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Humanized bone facilitates prostate cancer metastasis and recapitulates therapeutic effects of zoledronic acid in vivo

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Bone Research 2019年第4期7卷 388-398页

作者： marietta landgraf Christoph ALahr Alvaro Sanchez-Herrero Christoph Meinert Ali Shokoohmand Pamela MPollock Dietmar WHutmacher Abbas Shafiee Jacqui AMcGovern Centre in Regenerative Medicine Institute of Health and Biomedical InnovationQueensland University of TechnologyBrisbaneAustralia School of Biomedical Science Institute of Health and Biomedical InnovationTranslational Research InstituteQueensland University of TechnologyBrisbaneAustralia Australian Research Council(ARC)Training Centre in Additive Biomanufacturing Queensland University of TechnologyBrisbaneAustralia UQ Diamantina Institute Translational Research InstituteThe University of QueenslandBrisbaneQLDAustralia

Advanced prostate cancer(PCa)is known for its high prevalence to metastasize to bone,at which point it is considered *** significant effort,there is no animal model capable of recapitulating the complexity of PCa bone *** humanized mouse model for PCa bone metastasis used in this study aims to provide a platform for the assessment of new drugs by recapitulating the human–human cell interactions relevant for disease development and *** humanized tissueengineered bone construct(hTEBC)was created within NOD-scid IL2rgnull(NSG)mice and was used for the study of experimental PC3-Luc bone *** was confirmed that PC3-Luc cells preferentially grew in the hTEBC compared with murine *** translational potential of the humanized mouse model for PCa bone metastasis was evaluated with two clinically approved osteoprotective therapies,the non-species-specific bisphosphonate zoledronic acid(ZA)or the human-specific antibody Denosumab,both targeting Receptor Activator of Nuclear Factor Kappa-Β***,but not Denosumab,significantly decreased metastases in hTEBCs,but not murine *** results highlight the importance of humanized models for the preclinical research on PCa bone metastasis and indicate the potential of the bioengineered mouse model to closely mimic the metastatic cascade of PCa cells to human ***,it will enable the development of new effective antimetastatic treatments.

关键词： metastasis PC3 drugs

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Dysfunction of the adhesion G protein-coupled receptor latrophilin 1(ADGRL1/LPHN1)increases the risk of obesity

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2298-2311页

作者： Heba ZabriTorsten Schöneberg AndréNguyen Dietzsch Hadi Al-Hasani Joachim Altschmied Katharina Bottermann Jana Brendler Judith Haendeler Susanne Horn Isabell Kaczmarek Antje Körner Kerstin Krause Kathrin landgraf Diana Le Duc Laura Lehmann Stefan Lehr Stephanie Pick Albert Ricken Rene Schnorr Angela Schulz Martina Strnadová Akhil Velluva Heba Zabri Torsten Schöneberg Doreen Thor Simone Prömel Rudolf Schönheimer Institute of Biochemistry Medical FacultyLeipzig UniversityLeipzigGermany Institute for Clinical Biochemistry and Pathobiochemistry Medical FacultyGerman Diabetes CenterLeibniz Center for Diabetes Research at Heinrich Heine University DüsseldorfDüsseldorfGermany German Center for Diabetes Research(DZD e.V.) Munich-NeuherbergGermany Cardiovascular Degeneration Clinical Chemistry and Laboratory DiagnosticsMedical FacultyUniversity Hospital and Heinrich Heine University DüsseldorfDüsseldorfGermany Cardiovascular Research Institute(CARID) Medical FacultyUniversity Hospital and Heinrich Heine University DüsseldorfDüsseldorfGermany Institute of Pharmacology Medical FacultyUniversity Hospital and Heinrich Heine University DüsseldorfDüsseldorfGermany Institute of Anatomy Medical FacultyLeipzig UniversityLeipzigGermany Center for Pediatric Research Hospital for Children and AdolescentsMedical FacultyLeipzig UniversityLeipzigGermany Helmholtz Institute for Metabolic Obesity and Vascular Research(HI-MAG)of the Helmholtz Zentrum München at the University of Leipzig and University Hospital LeipzigLeipzigGermany Department of Endocrinology NephrologyRheumatologyLeipzig University Medical CenterLeipzigGermany Institute of Human Genetics Leipzig University Medical CenterLeipzigGermany Institute of Cell Biology Department of BiologyHeinrich Heine University DüsseldorfDüsseldorfGermany School of Medicine University of Global Health EquityKigaliRwanda

Obesity is one of the diseases with severe health consequences and rapidly increasing worldwide *** the complex network of food intake and energy balance regulation is an essential prerequisite for pharmacological intervention with obesity.G protein-coupled receptors(GPCRs)are among the main modulators of metabolism and energy ***,for instance,regulate appetite and satiety in certain hypothalamic neurons,as well as glucose and lipid metabolism and hormone secretion from *** in some GPCRs,such as the melanocortin receptor type 4(MC4R),have been associated with early-onset ***,we identified the adhesion GPCR latrophilin 1(ADGRL1/LPHN1)as a member of the regulating network governing food intake and the maintenance of energy *** of the highly conserved receptor in mice results in increased food consumption and severe obesity,accompanied by dysregulation of glucose ***,we identified a partially inactivating mutation in human ADGRL1/LPHN1 in a patient suffering from ***,we propose that LPHN1 dysfunction is a risk factor for obesity development.

关键词： obesity metabolism intake

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Approaches to quantify axonal morphology for the analysis of axonal degeneration

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Neural Regeneration Research 2023年第2期18卷 309-310页

作者： Alex Palumbo marietta Zille Department of Neurobiology Harvard Medical School Department of Cancer Biology Dana-Farber Cancer InstituteBostonMAUSA Department of Pharmaceutical Sciences Division of Pharmacology and ToxicologyUniversity of ViennaViennaAustria

Morphological hallmarks of axonal degeneration(AxD):Axons transmit signals from one neuron to another and a re crucial for the proper communication in the nervous ***,the disintegration of axons,a process named AxD,ha... 详细信息

关键词： degeneration axonal Morphological

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Noise and vibration measurements in a Viking military vehicle

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Defence Technology（防务技术） 2021年第6期17卷 1976-1987页

作者： Gurmail S.Paddan marietta L.L.McIlraith Institute of Naval Medicine Crescent RoadAlverstokeHampshirePO122DLUK Formerly at Institute of Naval Medicine Crescent RoadAlverstokeHampshirePO122DLUK

Noise and whole-body vibration measurements were made in a Viking military vehicle to determine the variation that should be expected during repeat measures,the effect of speed(up to 60 km/h in 5 km/h increments),and during travel over different types of terrain(comprising concrete road,gravel track and rough cross-country).Measurements were made at various crew positions(including the driver and commander)in both the front and the rear cabs in the *** translational axes of vibration were measured in each *** speeds were investigated over road(35 km/h and 55e60 km/h)and gravel(20 km/h and 35 km/h)*** effect of varying speed of the vehicle on the measured noise and vibration magnitudes was also *** highest sound pressure level(LAeq)of 104 dB(A)was measured at the commander’s standing position during travel over concrete road at 55 km/*** noise levels occurred for a standing commander compared with when sitting on the seat.A maximum single axis frequency-weighted vibration magnitude of 1.0 m/s^(2) *** measured on the driver’s seat during travel over track at 35 km/*** vibration magnitudes occurred during travel over track compared with travel over *** noise and vibration exposure of crew within the Viking vehicle increased with increasing speed of the vehicle.

关键词： Noise Whole-body vibration Vibration dose value Viking military vehicle

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Germline MLH1 and MSH2 mutational spectrum including frequent large genomic aberrations in Hungarian hereditary non-polyposis colorectal cancer families:Implications for genetic testing

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World Journal of Gastroenterology 2007年第19期13卷 2727-2732页

作者： Janos Papp marietta E Kovacs Edith Olah Department of Molecular Genetics National Institute of Oncology Rath Gy. u. 7-9 H-1122 Budapest Hungary

AIM: To analyze the prevalence of germline MLH1 and MSH2 gene mutations and evaluate the clinical characteristics of Hungarian hereditary non-polyposis colorectal cancer (HNPCC) families. METHODS: Thirty-six kindreds were tested for mutations using conformation sensitive gel electrophoreses, direct sequencing and also screening for genomic rearrangements applying multiplex ligation-dependent probe amplifi cation (MLPA). RESULTS: Eighteen germline mutations (50%) were identifi ed, 9 in MLH1 and 9 in MSH2. Sixteen of these sequence alterations were considered pathogenic, the remaining two were non-conservative missense alterations occurring at highly conserved functional motifs. The majority of the defi nite pathogenic mutations (81%, 13/16) were found in families fulfilling the stringent Amsterdam Ⅰ/Ⅱ criteria, including three rearrangements revealed by MLPA (two in MSH2 and one in MLH1). However, in three out of sixteen HNPCC-suspected families (19%), a disease-causing alteration could be revealed. Furthermore, nine mutations described here are novel, and none of the sequence changes were found in more than one ***: Our study describes for the f irst time the prevalence and spectrum of germline mismatch repair gene mutations in Hungarian HNPCC and suspected-HNPCC families. The results presented here suggest that clinical selection criteria should be relaxed and detection of genomic rearrangements should be included in genetic screening in this population.

关键词： Germline mutation Hereditary non-polyposis colorectal cancer MLH1 MSH2 Rearrangement

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Correlation analysis of celiac sprue tissue transglutaminase and deamidated gliadin IgG/IgA

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World Journal of Gastroenterology 2009年第7期15卷 845-848页

作者： Eric V marietta Shadi Rashtak Joseph A Murray Department of Immunology Mayo Clinic College of Medicine Department of Gastroenterology and Hepatology Mayo Clinic College of Medicine

AIM:To indirectly determine if tissue transglutaminase(tTG)-specific T cells play a crucial role in the propagation of celiac ***:Anti-deamidated gliadin peptide(DGP) and anti-tTG IgA and IgG were measured in the sera of celiac patients(both untreated and treated).The correlations were determined by Spearman's rank correlation ***:In celiac patients,we found a very significant correlation between the production of DGP IgA and IgG(r = 0.75),indicating a simultaneous and ongoing production of these two isotypes reminiscent of oral vaccination ***,there was far less association between the production of tTG IgA and tTG IgG in celiac patients(r = 0.52).While tTG IgA was significantly correlated with DGP IgA(r = 0.80) and DGP IgG(r = 0.67),there was a weak correlation between production of anti-tTG IgG and the production of anti-DGP IgA(r = 0.38) and anti-DGP IgG(r = 0.43).CONCLUSION:These data demonstrate that the production of anti-tTG IgA is directly correlated to the production of anti-DGP IgG and IgA,whereas anti-tTG IgG is only weakly *** result therefore supports the hapten-carrier theory that in well-established celiac patients anti-tTG IgA is produced by a set of B cells that are reacting against the complex of tTG-DGP in the absence of a tTG-specific T cell.

关键词： Celiac disease Tissue transglutaminase Deamidated gliadin peptide Correlation IgG IgA

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Affairs happen---to whom？ A study on extrapair paternity in common nightingales

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Current Zoology 2017年第4期63卷 421-431页

作者： Conny landgraf Kerstin WILHELM Jutta WIRTH Michael WEISS Silke KIPPER Leibniz Institute for Zoo and Wildlife Research (IZW) Alfred-Kowalke-StraBe 17 10315 Berlin Germany Animal Behavior Group Free University of Berlin TakustraBe 6 14195 Berlin Germany Institute of Evolutionary Ecology and Conservation Genomics University of UIm Albert Einstein Allee 11 89069 UIm Germany Behavioural Ecology Group Department of Animal Sciences Wageningen University De Elst 1 6708 WD Wageningen The Netherlands Department of Exposition Unit Epidemiology Statistics and Mathematical Modelling Federal Institute for Risk Assessment (BfR) Max-Dohrn-Str. 8-10 10589 Berlin Germany Chair of Zoology School of Life Sciences Weihenstephan Technische Universitat Munchen LieseI-Beckmann-StraBe 4 85350 Freising Germany

Most birds engage in extrapair copulations despite great differences across and within species. Besides cost and benefit considerations of the two sex environmental factors have been found to alter mating strategies within or between populations and/or over time. For socially monogamous species, the main advantage that females might gain from mating with multiple males is probably increasing their offspring＇s genetic fitness. Since male （genetic） quality is mostly not directly meas- urable for female birds, （extrapair） mate choice is based on male secondary traits. In passerines male song is such a sexual ornament indicating male phenotypic and/or genetic quality and song repertoires seem to affect female mate choice in a number of species. Yet their role in extrapair mating behavior is not well understood. In this study, we investigated the proportion of extrapair paternity （EPP） in a population of common nightingales Luscinia megarhynchos. We found that EPP rate was rather high （21.5% of all offspring tested） for a species without sexual dimorphism and high levels of paternal care. Furthermore, the occurrence of EPP was strongly related to the spatial distribution of male territories with males settling in densely occupied areas having higher proportions of extrapair young within their own brood. Also, song repertoire size affected EPP： here larger repertoires of social mates were negatively related to the probability of being cuck- olded. When directly comparing repertoires sizes of social and extrapair mates, extrapair mates tended to have larger repertoires. We finally discuss our results as a hint for a flexible mating strat- egy in nightingales where several factors--including ecological as well as male song features-- need to be considered when studying reproductive behavior in monogamous species with complex song.

关键词： common nightingale direct fitness extrapair paternity Luscinia megarhynchos repertoire size territorial settlement.

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Pulmonary Metastases in Colorectal Cancer: Review on Diagnosis,Management and Prognosis

Pulmonary Metastases in Colorectal Cancer: Review on Diagnos...

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作者： Audrey marietta（应明洁）重庆医科大学

学位级别：硕士

Colorectal cancer is the third most common incidence of malignant tumor and fourth deadliest in the *** better understanding of tumor biology and development of surgical technique,present available regional control of the disease is already quite ***,major concerns still remain for the control of the progressive disease,especially late stage cancer with distant organ *** is the most common distant organ metastases after the liver from the primary colorectal *** is the first organ reached by circulatory pathway beside the liver because of its vascular anatomy and circulatory *** distant site of metastases such as brain and bone are proven most commonly accompanied with lung metastases in latest SEER *** of lung metastases are recommended to be confirmed with routine chest CT and tumor marker level detection,especially *** examination technique that can be run as supportive test such as MRI for other soft tissue and lymph node assessment,genetic and immunology testing may also be beneficial in confirmation and prognosis prediction of the *** pre-surgery assessment must be done with consensus discussion in a Multidisciplinary Team meeting,mainly to decide whether lung lesion can be defined as metastatic lesion and confirmed its *** til today,the most effective management for resectable metastatic lesion is surgical removal via thoracotomy or *** local control of micronodule and other multiple oligometastatic nodule limited to the lung,image-assisted thermal ablation such as RFA,cryoablation and MWA or even *** locoregional and systemic control,combination of chemoregiments are still used as first *** testing and molecular detection plays important role for systemic treatment selection,therefore it must be done especially in patient with non-resectable lesion and/or patient considered for adjuvant *** factor of the overall survival in patient

关键词： colorectal cancer metastases lung metastases pulmonary metastasectomy prognosis

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Language Shift,Death,and Maintenance of Native American Languages

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外国语 2002年第6期25卷 18-33页

作者： Janie Rees-Miller (marietta College, U.S.A) mariettaCollege U.S.A

Janie Rees-Miller is Chair of Modern Languages and Director of English as a Second Language at marietta College, marietta, Ohio, USA. She is co-editor of the Handbook of Linguistics, published by Blackwell and distributed in China by the Foreign Language Teaching and Research Press, Beijing. She is also co-editor of Contemporary Linguistics, 4th US edition, the most widely sold introductory linguistics textbook in the United States. Her research interests include applied linguistics, second language pedagogy, and Native American languages, and she has published in journals such as the Journal of Pragmatics, TESOL Quarterly, and Anthropological Linguistics.

关键词：语言表达能力美式英语学习手段文化背景

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Inflammatory bowel disease-related colorectal cancer:Past,present and future perspectives

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World Journal of Gastrointestinal Oncology 2022年第3期14卷 547-567页

作者： Snehali Majumder Uday Nagesh Shivaji Rangarajan Kasturi Alben Sigamani Subrata Ghosh marietta Iacucci Department of Clinical Research Narayana HealthBangalore 560099KarnatakaIndia National Institute for Health Research Birmingham Biomedical Research Centre University Hospitals BirminghamBirmingham B152THUnited Kingdom Institute of Immunology and Immunotherapy University of BirminghamBirmingham B152THUnited Kingdom Department of Gastroenterology Narayana HealthBangalore 560099India

Inflammatory bowel disease-related colorectal cancer(IBD-CRC)is one of the most serious complications of IBD contributing to significant mortality in this cohort of *** is often associated with diet and lifestyle-related gut microbial dysbiosis,the interaction of genetic and environmental factors,leading to chronic gut *** to the“common ground hypothesis”,microbial dysbiosis and intestinal barrier impairment are at the core of the chronic inflammatory process associated with *** the many underlying factors known to increase the risk of IBD-CRC,perhaps the most important factor is chronic persistent *** persistent inflammation in the colon results in increased proliferation of cells necessary for repair but this also increases the risk of dysplastic changes due to chromosomal and microsatellite *** pathways have been identified,regulated by many positive and negative factors involved in the development of cancer,which in this case follows the‘inflammation-dysplasia-carcinoma’*** to lower this risk are extremely important to reduce morbidity and mortality due to IBD-CRC,among which colonoscopic surveillance is the most widely accepted and implemented modality,forming part of many national and international ***,the effectiveness of surveillance in IBD has been a topic of much debate in recent years for multiple reasons—cost-benefit to health systems,resource requirements,and also because of studies showing conflicting long-term *** review provides a comprehensive overview of past,present,and future perspectives of *** explore and analyse evidence from studies over decades and current best practices followed *** the future directions section,we cover emerging novel endoscopic techniques and artificial intelligence that could play an important role in managing the risk of IBD-CRC.

关键词： Inflammatory bowel disease Colorectal cancer Colitis-associated cancer Surveillance in inflammatory bowel disease Dye-spray colonoscopy Adenomas Dysplasia Colectomy

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