with ***, we elaborate on recent research advances on carbon dot-based sensors for the selective and sensitive detection of a wide range of analytes, including heavy metals, cations, anions, biomolecules, biomarkers,nitroaromatic explosives, pollutants, vitamins, and ***, we provide a concluding perspective on the overall status, challenges, and future directions for the use of carbon dots in real-life sensing.

关键词： Carbon dots Heavy metal sensing Photoluminescence mechanism Sensing mechanism Sensor design

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Future is ready for swallowable sensors

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Hepatobiliary Surgery and Nutrition 2019年第3期8卷 267-269页

作者： Kourosh Kalantar-Zadeh stephanie A.Ward University of New South Wales(UNSW) School of Chemical EngineeringKensingtonAustralia Department of Epidemiology and Preventive Medicine Monash UniversityMelbourneAustralia

You may have noticed that even just before the onset of a simple cold or a minor fever,disordered gut function may be *** addition to coryzal symptoms and fever,abdominal discomfort or altered bowel function are not uncommon as accompanying symptoms,such as bloating,abdominal pain,nausea,vomiting,constipation or *** is not surprising,as the gut walls are porous,allowing the absorption of nutrients from food *** gut mucosa very rapidly exchanges certain chemicals in body fluid compartments with gut liquid and gaseous *** is likely that imbalance of the body chemical contents,as a result of a health disorder,rapidly shows itself as changes in gut contents.

关键词： diarrhea intake walls

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Inflammation-associated microsatellite alterations:Mechanisms and significance in the prognosis of patients with colorectal cancer

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World Journal of Gastrointestinal Oncology 2018年第1期10卷 1-14页

作者： Minoru Koi stephanie S Tseng-Rogenski John M Carethers Department of Internal Medicine and Comprehensive Cancer Center University of MichiganAnn ArborMI 48109-5368United States

Microsatellite alterations within genomic DNA frameshift as a result of defective DNA mismatch repair(MMR). About 15% of sporadic colorectal cancers(CRCs) manifest hypermethylation of the DNA MMR gene MLH1, resulting in mono-and di-nucleotide frameshifts to classify it as microsatellite instability-high(MSI-H) and hypermutated, and due to frameshifts at coding microsatellites generating neo-antigens, produce a robust protective immune response that can be enhanced with immune checkpoint blockade. More commonly, approximately 50% of sporadic nonMSI-H CRCs demonstrate frameshifts at di-and tetra-nucleotide microsatellites to classify it as MSIlow/elevated microsatellite alterations at selected tetranucleotide repeats(EMAST) as a result of functional somatic inactivation of the DNA MMR protein MSH3 via a nuclear-to-cytosolic displacement. The trigger for MSH3 displacement appears to be inflammation and/or oxidative stress, and unlike MSI-H CRC patients, patients with MSI-L/EMAST CRCs show poor prognosis. These inflammatory-associated microsatellite alterations are a consequence of the local tumor microenvironment, and in theory, if the microenvironment is manipulated to lower inflammation, the microsatellite alterations and MSH3 dysfunction should be corrected. Here we describe the mechanisms and significance of inflammatory-associated microsatellite alterations, and propose three areas to deeply explore the consequences and prevention of inflammation's effect upon the DNA MMR system.

关键词： Microsatellite instability Microsatellite stable Elevated microsatellite alterations at selected tetranucleotide repeats Colorectal cancer Mismatch repair Inflammation MSH3

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Contrast-enhanced ultrasound of focal liver masses

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Hepatoma Research 2020年第9期6卷 10-20页

作者： stephanie R.Wilson Christina Merrill Department of Radiology University of CalgaryCalgary T2N 2T9Canada Department of Radiology Foothills Medical CentreCalgary T2N 2T9Canada.

Non-invasive imaging is the current method of choice for the characterization of frequently discovered focal liver *** historically,contrast-enhanced computed tomography(CT)and magnetic resonance(MR)scans have been selected for this purpose,contrast-enhanced ultrasound(CEUS)now offers a less expensive and safer method to acquire the same *** with the intravenous injection of a microbubble contrast agent,CEUS provides some unique advantages that make it a valuable addition to an imaging *** is performed in dynamic real-time,providing superior temporal resolution compared to other modalities and allowing detection of enhancement regardless of its timing or *** is performed with a purely intravascular contrast agent,providing accurate depiction of the presence of microbubbles in the circulation in all phases of *** compares with CT and MR contrast agents,which have a well-recognized interstitial *** discordant imaging may occur especially in the portal venous phase,when CT and MR may show pseudoenhancement from interstitial contrast,while CEUS will accurately show washout in malignant ***,the contrast specific software used to perform CEUS has an excellent subtraction technique,which produces a contrast only image with high sensitivity to enhancement in thin septations and small *** makes a positive contribution to liver mass characterization in any situation.

关键词： Contrast-enhanced ultrasound liver cancer diagnosis

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Expression of the human TSPY gene in the brains of transgenic mice suggests a potential role of this Y chromosome gene in neural functions

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Journal of Genetics and Genomics 2011年第5期38卷 181-191页

作者： Tatsuo Kido stephanie Schubert Jrg Schmidtke Yun-Fai Chris Lau Division of Cell and Developmental Genetics Department of MedicineVA Medical Centerand Institute for Human GeneticsUniversity of California Institute of Human Genetics Hannover Medical School

The testis specific protein Y-encoded （TSPY） is a member of TSPY/SET/NAP1 superfamily, encoded within the gonadoblastoma locus on the Y chromosome. TSPY shares a highly conserved SET/NAP-domain responsible for protein--protein interaction among TSPY/SET/NAP 1 proteins. Accumulating data, so far, support the role of TSPYas the gonadoblastoma gene, involved in germ cell tumorigenesis. The X-chromosome homolog of TSPY, TSPX is expressed in various tissues at both fetal and adult stages, including the brain, and is capable of interacting with the multi-domain adapter protein CASK, thereby influencing the synaptic and transcriptional functions and developmental regulation of CASK in the brain and other neural tissues. Similar to TSPX, we demonstrated that TSPY could interact with CASK at its SET/NAP-domain in cultured cells. Transgenic mice harboring a human TSPYgene and flanking sequences showed specific expression of the human TSPYtransgene in both testis and brain. The neural expression pattern of the human TSPYgene overlapped with those of the endogenous mouse Cask and Tspx gene. Similarly with TSPX, TSPY was co-localized with CASK in neuronal axon fibers in the brain, suggesting a potential role（s） of TSPY in development and/or physiology of the nervous system.

关键词： TSPY TSPX CASK Y chromosome Neuron Testis

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A new look at auranofin,dextromethorphan and rosiglitazone for reduction of glia-mediated inflammation in neurodegenerative diseases

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Neural Regeneration Research 2015年第3期10卷 391-393页

作者： Jocelyn M.Madeira stephanie M.Schindler Andis Klegeris Department of Biology University of British Columbia Okanagan Campus

Neurodegenerative disorders including Alzheimer＇s disease are characterized by chronic in- flammation in the central nervous system. The two main glial types involved in inflammatory reactions are microglia and astrocytes. While these cells normally protect neurons by providing nutrients and growth factors, disease specific stimuli can induce glial secretion of neurotoxins. It has been hypothesized that reducing glia-mediated inflammation could diminish neuronal loss. This hypothesis is supported by observations that chronic use of non-steroidal anti-inflamma- tory drugs （NSAIDs） is linked with lower incidences of neurodegenerative disease. It is possible that the NSAIDs are not potent enough to appreciably reduce chronic neuroinflammation after disease processes are fully established. Gold thiol compounds, including auranofin, comprise an- other class of medications effective at reducing peripheral inflammation. We have demonstrated that auranofin inhibits human microglia- and astrocyte-mediated neurotoxicity. Other drugs which are currently used to treat peripheral inflammatory conditions could be helpful in neu- rodegenerative disease. Three different classes of anti-inflammatory compounds, which have a potential to inhibit neuroinflammation are highlighted below.

关键词： auranofin dextromethorphan rosiglitazone Alzheimer's disease neuroinflammation neurodegeneration rnicroglia astrocytes

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Obesity： modern man＇s fertility nemesis

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Asian Journal of Andrology 2010年第4期12卷 480-489页

作者： stephanie Cabler Ashok Agarwal Margot Flint Stefan S. Du Plessis Center for Reproductive Medicine The Cleveland Clinic 9500 Euclid Avenue Cleveland OH 44195 USA Division of Medical Physiology Faculty of Health Sciences Stellenbosch University PO Box 19063 Tygerberg 7505 South Africa

The obesity pandemic has grown to concerning proportions in recent years, not only in the Western World, but in developing countries as well. The corresponding decrease in male fertility and fecundity may be explained in parallel to obesity, and obesity should be considered as an etiology of male fertility. Studies show that obesity contributes to infertility by reducing semen quality, changing sperm proteomes, contributing to erectile dysfunction, and inducing other physical problems related to obesity. Mechanisms for explaining the effect of obesity on male infertility include abnormal reproductive hormone levels, an increased release of adipose-derived hormones and adipokines associated with obesity, and other physical problems including sleep apnea and increased scrotal temperatures. Recently, genetic factors and markers for an obesity-related infertility have been discovered and may explain the difference between fertile obese and infertile obese men. Treatments are available for not only infertility related to obesity, but also as a treatment for the other comorbidities arising from obesity. Natural weight loss, as well as bariatric surgery are options for obese patients and have shown promising results in restoring fertility and normal hormonal profiles. Therapeutic interventions including aromatase inhibitors, exogenous testosterone replacement therapy and maintenance and regulation of adipose-derived hormones, particularly leptin, may also be able to restore fertility in obese males. Because of the relative unawareness and lack of research in this area, controlled studies should be undertaken and more focus should be given to obesity as an etiolgy of male infertility.

关键词： adipokines infertility leptin obesity spermatozoa

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Social Mix in New Town Housing Development: A Case Study of Cosmo City,South Africa

Social Mix in New Town Housing Development: A Case Study of ...

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作者： stephanie Clare Farrand 上海交通大学

学位级别：硕士

The impending decades will see the developing world experience a dramatic increase in the percentage of its urban *** rapid and extensive urbanization trend will impact human spatial development,resource allocation,inequality levels and,quality of *** South Africa,the province of Gauteng has long retained an urbanization rate exceeding all other South African *** rapidly growing urban population in Gauteng presents a multitude of challenges for government,significantly,the growing demand for housing and the increasing segregation of social ***,since 1994,a national housing shortage has fueled the drastic increase in both,numbers of and,densities within informal *** these informal settlements,residents are subjected to substandard living conditions with little,if any,access to basic *** with a general lack of economic opportunities,many inhabitants turn to illegal activities as a means to *** phenomenon threatens not only the stability of Gauteng but also,the urbanization process in South *** the recent decade,both central and local governments in South Africa have promoted extensive developments with an aim to solve housing shortage and social *** new town projects underline the creation of socially mixed *** Cosmo City – a government initiated mixed-income housing development in Gauteng Province – as a case study,this study aims to evaluate the responses taken by government at national,provincial and municipal levels in addressing the severe housing shortage,and to examine the implications on social mix from the mixed-income housing *** main research questions include how is the new town of Cosmo City implemented as a project embracing an extensive urban development approach and,to what extent is Cosmo City governed towards social mix?The methodological approach to this investigation incorporates in-depth analysis of related published literature a

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