bluuebunny/crossref_metadata_2025_split huggingface dataset:
Liar, a novel Lyn-binding nuclear/cytoplasmic shuttling protein that influences erythropoietin-induced differentiation
Authors: Samuels Amy L. , Klinken S. Peter , Ingley Evan 
Published: December 2008

AbstractErythropoiesis is primarily controlled by erythropoietin (Epo), which stimulates proliferation, differentiation, and survival of erythroid precursors. We have previously shown that the tyrosine kinase Lyn is critical for transducing differentiation signals emanating from the activated Epo receptor. A yeast 2-hybrid screen for downstream effectors of Lyn identified a novel protein, Liar (Lyn-interacting ankyrin repeat), which forms a multiprotein complex with Lyn and HS1 in erythroid cells. Interestingly, 3 of the ankyrin repeats of Liar define a novel SH3 binding region for Lyn and HS1. Liar also contains functional nuclear localization and nuclear export sequences and shuttles rapidly between the nucleus and cytoplasm. Ectopic expression of Liar inhibited the differentiation of normal erythroid progenitors, as well as immortalized erythroid cells. Significantly, Liar affected Epo-activated signaling molecules including Erk2, STAT5, Akt, and Lyn. These results show that Liar is a novel Lyn-interacting molecule that plays an important role in regulating intracellular signaling events associated with erythroid terminal differentiation.
Selective roles for antiapoptotic MCL-1 during granulocyte development and macrophage effector function
Authors: Steimer Desiree A. , Boyd Kelli , Takeuchi Osamu , Fisher Jill K. , Zambetti Gerard P. , Opferman Joseph T. 
Published: December 2008

AbstractDuring hematopoiesis, myeloid cell leukemia-1 (MCL-1) mediates the survival of bone marrow progenitors and lymphocytes. However, its requirement during myeloid cell differentiation, development, and effector function is less clear. Lineage-specific deletion of MCL-1 in myeloid precursors results in neutropenia due to death during differentiation. The loss of mature neutrophils induced by Mcl-1 deletion was not rescued by genetic deletion of proapoptotic Bim and Puma or by exogenous cytokine treatment. However, blockade of intrinsic apoptosis by lineage-specific deletion of both multidomain proapoptotics Bax and Bak was capable of rescuing the neutropenia associated with Mcl-1 deletion. In the monocytic lineage, despite efficient Mcl-1 deletion, monocytes and macrophages undergo normal development. During the phagocytosis of extracellular bacteria, macrophages concomitantly increase the expression of both MCL-1 and BIM. However, Mcl-1–deficient macrophages exhibit increased sensitivity to death during bacterial phagocytosis that can be abolished by codeletion of Bim. These data suggest that MCL-1 may be necessary to antagonize BIM during macrophage effector responses. Thus, MCL-1 plays selective roles in myeloid development, being required for neutrophil development and setting the threshold for apoptosis during a macrophage effector response.
Loss of red cell chemokine scavenging promotes transfusion-related lung inflammation
Authors: Mangalmurti Nilam S. , Xiong Zeyu , Hulver Mei , Ranganathan Mrunalini , Liu Xiang Hong , Oriss Timothy , Fitzpatrick Meghan , Rubin Marc , Triulzi Darrell , Choi Augustine , Lee Janet S. 
Published: December 2008

AbstractRed cell transfusions are associated with the development of acute lung injury in the critically ill. Recent evidence suggests that storage induced alterations of the red blood cell (RBC) collectively termed the “storage lesion” may be linked with adverse biologic consequences. Using a 2-event model of systemic endotoxemia followed by a secondary challenge of RBC transfusion, we investigated whether purified RBC concentrates from syngeneic C57BL/6 mice altered inflammatory responses in murine lungs. Transfusion of RBCs stored for 10 days increased neutrophil counts, macrophage inflammatory protein-2 (MIP-2) and chemokine (KC) concentrations in the airspaces, and lung microvascular permeability compared with transfusion of less than 1-day-old RBCs. Because RBCs have been shown to scavenge inflammatory chemokines through the blood group Duffy antigen, we investigated the expression and function of Duffy during storage. In banked human RBCs, both Duffy expression and chemokine scavenging function were reduced with increasing duration of storage. Transfusion of Duffy knockout RBCs into Duffy wild-type en-dotoxemic mice increased airspace neutrophils, inflammatory cytokine concentrations, and lung microvascular permeability compared with transfusion of Duffy wild-type RBCs. Thus, reduction in erythrocyte chemokine scavenging is one functional consequence of the storage lesion by which RBC transfusion can augment existing lung inflammation.
Transcriptome analysis of mammary epithelial subpopulations identifies novel determinants of lineage commitment and cell fate
Authors: Kendrick Howard , Regan Joseph L , Magnay Fiona-Ann , Grigoriadis Anita , Mitsopoulos Costas , Zvelebil Marketa , Smalley Matthew J 
Published: December 2008

AbstractBackgroundUnderstanding the molecular control of cell lineages and fate determination in complex tissues is key to not only understanding the developmental biology and cellular homeostasis of such tissues but also for our understanding and interpretation of the molecular pathology of diseases such as cancer. The prerequisite for such an understanding is detailed knowledge of the cell types that make up such tissues, including their comprehensive molecular characterisation. In the mammary epithelium, the bulk of the tissue is composed of three cell lineages, namely the basal/myoepithelial, luminal epithelial estrogen receptor positive and luminal epithelial estrogen receptor negative cells. However, a detailed molecular characterisation of the transcriptomic differences between these three populations has not been carried out.ResultsA whole transcriptome analysis of basal/myoepithelial cells, luminal estrogen receptor negative cells and luminal estrogen receptor positive cells isolated from the virgin mouse mammary epithelium identified 861, 326 and 488 genes as highly differentially expressed in the three cell types, respectively. Network analysis of the transcriptomic data identified a subpopulation of luminal estrogen receptor negative cells with a novel potential role as non-professional immune cells. Analysis of the data for potential paracrine interacting factors showed that the basal/myoepithelial cells, remarkably, expressed over twice as many ligands and cell surface receptors as the other two populations combined. A number of transcriptional regulators were also identified that were differentially expressed between the cell lineages. One of these,Sox6, was specifically expressed in luminal estrogen receptor negative cells and functional assays confirmed that it maintained mammary epithelial cells in a differentiated luminal cell lineage.ConclusionThe mouse mammary epithelium is composed of three main cell types with distinct gene expression patterns. These suggest the existence of a novel functional cell type within the gland, that the basal/myoepithelial cells are key regulators of paracrine signalling and that there is a complex network of differentially expressed transcription factors controlling mammary epithelial cell fate. These data will form the basis for understanding not only cell fate determination and cellular homeostasis in the normal mammary epithelium but also the contribution of different mammary epithelial cell types to the etiology and molecular pathology of breast disease.
Congenital diaphragamatic hernia associated with aortic coarctation: a case report
Authors: Okawada Manabu , Yanai Toshihiro , Yamataka Atsuyuki , Okazaki Tadaharu , Kobayashi Hiroyuki , Kawasaki Shiori , Lane Geoffrey J , Miyano Takeshi 
Published: December 2008

Abstract
Congenital diaphragmatic hernia associated with cardiac anomalies is a major therapeutic challenge. We report a case of Congenital diaphragmatic hernia associated with coarctation of the aorta.
Randomized Controlled Trial of Resistance or Aerobic Exercise in Men Receiving Radiation Therapy for Prostate Cancer
Authors: Segal Roanne J. , Reid Robert D. , Courneya Kerry S. , Sigal Ronald J. , Kenny Glen P. , Prud'Homme Denis G. , Malone Shawn C. , Wells George A. , Scott Chris G. , Slovinec D'Angelo Monika E. 
Published: December 2008

Purpose Radiotherapy for prostate cancer (PCa) may cause unfavorable changes in fatigue, quality of life (QOL), and physical fitness. We report results from the Prostate Cancer Radiotherapy and Exercise Versus Normal Treatment study examining the effects of 24 weeks of resistance or aerobic training versus usual care on fatigue, QOL, physical fitness, body composition, prostate-specific antigen, testosterone, hemoglobin, and lipid levels in men with PCa receiving radiotherapy. Patients and Methods Between 2003 and 2006, we conducted a randomized controlled trial in Ottawa, Canada, where 121 PCa patients initiating radiotherapy with or without androgen deprivation therapy were randomly assigned to usual care (n = 41), resistance (n = 40), or aerobic exercise (n = 40) for 24 weeks. Our primary end point was fatigue assessed by the Functional Assessment of Cancer Therapy–Fatigue scale. Results The follow-up assessment rate for our primary end point of fatigue was 92.6%. Median adherence to prescribed exercise was 85.5%. Mixed-model repeated measures analyses indicated both resistance (P =.010) and aerobic exercise (P = .004) mitigated fatigue over the short term. Resistance exercise also produced longer-term improvements (P = .002). Compared with usual care, resistance training improved QOL (P = .015), aerobic fitness (P = .041), upper- (P < .001) and lower-body (P < .001) strength, and triglycerides (P = .036), while preventing an increase in body fat (P = .049). Aerobic training also improved fitness (P = .052). One serious adverse event occurred in the group that performed aerobic exercise. Conclusion In the short term, both resistance and aerobic exercise mitigated fatigue in men with PCa receiving radiotherapy. Resistance exercise generated longer-term improvements and additional benefits for QOL, strength, triglycerides, and body fat.
Prognostic Value of Minimal Residual Disease Quantification Before Allogeneic Stem-Cell Transplantation in Relapsed Childhood Acute Lymphoblastic Leukemia: The ALL-REZ BFM Study Group
Authors: Bader Peter , Kreyenberg Hermann , Henze Günter H.R. , Eckert Cornelia , Reising Miriam , Willasch Andre , Barth Andrea , Borkhardt Arndt , Peters Christina , Handgretinger Rupert , Sykora Karl-Walter , Holter Wolfgang , Kabisch Hartmut , Klingebiel Thomas , von Stackelberg Arend 
Published: December 2008

Purpose Minimal residual disease (MRD) before allogeneic stem-cell transplantation was shown to predict outcome in children with relapsed acute lymphoblastic leukemia (ALL) in retrospective analysis. To verify this, the Acute Lymphoblastic Leukemia Relapse Berlin-Frankfurt-Münster (ALL-REZ BFM) Study Group conducted a prospective trial. Patients and Methods Between March 1999 and July 2005, 91 children with relapsed ALL treated according to the ALL-REZ BFM 96 or 2002 protocols and receiving stem-cell transplantation in ≥ second remission were enrolled. MRD quantification was performed by real-time polymerase chain reaction using T-cell receptor and immunoglobulin gene rearrangements. Results Probability of event-free survival (pEFS) and cumulative incidence of relapse (CIR) in 45 patients with MRD ≥ 10−4 leukemic cells was 0.27 and 0.57 compared with 0.60 and 0.13 in 46 patients with MRD less than 10−4 leukemic cells (EFS, P = .004; CIR, P < .001). Intermediate-risk patients (strategic group S1) with MRD ≥ 10−4 leukemic cells (n = 14) had a pEFS of 0.20 and CIR of 0.73, whereas patients with MRD less than 10−4 leukemic cells (n = 21) had a pEFS of 0.68 and CIR of 0.09 (EFS, P = .020; CIR, P < .001). High-risk patients (S3/4, third complete remission) who received transplantation with an MRD load of less than 10−4 leukemic cells (n = 25) showed a pEFS and CRI of 0.53 and 0.18, respectively. In contrast, pEFS and CRI were 0.30 and 0.50 in patients who received transplantation with an MRD load of ≥ 10−4 leukemic cells. Multivariate Cox regression analysis revealed MRD as the only independent parameter predictive for EFS (P = .006). Conclusion MRD is an important predictor for post-transplantation outcome. As a result, new strategies with modified stem-cell transplantation procedures will be evaluated in ALL-BFM trials.
Ductal Carcinoma in Situ: State of the Science and Roadmap to Advance the Field
Authors: Kuerer Henry M. , Albarracin Constance T. , Yang Wei T. , Cardiff Robert D. , Brewster Abenaa M. , Symmans W. Fraser , Hylton Nola M. , Middleton Lavinia P. , Krishnamurthy Savitri , Perkins George H. , Babiera Gildy , Edgerton Mary E. , Czerniecki Brian J. , Arun Banu K. , Hortobagyi Gabriel N. 
Published: December 2008

PurposeDuctal carcinoma in situ (DCIS) is the fourth leading cancer for women in the United States. Understanding of the biology and clinical behavior of DCIS is imperfect. This article highlights the current knowledge base and the scientific roadmap needed to advance the field.MethodsThis article is based on work done by and consultations obtained from leading experts in the field over a 6-month period that culminated in a full-day symposium designed to systematically review the most pertinent MEDLINE published reports and develop a roadmap to elucidate the molecular steps of carcinogenesis, reduce the extent or prevent the need for therapies, eliminate recurrences, and reduce morbidity.ResultsExpression profiling of pure DCIS will help elucidate the molecular characteristics that distinguish high-risk lesions from clinically irrelevant lesions. The development of new methods of extracting RNA from processed tissues may provide opportunities for research. Mammography often underestimates the pathologic extent of DCIS; other imaging methods need to be investigated for detection and monitoring of disease stability or progression. Novel biologic agents are being delivered in neoadjuvant clinical trials, and alternative methods for breast irradiation are being studied. Future trials of treatment versus no treatment for biologically selected cases of DCIS should be developed.ConclusionThere is a critical need for a concerted international effort among patients with DCIS, clinicians, and basic scientists to conduct the research necessary to improve fundamental understanding of the biology and clinical behavior of DCIS and prevent development of invasive breast cancer.
Intensive Multimodality Treatment for Children With Newly Diagnosed CNS Atypical Teratoid Rhabdoid Tumor
Authors: Chi Susan N. , Zimmerman Mary Ann , Yao Xiaopan , Cohen Kenneth J. , Burger Peter , Biegel Jaclyn A. , Rorke-Adams Lucy B. , Fisher Michael J. , Janss Anna , Mazewski Claire , Goldman Stewart , Manley Peter E. , Bowers Daniel C. , Bendel Anne , Rubin Joshua , Turner Christopher D. , Marcus Karen J. , Goumnerova Liliana , Ullrich Nicole J. , Kieran Mark W. 
Published: December 2008

Purpose Atypical teratoid rhabdoid tumor (ATRT) of the CNS is a highly malignant neoplasm primarily affecting young children, with a historic median survival ranging from 6 to 11 months. Based on a previous pilot series, a prospective multi-institutional trial was conducted for patients with newly diagnosed CNS ATRT. Patients and Methods Treatment was divided into five phases: preirradiation, chemoradiation, consolidation, maintenance, and continuation therapy. Intrathecal chemotherapy was administered, alternating intralumbar and intraventricular routes. Radiation therapy (RT) was prescribed, either focal (54 Gy) or craniospinal (36 Gy, plus primary boost), depending on age and extent of disease at diagnosis. Results Between 2004 and 2006, 25 patients were enrolled; 20 were eligible for evaluation. Median age at diagnosis was 26 months (range, 2.4 months to 19.5 years). Gross total resection of the primary tumor was achieved in 11 patients. Fourteen patients had M0 disease at diagnosis, one patient had M2 disease, and five patients had M3 disease. Fifteen patients received radiation therapy: 11 focal and four craniospinal. Significant toxicities, in addition to the expected, included radiation recall (n = 2) and transverse myelitis (n = 1). There was one toxic death. Of the 12 patients who were assessable for chemotherapeutic response (pre-RT), the objective response rate was 58%. The objective response rate observed after RT was 38%. The 2-year progression-free and overall survival rates are 53% ± 13% and 70% ± 10%, respectively. Median overall survival has not yet been reached. Conclusion This intensive multimodality regimen has resulted in a significant improvement in time to progression and overall survival for patients with this previously poor-prognosis tumor.
Implementation of semi-active damping on a tri-axle heavy-vehicle suspension
Authors: Roebuck R L , Cebon D 
Published: December 2008

A semi-active truck damper was developed in conjunction with a commercial shock absorber manufacturer. A linearized damper model was developed for control system design purposes. Open- and closed-loop damper force tracking control was implemented, with tests showing that an open-loop approach gave the best compromise between response speed and accuracy. A hardware-in-the-loop test facility was used to investigate performance of the damper when combined with a simulated quarter-car model. The input to the vehicle model was a set of randomly generated road profiles, each profile traversed at an appropriate speed. Modified skyhook damping tests showed a simultaneous improvement over the optimum passive case of 13 per cent in vertical body acceleration and 8 per cent in dynamic tyre forces. Full-scale vehicle tests of the damper on a heavy tri-axle trailer were carried out. Implementation of modified skyhook damping yielded a simultaneous improvement over the optimum passive case of 8 per cent in vertical body acceleration and 8 per cent in dynamic tyre forces.
Potential Risk Factors for Knee Injuries in Alpine Skiers
Authors: Burtscher M. , Sommersacher R. , Ruedl G. , Nachbauer W. 
Published: December 2008

Abstract
Objectives: To identify potential risk factors for knee injury in female alpine skiers. Methods: Injury survey in the winter season 2005 in one big Austrian ski area. Data collection on all injured skiers who needed evacuation included demographic variables, weather and snow conditions, circumstances of the skiing accident, the type of ski used, and injury location. Results: In total, 344 injured alpine skiers (41.3 % males, 58.7 % females) who needed evacuation were recorded. Twenty six percent of the injured male skiers and 47 % of the injured female skiers had knee injury. Female skiers with knee injuries were older, reported less regular physical activity, had more injuries in the morning hours and on cold days, and were not as likely to be using newly adjusted bindings in comparison to female skiers with non-knee injuries. Conclusion: This study found a set of potential risk factors for knee injury in female skiers. This is considered to be a valuable basis for more in-depth studies evaluating causal connections between these factors and the risk for knee injuries in female skiers.
Local Phylogeny Mapping of Quantitative Traits: Higher Accuracy and Better Ranking Than Single-Marker Association in Genomewide Scans
Authors: Besenbacher Søren , Mailund Thomas , Schierup Mikkel H 
Published: December 2008

Abstract
We present a new method, termed QBlossoc, for linkage disequilibrium (LD) mapping of genetic variants underlying a quantitative trait. The method uses principles similar to a previously published method, Blossoc, for LD mapping of case/control studies. The method builds local genealogies along the genome and looks for a significant clustering of quantitative trait values in these trees. We analyze its efficiency in terms of localization and ranking of true positives among a large number of negatives and compare the results with single-marker approaches. Simulation results of markers at densities comparable to contemporary genotype chips show that QBlossoc is more accurate in localization of true positives as expected since it uses the additional information of LD between markers simultaneously. More importantly, however, for genomewide surveys, QBlossoc places regions with true positives higher on a ranked list than single-marker approaches, again suggesting that a true signal displays itself more strongly in a set of adjacent markers than a spurious (false) signal. The method is both memory and central processing unit (CPU) efficient. It has been tested on a real data set of height data for 5000 individuals measured at ∼317,000 markers and completed analysis within 5 CPU days.
TheSaccharomyces cerevisiae PRM1Homolog inNeurospora crassaIs Involved in Vegetative and Sexual Cell Fusion Events but Also Has Postfertilization Functions
Authors: Fleißner André , Diamond Spencer , Glass N Louise 
Published: December 2008

AbstractCell–cell fusion is essential for a variety of developmental steps in many eukaryotic organisms, during both fertilization and vegetative cell growth. Although the molecular mechanisms associated with intracellular membrane fusion are well characterized, the molecular mechanisms of plasma membrane merger between cells are poorly understood. In the filamentous fungus Neurospora crassa, cell fusion events occur during both vegetative and sexual stages of its life cycle, thus making it an attractive model for studying the molecular basis of cell fusion during vegetative growth vs. sexual reproduction. In the unicellular yeast Saccharomyces cerevisiae, one of the few proteins implicated in plasma membrane merger during mating is Prm1p; prm1Δ mutants show an ∼50% reduction in mating cell fusion. Here we report on the role of the PRM1 homolog in N. crassa. N. crassa strains with deletions of a Prm1-like gene (Prm1) showed an ∼50% reduction in both vegetative and sexual cell fusion events, suggesting that PRM1 is part of the general cell fusion machinery. However, unlike S. cerevisiae, N. crassa strains carrying a Prm1 deletion exhibited complete sterility as either a male or female mating partner, a phenotype that was not complemented in a heterokaryon with wild type (WT). Crosses with ΔPrm1 strains were blocked early in sexual development, well before development of ascogenous hyphae. The ΔPrm1 sexual defect in N. crassa was not suppressed by mutations in Sad-1, which is required for meiotic silencing of unpaired DNA (MSUD). However, mutations in Sad-1 increased the number of progeny obtained in crosses with a ΔPrm1 (Prm1-gfp) complemented strain. These data indicate multiple roles for PRM1 during sexual development.