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| 1 | High-throughput screening of mouse gene knockouts identifies established and novel skeletal phenotypes显示文摘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, Dkk1, Duoxa2, Enpp1, Fgf23, Kiss1/Kiss1 r, Kl(Klotho),Lrp5, Mstn, Neo1, Npr2, Ostm1, Postn, Sfrp4, Slc30a5, Slc39a13, Sost, Sumf1, Src, Wnt10b), five novel genes extensively characterized(Cldn18, Fam20 c, Lrrk1, Sgpl1, Wnt16), five novel genes with preliminary characterization(Agpat2, Rassf5, Slc10a7, Slc26a7, Slc30a10) and three novel undisclosed genes coding for potential osteoporosis drug targets. | Robert Brommage Jeff Liu Gwenn M Hansen Laura L Kirkpatrick David G Potter Arthur T Ss Brian Zambrowicz David R Powell Peter Vogel | 2014 | Bone Research2014,2,3: | 7 |
| 2 | Plant cytochrome P450 plasticity and evolution显示文摘The superfamily of cytochrome P450(CYP)enzymes plays key roles in plant evolution and metabolic diversification.This review provides a status on the CYP Iandscape within green algae and land plants.The 11 conserved CYP clans known from vascular plants are all present in green algae and several green algaespecific clans are recognized.Clan 71,72,and 85 remain the largest CYP clans and include many taxaspecific CYP(sub)families reflecting emergence of linage-specific pathways.Molecular features and dynamics of CYP plasticity and evolution are discussed and exemplified by selected biosynthetic pathways.High substrate promiscuity is commonly observed for CYPs from large families,favoring retention of gene duplicates and neofunctionalization,thus seeding acquisition of new functions.Elucidation of biosynthetic pathways producing metabolites with sporadic distribution across plant phylogeny reveals multiple exampies of convergent evolution where CYPs have been independently recruited from the same or different CYP families,to adapt to similar environmental challenges or ecological niches.Sometimes only a single or a few mutations are required for functional interconversion.A compilation of functionally characterized plant CYPs is provided online through the Plant P450 Database(erda.dk/public/vgrid/PlantP450/). | Cecilie Cetti Hansen David R.Nelson Birger Lindberg Moller Daniele Werck-Reichhart | 2021 | Molecular Plant2021,14,8: | 6 |
| 3 | Forkhead domain mutations in FOXA1 drive prostate cancer progression显示文摘Dear Editor,F0XA1 (Forkhead Box Protein A1)is a pioneer transcription factor (TF) that functions to loosen the compact chromatin structure to facilitate binding of other TFs such as estrogen receptor and androgen receptor (AR).1,2 AR is a nuclear receptor functioning as a ligand-dependent TF that plays a pivotal role in driving the initiation of prostate cancer (Pca) and the development of castration-resistant Pca (CRPC). | Shuai Gao Sujun Chen Dong Han David Barrett Wanting Han Musaddeque Ahmed Susan Patalano Jill A. Macoska Housheng Hansen He Changmeng Cai | 2019 | Cell Research2019,29,9: | 3 |
| 4 | Tackling the Wicked Problem of Measuring What Matters:Framing the Questions显示文摘Purpose:Making policy makers,researcher,education leaders,and assessment developers aware that what matters in education assessment is a wicked problem that cannot be easily solved following traditional approaches.Design/Approach/Methods:Starting from the questions that what matters in education assessment,this article presented such questions as a wicked problem because there is no consensus,not right or wrong answer,and certain solutions may lead to side effects on students and society.Therefore,a new approach of ecology should be involved,and different education outcomes or intended qualities of learners are presented in complex relationships.Findings:Deciding what matters in education assessment is a wicked question.It is not a tame or technology problem and can be resolved by any conventional approaches.What is pivotal now is to decipher what matters in education and then what should be measured and ultimately how to measure.The ecology and collaborate approach deliberated in this article could expedite such a process.Originality/Value:This article advocates paradigm change in understanding and resolving one of the most urgent problems in education.It provides an ecology explanation of the relationships that exist among the different education outcomes and students’qualities.By guiding through the dissecting of the problem step by step,this article has demonstrated a unique angle of understanding the wicked problem. | Yong Zhao Michael Wehmeyer James Basham David Hansen | 2019 | ECNU Review of Education2019,2,3: | 3 |
| 5 | Towards a standard diet-induced and biopsy-confirmed mouse model of non-alcoholic steatohepatitis: Impact of dietary fat source显示文摘BACKGROUND The trans-fat containing AMLN(amylin liver non-alcoholic steatohepatitis,NASH)diet has been extensively validated in C57BL/6J mice with or without the Lep^ob/Lep^ob(ob/ob)mutation in the leptin gene for reliably inducing metabolic and liver histopathological changes recapitulating hallmarks of NASH.Due to a recent ban on trans-fats as food additive,there is a marked need for developing a new diet capable of promoting a compatible level of disease in ob/ob and C57BL/6J mice.AIM To develop a biopsy-confirmed mouse model of NASH based on an obesogenic diet with trans-fat substituted by saturated fat.METHODS Male ob/ob mice were fed AMLN diet or a modified AMLN diet with trans-fat(Primex shortening)substituted by equivalent amounts of palm oil[Gubra amylin NASH,(GAN)diet]for 8,12 and 16 wk.C57BL/6J mice were fed the same diets for 28 wk.AMLN and GAN diets had similar caloric content(40%fat kcal),fructose(22%)and cholesterol(2%)level.RESULTS The GAN diet was more obesogenic compared to the AMLN diet and impaired glucose tolerance.Biopsy-confirmed steatosis,lobular inflammation,hepatocyte ballooning,fibrotic liver lesions and hepatic transcriptome changes were similar in ob/ob mice fed the GAN or AMLN diet.C57BL/6J mice developed a mild to moderate fibrotic NASH phenotype when fed the same diets.CONCLUSION Substitution of Primex with palm oil promotes a similar phenotype of biopsyconfirmed NASH in ob/ob and C57BL/6J mice,making GAN diet-induced obese mouse models suitable for characterizing novel NASH treatments. | Michelle L Boland Denise Oro Kirstine S T■lb■l Sebastian T Thrane Jens Christian Nielsen Taylor S Cohen David E Tabor Fiona Fernandes Andrey Tovchigrechko Sanne S Veidal Paul Warrener Bret R Sellman Jacob Jelsing Michael Feigh Niels Vrang James L Trevaskis Henrik H Hansen | 2019 | World Journal of Gastroenterology2019,25,33: | 3 |
| 6 | Ineffective oesophageal motility:Manometric subsets exhibit different symptom profiles显示文摘AIM:To compare the demographic and clinical features of different manometric subsets of ineffective oesophageal motility(IOM;defined as ≥ 30% wet swallows with distal contractile amplitude < 30 mmHg) ,and to determine whether the prevalence of gastro-oesophageal reflux differs between IOM subsets. METHODS:Clinical characteristics of manometric subsets were determined in 100 IOM patients(73 female,median age 58 years) and compared to those of 100 age-and gender-matched patient controls with oesophageal symptoms,but normal manometry. Supine oesophageal manometry was performed with an eight-channel DentSleeve water-perfused catheter,and an ambulatory pH study assessed gastro-oesophageal reflux. RESULTS:Patients in the IOM subset featuring a majority of low-amplitude simultaneous contractions(LASC) experienced less heartburn(prevalence 26%) ,but more dysphagia(57%) than those in the IOM subset featuring low-amplitude propagated contractions(LAP;heartburn 70%,dysphagia 24%;both P ≤ 0.01) . LASC patients also experienced less heartburn and more dysphagia than patient controls(heartburn 68%,dysphagia 11%;both P < 0.001) . The prevalence of heartburn and dysphagia in IOM patients featuring a majority of non-transmitted sequences(NT) was 54%(P = 0.04 vs LASC) and 36%(P < 0.01 vs controls) ,respectively. No differences inage and gender distribution,chest pain prevalence,acid exposure time(AET) and symptom/reflux association existed between IOM subsets,or between subsets and controls. CONCLUSION:IOM patients with LASC exhibit a different symptom profile to those with LAP,but do not differ in gastro-oesophageal reflux prevalence. These findings raise the possibility of different pathophysiological mechanisms in IOM subsets,which warrants further investigation. | Horst Gunter Haack Ross David Hansen Allison Malcolm John Edward Kellow | 2008 | World Journal of Gastroenterology2008,14,23: | 2 |
| 7 | Genomic surveillance of Nevada patients revealed prevalence of unique SARS-CoV-2 variants bearing mutations in the RdRp gene显示文摘Patients with signs of COVID-19 were tested through diagnostic RT-PCR for SARS-CoV-2 using RNA extracted from the nasopharyngeal/nasal swabs.To determine the variants of SARS-CoV-2 circulating in the state of Nevada,specimens from 200 COVID-19 patients were sequenced through our robust sequencing platform,which enabled sequencing of SARS-CoV-2 from specimens with even very low viral loads,without the need of culture-based amplification.High genome coverage allowed the identification of single and multi-nucleotide variants in SARS-CoV-2 in the community and their phylogenetic relationships with other variants present during the same period of the outbreak.We report the occurrence of a novel mutation at 323aa (314aa of orf1b) of nsp12 (RNA-dependent RNA polymerase) changed to phenylalanine(F) from proline (P),in the first reported isolate of SARS-CoV-2,Wuhan-Hu-1.This 323F variant was present at a very high frequency in Northern Nevada.Structural modeling determined this mutation in the interface domain,which is important for the association of accessory proteins required for the polymerase.In conclusion,we report the introduction of specific SARS-CoV-2 variants at very high frequency in distinct geographic locations,which is important for understanding the evolution and circulation of SARS-CoV-2variants of public health importance,while it circulates in humans. | Paul D.Hartley Richard L.Tillett David P.AuCoin Joel R.Sevinsky Yanji Xu Andrew Gorzalski Mark Pandori Erin Buttery Holly Hansen Michael A.Picker Cyprian C.Rossetto Subhash C.Verma | 2021 | Journal of Genetics and Genomics2021,48,1: | 2 |
| 8 | Phonocardiography as a Monitor of Cardiac Performance During Anesthesia显示文摘 | Peter B. Hansen Aldo A. Luisada David J. Miletich Ronald F. Albrecht | 1989 | Anesthesia & Analgesia1989,,3: | 1 |
| 9 | Ursodiol and Colorectal Cancer or Dysplasia Risk in Primary Sclerosing Cholangitis and Inflammatory Bowel Disease: A Meta-Analysis显示文摘 | Jonathan D. Hansen Sonal Kumar Wai-Kit Lo David M. Poulsen Umme-Aiman Halai Kathy C. Tater | 2013 | Digestive Diseases and Sciences2013,,11: | 1 |
| 10 | Development and Evolution of the Human Neocortex显示文摘 | Jan H. Lui David V. Hansen Arnold R. Kriegstein | 2011 | Cell2011,,1: | 1 |
| 11 | Parametric reverse correlation reveals spatial linearity of retinotopic human V1 BOLD response显示文摘 | HANSEN K A DAVID S V GALLANT J L | 2004 | Neuroimage2004,23,1: | 1 |
| 12 | Development of humanized antibodies as cancer therapeutics显示文摘 | Zhengxing Qu Gary L. Griffiths William A. Wegener Chien-Hsing Chang Serengulam V. Govindan Ivan D. Horak Hans J. Hansen David M. Goldenberg | 2005 | Methods2005,,1: | 1 |
| 13 | Molecular imprinting in sol-gel materi- al : recent applications 显示文摘 | David E Hansen | 2005 | Microchim Acta2005,149,: | 1 |
| 14 | Preparation of a pure autologous biodegradable fibrin matrix for tissue engineering显示文摘 | A. Haisch Dr A. Loch J. David A. Pru? R. Hansen M. Sittinger | 2000 | Medical & Biological Engineering & Computing2000,,6: | 1 |
| 15 | Phonocardiography as amonitor of cardiac performance during anesthesia 显示文摘 | Hansen PB Luisada AA David J | 1989 | AnesthAnalg1989,68,3: | 1 |
| 16 | Discussion of 'on the use of the Kozeny-Carman equation to predict the hydraulic conductivity of soils显示文摘 | HANSEN DAVID | 2004 | Canadian Geoteehnieal Journal2004,41,5: | 1 |
| 17 | Collagenous colitis in setting of nonsteroidal antiinflammatory drugs and antibiotics显示文摘 | Dr. Francis M. Giardiello MD F. Christian Hansen MD Audrey J. Lazenby MD David B. Hellman MD Francis D. Milligan MD Theodore M. Bayless MD John H. Yardley MD | 1990 | Digestive Diseases and Sciences1990,,2: | 1 |
| 18 | The HvNAC6 transcription factor: a positive regulator of penetration resistance in barley and Arabidopsis显示文摘 | Michael Krogh Jensen Jesper Henrik Rung Per Langkjaer Gregersen Torben Gjetting Anja Thoe Fuglsang Michael Hansen Nina Joehnk Michael Foged Lyngkjaer David B. Collinge | 2007 | Plant Molecular Biology (-)2007,,1: | 1 |
| 19 | 90Y Radioembolization for Metastatic Neuroendocrine Liver Tumors: Preliminary Results From a Multi-institutional Experience显示文摘 | Thomas K. Rhee Robert J. Lewandowski David M. Liu Mary F. Mulcahy Gary Takahashi Paul D. Hansen Al B. Benson Andrew S. Kennedy Reed A. Omary Riad Salem | 2008 | Annals of Surgery2008,,6: | 1 |
| 20 | CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group显示文摘 | Michael Pfreundschuh Lorenz Trümper Anders ?sterborg Ruth Pettengell Marek Trneny Kevin Imrie David Ma Devinder Gill Jan Walewski Pier-Luigi Zinzani Rolf Stahel Stein Kvaloy Ofer Shpilberg Ulrich Jaeger Mads Hansen Tuula Lehtinen Armando López-Guillermo C | 2006 | Lancet Oncology2006,,5: | 1 |