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R-spondin-2 is a Wnt agonist that regulates osteoblast activity and bone mass

Bone Research 2018年第3期6卷 289-302页

作者： m.Noelle Knight Kannan Karuppaiah michele Lowe Sarthak mohanty Robert L.Zondervan Sheila Bell Jaimo Ahn Kurt D.Hankenson Department of Orthopaedic Surgery Perelman School of Medicine University of Pennsylvania Department of Orthopaedic Surgery University of Michigan Medical School Division of Pulmonary Biology Cincinnati Children's Hospital Medical Center

The R-spondin family of proteins are Wnt agonists, and the complete embryonic disruption of Rspo2 results in skeletal developmental defects that recapitulate the phenotype observed with Lrp5/6 deficiency. Previous work has shown that R-spondin-2(Rspo2, RSPO2) is both highly expressed in Wnt-stimulated pre-osteoblasts and its overexpression induces osteoblast differentiation in the same cells, supporting its putative role as a positive autocrine regulator of osteoblastogenesis. However, the role of Rspo2 in regulating osteoblastogenesis and bone formation in postnatal bone has not been explored. Here we show that limb-bud progenitor cells from Rspo2 knockout mice undergo reduced mineralization during osteoblastogenesis in vitro and have a corresponding alteration in their osteogenic gene expression profile. We also generated the first Rspo2 conditional knockout(Rspo2 floxed) mouse and disrupted Rspo2 expression in osteoblast-lineage cells by crossing to the Osteocalcin-cre mouse line(Ocncre + Rspo2 ^(f/f)). Ocn-cre + Rspo2 f/fmale and female mice at 1, 3, and 6 months were examined. Ocn-cre + Rspo2 f/fmice are decreased in overall body size compared to their control littermates and have decreased bone mass. Histomorphometric analysis of1-month-old mice revealed a similar number of osteoblasts and mineralizing surface per bone surface with a simultaneous decrease in mineral apposition and bone formation rates. Consistent with this observation, serum osteocalcin in 3-month-old Ocn-cre +Rspo2 f/fwas reduced, and bone marrow-mesenchymal stem cells from Ocn-cre + Rspo2 f/fmice undergo less mineralization in ***, gene expression analysis and immunohistochemistry of mature bone shows reduced beta-catenin signaling in Ocn-cre +Rspo2 f/f. Overall, RSPO2 reduces osteoblastogenesis and mineralization, leading to reduced bone mass.

关键词： The R-spondin family Wnt-stimulated pre-osteoblasts

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PR-Set7 is Degraded in a Conditional Cul4A Transgenic mouse model of Lung Cancer

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中国肺癌杂志 2015年第6期18卷 345-350页

作者： Yang WANG Zhidong XU Jian-Hua mAO David.HSiEH Alfred AU David m. JABLONS Hui Li Liang YOU Thoracic Surgery Department Beijing Chao-Yang Hospital Capital University of Medical Science Thoracic Oncology Laboratory Department of Surgery Comprehensive Cancer Center University of California Life Sciences Division Lawrence Berkeley National Laboratory University of California Division of Diagnostic Pathology Comprehensive Cancer Center University of California

Background and objective maintenance of genomic integrity is essential to ensure normal organismal development and to prevent diseases such as ***-Set7(also known as Set8)is a cell cycle regulated enzyme that catalyses monomethylation of histone 4 at Lys20(H4K20me1)to promote chromosome condensation and prevent DNA *** studies show that CRL4CDT2-mediated ubiquitylation of PR-Set7 leads to its degradation during S phase and after DNA *** might occur to ensure appropriate changes in chromosome structure during the cell cycle or to preserve genome integrity after DNA *** We developed a new model of lung tumor development in mice harboring a conditionally expressed allele of *** have therefore used a mouse model to demonstrate for the first time that Cul4A is oncogenic in *** this model,staining of PR-Set7 in the preneoplastic and tumor lesions in Adeno cre-induced mouse lungs was *** we identified higher protein level changes ofγ-tubulin and pericentrin by *** The level of PR-Set7 down-regulated in the preneoplastic and adenocarcinomous lesions following over-expression of *** also identified higher levels of the proteins pericentrin andγ-tubulin in Cul4A mouse lungs induced by Adeno *** PR-Set7 is a direct target of Cul4A for degradation and involved in the formation of lung tumors in the conditional Cul4A transgenic mouse model.

关键词：临床诊断医学肺疾病

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The roles of canonical Wnt/β-catenin signaling in the adult dopaminergic neurogenesis

The roles of canonical Wnt/β-catenin signaling in the adult...

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中国神经科学学会第十二届全国学术会议

作者： Jingzhong Zhang Daniela m.Vogt Weisenhorn makoto m.Taketo Nilima Prakash Wolfgang Wurst Suzhou institute of Biomedical Engineering and Technology (SiBET) Chinese Academy of Sciences (CAS) institute of Developmental Genetics Helmholtz Centre Munich German Research Centre for Environmental Health (GmbH) and Technical University Munich Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) Standort münchen and max-Planck-institute of Psychiatry

Wnt/β-catenin signaling plays a critical role in the development of mesodiencephalic dopaminergic(md DA) neurons, but also in adult homeostasis and protection of these neurons. We have previously shown that Wnt1-mediated signaling is necessary and sufficient for the correct establishment of the md DA progenitor domain during early mouse embryonic development, and more recent data indicate a critical role of a precisely balanced Wnt/β-catenin signaling in the differentiation of these progenitor/precursor cells into mature md DA neurons. To assess the function of the Wnt/β-catenin pathway in the adult mouse brain under both basal and lesioned conditions, we constitutively activated the Wnt/β-catenin signaling pathway in Doublecortin(Dcx)-expressing adult neural precursor cells and newly generated neurons by crossing an inducible DCX-cre ERT2 transgenic mouse with Catnblox(ex3)/lox(ex3) mice and CAG-CATEGFP reporter mice. The Wnt/β-catenin signaling pathway is constitutively activated in the Catnblox(ex3)/lox(ex3)) mice by the cre-mediated removal of the 3 rd exon of the β-catenin(Catnb or Ctnnb1) gene encoding the phosphorylation sites that mediate its proteasomal degradation. We show here that constitutive activation of Wnt/β-catenin signaling in adult Dcx neural precursor cells did not lead to increased ubiquitous cell proliferation and/or tumorigenesis but increased the numbers of Tyrosine hydroxylase(Th, a marker for dopaminergic neurons) and EGFP double-positive cells in the olfactory bulbs(140% increase) and hypothalamus of adult DCX-cre ERT2;Catnblox(ex3)/lox(ex3);CAG-CAT-EGFP mice relative to the control, and very few double-positive cells were also detected in the ventral midbrain(Vm) of the mutant mice but not in the corresponding controls. By contrast, Th/EGFP double-positive cells were not detected in the cortex and dentate gyrus(hippocampus) of the mutant mice. To determine whether the β-catenin removed phosphorylation sites in Dcx neural precursor cells

关键词： Neural precursors Wnt/β-catenin DCX Transdifferentiation Dopaminergic neurons

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Liver-specific deletion of mechanistic target of rapamycin does not protect against acetaminophen-induced liver injury in mice

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Liver Research 2021年第2期5卷 79-87页

作者： Hua Sun Hong-min Ni Jennifer m.mcCracken Jephte Y Akakpo Sam Fulte Tara mcKeen Hartmut Jaeschke Hua Wang Wen-Xing Ding Department of Pharmacology Toxicology and TherapeuticsThe University of Kansas Medical CenterKansas CityKSUSA Department of Oncology The First Affiliated Hospital of Anhui Medical UniversityHefeiChina

Background:Acetaminophen(APAP)overdose can cause liver injury and liver failure,which is one of the most common causes of drug-induced liver injury in the United *** activation of autophagy by inhibiting mechanistic target of rapamycin(mTOR)protects against APAP-induced liver injury likely via autophagic removal of APAP-adducts and damaged *** the present study,we aimed to investigate the role of genetic ablation of mTOR pathways in mouse liver in APAP-induced liver injury and liver repair/***:Albumin-cre(Alb-cre)mice,mTOR^(f/f) and Raptor^(f/f) mice(C57BL/6J background)were crossbred to produce liver-specific mTOR knockout(L-mTOR KO,Alb cret/-,mTOR^(f/f))and liver-specific Raptor KO(L-Raptor,Alb cret/-,Raptor^(f/f))***-cre littermates were used as wild-type(WT)*** mice were treated with APAP for various time points for up to 48 *** injury,cell proliferation,autophagy and mTOR activation were ***:We found that genetic deletion of neither Raptor,an important adaptor protein in mTOR complex 1,nor mTOR,in the mouse liver significantly protected against APAP-induced liver injury despite increased hepatic autophagic *** deletion of Raptor or mTOR in mouse livers did not affect APAP metabolism and APAP-induced c-Jun N-terminal kinase(JNK)activation,but slightly improved mouse survival likely due to increased hepatocyte ***:Our results indicate that genetic ablation of mTOR in mouse livers does not protect against APAP-induced liver injury but may slightly improve liver regeneration and mouse survival after APAP overdose.

关键词： Acetaminophen(APAP) Autophagy Hepatotoxicity Liver injury Liver regeneration mechanistic target of rapamycin(mTOR) Regulatory associated protein of mTOR complex(Raptor)

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Sexual assaults in therapeutic relationships: prevalence, risk factors and consequences

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Health 2010年第9期2卷 1018-1026页

作者： C. Eichenberg m. Becker-Fischer G. Fischer 不详

A law has been passed in Germany (paragraph 174c StGB), which prohibits therapists from having sexual contact with their patients. This provides the background for a follow-up survey to the previous study completed by Becker- Fischer and Fischer in 1995. The results of this survey are discussed here on the basis of the current status of research concerning preva- lence and risk factors of sexual assaults in therapeutic relationships. The focus of the re- search lies in determining the specific condi- tions of sexual assaults in psychotherapy and psychiatry, risk variables of the therapists and patients, the effects it has on the patients as well as the legal consequences it results in. To en- sure the comparability of the data, an online version of the Questionnaire about Sexual Con- tacts in Psychotherapy and Psychiatry (SKPP;Becker-Fischer, Fischer & Jerouschek) was cre- ated and a survey of N = 77 affected patients was conducted. The majority of the participants in the study reported a serious decline in their overall well being following the incident. How- ever only very few undertook legal steps - only in three cases did it come to a legal procedure. The assumption that sexual contacts in psy- chotherapy result in extremely damaging con- sequences to patients, was affirmed. Despite the changed legal situation, therapists in Ger- many are still not held legally responsible more often than they were 10 years ago. Based on these results a more intensive education of the patients concerning their legal rights is recom- mended.

关键词： Sexual Assaults Psychotherapy Patient Abuse Professionale misconduct

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An essential role of iP3Rs in early T-cell development

An essential role of IP3Rs in early T-cell development

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第九届全国钙信号和细胞功能研讨会

作者： Rafael Gomez-Amaro David Stachura David Traver Sylvia m Evans Skaggs School of Pharmacy University of California-San Diego9500 Gilman DriveLa JollaCalifornia92093USA Department of Biology University of California-San Diego9500 Gilman DriveLa JollaCalifornia92093USA

iP3Rs are a family of intracellular Ca release channels locating in the membrane of endoplasmic reticulum,which in mammals are encoded by three distinct genes,iP3R1, iP3R2 and *** described here at the first time that conditional deletion of all three types of iP3Rs in hematopoietic stem cells by Tie2-cre resulted in developmental block from double negative T cell to double positive T cell transition,and the late onset of T-cell acute lymphoblastic leukemia(T-ALL).We revealed that iP3R-mediated Ca release downstream of pre-T cell receptors is required for survival,differentiation and

关键词： Cell=T cell method=confocal imaging Topic=development

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REDD1介导子宫内过量糖皮质激素对棕色脂肪发育和产热功能的抑制

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Science Bulletin 2021年第5期66卷 478-489,M0004页

作者：陈彦廷胡云杨启元刘向东 Jun Seok Son Jeanene m.de Avila 朱美君杜敏 Nutrigenomics and Growth Biology Laboratory Department of Animal SciencesWashington State UniversityPullmanWA 99164USA School of Food Sciences Washington State UniversityPullmanWA 99164USA

母体应激导致子宫内糖皮质激素升高,增加后代能量代谢紊乱和肥胖风险.尽管棕色脂肪对于维护机体正常代谢和产热极其重要,但是子宫内过量糖皮质激素是否会影响后代棕色脂肪发育、线粒体解偶联产热及其调控机制,目前缺乏研究.本文通过对... 详细信息

母体应激导致子宫内糖皮质激素升高,增加后代能量代谢紊乱和肥胖风险.尽管棕色脂肪对于维护机体正常代谢和产热极其重要,但是子宫内过量糖皮质激素是否会影响后代棕色脂肪发育、线粒体解偶联产热及其调控机制,目前缺乏研究.本文通过对怀孕老鼠注射与母体应激相同剂量的糖皮质激素,发现伴随着激活棕色脂肪中糖皮质激素受体响应蛋白REDD1,胎儿和新生儿不仅表现出棕色脂肪发育障碍、体温和存活率下降,而且棕色脂肪中Ppargc1a替代性启动子转录水平以及线粒体合成显著降低.在诱导胚胎成纤维细胞分化成棕色脂肪细胞过程中,通过敲降和过表达Redd1和Ppargc1a,进一步发现REDD1会抑制PKA-creB蛋白磷酸化,降低了creB蛋白与Ppargc1a替代性启动子cAmP调控元件的结合,导致棕色脂肪细胞分化、线粒体合成和解偶联产热功能受损.本研究揭示了在孕期过量糖皮质激素条件下, Redd1抑制Ppargc1a替代性启动子表达和棕色脂肪细胞分化,引起后代线粒体产热障碍和能量代谢紊乱,为药物研发以促进胎儿正常发育提供了新思路.

关键词：棕色脂肪细胞糖皮质激素子宫内发育障碍蛋白磷酸化胚胎成纤维细胞药物研发解偶联

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Analysis of enteric neuronal circuitry in the mouse colon using live calcium imaging

Analysis of enteric neuronal circuitry in the mouse colon us...

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中国神经科学学会第十二届全国学术会议

作者： Zhi-Ling Li marlene-m HAO Werend BOESmANS Pieter VANDRN BERGHE Lab for Enteric Neuroscience (LENS) TARGID Department of Anatomy & Cell Biology University of Melbourne

Objective Different regions of the gut exhibit specific motility patterns regulated by the enteric nervous system(ENS). Currently, little is known about how ENS circuits are differentially organized to generate these regionally distinct motility patterns. The present study aims to explore whether calcium imaging of the ENS can uncover differences in neuronal circuits present in the proximal and distal colon. methods Live Ca imaging was performed on myenteric plexus preparations from adult Wnt1-cre;R26-GCa mP3 mice, where all enteric neurons express the genetically-encoded Ca indicator, GCamP3. Focal electrical stimulation was applied(300μsec, 20 Hz, 2 sec) and responses in individual neurons were analyzed. immunohistochemistry was performed to compare differences in the neuronal density and phenotype. Furthermore, we transduced the mouse ENS using AAV9-CmV-GFP which made it possible to trace the projections of individual myenteric neurons. Results Using a low magnification(5 X) lens, we were able to simultaneously record the intracellular Ca changes from a large population of neurons spread over many different myenteric ganglia(up to 1.3 mm x 1.7 mm field of view). Analysis of the number of Hu+ myenteric neurons and the intraganglionic fibers showed that both these parameters were significantly higher in the proximal colon, which reflects the higher density of the myenteric neurons and higher packing of intraganglionic fibers at the stimulation site. Live Ca imaging showed that application of the nicotinic receptor antagonist, hexamethonium(200μm), significantly decreased the electricallyevoked Ca transients in the majority of neurons in both regions. moreover, fraction of neurons in which Ca responses were completely abolished by hexamethonium was significantly larger in the distal colon in comparison with the proximal colon. Quantification of the proportion of Ch AT+ and n NOS+ myenteric neurons indicated that the ratio of nitrergic neurons is higher in the distal

关键词： AAV9 Adeno-associated virus Calcium imaging Colon Enteric nervous system myenteric plexus Neuronal circuitry

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Hydrogen isotopes in palmitic and stearic acids in suspended particles from the Changjiang River Estuary

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Science China Earth Sciences 2016年第2期59卷 981-988页

作者： XiNG Lei Julian P.SACHS ZHANG HaiLong Li Li Ji ZhongQiang ZHAO meiXun Key Laboratory of marine Chemistry Theory and Technology Ministry of Education Ocean University of China Qingdao 266100 China Qingdao Collaborative innovation Center of marine Science and Technology Qingdao 266100 China School of Oceanography University of Washington Seattle WA 98195 USA State Key Laboratory of Satellite Ocean Environment Dynamics Second Institute of Oceanography State Oceanic Administration Hangzhou 310012 China

在类脂化合物 biomarkers 的氢同位素能在 hydrologic 周期跟踪过去的变化。最近的研究为重建的份量上在 microalgal 类脂化合物揭示了氢同位素的潜力水 2 H (D) 价值和咸度。在这研究，我们从 Changjiang 河河口(cre ) 沿着一个咸度坡... 详细信息

在类脂化合物 biomarkers 的氢同位素能在 hydrologic 周期跟踪过去的变化。最近的研究为重建的份量上在 microalgal 类脂化合物揭示了氢同位素的潜力水 2 H (D) 价值和咸度。在这研究，我们从 Changjiang 河河口(cre ) 沿着一个咸度坡度收集了推迟的粒子，并且在这些粒子在丰满的酸测量了 D 价值。结果显示水的 D 价值从 cre 与咸度高度被相关，与从另外的河口的结果一致。在十六酸酸和硬脂的酸的 D 价值从 cre 与水的 D 价值有积极关联。在 cre，当咸度增加了，不过，在相对水的丰满的酸的氢同位素分别增加了，在在有在 microalgal 文化和领域研究发现的咸度的氢同位素分别的趋势对面。当咸度增加了点亮可获得性，我们在氢同位素分别归因增加，它在在河口的结束混合地区的粒子富人是多半更低的，并且潜在地也到在 cre 的丰满的酸的多重来源。

关键词：氢同位素十六酸酸硬脂的酸 Changjiang 河河口咸度

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incidence of Oxa23 and Oxa51 Genes Associated with Bacterial isolated from Patients with Urosepsis: Single Centre Prespective

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American Journal of molecular Biology 2022年第3期12卷 85-96页

作者： Salma Omer ibrahim Elimam m. A. mohammed Sami mahjoub Taha Sanaa mohammed Yousif Hajir Omer Omer Omer mirghani Seif-Elnasr Seitelbanat Yassin Yousif Abdelhameed mohammed Omer Abu Elhasan mohamed Taj-Eldin Adam Dawoud Abakar Elhadi Abdalla Ahmed Salaheldein G. Elzaki Department of medical microbiology Faculty of Medical Lab Sciences University of Gezira Wad Medani Sudan Department of Urology Faculty of Medicine University of Gezira Wad Medani Sudan National Blood Bank Ministry of Health Khartoum Sudan University Hospital Galway Galway Ireland Department of Urology Gezira Hospital for Renal Disease and Surgery Wad Medani Sudan Department of Pharmaceutics Faculty of Pharmacy University of Gezira Wad Medani Sudan Department of Clinical Chemistry National Cancer Institute University of Gezira Wad Medani Sudan Department of medical microbiology Wad Medani College for Medical Science and Technology Wad Medani Sudan Department of medical Parasitology Faculty of Medical Laboratory Sciences University of Gezira Wad Medani Sudan Department of Epidemiology Tropical Medicine Research Institute Khartoum Sudan

Background: Urosepsis is one of the most common infections that require empirical broad spectrum antibiotics immediately after diagnosis. This has led to development of bacterial resistance by acquiring the capability to destroy the β-lactam ring. methodology: This is a cross-sectional hospital-based study. The study was conducted from 2019 to 2020 at Gezira Hospital for Renal diseases and surgery (GHRDS). A hundred patients were diagnosed clinically with urosepsis and the isolated organisms were Escherichia coli, Staphylococcus aureus, Proteus mirabilis, Klebsiella pneumonia and Pseudomonas aeruginosa. The susceptibility test was conducted by Kirby Bauer disc diffusion technique according to clinical laboratory standard institute (CLSi) guidelines. Seventy eight samples of bacterial genomic DNA were confirmed by 16srRNA and multiplex PCR, were performed for genotypic blaOXA-51 and blaOXA-23 gene characterization of isolated bacteria. Then gel electrophoresis was used to identify the presence or absence of (blaOXA-51 and blaOXA-23) genes. Results: 88.5% (69/78) in 16srRNA detected. Using multiplex PCR, the frequencies of blaOXA-51 and blaOXA-23 genes were 13% and 10.1%, respectively. The percentages of isolates which yielded both blaOXA-51 and blaOXA-23 among P. aeruginosa was 25% (1/4), among K. pneumonia was 17% (1/6), and among E. coli was 8% (3/37). Only blaOXA-51 was detected in P. mirabilis 10% (1/10) and only blaOXA-23 was detected in S. aureus 5% (1/18). Conclusion: in this study, the presence of blaOXA-51 and blaOXA-23 genes was increased in the isolated bacteria.

关键词： Urosepsis Carbapenem-Resistant Enterobacteriaceae (cre) blaOXA-51 and blaOXA-23

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