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Dog10K: an international sequencing effort to advance studies of canine domestication, phenotypes and health

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National Science Review 2019年第4期6卷 810-824页

作者： Elaine A.Ostrander Guo-Dong Wang Greger Larson Bridgett m.von Holdt brian W.Davis Vidhya Jagannathan Christophe Hitte Robert K.Wayne Ya-Ping Zhang National Human Genome Research Institute National Institutes of Health State Key Laboratory of Genetic Resources and Evolution Kunming Institute of Zoology Chinese Academy of Sciences Center for Excellence in Animal Evolution and Genetics Chinese Academy of Sciences Palaeogenomics and Bio-Archaeology Research Network School of Archaeology University of Oxford Department of Ecology and Evolutionary Biology Princeton University College of Veterinary medicine and Biomedical Sciences Texas A&M University Institute of Genetics Vetsuisse Faculty University of Bern IGDR CNRS University of Rennes Department of Ecology and Evolutionary Biology University of CaliforniaLos Angeles the Dog10K Consortium

Dogs are the most phenotypically diverse mammalian species, and they possess more known heritable disorders than any other non-human mammal. Efforts to catalog and characterize genetic variation across well-chosen populations of canines are necessary to advance our understanding of their evolutionary history and genetic architecture. To date, no organized effort has been undertaken to sequence the world's canid populations. The Dog10 K Consortium(http://***10 ***) is an international collaboration of researchers from across the globe who will generate 20× whole genomes from 10 000 canids in 5 *** effort will capture the genetic diversity that underlies the phenotypic and geographical variability of modern canids worldwide. Breeds, village dogs, niche populations and extended pedigrees are currently being sequenced, and de novo assemblies of multiple canids are being constructed. This unprecedented dataset will address the genetic underpinnings of domestication, breed formation, aging, behavior and morphological variation. more generally, this effort will advance our understanding of human and canine health.

关键词： genomics genome-wide association studies(GWAS) breed selection variation evolution

Label-free detection of single nanoparticles and biological molecules using microtoroid optical resonators

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Light(Science & Applications) 2016年第1期5卷 863-868页

作者： Judith Su Alexander FG Goldberg brian m Stoltz Division of Biology and Biological Engineering California Institute of TechnologyPasadenaCAUSA Divison of Chemistry and Chemical Engineering California Institute of TechnologyPasadenaCAUSA

Single-molecule detection is one of the fundamental challenges of modern *** experiments often use labels that can be expensive,difficult to produce,and for small analytes,might perturb the molecular events being *** size plays an important role in determining *** we use laser-frequency locking in the context of sensing to improve the signal-to-noise ratio of microtoroid optical resonators to the extent that single nanoparticles 2.5 nm in radius,and 15.5 kDa molecules are detected in aqueous solution,thereby bringing these detectors to the size limits needed for detecting the key macromolecules of the *** results,covering several orders of magnitude of particle radius(100 nm to 2 nm),agree with the‘reactive’model prediction for the frequency shift of the resonator upon particle *** confirms that the main contribution of the frequency shift for the resonator upon particle binding is an increase in the effective path length due to part of the evanescent field coupling into the adsorbed *** anticipate that our results will enable many applications,including more sensitive medical diagnostics and fundamental studies of single receptor–ligand and protein–protein interactions in real time.

关键词： biosensing frequency locking label-free microtoroid single molecule

A targetable pathway to eliminate TRA-1-60^(+)/TRA-1-81^(+)chemoresistant cancer cells

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Journal of molecular Cell Biology 2023年第6期15卷 25-39页

作者： Lei Tan Xiaohua Duan Pratyusha mutyala Ting Zhou Sadaf Amin Tuo Zhang brian Herbst Gokce Askan Tomer Itkin Zhaoying Xiang Fabrizio michelassi michael D.Lieberman Christine AIacobuzio-Donahue Steven DLeach Todd Evans Shuibing Chen Department of Surgery Weill Cornell MedicineNew YorkNY 10065USA Center for Energy metabolism and Reproduction Institute of Biomedicine and BiotechnologyShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China Center for Genomic Health Weill Cornell MedicineNew YorkNY 10065USA The SKI Stem Cell Research Facility The Center for Stem Cell Biology and Developmental Biology ProgramMemorial Sloan Kettering Cancer CenterNew YorkNY 10065USA Genomic Resource Core Facility Weill Cornell Medical CollegeNew YorkNY 10065USA Rubenstein Center for Pancreatic Cancer Research Memorial Sloan Kettering Cancer CenterNew YorkNY 10065USA Division of Regenerative medicine Hartman Institute for Therapeutic Organ RegenerationAnsary Stem Cell InstituteDepartment of MedicineWeill Cornell MedicineNew YorkNY 10065USA Dartmouth Cancer Center Darmouth CollegeHanoverNH 03755USA

Chemoresistance is a primary cause of treatment failure in pancreatic *** cell surface markers specifically expressed in chemoresistant cancer cells(CCCs)could facilitate targeted therapies to overcome *** performed an antibody-based screen and found that TRA-1-60 and TRA-1-81,two‘stemness’cell surface markers,are highly enriched in ***-more,TRA-1-60^(+)/TRA-1-81^(+)cells are chemoresistant compared to TRA-1-60^(-)/TRA-1-81^(-)*** profiling identified UGT1A10,shown to be both necessary and sufficient to maintain TRA-1-60/TRA-1-81 expression and *** a high-content chemical screen,we identified Cymarin,which downregulates UGT1A10,eliminates TRA-1-60/TRA-1-81 expression,and increases chemosensitivity both in vitro and in ***,TRA-1-60/TRA-1-81 expression is highly specific in primary cancer tissue and positively correlated with chemoresistance and short survival,which highlights their potentiality for targeted ***,we discovered a novel CCC surface marker regulated by a pathway that promotes chemoresistance,as well as a leading drug candidate to target this pathway.

关键词： pancreatic cancer TRA-1-60/TRA-1-81 chemoresistance UGT1A10 Cymarin

The Sediment and Hydrographic Characteristics of Three Horseshoe Crab Nursery Beaches in Hong Kong

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Journal of Ocean University of Qingdao 2003年第1期2卷 35-43页

作者： Helen m.C. Chiu brian morton Environmental Resources management (ERm)-Hong Kong Ltd Swire Institute of Marine Science and Department of Ecology and Biodiversity 979 King's Road Taikoo Place Island East Hong Kong University of Hong

Horseshoe crab juveniles have been recorded from sand and sandy-mud nursery beaches at Pak Nai (western New Territories), San Tau and Shui Hau (Lantau Island), Hong Kong. In order to provide a better understanding of these beaches and to identify those plausible factors which have made them preferred by spawning horseshoe crabs, environmental parameters, including temperature, salinity, pH and dissolved oxygen content of the water, and particle size distribution and organic matter content of the sediments at the three sites, were determined and compared. The hydrographic and sediment data obtained for the three study sites have revealed some common environmental features. The three nursery beaches are relatively remote, and far (in Hong Kong terms) from urbanized and densely populated areas. The beaches are generally well sheltered from strong wave action and inundated regularly by estuarine waters. Horseshoe crab adults tend to select these beaches for spawning as their protected features ensures the laid eggs are less likely to be washed out of the sand, and hatched juveniles can feed on the meiofauna and grow. Sediments of the three beaches largely comprise medium-sized sand particles and are moderately sorted, suggesting medium porosity and good water permeability. Such a sand type, with the generally high oxygen levels in incursing waters, may help create a well-oxygenated micro-environment for the normal development of horseshoe crab eggs, larvae and juveniles. Lantau Island beaches at San Tau and Shui Hau are relatively free from organic pollution, as reflected in generally high dissolved oxygen level, and low BOD 5 and ammonia nitrogen values. Pak Nai is, however, more polluted.

关键词：沉积水地理特征螃蟹海滩环境因素香港

IN VIVO NEAR-INFRAREDFLUORESCENCEImAGING OF HUmANCOLONADENOCARCINOmABY SPECIFIC ImmUNOTARGETINGOFA TUmOR-ASSOCIATEDmUCIN

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Journal of Innovative Optical Health Sciences 2009年第4期2卷 407-422页

作者： RALPH S.DACOSTA YING TANG TUULA KALLIOmAKI RAYmOND m.REILLY ROBERT WEERSINK ALISHA R.ELFORD NORmAN E.mARCON brian C.WILSON Division of Biophysics and Bioimaging Ontario Cancer Institute 610 University of TorontoTorontoOntarioM5G 2M9Canada Department of medical Biophysics University of Toronto Princess Margaret Hospital/Ontario Cancer Institute University Health NetworkTorontoOntarioCanada NIH/NCI Radiation Oncology Branch BethesdaMDUSA Division of Clinical Investigation and Human Physiology Toronto General Hospital Research Institute and University of Toronto Leslie Dan Faculty of Pharmacy TorontoOntarioCanada Laboratory for Applied Biophotonics University Health Network TorontoOntarioCanada Campbell Family Institute for Breast Cancer Research University Health Network/Ontario Cancer Institute Department of medical Biophysics and Immunology Toronto OntarioCanada St.michael’s Hospital Center for Therapeutic Endoscopy and Endoscopic Oncology Toronto OntarioCanada

Background and Aims: Accurate endoscopic detection of premalignant lesions and earlycancers in the colon is essential for cure, since prognosis is closely related to lesion size andstage. Although it has great clinical potential, autofluorescence endoscopy has limited tumorto-normal tissue image contrast for detecting small preneoplastic lesions. We have developed amolecularly specific, near-infrared fluorescent monoclonal antibody (CC49) bioconjugate whichtargets tumor-associated glycoprotein 72 (TAG72), as a contrast agent to improve fluorescencebased endoscopy of colon cancer. methods: The fluorescent anti-TAG72 conjugate was evaluated in vitro and in vivo in athymic nude mice bearing human colon adenocarcinoma (LS174T)subcutaneous tumors. Autofluorescence, a fluorescent but irrelevant antibody and the free fluorescent dye served as controls. Fluorescent agents were injected intravenously, and in vivowhole body fluorescence imaging was performed at various time points to determine pharmacokinetics, followed by ex vivo tissue analysis by confocal fluorescence microscopy and histology Results: Fluorescence microscopy and histology confirmed specific LS174T cell membrane targeting of labeled CC49 in vitro and ex vivo. In vivo fluorescence imaging demonstrated significant tumor-to-normal tissue contrast enhancement with labeled-CC49 at three hours postinjection, with maximum contrast after 48 h. Accumulation of tumor fluorescence demonstratedthat modification of CC49 antibodies did not alter their specific tumor-localizing properties, andwas antibody-dependent since controls did not produce detectable tumor fluorescence. Conclusions: These results show proof-of-principle that our near-infrared fluorescent-antibody probetargeting a tumor-associated mucin detects colonic tumors at the molecular level in real time,and offer a basis for future improvement of image contrast during clinical fluorescence endoscopy.

关键词： Autofluorescence imaging endoscopy colon adenocarcinoma TAG72 CC49 mucin monoclonal antibody conjugate confocal fluorescence microscopy.

Diagnostic accuracy of tests for Helicobacter pylori in an Alaska Native population

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World Journal of Gastroenterology 2011年第42期17卷 4682-4688页

作者： Dana L Bruden michael G Bruce Karen m miernyk Julie morris Debby Hurlburt Thomas W Hennessy Helen Peters Frank Sacco Alan J Parkinson brian J mcmahon Arctic Investigations Program Division of Preparedness and Emerging InfectionsNational Center for Emerging Zoonoses and Infectious DiseasesCenters for Disease Control and Prevention Alaska Native Tribal Health Consortium Anchorage

AIm:To evaluate the accuracy of two non-invasivetests in a population of Alaska Native persons. Highrates of Helico bacter pylori(H. pylori) infection,H. pylori treatment failure,and gastric cancer in this population necessitate documentation of infection status atmultiple time points over a patient's ***:In 280 patients undergoing endoscopy,H. pylori was diagnosed by culture,histology,rapidurease test,13C urea breath test(UBT) ,and immuno-globulin G antibodies to H. pylori in serum. The performances of 13C-UBT and antibody test were compared to a gold standard defined by a positive H. pylori testby culture or,in case of a negative culture result,bypositive histology and a positive rapid urease ***:The sensitivity and specificity of the 13C-UBT were 93% and 88%,respectively,relative to thegold standard. The antibody test had an equivalents ensitivity of 93% with a reduced specificity of 68%.The false positive results for the antibody test were as-sociated with previous treatment for an H. pylori infection [relative risk(RR) = 2.8]. High levels of antibodiesto H. pylori were associated with chronic gastritis and male gender,while high scores in the 13C-UBT testwere associated with older age and with the H. pyloribacteria load on histological examination(RR = 4.4) .CONCLUSION:The 13C-UBT out performed the anti-body test for H. pylori and could be used when a non-invasive test is clinically necessary to document treatment out come or when monitoring for reinfection.

关键词：阿拉斯加幽门螺杆菌测试人口幽门螺旋杆菌准确率原住民抗体检测

Civil-GIS incorporated approach for water resource management in a developed catchment for urban-geomorphic sustainability:Tallowa Dam,southeastern Australia

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International Soil and Water Conservation Research 2016年第4期4卷 304-313页

作者： Ali K.m.Al-Nasrawi brian G.Jones Yasir m.Alyazichi Sarah m.Hamylton mohammed T.Jameel Ali Faraj Hammadi School of Earth and Environmental Sciences University of WollongongNSW 2522Australia School of Civil Mining&Environmental EngineeringUniversity of WollongongNSW 2522Australia School of mechanical Materials and Mechatronics EngineeringUniversity of WollongongNSW 2522Australia

Damming rivers causes two main problems affecting a river's geomorphic ecosystem and its water *** Tallowa Dam on the Shoalhaven River in southeastern NSW,Australia,provides a case study to find the best sustainable solutions to avoid these *** project uses a civil-infrastructure idea to design a grid of collector pipes from the reservoir bottom *** data analysis using ArcGIS 10.2 is used to determine the best grid location for the pipes in the *** and sediment samples have been analysed for grain size,heavy metal and organic matter *** dam has led to a significant decline in sediment transport and water discharge to the lower reaches of the river which has resulted in greater erosion of sediment and higher salinity rates within the lower river and coastal *** quality in the reservoir has been affected by increased sediment accumulation,particularly mud,which has increased the amount of heavy metal and nutrient pollution that could eventually affect the water users.A proposed solution is to use over-storage water to remove accumulated sediment from the base of the dam through a net of collector pipes controlled by automechanical gates,instead of flowing over the top of the *** would maximize the volume of upstream sediment and contained pollutants that can be released from the reservoir into the downstream river ecosystems as well as providing better water quality and a longer water storage time.

关键词： Water quality Geomorphology Pollutants Civil-infrastructure GIS-detection

Proximal White Onychomycosis in an Immunocompetent Patient: A Case Report

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Case Reports in Clinical medicine 2015年第1期4卷 41-44页

作者： brian m. Schmidt Crystal Holmes Department of Podiatric medicine and Surgery Yale New Haven Hospital/DVA West Haven New Haven CT USA Department of Internal medicine University of Michigan Ann Arbor MI USA

Objective: Onychomycosis is a diagnosis of fungal organisms in the nail unit. It frequently occurs in both the immunocompetent and immunocompromised patient. A variant of onychomycosis is proxiaml onychomycosis that occurs on the most proximal aspect of the nail. Proximal onychomycosis is known to be commonly associated with immunocompromised status. Study Design: A case report of a veteran who presented a dermatology clinic with complaint of solitary nail discoloration that was recalcitrant to over-the-counter therapy including topical hydrogen peroxide and foot soaks without improvement. Results and Conclusions: This individual case report demonstrates that pedal proximal onychomycosis can be associated with non-dermatophyte organisms, identified as Fusarium species, in immunocompetent individuals. The finding of pedal proximal onychomycosis caused by a Fusarium non-dermatophytic mold has not been reported. The veteran was successfully cured of the condition with treatment via oral terbinafine for a ninety-day course while monitoring patient’s liver function test for any complications.

关键词： Proximal Onychomycosis Nail Fungus Onychcomycosis

High-throughput screening of mouse gene knockouts identifies established and novel skeletal phenotypes

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Bone Research 2014年第3期2卷 152-181页

作者： Robert Brommage Jeff Liu Gwenn m Hansen Laura L Kirkpatrick David G Potter Arthur T Ss brian Zambrowicz David R Powell Peter Vogel Lexicon Pharmaceuticals The Woodlands TX USA

Screening gene function in vivo is a powerful approach to discover novel drug targets. We present high-throughput screening （HTS） data for 3 762 distinct global gene knockout （KO） mouse lines with viable adult homozygous mice generated using either gene-trap or homologous recombination technologies. Bone mass was determined from DEXA scans of male and female mice at 14 weeks of age and by microCT analyses of bones from male mice at 16 weeks of age. Wild-type （WT） cagemates/littermates were examined for each gene KO. Lethality was observed in an additional 850 KO lines. Since primary HTS are susceptible to false positive findings, additional cohorts of mice from KO lines with intriguing HTS bone data were examined. Aging, ovariectomy, histomorphometry and bone strength studies were performed and possible non-skeletal phenotypes were explored. Together, these screens identified multiple genes affecting bone mass： 23 previously reported genes （Calcr, Cebpb, Crtap, Dcstamp, Dkkl, Duoxa2, Enppl, Fgf23, Kissl/Kisslr, Kl （Klotho）, Lrp5, mstn, Neol, Npr2, Ostml, Postn, Sfrp4, S1c30a5, Sic39a13, Sost, Sumf1, Src, Wnt10b）, five novel genes extensively characterized （Cldn18, Fam20c, Lrrkl, Sgpll, Wnt16）, five novel genes with preliminary characterization （Agpat2, RassfS, Slc10a7, Stc26a7, Slc30a10） and three novel undisclosed genes coding for potential osteoporosis drug targets.

关键词： KO High-throughput screening of mouse gene knockouts identifies established and novel skeletal phenotypes BmD HTS DEXA gene