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GST Primary GST Primary Best Strategies for Health Care Quality Im... Best Strategies for Health Care Quality Improvement - Diabetes Quality Improvement Strategies for Antibio... Kathryn McDonald, Stanford-UCSF Evidence-b... Systematic review assessing the effect of ... Quality Improvement Strategies for Antibiotics Management Kathryn McDonald, Stanford-UCSF Evidence-based Practice Center, 117 Encina Commons, Stanford, CA 94305-6019, Kathy.mcdonald@stanford.edu Systematic review assessing the effect of quality improvement strategies on appropriate prescribing of antibiotics and appropriate choice of antibiotics. Adherence Adherence Assistive Devices Assistive Devices Childhood Burn Hanson MacMillan Childhood Burn Hanson MacMillan CLSA_9 CLSA_9 Cyberabuse Cyberabuse Cognitive Behavioural Therapy for Violent ... This review included randomized trials abo... Cognitive Behavioural Therapy for Violent Men who Batter Their Partners This review included randomized trials about the effects of cognitive behavioral therapy on domestic violence. The intervention included programs based on the Duluth Model. The violence had to be committed by a male toward his female partner. The violence also had to be physical. The primary outcomes were new arrests and convictions, and new reports of violence. CABG vs PCI CABG vs PCI Quality Improvement Strategies for Prevent... Quality Improvement Strategies for Preventing Nosocomial Infections (Created 17-Feb-06) Quality Improvement Strategies for Asthma ... Quality Improvement Strategies for Asthma Control Erectile Dysfunction (Created 30-Jan-06) Erectile Dysfunction (Created 30-Jan-06) Inequality - Smoking Cessation to Reduce S... This review was the first part of a projec... Inequality - Smoking Cessation to Reduce Socio-Economic Differences This review was the first part of a project about inequality. It included randomized trials about the effect of smoking cessation interventions on reducing socio-economic differences. The studies had to report data either on persons with low socio-economic groups status or, preferably, on both low and high socio-economic groups. Diet and Physical Activity to Reduce Socio... This review was the second part in a proje... Diet and Physical Activity to Reduce Socio-Economic Differences This review was the second part in a project about inequality. It included randomized trials about the effect of interventions on reducing socio-economic differences in diet and physical activity. The studies had to report data either on persons with low socio-economic groups status or, preferably, on both low and high socio-economic groups. Workfare The data in SRS are not identical to the d... Workfare The data in SRS are not identical to the data in the published report. We used SRS only for an updated search. The review included randomized trials about the effect of welfare-to-work programs. Participants were welfare recipients. There were basically two types of programs. The educational type tried to build knowledge and skills in order to help the welfare recipients acquire jobs that could support them economically. The "work first" approach was more aimed at getting the participants quickly into a job. Exercise interventions for the management ... The objective of this systematic review wa... Exercise interventions for the management of frailty The objective of this systematic review was to examine the effectiveness of current exercise interventions on the management of frailty. A comprehensive search of Medline, Embase, Psycinfo, Cinahl, Scopus, Ageline, Eric, and SportDiscus databases was conducted and produced 1808 citations. So far we have completed 2 levels of “title and abstract” screening and we ended up with 262 articles. We have just started the full text screening. Eligibility criteria included original studies whose participants were identified as frail or prefrail with specific criteria and in which structured physical activity was included as at least one component of the intervention. Create a free account, build a dictionary with saved terms to re-use later! Public Domestic Violence - Using Cognitive Behavior Therapy Smoking Cessation to Reduce Socio-Economic Differences Diet and Physical Activity to Reduce Socio-Economic Differences Workfare Exercise Interventions for the Management of Frailty Search     Simple Advanced Refine (4 coded questions)  Any of these:   Exact Phrase: All of these: None of these: Author: Periodical: Projects: No restrictions   Libraries: Public   Select SRS Projects Show Saved Terms Select Library Show articles that do not have abstracts  Type of Article Clinical Trial Editorial Letter Meta-Analysis Practice Guideline Randomized Controlled Trial Review Addresses Bibliography Biography Case Reports Classical Article Clinical Conference Clinical Trial, Phase I Clinical Trial, Phase II Clinical Trial, Phase III Clinical Trial, Phase IV Comment Comparative Study Consensus Development Conference Consensus Development Conference, NIH Controlled Clinical Trial Corrected and Republished Article Dictionary Directory Duplicate Publication English Abstract Evaluation Studies Festschrift Government Publications Guideline Historical Article Interview In Vitro Journal Article Lectures Legal Cases Legislation Multicenter Study News Newspaper Article Overall Patient Education Handout Periodical Index Published Erratum Retracted Publication Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. 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Retraction of Publication Scientific Integrity Review Support of Research Technical Report Twin Study Validation Studies Not a Primary Study or Review Unknown Primary Study Case Series Case Control Cohort Study Observational Study Qualitative Research CBA or ITS Registry Double Blind Controlled before after study Quasi-randomized trial Simple before after study Cluster-RCT Non-Randomized Study Report Book Book chapter Dissertation Conference procedings Secondary Research Not RCT Humans or Animals Humans Animals Ages All Infant: birth-23 months All Child: 0-18 years All Adult: 19+ years Newborn: birth-1 month Infant: 1-23 months Preschool Child: 2-5 years Child: 6-12 years Adolescent: 13-18 years Adult: 19-44 years Middle Aged: 45-64 years Middle Aged + Aged: 45+ years Aged: 65+ years 80 and over: 80+ years Undetermined Language English French German Italian Japanese Russian Spanish Afrikaans Albanian Unknown Arabic Armenian Azerbaijani Bosnian Bulgarian Catalan Chinese Croatian Czech Danish Dutch Esperanto Estonian Finnish Georgian Greek, Modern Hebrew Hindi Hungarian Icelandic Indonesian Kinyarwanda Korean Latin Latvian Lithuanian Macedonian Malay Malayalam Maori Multiple Languages Norwegian Persian Polish Portuguese Pushto Romanian Sanskrit Scottish gaelic Serbian Slovak Slovenian Swedish Thai Turkish Ukrainian Vietnamese Not English Not French Results(1-25 of 6,114) Sort By: Publication Date Relevance Took: 0.685 seconds to search 17,750,454  Action: Copy Results to new Clipboard Build Search Link Page 1 of 245 1 2 3 4 > Last >> (6114 articles found) Stem cell mobilization with cyclophosphamide overcomes the suppressive effect of lenalidomide therapy on stem cell collection in multiple myeloma. Jul 2008 Tomer Mark,Jessica Stern,Jessica R Furst,David Jayabalan,Faiza Zafar,April LaRow,Roger N Pearse,John Harpel,Tsiporah Shore,Michael W Schuster,John P Leonard,Paul J Christos,Morton Coleman,Ruben Niesvizky A total of 28 treatment-naïve patients with stage II or III multiple myeloma (MM) were treated with the combination of clarithromycin, lenalidomide, and dexamethasone (BiRD). Stem cells were collected following granulocyte-colony stimulating factor (G-CSF) or cyclophosphamide (Cy) plus G-CSF mobili... ( view more )zation at maximum response. Sufficient stem cells for 2 autologous stem cell transplants were collected from all patients mobilized with Cy plus G-CSF, versus 33% mobilized with G-CSF alone (P < .0001). The duration of prior lenalidomide therapy did not correlate with success of stem cell harvests (P = .91). In conclusion, Cy can be added to G-CSF for stem cell mobilization to successfully overcome the suppressive effect of prior treatment with lenalidomide. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles A comparison of native speaker and American adult learner Vietnamese lexical tones. May 2008 Allison Blodgett,Jessica Bauman,Anita Bowles,Lykara Charters,Anton Rytting,Jessica Shamoo,Matthew Winn This study introduces a modification of the traditional carrier sentence elicitation task, provides new native speaker data regarding aspects of pitch and voice quality in Vietnamese lexical tones, and provides an empirical description of non-native speaker errors in tone production. Participants p... ( view more )roduce a series of three-word utterances in response to target words that appear individually on a computer screen in one of four colors. In this way, participants actively describe a changing event, while critical components remain constant: the identity of the word preceding the target, the target position (utterance medial), and the target's focus structure. Native speaker results are consistent with existing descriptions of fundamental frequency contours and creakiness. In addition, they provide evidence supporting claims that breathiness can occur in two different tones: the falling tone (huyen) and curve tone (hoi). Non-native speaker results suggest that adult learners struggle with voice quality distinctions and pitch shape. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Vietnamese monophthong vowel production by native speakers and American adult learners. May 2008 Matthew Winn,Allison Blodgett,Jessica Bauman,Anita Bowles,Lykara Charters,Anton Rytting,Jessica Shamoo This study provides new native speaker data regarding the vowel space and duration contrasts of Vietnamese monophthongs. These data add to existing empirical accounts and raise questions about descriptions aimed at adult language learners. In addition, specific acoustic measures target difficulties... ( view more ) that English-speaking adults encounter when producing Vietnamese vowels. These measures include the rounding distinction for back vowels, height distinction for central vowels, and duration distinction between short and long vowels. Results show that adult learners exhibit greater variability and overall less accurate production than native speakers for the high-back unrounded vowel u', with slightly better performance for the mid-back unrounded vowel o', perhaps because it is similar to English Lambda . Additionally, these learners demonstrate varying levels of success with regard to the production of central vowel height but generally fail to distinguish the two vowel duration categories exhibited by native speakers. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Mechanisms of specific and nonspecific binding of architectural proteins in prokaryotic gene regulation. Mar 25, 2008 James M Benevides,Jessica Danahy,Jessica Kawakami,George J Thomas IHF and HU are small basic proteins of eubacteria that bind as homodimers to double-stranded DNA and bend the duplex to promote architectures required for gene regulation. These architectural proteins share a common alpha/beta fold but exhibit different nucleic acid binding surfaces and distinct fu... ( view more )nctional roles. With respect to DNA-binding specificity, for example, IHF is sequence specific, while HU is not. We have employed Raman difference spectroscopy and gel mobility assays to characterize the molecular mechanisms underlying such differences in DNA recognition. Parallel studies of solution complexes of IHF and HU with the same DNA nonadecamer (5' --> 3' sequence: TC TAAGTAGTTGATTCATA, where the phage lambda H1 consensus sequence of IHF is underlined) show the following. (i) The structure of the targeted DNA site is altered much more dramatically by IHF than by HU binding. (ii) In the IHF complex, the structural perturbations encompass both the sugar-phosphate backbone and the bases of the consensus sequence, whereas only the DNA backbone is altered by HU binding. (iii) In the presence of excess protein, complexes of order higher than 1 dimer per duplex are detected for HU:DNA, though not for IHF:DNA. The results differentiate structural motifs of IHF:DNA and HU:DNA solution complexes, provide Raman signatures of prokaryotic sequence-specific and nonspecific recognition, and suggest that the architectural role of HU may involve the capability to recruit additional binding partners to even relatively short DNA sequences. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Part-time physicians...prevalent, connected, and satisfied. Mar 2008 Hilit F Mechaber,Rachel B Levine,Linda Baier Manwell,Marlon P Mundt,Mark Linzer,MEMO Investigators ,Mark Schwartz,Deborah Dowell,Perry An,Karla Felix,Julia McMurray,James Bobula,Mary Beth Plane,William Scheckler,John Frey,Jessica Sherrieb,Jessica Grettie,Barbara Horner-Ibler,Ann Maguire,Laura Paluch,Bernice Man,Anita Varkey,Elizabeth Arce,Joseph Rabatin,Elianne Riska,JudyAnn Bigby,Thomas R Konrad,Peggy Leatt,Stewart Babbott,Eric Williams OBJECTIVE: The health care workforce is evolving and part-time practice is increasing. The objective of this work is to determine the relationship between part-time status, workplace conditions, and physician outcomes. DESIGN: Minimizing error, maximizing outcome (MEMO) study surveyed generalist ph... ( view more )ysicians and their patients in the upper Midwest and New York City. MEASUREMENTS AND MAIN RESULTS: Physician survey of stress, burnout, job satisfaction, work control, intent to leave, and organizational climate. Patient survey of satisfaction and trust. Responses compared by part-time and full-time physician status; 2-part regression analyses assessed outcomes associated with part-time status. Of 751 physicians contacted, 422 (56%) participated. Eighteen percent reported part-time status (n = 77, 31% of women, 8% of men, p < .001). Part-time physicians reported less burnout (p < .01), higher satisfaction (p < .001), and greater work control (p < .001) than full-time physicians. Intent to leave and assessments of organizational climate were similar between physician groups. A survey of 1,795 patients revealed no significant differences in satisfaction and trust between part-time and full-time physicians. CONCLUSIONS: Part-time is a successful practice style for physicians and their patients. If favorable outcomes influence career choice, an increased demand for part-time practice is likely to occur. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Stabilizing formulations for inhalable powders of live-attenuated measles virus vaccine. Mar 2008 Jessica L Burger,Stephen P Cape,Chad S Braun,David H McAdams,Jessica A Best,Pradnya Bhagwat,Pankaj Pathak,Lia G Rebits,Robert E Sievers Carbon dioxide Assisted Nebulization with a Bubble Dryer((R)) (CAN-BD) processing allows particles to be made in the 3-5 mum size range, which is desirable for lung delivery, without destroying biological activity. In response to the Grand Challenge in Global Health Initiative #3, we have been deve... ( view more )loping an inhalable needle-free live-attenuated measles virus vaccine for use in developing countries. Measles was chosen because it is the number one vaccine preventable killer of children worldwide. Powders were processed by CAN-BD, where a solution containing excipients and live-attenuated measles virus in water was mixed intimately with supercritical or near superctitical carbon dioxide to form an emulsion. The emulsion was expanded to atmospheric pressure through a flow restrictor. The resulting plume was dried by heated nitrogen and the powders collected on a filter at the bottom of the drying chamber. Powders were analyzed using varying techniques including X-ray diffraction, scanning electron microscopy, Andersen cascade impaction, differential scanning calorimetery, Karl Fischer titration, and viral plaque assay. CAN-BD has been used to produce powders of live-attenuated measles virus vaccine with characteristics desirable for lung delivery. The powders retain viral activity through forming and drying the microparticles by CAN-BD, and have passed the WHO stability test for 1 week at 37 degrees C. The powders have an amorphous character and a glass transition temperature of around 60 degrees C. Lyophilization, the present standard commercial method of processing measles vaccine makes solids with a water content of less than 1%. By substituting myo-inositol for sorbitol and using the CAN-BD drying technique the water content can be lowered to 0.5%. The most successful formulations to date have been based conceptually on the current lyophilized formulation, but with modifications to the type and amounts of sugar. Of current interest are formulations containing myo-inositol, as they retain high viral activity and have low initial water content. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles BiRD (Biaxin [clarithromycin]/Revlimid [lenalidomide]/dexamethasone) combination therapy results in high complete- and overall-response rates in treatment-naive symptomatic multiple myeloma. Feb 1, 2008 Ruben Niesvizky,David S Jayabalan,Paul J Christos,Jessica R Furst,Tara Naib,Scott Ely,Jessica Jalbrzikowski,Roger N Pearse,Faiza Zafar,Karen Pekle,April Larow,Richard Lent,Tomer Mark,Hearn J Cho,Tsiporah Shore,Jeffrey Tepler,John Harpel,Michael W Schuster,Susan Mathew,John P Leonard,Madhu Mazumdar,Selina Chen-Kiang,Morton Coleman This trial determined the safety and efficacy of the combination regimen clarithromycin (Biaxin), lenalidomide (Revlimid), and dexamethasone (BiRD) as first-line therapy for multiple myeloma. Patients received BiRD in 28-day cycles. Dexamethasone (40 mg) was given orally once weekly, clarithromycin... ( view more ) (500 mg) was given orally twice daily, and lenalidomide (25 mg) was given orally daily on days 1 to 21. Objective response was defined by standard criteria (ie, decrease in serum monoclonal protein [M-protein] by at least 50%, and a decrease in urine M-protein by at least 90%). Of the 72 patients enrolled, 65 had an objective response (90.3%). A combined stringent and conventional complete response rate of 38.9% was achieved, and 73.6% of the patients achieved at least a 90% decrease in M-protein levels. This regimen did not interfere with hematopoietic stem-cell harvest. Fifty-two patients who did not go on to receive transplants received continued therapy (complete response, 37%; very good partial response, 33%). The major adverse events were thromboembolic events, corticosteroid-related morbidity, and cytopenias. BiRD is an effective regimen with manageable side effects in the treatment of symptomatic, newly diagnosed multiple myeloma. This trial was registered at www.clinicaltrials.gov as #NCT00151203. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Adult glial precursor proliferation in mutant SOD1G93A mice. Jan 15, 2008 Tim Magnus,Jessica Carmen,Jessica Deleon,Haipeng Xue,Andrea C Pardo,Angelo C Lepore,Mark P Mattson,Mahendra S Rao,Nicholas J Maragakis The focus of most neurodegenerative disease studies has been on neuronal death in particular subpopulations of the central nervous system. The associated response of glial populations has been ascribed the term "reactive astrocytosis." This has been defined as the proliferation of astrocytes accomp... ( view more )anied by cellular hypertrophy and changes in gene expression following injury to the central nervous system. Yet the significance of that response to disease course is debated. In both human ALS and in the SOD1G93A mouse model of ALS, reactive astrocytosis is a hallmark of the disease--particularly at endstage. The brain also harbors immature progenitors which have the capacity for differentiation into both glial and neuronal lineages. We examined whether glial progenitors in the adult spinal cord of SOD1G93A mice become activated and contribute the astroglial response observed in this model. We found that the glial progenitor proteoglycan NG2 is increased in parallel with GFAP during the symptomatic phase of the disease and that there is a differential in vitro response of SOD1G93A glial progenitors to inflammatory cytokines when compared to wildtype mouse glial progenitors. This response was accompanied by the proliferation of glial progenitors but not mature GFAP+ astrocytes, through the translocation of the transcription factor Olig2 from the nucleus to the cytoplasm-resulting in astrocyte differentiation. These data suggest that adult glial progenitors from SOD1G93A mice differentially respond to inflammatory cytokines and contribute to the observed reactive astrocytosis observed in SOD1G93A mouse lumbar spinal cord. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles TER1, the RNA subunit of fission yeast telomerase. Jan 2008 Jessica Leonardi,Jessica A Box,Jeremy T Bunch,Peter Baumann Telomerase is the ribonucleoprotein complex that adds telomeric repeats to the ends of chromosomes. Its protein subunit TERT is highly conserved among eukaryotes, whereas the RNA subunit varies greatly in size and sequence, hindering the identification of telomerase RNAs in some important model org... ( view more )anisms. Here we report the identification and functional characterization of TER1, the telomerase RNA component from fission yeast Schizosaccharomyces pombe. Deletion of ter1+ caused progressive shortening of telomeres and cellular senescence followed by chromosome circularization. Interactions between Est1 and Trt1, the two known protein components of fission yeast telomerase, were dependent on TER1, supporting its role as a scaffold for the assembly of protein subunits. Using a series of template mutations, we show that translocation or dissociation site variability and template-primer slippage account for the sequence heterogeneity of fission yeast telomeres. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Prophylactic low-dose aspirin is effective antithrombotic therapy for combination treatments of thalidomide or lenalidomide in myeloma. Dec 2007 Ruben Niesvizky,Déborah Martínez-Baños,Jessica Jalbrzikowski,Paul Christos,Jessica Furst,Maria De Sancho,Tomer Mark,Roger Pearse,Madhu Mazumdar,Faiza Zafar,Karen Pekle,John Leonard,David Jayabalan,Morton Coleman Multiple myeloma (MM) patients have a propensity for thromboembolic events (TE), and treatment with thalidomide/dexamethasone or lenalidomide/dexamethasone increases this risk. This report describes the use of low-dose aspirin (81 mg) as primary thromboprophylaxis in three series of MM patients rec... ( view more )eiving thalidomide or lenalidomide with other drugs. In the first regimen (clarithromycin, thalidomide, dexamethasone), initiation of low-dose aspirin negated the occurrence of any further TE. In a second study, prophylactic aspirin given with thalidomide/dexamethasone resulted in a rate of TE similar to that seen with dexamethasone alone (without aspirin). A third study (n = 72) evaluated thrombosis rates with aspirin and a lenalidomide-containing regimen (clarithromycin, lenalidomide, dexamethasone). Of nine occurrences of thromboembolism, five were associated with aspirin interruption or poor compliance. Low-dose aspirin appears to reduce the incidence of thrombosis with these regimens. Routine use of aspirin as antithrombotic prophylaxis in MM patients receiving immunomodulatory drugs with corticosteroids is warranted. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Endotoxin priming of neutrophils requires NADPH oxidase-generated oxidants and is regulated by the anion transporter ClC-3. Nov 23, 2007 Jessica G Moreland,A Paige Davis,James J Matsuda,Jessica S Hook,Gail Bailey,William M Nauseef,Fred S Lamb Several soluble mediators, including endotoxin, prime neutrophils for an enhanced respiratory burst in response to subsequent stimulation. Priming of neutrophils occurs in vitro, and primed neutrophils are found in vivo. We previously localized the anion transporter ClC-3 to polymorphonuclear leuko... ( view more )cytes (PMN) secretory vesicles and demonstrated that it is required for normal NADPH oxidase activation in response to both particulate and soluble stimuli. We now explore the contribution of the NADPH oxidase and ClC-3 to endotoxin-mediated priming. Lipooligosaccharide (LOS) from Neisseria meningitidis enhances the respiratory burst in response to formyl-Met-Leu-Phe, an effect that was impaired in PMNs lacking functional ClC-3 and under anaerobic conditions. Mobilization of receptors to the cell surface and phosphorylation of p38 MAPK by LOS were both impaired in PMN with the NADPH oxidase chemically inhibited or genetically absent and in cells lacking functional ClC-3. Furthermore, inhibition of the NADPH oxidase or ClC-3 in otherwise unstimulated cells elicited a phenotype similar to that seen after endotoxin priming, suggesting that basal oxidant production helps to maintain cellular quiescence. In summary, NADPH oxidase activation was required for LOS-mediated priming, but basal oxidants kept unstimulated cells from becoming primed. ClC-3 contributes to both of these processes. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Genome-wide detection and characterization of positive selection in human populations. Oct 18, 2007 Pardis C Sabeti,Patrick Varilly,Ben Fry,Jason Lohmueller,Elizabeth Hostetter,Chris Cotsapas,Xiaohui Xie,Elizabeth H Byrne,Steven A McCarroll,Rachelle Gaudet,Stephen F Schaffner,Eric S Lander,International HapMap Consortium ,Kelly A Frazer,Dennis G Ballinger,David R Cox,David A Hinds,Laura L Stuve,Richard A Gibbs,John W Belmont,Andrew Boudreau,Paul Hardenbol,Suzanne M Leal,Shiran Pasternak,David A Wheeler,Thomas D Willis,Fuli Yu,Huanming Yang,Changqing Zeng,Yang Gao,Haoran Hu,Weitao Hu,Chaohua Li,Wei Lin,Siqi Liu,Hao Pan,Xiaoli Tang,Jian Wang,Wei Wang,Jun Yu,Bo Zhang,Qingrun Zhang,Hongbin Zhao,Hui Zhao,Jun Zhou,Stacey B Gabriel,Rachel Barry,Brendan Blumenstiel,Amy Camargo,Matthew Defelice,Maura Faggart,Mary Goyette,Supriya Gupta,Jamie Moore,Huy Nguyen,Robert C Onofrio,Melissa Parkin,Jessica Roy,Erich Stahl,Ellen Winchester,Liuda Ziaugra,David Altshuler,Yan Shen,Zhijian Yao,Wei Huang,Xun Chu,Yungang He,Li Jin,Yangfan Liu,Yayun Shen,Weiwei Sun,Haifeng Wang,Yi Wang,Ying Wang,Xiaoyan Xiong,Liang Xu,Mary M Y Waye,Stephen K W Tsui,Hong Xue,J Tze-Fei Wong,Luana M Galver,Jian-Bing Fan,Kevin Gunderson,Sarah S Murray,Arnold R Oliphant,Mark S Chee,Alexandre Montpetit,Fanny Chagnon,Vincent Ferretti,Martin Leboeuf,Jean-François Olivier,Michael S Phillips,Stéphanie Roumy,Clémentine Sallée,Andrei Verner,Thomas J Hudson,Pui-Yan Kwok,Dongmei Cai,Daniel C Koboldt,Raymond D Miller,Ludmila Pawlikowska,Patricia Taillon-Miller,Ming Xiao,Lap-Chee Tsui,William Mak,You Qiang Song,Paul K H Tam,Yusuke Nakamura,Takahisa Kawaguchi,Takuya Kitamoto,Takashi Morizono,Atsushi Nagashima,Yozo Ohnishi,Akihiro Sekine,Toshihiro Tanaka,Tatsuhiko Tsunoda,Panos Deloukas,Christine P Bird,Marcos Delgado,Emmanouil T Dermitzakis,Rhian Gwilliam,Sarah Hunt,Jonathan Morrison,Don Powell,Barbara E Stranger,Pamela Whittaker,David R Bentley,Mark J Daly,Paul I W de Bakker,Jeff Barrett,Yves R Chretien,Julian Maller,Steve McCarroll,Nick Patterson,Itsik Pe'er,Alkes Price,Shaun Purcell,Daniel J Richter,Pardis Sabeti,Richa Saxena,Stephen F Schaffner,Pak C Sham,Patrick Varilly,David Altshuler,Lincoln D Stein,Lalitha Krishnan,Albert Vernon Smith,Marcela K Tello-Ruiz,Gudmundur A Thorisson,Aravinda Chakravarti,Peter E Chen,David J Cutler,Carl S Kashuk,Shin Lin,Gonçalo R Abecasis,Weihua Guan,Yun Li,Heather M Munro,Zhaohui Steve Qin,Daryl J Thomas,Gilean McVean,Adam Auton,Leonardo Bottolo,Niall Cardin,Susana Eyheramendy,Colin Freeman,Jonathan Marchini,Simon Myers,Chris Spencer,Matthew Stephens,Peter Donnelly,Lon R Cardon,Geraldine Clarke,David M Evans,Andrew P Morris,Bruce S Weir,Tatsuhiko Tsunoda,Todd A Johnson,James C Mullikin,Stephen T Sherry,Michael Feolo,Andrew Skol,Houcan Zhang,Changqing Zeng,Hui Zhao,Ichiro Matsuda,Yoshimitsu Fukushima,Darryl R Macer,Eiko Suda,Charles N Rotimi,Clement A Adebamowo,Ike Ajayi,Toyin Aniagwu,Patricia A Marshall,Chibuzor Nkwodimmah,Charmaine D M Royal,Mark F Leppert,Missy Dixon,Andy Peiffer,Renzong Qiu,Alastair Kent,Kazuto Kato,Norio Niikawa,Isaac F Adewole,Bartha M Knoppers,Morris W Foster,Ellen Wright Clayton,Jessica Watkin,Richard A Gibbs,John W Belmont,Donna Muzny,Lynne Nazareth,Erica Sodergren,George M Weinstock,David A Wheeler,Imtaz Yakub,Stacey B Gabriel,Robert C Onofrio,Daniel J Richter,Liuda Ziaugra,Bruce W Birren,Mark J Daly,David Altshuler,Richard K Wilson,Lucinda L Fulton,Jane Rogers,John Burton,Nigel P Carter,Christopher M Clee,Mark Griffiths,Matthew C Jones,Kirsten McLay,Robert W Plumb,Mark T Ross,Sarah K Sims,David L Willey,Zhu Chen,Hua Han,Le Kang,Martin Godbout,John C Wallenburg,Paul L'Archevêque,Guy Bellemare,Koji Saeki,Hongguang Wang,Daochang An,Hongbo Fu,Qing Li,Zhen Wang,Renwu Wang,Arthur L Holden,Lisa D Brooks,Jean E McEwen,Mark S Guyer,Vivian Ota Wang,Jane L Peterson,Michael Shi,Jack Spiegel,Lawrence M Sung,Lynn F Zacharia,Francis S Collins,Karen Kennedy,Ruth Jamieson,John Stewart With the advent of dense maps of human genetic variation, it is now possible to detect positive natural selection across the human genome. Here we report an analysis of over 3 million polymorphisms from the International HapMap Project Phase 2 (HapMap2). We used 'long-range haplotype' methods, whic... ( view more )h were developed to identify alleles segregating in a population that have undergone recent selection, and we also developed new methods that are based on cross-population comparisons to discover alleles that have swept to near-fixation within a population. The analysis reveals more than 300 strong candidate regions. Focusing on the strongest 22 regions, we develop a heuristic for scrutinizing these regions to identify candidate targets of selection. In a complementary analysis, we identify 26 non-synonymous, coding, single nucleotide polymorphisms showing regional evidence of positive selection. Examination of these candidates highlights three cases in which two genes in a common biological process have apparently undergone positive selection in the same population:LARGE and DMD, both related to infection by the Lassa virus, in West Africa;SLC24A5 and SLC45A2, both involved in skin pigmentation, in Europe; and EDAR and EDA2R, both involved in development of hair follicles, in Asia. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles A second generation human haplotype map of over 3.1 million SNPs. Oct 18, 2007 International HapMap Consortium ,Kelly A Frazer,Dennis G Ballinger,David R Cox,David A Hinds,Laura L Stuve,Richard A Gibbs,John W Belmont,Andrew Boudreau,Paul Hardenbol,Suzanne M Leal,Shiran Pasternak,David A Wheeler,Thomas D Willis,Fuli Yu,Huanming Yang,Changqing Zeng,Yang Gao,Haoran Hu,Weitao Hu,Chaohua Li,Wei Lin,Siqi Liu,Hao Pan,Xiaoli Tang,Jian Wang,Wei Wang,Jun Yu,Bo Zhang,Qingrun Zhang,Hongbin Zhao,Hui Zhao,Jun Zhou,Stacey B Gabriel,Rachel Barry,Brendan Blumenstiel,Amy Camargo,Matthew Defelice,Maura Faggart,Mary Goyette,Supriya Gupta,Jamie Moore,Huy Nguyen,Robert C Onofrio,Melissa Parkin,Jessica Roy,Erich Stahl,Ellen Winchester,Liuda Ziaugra,David Altshuler,Yan Shen,Zhijian Yao,Wei Huang,Xun Chu,Yungang He,Li Jin,Yangfan Liu,Yayun Shen,Weiwei Sun,Haifeng Wang,Yi Wang,Ying Wang,Xiaoyan Xiong,Liang Xu,Mary M Y Waye,Stephen K W Tsui,Hong Xue,J Tze-Fei Wong,Luana M Galver,Jian-Bing Fan,Kevin Gunderson,Sarah S Murray,Arnold R Oliphant,Mark S Chee,Alexandre Montpetit,Fanny Chagnon,Vincent Ferretti,Martin Leboeuf,Jean-François Olivier,Michael S Phillips,Stéphanie Roumy,Clémentine Sallée,Andrei Verner,Thomas J Hudson,Pui-Yan Kwok,Dongmei Cai,Daniel C Koboldt,Raymond D Miller,Ludmila Pawlikowska,Patricia Taillon-Miller,Ming Xiao,Lap-Chee Tsui,William Mak,You Qiang Song,Paul K H Tam,Yusuke Nakamura,Takahisa Kawaguchi,Takuya Kitamoto,Takashi Morizono,Atsushi Nagashima,Yozo Ohnishi,Akihiro Sekine,Toshihiro Tanaka,Tatsuhiko Tsunoda,Panos Deloukas,Christine P Bird,Marcos Delgado,Emmanouil T Dermitzakis,Rhian Gwilliam,Sarah Hunt,Jonathan Morrison,Don Powell,Barbara E Stranger,Pamela Whittaker,David R Bentley,Mark J Daly,Paul I W de Bakker,Jeff Barrett,Yves R Chretien,Julian Maller,Steve McCarroll,Nick Patterson,Itsik Pe'er,Alkes Price,Shaun Purcell,Daniel J Richter,Pardis Sabeti,Richa Saxena,Stephen F Schaffner,Pak C Sham,Patrick Varilly,David Altshuler,Lincoln D Stein,Lalitha Krishnan,Albert Vernon Smith,Marcela K Tello-Ruiz,Gudmundur A Thorisson,Aravinda Chakravarti,Peter E Chen,David J Cutler,Carl S Kashuk,Shin Lin,Gonçalo R Abecasis,Weihua Guan,Yun Li,Heather M Munro,Zhaohui Steve Qin,Daryl J Thomas,Gilean McVean,Adam Auton,Leonardo Bottolo,Niall Cardin,Susana Eyheramendy,Colin Freeman,Jonathan Marchini,Simon Myers,Chris Spencer,Matthew Stephens,Peter Donnelly,Lon R Cardon,Geraldine Clarke,David M Evans,Andrew P Morris,Bruce S Weir,Tatsuhiko Tsunoda,James C Mullikin,Stephen T Sherry,Michael Feolo,Andrew Skol,Houcan Zhang,Changqing Zeng,Hui Zhao,Ichiro Matsuda,Yoshimitsu Fukushima,Darryl R Macer,Eiko Suda,Charles N Rotimi,Clement A Adebamowo,Ike Ajayi,Toyin Aniagwu,Patricia A Marshall,Chibuzor Nkwodimmah,Charmaine D M Royal,Mark F Leppert,Missy Dixon,Andy Peiffer,Renzong Qiu,Alastair Kent,Kazuto Kato,Norio Niikawa,Isaac F Adewole,Bartha M Knoppers,Morris W Foster,Ellen Wright Clayton,Jessica Watkin,Richard A Gibbs,John W Belmont,Donna Muzny,Lynne Nazareth,Erica Sodergren,George M Weinstock,David A Wheeler,Imtaz Yakub,Stacey B Gabriel,Robert C Onofrio,Daniel J Richter,Liuda Ziaugra,Bruce W Birren,Mark J Daly,David Altshuler,Richard K Wilson,Lucinda L Fulton,Jane Rogers,John Burton,Nigel P Carter,Christopher M Clee,Mark Griffiths,Matthew C Jones,Kirsten McLay,Robert W Plumb,Mark T Ross,Sarah K Sims,David L Willey,Zhu Chen,Hua Han,Le Kang,Martin Godbout,John C Wallenburg,Paul L'Archevêque,Guy Bellemare,Koji Saeki,Hongguang Wang,Daochang An,Hongbo Fu,Qing Li,Zhen Wang,Renwu Wang,Arthur L Holden,Lisa D Brooks,Jean E McEwen,Mark S Guyer,Vivian Ota Wang,Jane L Peterson,Michael Shi,Jack Spiegel,Lawrence M Sung,Lynn F Zacharia,Francis S Collins,Karen Kennedy,Ruth Jamieson,John Stewart We describe the Phase II HapMap, which characterizes over 3.1 million human single nucleotide polymorphisms (SNPs) genotyped in 270 individuals from four geographically diverse populations and includes 25-35% of common SNP variation in the populations surveyed. The map is estimated to capture untyp... ( view more )ed common variation with an average maximum r2 of between 0.9 and 0.96 depending on population. We demonstrate that the current generation of commercial genome-wide genotyping products captures common Phase II SNPs with an average maximum r2 of up to 0.8 in African and up to 0.95 in non-African populations, and that potential gains in power in association studies can be obtained through imputation. These data also reveal novel aspects of the structure of linkage disequilibrium. We show that 10-30% of pairs of individuals within a population share at least one region of extended genetic identity arising from recent ancestry and that up to 1% of all common variants are untaggable, primarily because they lie within recombination hotspots. We show that recombination rates vary systematically around genes and between genes of different function. Finally, we demonstrate increased differentiation at non-synonymous, compared to synonymous, SNPs, resulting from systematic differences in the strength or efficacy of natural selection between populations. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Genomewide clonal analysis of lethal mutations in the Drosophila melanogaster eye: comparison of the X chromosome and autosomes. Oct 2007 Gerald B Call,John M Olson,Jiong Chen,Nikki Villarasa,Kathy T Ngo,Allison M Yabroff,Shawn Cokus,Matteo Pellegrini,Elena Bibikova,Chris Bui,Albert Cespedes,Cheryl Chan,Stacy Chan,Amrita K Cheema,Akanksha Chhabra,Vida Chitsazzadeh,Minh-Tu Do,Q Angela Fang,Andrew Folick,Gelsey L Goodstein,Cheng R Huang,Tony Hung,Eunha Kim,William Kim,Yulee Kim,Emil Kohan,Edward Kuoy,Robert Kwak,Eric Lee,JiEun Lee,Henry Lin,H-C Angela Liu,Tatiana Moroz,Tharani Prasad,Sacha L Prashad,Alexander N Patananan,Alma Rangel,Desiree Rosselli,Sohrab Sidhu,Daniel Sitz,Chelsea E Taber,Jingwen Tan,Kasey Topp,PhuongThao Tran,Quynh-Minh Tran,Mary Unkovic,Maggie Wells,Jessica Wickland,Kevin Yackle,Amir Yavari,Jesse M Zaretsky,Christopher M Allen,Latifat Alli,Ju An,Abbas Anwar,Sonia Arevalo,Danny Ayoub,Shawn S Badal,Armonde Baghdanian,Arthur H Baghdanian,Sara A Baumann,Vivian N Becerra,Hei J Chan,Aileen E Chang,Xibin A Cheng,Mabel Chin,Fleurette Chong,Carlyn Crisostomo,Sanjit Datta,Angela Delosreyes,Francie Diep,Preethika Ekanayake,Mark Engeln,Elizabeth Evers,Farzin Farshidi,Katrina Fischer,Arlene J Formanes,Jun Gong,Riju Gupta,Blake E Haas,Vicky Hahm,Michael Hsieh,James Z Hui,Mei L Iao,Sophia D Jin,Angela Y Kim,Lydia S-H Kim,Megan King,Chloe Knudsen-Robbins,David Kohanchi,Bogdana Kovshilovskaya,Amy Ku,Raymond W Kung,Mark E L Landig,Stephanie S Latterman,Stephanie S Lauw,Daniel S Lee,Joann S Lee,Kai C Lei,Lesley L Leung,Renata Lerner,Jian-ya Lin,Kathleen Lin,Bryon C Lim,Crystal P Y Lui,Tiffany Q Liu,Vincent Luong,Jacob Makshanoff,An-Chi Mei,Miguel Meza,Yara A Mikhaeil,Majid Moarefi,Long H Nguyen,Shekhar S Pai,Manish Pandya,Aadit R Patel,Paul D Picard,Michael M Safaee,Carol Salame,Christian Sanchez,Nina Sanchez,Christina C Seifert,Abhishek Shah,Oganes H Shilgevorkyan,Inderroop Singh,Vanessa Soma,Junia J Song,Neetika Srivastava,Jennifer L StaAna,Christie Sun,Diane Tan,Alison S Teruya,Robyn Tikia,Trinh Tran,Emily G Travis,Jennifer D Trinh,Diane Vo,Thomas Walsh,Regan S Wong,Katherine Wu,Ya-Whey Wu,Nkau X V Yang,Michael Yeranosian,James S Yu,Jennifer J Zhou,Ran X Zhu,Anna Abrams,Amanda Abramson,Latiffe Amado,Jenny Anderson,Keenan Bashour,Elsa Beyer,Allen Bookatz,Sarah Brewer,Natalie Buu,Stephanie Calvillo,Joseph Cao,Amy Chan,Jenny Chan,Aileen Chang,Daniel Chang,Yuli Chang,YiBing Chen,Joo Choi,Jeyling Chou,Peter Dang,Sumit Datta,Ardy Davarifar,Artemis Deravanesian,Poonam Desai,Jordan Fabrikant,Shahbaz Farnad,Katherine Fu,Eddie Garcia,Nick Garrone,Srpouhi Gasparyan,Phyllis Gayda,Sherrylene Go,Chad Goffstein,Courtney Gonzalez,Mariam Guirguis,Ryan Hassid,Brenda Hermogeno,Julie Hong,Aria Hong,Lindsay Hovestreydt,Charles Hu,Devon Huff,Farid Jamshidian,James Jen,Katrin Kahen,Linda Kao,Melissa Kelley,Thomas Kho,Yein Kim,Sarah Kim,Brian Kirkpatrick,Adam Langenbacher,Santino Laxamana,Janet Lee,Chris Lee,So-Youn Lee,ToHang S Lee,Toni Lee,Gemma Lewis,Sheila Lezcano,Peter Lin,Thanh Luu,Julie Luu,Will Marrs,Erin Marsh,Jamie Marshall,Sarah Min,Tanya Minasian,Helena Minye,Amit Misra,Miles Morimoto,Yasaman Moshfegh,Jessica Murray,Kha Nguyen,Cynthia Nguyen,Ernesto Nodado,Amanda O'Donahue,Ndidi Onugha,Nneka Orjiakor,Bhavin Padhiar,Eric Paul,Mara Pavel-Dinu,Alex Pavlenko,Edwin Paz,Sarah Phaklides,Lephong Pham,Preethi Poulose,Russell Powell,Aya Pusic,Divi Ramola,Kirsten Regalia,Meghann Ribbens,Bassel Rifai,Manyak Saakyan,Pamela Saarikoski,Miriam Segura,Farnaz Shadpour,Aram Shemmassian,Ramnik Singh,Vivek Singh,Emily Skinner,Daniel Solomin,Kosha Soneji,Kristin Spivey,Erika Stageberg,Marina Stavchanskiy,Leena Tekchandani,Leo Thai,Jayantha Thiyanaratnam,Maurine Tong,Aneet Toor,Steve Tovar,Kelly Trangsrud,Wah-Yung Tsang,Marc Uemura,Emily Vollmer,Emily Weiss,Damien Wood,Joy Wu,Sophia Wu,Winston Wu,Qing Xu,Yuki Yamauchi,Will Yarosh,Laura Yee,George Yen,Utpal Banerjee Using a large consortium of undergraduate students in an organized program at the University of California, Los Angeles (UCLA), we have undertaken a functional genomic screen in the Drosophila eye. In addition to the educational value of discovery-based learning, this article presents the first com... ( view more )prehensive genomewide analysis of essential genes involved in eye development. The data reveal the surprising result that the X chromosome has almost twice the frequency of essential genes involved in eye development as that found on the autosomes. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Widespread lateral gene transfer from intracellular bacteria to multicellular eukaryotes. Sep 21, 2007 Julie C Dunning Hotopp,Michael E Clark,Deodoro C S G Oliveira,Jeremy M Foster,Peter Fischer,Mónica C Muñoz Torres,Jonathan D Giebel,Nikhil Kumar,Nadeeza Ishmael,Shiliang Wang,Jessica Ingram,Rahul V Nene,Jessica Shepard,Jeffrey Tomkins,Stephen Richards,David J Spiro,Elodie Ghedin,Barton E Slatko,Hervé Tettelin,John H Werren Although common among bacteria, lateral gene transfer-the movement of genes between distantly related organisms-is thought to occur only rarely between bacteria and multicellular eukaryotes. However, the presence of endosymbionts, such as Wolbachia pipientis, within some eukaryotic germlines may fa... ( view more )cilitate bacterial gene transfers to eukaryotic host genomes. We therefore examined host genomes for evidence of gene transfer events from Wolbachia bacteria to their hosts. We found and confirmed transfers into the genomes of four insect and four nematode species that range from nearly the entire Wolbachia genome (>1 megabase) to short (<500 base pairs) insertions. Potential Wolbachia-to-host transfers were also detected computationally in three additional sequenced insect genomes. We also show that some of these inserted Wolbachia genes are transcribed within eukaryotic cells lacking endosymbionts. Therefore, heritable lateral gene transfer occurs into eukaryotic hosts from their prokaryote symbionts, potentially providing a mechanism for acquisition of new genes and functions. ( view less ) View Full Abstract View Article Details   Related Articles Lenalidomide-induced myelosuppression is associated with renal dysfunction: adverse events evaluation of treatment-naïve patients undergoing front-line lenalidomide and dexamethasone therapy. Sep 2007 Ruben Niesvizky,Tara Naib,Paul J Christos,David Jayabalan,Jessica R Furst,Jessica Jalbrzikowski,Faiza Zafar,Tomer Mark,Richard Lent,Roger N Pearse,Scott Ely,John P Leonard,Madhu Mazumdar,Selina Chen-Kiang,Morton Coleman Data on 72 patients receiving lenalidomide/dexamethasone for multiple myeloma (MM) was used to determine the factors that are associated with lenalidomide-induced myelosuppression. Eight of 14 patients with grade > or =3 myelosuppression had baseline creatinine clearance (CrCl) < or =0.67 ml/s. Kap... ( view more )lan-Meier analysis by log-rank test demonstrated a significant association (P < 0.0001) between renal insufficiency and time to myelosuppression (hazard ratio = 8.4; 95% confidence interval 2.9-24.7, P = 0.0001). Therefore, CrCl is inversely associated with significant myelosuppression. Caution should be exercised when lenalidomide therapy is commenced and CrCl should be incorporated as a determinant of the initial dosing of lenalidomide in MM patients. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Human adiponectin inhibits cell growth and induces apoptosis in human endometrial carcinoma cells, HEC-1-A and RL95 2. Sep 2007 Li Cong,Jessica Gasser,Jessica Zhao,Baofeng Yang,Fanghong Li,Allan Z Zhao Obesity is one of the well-established risk factors for endometrial cancer. Recent clinical studies have demonstrated that circulating adiponectin concentrations are inversely correlated with the incidence of endometrial carcinoma. Such epidemiological findings are consistent with the paradoxical o... ( view more )bservations that adiponectin levels are reduced in obesity. This study investigated the direct effects of adiponectin on two endometrial carcinoma cell lines, HEC-1-A and RL95-2. These cell lines express both variants of adiponectin receptors, adipo-R1 and adipo-R2. Adiponectin treatment leads to suppression of cell proliferation in both cell types, which is primarily due to the significant increase of cell populations at G(1)/G(0)-phase and to the induction of apoptosis. The inhibition of growth in these two cell lines appears to be mediated by different signaling pathways. Although adiponectin treatment markedly increases the phosphorylation (Thr172) of AMP-activated protein kinase alpha in both HEC-1-A and RL95-2 within 30 min, prolonged exposure (48 h) leads to inactivation of Akt as well as reduction of cyclin D1 protein expression in HEC-1-A cells. In contrast, similar treatment of RL95-2 cells with adiponectin, while having no effects on Akt activity and cyclin D1 expression, causes a decrease in cyclin E2 expression and the activity of mitogen-activated kinase (p42/44). We conclude that adiponectin exerts direct anti-proliferative effects on HEC-1-A and RL95-2 cells by inducing cell cycle arrest and apoptosis. Depending on the genotypes of the endometrial cancer cells, the inhibitory effects of adiponectin are associated with the reduction of different pro-growth regulators of cell cycle and signaling proteins. Our study thus provides a cellular mechanism underlying the linkages between endometrial cancer and obesity. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles cAMP response element-binding protein deficiency allows for increased neurogenesis and a rapid onset of antidepressant response. Jul 18, 2007 Tamar L Gur,Alana C Conti,Jessica Holden,Anita J Bechtholt,Tiffany E Hill,Irwin Lucki,Jessica E Malberg,Julie A Blendy cAMP response element-binding protein (CREB) has been implicated in the molecular and cellular mechanisms of chronic antidepressant (AD) treatment, although its role in the behavioral response is unclear. CREB-deficient (CREB(alpha delta) mutant) mice demonstrate an antidepressant phenotype in the ... ( view more )tail suspension test (TST) and forced-swim test. Here, we show that, at baseline, CREB(alpha delta) mutant mice exhibited increased hippocampal cell proliferation and neurogenesis compared with wild-type (WT) controls, effects similar to those observed in WT mice after chronic desipramine (DMI) administration. Neurogenesis was not further augmented by chronic DMI treatment in CREB(alpha delta) mutant mice. Serotonin depletion decreased neurogenesis in CREB(alpha delta) mutant mice to WT levels, which correlated with a reversal of the antidepressant phenotype in the TST. This effect was specific for the reversal of the antidepressant phenotype in these mice, because serotonin depletion did not alter a baseline anxiety-like behavior in CREB(alpha delta) mutant mice. The response to chronic AD treatment in the novelty-induced hypophagia (NIH) test may rely on neurogenesis. Therefore, we used this paradigm to evaluate chronic AD treatment in CREB(alpha delta) mutant mice to determine whether the increased neurogenesis in these mice alters their response in the NIH paradigm. Whereas both WT and CREB(alpha delta) mutant mice responded to chronic AD treatment in the NIH paradigm, only CREB(alpha delta) mutant mice responded to acute AD treatment. However, in the elevated zero maze, DMI did not reverse anxiety behavior in mutant mice. Together, these data show that increased hippocampal neurogenesis allows for an antidepressant phenotype as well as a rapid onset of behavioral responses to AD treatment. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles A comparison of taxon co-occurrence patterns for macro- and microorganisms. Jun 2007 M Claire Horner-Devine,Jessica M Silver,Mathew A Leibold,Brendan J M Bohannan,Robert K Colwell,Jed A Fuhrman,Jessica L Green,Cheryl R Kuske,Jennifer B H Martiny,Gerard Muyzer,Lise Ovreås,Anna-Louise Reysenbach,Val H Smith We examine co-occurrence patterns of microorganisms to evaluate community assembly "rules". We use methods previously applied to macroorganisms, both to evaluate their applicability to microorganisms and to allow comparison of co-occurrence patterns observed in microorganisms to those found in macr... ( view more )oorganisms. We use a null model analysis of 124 incidence matrices from microbial communities, including bacteria, archaea, fungi, and algae, and we compare these results to previously published findings from a meta-analysis of almost 100 macroorganism data sets. We show that assemblages of microorganisms demonstrate nonrandom patterns of co-occurrence that are broadly similar to those found in assemblages of macroorganisms. These results suggest that some taxon co-occurrence patterns may be general characteristics of communities of organisms from all domains of life. We also find that co-occurrence in microbial communities does not vary among taxonomic groups or habitat types. However, we find that the degree of co-occurrence does vary among studies that use different methods to survey microbial communities. Finally, we discuss the potential effects of the undersampling of microbial communities on our results, as well as processes that may contribute to nonrandom patterns of co-occurrence in both macrobial and microbial communities such as competition, habitat filtering, historical effects, and neutral processes. ( view less ) View Full Abstract View Article Details   Related Articles Can the MMPI-2 discriminate between mild-moderate TBI and other neurologic and psychiatric populations? Dec 2006 Jessica Foley,Jessica Garcia,Kristen Harris,Charles Golden,Mark Todd MMPI-2 maintains an extensive empirical base with psychiatric populations, although more recently, neurologically compromised patients have documented unique elevation patterns. This study examined mild-moderate TBI patients, Alzheimer's Dementia patients, and Psychiatric controls on MMPI-2 scales.... ( view more ) Participants included 160 outpatients (TBI n = 26, AD n = 74, Psychiatric n = 60). Controlling for family-wise-error, five ANCOVAs were conducted on five MMPI-2 scales, correcting for age and education. TBI and Psychiatric group means were significantly higher than AD group means for scales Hypochondriasis, Depression, and Hysteria at an alpha of .01. Results support previous research with mild TBI patients, and further document a unique pattern of elevations in this population. ( view less ) View Full Abstract View Article Details   Related Articles Activation of mammalian target of rapamycin and the p70 S6 kinase by arsenic trioxide in BCR-ABL-expressing cells. Nov 2006 Patrick Yoon,Nick Giafis,Jessica Smith,Heather Mears,Efstratios Katsoulidis,Antonella Sassano,Jessica Altman,Amanda J Redig,Martin S Tallman,Leonidas C Platanias Arsenic trioxide (As(2)O(3)) exhibits important antitumor activities in vitro and in vivo, but the precise mechanisms by which it induces its effects are not known. We provide evidence that during treatment of BCR-ABL-expressing cells with As(2)O(3), there is activation of a cellular pathway involv... ( view more )ing the p70 S6 kinase (p70S6K). Our data show that p70S6K is rapidly phosphorylated on Thr(421) and Ser(424) and is activated in an As(2)O(3)-inducible manner. The mammalian target of rapamycin (mTOR) is also phosphorylated/activated in an As(2)O(3)-inducible manner, and its activity is required for downstream engagement of p70S6K. p70S6K subsequently phosphorylates the S6 ribosomal protein on Ser(235)/Ser(236) and Ser(240)/Ser(244) to promote initiation of mRNA translation. Treatment of chronic myelogenous leukemia-derived cell lines with As(2)O(3) also results in phosphorylation of the 4E-BP1 repressor of mRNA translation on Thr(37)/Thr(46) and Thr(70), sites required for its deactivation and its dissociation from the eukaryotic initiation factor 4E complex to allow cap-dependent mRNA translation. In studies to determine the functional relevance of this pathway, we found that inhibition of mTOR and downstream cascades enhances induction of apoptosis by As(2)O(3). Consistent with this, the mTOR inhibitor rapamycin strongly potentiated As(2)O(3)-mediated suppression of primitive leukemic progenitors from the bone marrow of chronic myelogenous leukemia patients. Altogether, our data show that the mTOR/p70S6K pathway is activated in a negative feedback regulatory manner in response to As(2)O(3) in BCR-ABL-transformed cells and plays a key regulatory role in the induction of anti-leukemic responses. ( view less ) View Full Abstract View Article Details   Related Articles Biologic significance of false-positive magnetic resonance imaging enhancement in the setting of ductal carcinoma in situ. Oct 2006 Anjali S Kumar,Daniel F Chen,Alfred Au,Yunn-Yi Chen,Jessica Leung,Elisabeth R Garwood,Jessica Gibbs,Nola Hylton,Laura J Esserman BACKGROUND: Imaging patterns of benign proliferative processes often complicate the assessment of ductal carcinoma in situ (DCIS) by magnetic resonance imaging (MRI). We investigated the pathologic and biologic characteristics of false positive enhancement by breast MRI. METHODS: DCIS (n = 45), ben... ( view more )ign (n = 5), and false-positive (MRI enhancement and nonmalignant pathology) (n = 10) cases were characterized by immunohistochemistry and MRI features. RESULTS: For DCIS cases, images that overestimated pathologic size had heterogeneous enhancement on MR, were estrogen receptor positive, and were low grade by pathology. False-positives had higher rates of proliferation, angiogenesis, and inflammation compared with benign tissue but lower values than DCIS. Benign proliferative processes accounted for all false-positive and size overestimated cases. CONCLUSIONS: Lesions that enhance on MRI have higher proliferation, angiogenesis, and inflammation compared with nonproliferative breast tissue. Benign proliferative processes often enhance on MRI and are difficult to differentiate from low-grade, ER+ DCIS lesions. False-positive MRI enhancement may reflect a spectrum of change within high-risk tissue. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Development of 125I-methylene blue for sentinel lymph node biopsy. Sep 15, 2006 Shawn J Stafford,Jessica L Wright,Joshua Schwimer,Catherine T Anthony,Jason D Cundiff,Jessica L Thomson,Yi-Zarn Wang,Gregory Espenan,Thomas Maloney,Arthur Camp,Eugene A Woltering BACKGROUND: Sentinel lymph node biopsy is an established alternative to complete lymph node dissection in some patients. We have developed a novel, radiolabeled methylene blue dye that may be a useful alternative to the traditional two-step procedure involving 99mTc-labeled colloid and unlabeled bl... ( view more )ue dye. We hypothesize that 125I-labeled methylene blue will be rapidly absorbed into the lymphatics and transported to the drainage basin containing the sentinel nodes. MATERIALS AND METHODS: Rabbits footpads were injected with 1 mCi of 125I-labeled methylene blue admixed with unlabeled dye. A hand-held gamma detection device allowed tracking of radiolabeled dye to nodes in the popliteal and inguinal regions. At pre-established time points animals were sacrificed, and the nodal basin dissected. Nodal radioactivity as well as uptake of blue dye was recorded. RESULTS: The spread of the radiolabeled methylene blue compound from the footpad to the popliteal lymph nodes occurred in 5-10 min. CONCLUSION: The radiolabeled dye rapidly progresses through lymphatics to the draining nodes. Use of radiolabeled methylene blue may be an attractive alternative to current two-step sentinel node techniques, as it may be less painful, and may reduce the cost associated with the time-delay between the injection of the radioactive compound and surgery. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Cutting edge: inhibition of TLR and FcR responses in macrophages by triggering receptor expressed on myeloid cells (TREM)-2 and DAP12. Aug 15, 2006 Jessica A Hamerman,Jessica R Jarjoura,Mary Beth Humphrey,Mary C Nakamura,William E Seaman,Lewis L Lanier DAP12 is an ITAM-containing adapter that associates with receptors in myeloid and NK cells. DAP12-associated receptors can give activation signals leading to cytokine production; however, in some situations, DAP12 inhibits cytokine production stimulated through TLRs and FcRs. Here we show that Trig... ( view more )gering Receptor Expressed on Myeloid cells (TREM)-2 is responsible for the DAP12-mediated inhibition in mouse macrophages. A chimeric receptor composed of the extracellular domain of TREM-2 and the cytoplasmic domain of DAP12 inhibited the TLR- and FcR-induced TNF production of DAP12-deficient macrophages, whereas a TREM-1 chimera did not. In wild-type macrophages, TREM-2 knockdown increased TLR-induced TNF production. A TREM-2 Fc fusion protein bound to macrophages, indicating that macrophages express a TREM-2 ligand. Thus, the interaction of TREM-2 and its ligand results in an inhibitory signal that can reduce the inflammatory response. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Disorders of water metabolism following transsphenoidal pituitary surgery: A single institution's experience. 2006 Jessica R Adams,Lewis S Blevins,George S Allen,Denise K Verity,Jessica K Devin Disorders of water metabolism are a common complication of pituitary surgery. The primary purpose of this study was to determine the incidence and duration of post-surgical diabetes insipidus (DI) at our institution. Secondary objectives included characterizing the incidence of post-operative hypon... ( view more )atremia as well as delineating factors associated with the onset of these complications. Records of 319 patients who underwent transsphenoidal pituitary surgery at the authors' institution between 1998 and 2005 were reviewed for the presence of disorders of water metabolism using pre-specified criteria. DI was diagnosed in 59 (18.5%) of our patients at a mean time of 13.6 h following surgery. DI resolved in nearly half of our patients within one week. Approximately 80% of our patients enjoyed resolution of DI at a mean time of 2.9 months following surgery. Duration of DI was not significantly influenced by tumor size or location. Additionally, 28 (8.8%) of our patients exhibited a period of hyponatremia at a mean time of 4 days following surgery. One quarter of these patients carried a diagnosis of Cushing's disease. We herein report an incidence of DI as well as hyponatremia within our post-operative population comparable to that reported by other high-volume pituitary centers. Over half of our patients still exhibited DI at the time of discharge, therefore, patient education regarding the treatment of DI, signs of its resolution, and symptoms consistent with the onset of hyponatremia should be an integral part of every hospitalization. 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