bluuebunny/crossref_metadata_2025_split huggingface dataset:
TGF-β-Superfamily Signaling Regulates Embryonic Stem Cell Heterogeneity: Self-Renewal as a Dynamic and Regulated Equilibrium
Authors: Galvin-Burgess Katherine E. , Travis Emily D. , Pierson Kelsey E. , Vivian Jay L. 
Published: October 2012

Abstract
Embryonic stem cells dynamically fluctuate between phenotypic states, as defined by expression levels of genes such as Nanog, while remaining pluripotent. The dynamic phenotype of stem cells is in part determined by gene expression control and dictated by various signaling pathways and transcriptional regulators. We sought to define the activities of two TGF-β-related signaling pathways, bone morphogenetic protein (BMP) and Nodal signaling, in modulating mouse embryonic stem (ES) cell heterogeneity in undifferentiated culture conditions. Both BMP and Nodal signaling pathways were seen to be active in distinct Nanog subpopulations, with subtle quantitative differences in activity. Pharmacological and genetic modulation of BMP or Nodal signaling strongly influenced the heterogeneous state of undifferentiated ES cells, as assessed by dynamic expression of Nanog reporters. Inhibition of Nodal signaling enhanced BMP activity, which through the downstream target Id factors, enhanced the capacity of ES cells to remain in the Nanog-high epigenetic state. The combined inhibition of Nodal and BMP signaling resulted in the accumulation of Nanog-negative cells, even in the presence of LIF, uncovering a shared role for BMP and Nodal signaling in maintaining Nanog expression and repression of differentiation. These results demonstrate a complex requirement for both arms of TGF-β-related signaling to influence the dynamic cellular phenotype of undifferentiated ES cells in serum-based media, and that differing subpopulations of ES cells in heterogeneous culture have distinct responses to these signaling pathways. Several pathways, including BMP, Nodal, and FGF signaling, have important regulatory function in defining the steady-state distribution of heterogeneity of stem cells.
Concise Review: The Evolution of human pluripotent stem cell culture: From feeder cells to synthetic coatings
Authors: Villa-Diaz L.G. , Ross A.M. , Lahann J. , Krebsbach P.H. 
Published: October 2012

Abstract
Current practices to maintain human pluripotent stem cells (hPSCs), which include induced pluripotent stem cells and embryonic stem cells, in an undifferentiated state typically depend on the support of feeder cells such as mouse embryonic fibroblasts (MEFs) or an extracellular matrix such as Matrigel. Culture conditions that depend on these undefined support systems limit our ability to interpret mechanistic studies aimed at resolving how hPSCs interact with their extracellular environment to remain in a unique undifferentiated state and to make fate-changing lineage decisions. Likewise, the xenogeneic components of MEFs and Matrigel ultimately hinder our ability to use pluripotent stem cells to treat debilitating human diseases. Many of these obstacles have been overcome by the development of synthetic coatings and bioreactors that support hPSC expansion and self-renewal within defined culture conditions that are free from xenogeneic contamination. The establishment of defined culture conditions and synthetic matrices will facilitate studies to more precisely probe the molecular basis of pluripotent stem cell self-renewal and differentiation. When combined with three-dimensional cultures in bioreactors, these systems will also enable large-scale expansion for future clinical applications.
mTORC1 and mTORC2 Play Different Roles in the Functional Survival of Transplanted Adipose-Derived Stromal Cells in Hind Limb Ischemic Mice Via Regulating Inflammation In Vivo
Authors: Fan Weiwei , Cheng Kang , Qin Xing , Narsinh Kazim H. , Wang Shenxu , Hu Sijun , Wang Yabin , Chen Yundai , Wu Joseph C. , Xiong Lize , Cao Feng 
Published: October 2012

Abstract
Poor cell survival severely limits the beneficial effects of stem cell therapy for peripheral arterial disease (PAD). This study was designed to investigate the role of mammalian target of rapamycin (mTOR) in the survival and therapeutic function of transplanted murine adipose-derived stromal cells (mADSCs) in a murine PAD model. mADSCs (1.0 × 107) were isolated from dual-reporter firefly luciferase and enhanced green fluorescent protein-positive transgenic mice, intramuscularly implanted into the hind limb of C57BL/6 mice after femoral artery ligation/excision, and monitored using noninvasive bioluminescence imaging (BLI). Although engrafted mADSCs produced antiapoptotic/proangiogenic effects in vivo by modulating the inflammatory and angiogenic cytokine response involving the mTOR pathway, longitudinal BLI revealed progressive death of post-transplant mADSCs within ∼4 weeks in the ischemic hind limb. Selectively targeting mTOR complex-1 (mTORC1) using low-dose rapamycin treatment with mADSCs attenuated proinflammatory cytokines (interleukin [IL]-1β and tumor necrosis factor-alpha [TNF-α]) expression and neutrophil/macrophage infiltration, which overtly promoted mADSCs viability and antiapoptotic/proangiogenic efficacy in vivo. However, targeting dual mTORC1/mTORC2 using PP242 or high-dose rapamycin caused IL-1β/TNF-α upregulation and anti-inflammatory IL-10, IL-6, and vascular endothelial growth factor/vascular endothelial growth factor receptor 2 downregulation, undermining the survival and antiapoptotic/proangiogenic action of mADSCs in vivo. Furthermore, low-dose rapamycin abrogated TNF-α secretion by mADSCs and rescued the cells from hypoxia/reoxygenation-induced death in vitro, while PP242 or high-dose rapamycin exerted proinflammatory effects and promoted cell death. In conclusion, mTORC1 and mTORC2 may differentially regulate inflammation and affect transplanted mADSCs' functional survival in ischemic hind limb. These findings uncover that mTOR may evolve into a promising candidate for mechanism-driven approaches to facilitate the translation of cell-based PAD therapy.
Cognitive engineering
Authors: Wilson Kyle M. , Helton William S. , Wiggins Mark W. 
Published: October 2012

AbstractCognitive engineering is the application of cognitive psychology and related disciplines to the design and operation of human–machine systems. Cognitive engineering combines both detailed and close study of the human worker in the actual work context and the study of the worker in more controlled environments. Cognitive engineering combines multiple methods and perspectives to achieve the goal of improved system performance. Given the origins of experimental psychology itself in issues regarding the design of human–machine systems, cognitive engineering is a core, or fundamental, discipline within academic psychology. WIREs Cogn Sci 2013, 4:17–31. doi: 10.1002/wcs.1204This article is categorized under:

Psychology > Reasoning and Decision Making
Species identification ofWickerhamomyces anomalusand related taxa usingβ‐tubulin(β‐tub) DNA barcode marker
Authors: Huang Chien‐Hsun , Chang Mu‐Tzu , Huang Lina 
Published: October 2012

AbstractWickerhamomyces anomalusis used in food and feed processing, although the species has been reported as an opportunistic human pathogen, predominantly in neonates. Neither phenotypic nor the most frequently applied genotypic marker (D1/D2 LSUribosomal DNA) provide sufficient resolution for accurate identification of this yeast. In this study, theβ‐tubulin gene was used for species identification by direct DNA sequencing and as marker in a species‐specific PCR assay. The results showed that all examinedW.anomalusstrains were clearly distinguished from the closely related species by comparative sequence analysis of theβ‐tubulin gene. In addition, the species‐specific primers were also developed based on theβ‐tubulin gene, which was employed for polymerase chain reaction with the template DNA ofWickerhamomycesstrains. A single 218 bp species‐specific band was found only inW.anomalus. Our data indicate that the phylogenetic relationships between these strains are easily resolved by sequencing of theβ‐tubulin gene and combined with species‐specific PCR assay. Copyright © 2012 John Wiley & Sons, Ltd.
Exoglucanase‐encoding genes from three Wickerhamomyces anomalus killer strains isolated from olive brine
Authors: Muccilli Serena , Wemhoff Sabrina , Restuccia Cristina , Meinhardt Friedhelm 
Published: October 2012

AbstractWickerhamomyces anomalus killer strains are important for fighting pathogenic yeasts and for controlling harmful yeasts and bacteria in the food industry. Targeted disruption of key genes in β‐glucan synthesis of a sensitive Saccharomyces cerevisiae strain conferred resistance to the toxins of W. anomalus strains BS91, BCA15 and BCU24 isolated from olive brine. Competitive inhibition of the killing activities by laminarin and pustulan refer to β‐1,3‐ and β‐1,6‐glucans as the main primary toxin targets. The extracellular exoglucanase‐encoding genes WaEXG1 and WaEXG2 from the three strains were sequenced and were found to display noticeable similarities to those from known potent W. anomalus killer strains. Accession Nos for WaEXG1 genes for the strains in brackets are JQ734563 (BS91), JQ734564 (BCA15) and JQ734565 (BCU24); for WaEXG2 genes JQ734566 (BS91), JQ734567 (BCA15) and JQ734568 (BCU24), respectively. Copyright © 2012 John Wiley & Sons, Ltd.
Minimally Invasive Partial Fasciectomy for Dupuytren's Contractures
Authors: Gelman Scott , Schlenker Robert , Bachoura Abdo , Jacoby Sidney M. , Lipman Jeffrey , Shin Eon K. , Culp Randall W. 
Published: October 2012

Background Numerous options exist for the treatment of Dupuytren's contracture. This study describes the technique and early results of partial fasciectomy through a mini-incision approach as an additional treatment option for Dupuytren's disease. Methods This procedure involves the excision of diseased Dupuytren's tissue with the use of multiple 1 cm transverse incisions. Patient demographics, digit involvement, the number of incisions required to release each digit, and complications were recorded for all patients. Range of motion data was obtained from a subgroup of patients that had at least 6 months of follow-up. A paired t test was used to compare preoperative and postoperative contracture. Results Sixty-seven patients underwent 75 procedures that involved 119 digits. The mean patient age at the time of surgery was 63 years (range, 33–95 years). A total of 32 digits (47 joints) were available for range of motion analysis. After a mean of 2.2 years following surgery, metacarpophalangeal joint contractures maintained correction (34° preoperatively, 19° postoperatively, p=0.008). After a mean postoperative duration of 2.0 years, proximal interphalangeal joint contractures trended worse than preoperative levels (39° preoperatively, 45° postoperatively, p=0.319). There was one major complication, which consisted of a nerve laceration that was identified and repaired intraoperatively. Conclusions Partial fasciectomy through the described mini-incision approach provides an additional surgical option for patients who desire a less invasive surgical procedure than traditional fascietomy. Although this procedure is safe and effective at achieving immediate cord release, maintenance of correction for proximal interphalangeal joint contractures remains problematic.
From west to east; experience with adapting a curriculum in evidence-based medicine
Authors: Widyahening Indah S. , Van der Heijden Geert J. M. G. , Moy Foong Ming , Van der Graaf Yolanda , Sastroasmoro Sudigdo , Bulgiba Awang 
Published: October 2012

Clinical epidemiology (CE) and evidence-based medicine (EBM) have become an important part of medical school curricula. This report describes the implementation and some preliminary outcomes of an integrated CE and EBM module in the Faculty of Medicine Universitas Indonesia (UI), Jakarta and in the University of Malaya (UM) in Kuala Lumpur. A CE and EBM module, originally developed at the University Medical Center Utrecht (UMCU), was adapted for implementation in Jakarta and Kuala Lumpur. Before the start of the module, UI and UM staff followed a training of teachers (TOT). Student competencies were assessed through pre and post multiple-choice knowledge tests, an oral and written structured evidence summary (evidence-based case report, EBCR) as well as a written exam. All students also filled in a module evaluation questionnaire. The TOT was well received by staff in Jakarta and Kuala Lumpur and after adaptation the CE and EBM modules were integrated in both medical schools. The pre-test results of UI and UM were significantly lower than those of UMCU students (p < 0.001). The post test results of UMCU students were comparable (p = 0.48) with UI, but significantly different (p < 0.001) from UM. Common problems for the modules in both UI and UM were limited access to literature and variability of the tutors’ skills. Adoption and integration of an existing Western CE-EBM teaching module into Asian medical curricula is feasible while learning outcomes obtained are quite similar.
GAP‐43 dependency defines distinct effects of netrin‐1 on cortical and spinal neurite outgrowth and directional guidance
Authors: Shen Yiping , Meiri Karina 
Published: October 2012

AbstractGrowth‐associated protein‐43 (GAP‐43) is a major nervous system protein whose phosphorylation by protein kinase C regulates growth cone responses to extracellular guidance cues via F‐actin. GAP‐43 is essential for axon pathfinding in both cortical afferents and efferents: when it is genetically deleted, somatosensory, auditory and visual somatotopic maps fail to form, and telencephalic commissural axons fail to cross the midline. Here we investigated whether the midline guidance cue netrin‐1 depends on GAP‐43 for its functions in neurite growth and guidance. We used 3‐dimensional collagen gel co‐cultures to show that both endogenous netrin‐1, expressed by the spinal cord floor plate, and recombinant netrin‐1, expressed by transfected COS7 cells, stimulate neurite outgrowth and chemotropic guidance of neocortical callosal axons. In contrast both were significantly inhibited in GAP‐43 (−/−) neocortical callosal axons, mimicking the in vivo phenotype. Conversely, neither netrin‐1‐stimulated neurite outgrowth nor guidance of dorsal spinal cord commissure axons were affected when GAP‐43 was absent, again consistent with in vivo phenotype but suggesting fundamental differences in how neocortical and spinal cord axons respond to netrin‐1. In addition, differences in GAP‐43 dependency also distinguished how ventrolateral cortical efferents respond to netrin‐1: in contrast to callosal neurites, in which netrin‐1 required GAP‐43 in order to stimulate both outgrowth and guidance, in ventrolateral efferents, netrin‐1 required GAP‐43 only to stimulate outgrowth, but not guidance. Moreover, netrin‐1 increased the numbers of both types of cortical, but not spinal neurites. The results demonstrate previously unappreciated diversity in how different classes of neurons respond to the same guidance cue.
LIGETI'S ‘LE GRAND MACABRE’: HOW HE SOLVED THE PROBLEM OF WRITING A MODERNIST OPERA
Authors: Searby Michael 
Published: October 2012

AbstractLigeti's Le Grand Macabre (1974–77) is one of the most successful operas of the 20th century in terms of the number of performances. Originally, Ligeti had intended to compose an ‘anti-opera’ in the manner of Kagel's Staatstheater, but changed his fundamental compositional approach during the process of composing the work. He realised that a more traditional opera with a clear narrative (unlike Kagel's avant-garde opera) was more suitable, and it therefore became necessary for him to transform his style to one in which the text was audible to an audience. As a result there is very little of his mature micropolyphonic technique in the resulting work, but rather there is an exploration of music from the past, and the use of parody. In composing his opera Ligeti revitalised his approach through a re-engagement with history, but combined with a modernist rigour; thus he was able to create a new and fruitful musical language, and to transform his compositional technique.
WALTON'S FINAL WORK: HARMONY AND THE ART OF (MAKE-BELIEVE) FUGUE
Authors: Rice Hugh Collins 
Published: October 2012

AbstractWalton's Prologo e Fantasia, written at the end of his life, is one of the few completed original works of his final decade. Undoubtedly flawed, it can be seen simply as an exemplar of Walton's failing creative powers and his sheer difficulty in writing any music at all. But it is also possible to discern in it continued experimentation with developing aspects of his language, especially seen in the context of his exploration of similar devices in preceding works. Analysis of his harmony shows development of greater ambiguity in a tonal context. And, while many of his other works contain significant fugal passages, particularly towards their conclusions, the use of a fuga finta here presents a different perspective on a typical Waltonian device. While the work does not stand alongside Walton's most important orchestral achievements, and performances will probably remain relatively few, it does nevertheless provide some interesting insights into the musical language of his post-war music.
Contrasting effects of associates and coordinates in children with and without language impairment: A picture–word interference study
Authors: BROOKS PATRICIA J. , SEIGER-GARDNER LIAT , SAILOR KEVIN 
Published: October 2012

ABSTRACTIn picture naming, semantic context words produce either facilitation or inhibition, depending on their relationship to the target-picture name. This study used the picture–word interference task to examine facilitative effects of associates (the word carrot paired with a picture of rabbit) and inhibitory effects of coordinates (mouse paired with a rabbit) in children and adults. Experiment 1 with adults (N = 44) documented robust associate and coordinate effects with either auditory or visual presentation of interfering words. Experiment 2 used auditory presentation of interfering words with children (N = 44, 6 years, 10 months to 11 years, half with typical development, half with specific language impairment). Children showed significant facilitation from associates but no reliable coordinate interference effect. The strength of the associative priming effect in children was correlated with their language abilities (Peabody Picture Vocabulary Test and Clinical Evaluation of Language Fundamentals scores). The results indicate the dominant role of association in facilitating word retrieval in speech production in children. In children with specific language impairment, lexical access gains weaker support from networks of associations in semantic memory.
Allegorical Erasmus: Bruno Maderna's Ritratto di Erasmo
Authors: Wetters Brent 
Published: October 2012

AbstractThis essay aims to find a unifying thread amid the eclectic works of Bruno Maderna, and also to situate his compositional philosophy in relation to his more famous colleagues of the Darmstadt Summer Courses. More than any of the other composers at Darmstadt, Maderna was committed to its ‘project’ and to the values it placed on musical discourse, in spite of the fact that he seemed to abstain from its often-heated polemics. In contrast to many of his colleagues, Maderna was not one to speak at length about his compositions, preferring to express himself through his music. However, one work – his 1969 radio documentary, Ritratto di Erasmo – makes a poignant statement both about his music and the post-war generation as a whole. By championing Erasmus's equivocation, the work reveals something of Maderna's relationship to the arguments at Darmstadt. Just as Erasmus was situated between Luther and the Catholic Church, Maderna seemed to sit silently in the middle, while the more ideologically inclined composers swarmed at the periphery.
Towards a multitudinous voice: Dario Fo's adaptation of L'Histoire du soldat
Authors: Casadei Delia , Carbotti Rossella 
Published: October 2012

AbstractDario Fo worked with La Scala only once, in 1978–79; the occasion was an adaptation of Ramuz and Stravinsky's L'Histoire du soldat (1918). This brief, pointedly anti-operatic work connected the dissident artist and a leading cultural institution at a time when both were re-evaluating their means of addressing the public. For Fo, as well as for the Italian Left at large, 1978 marked the ten-year anniversary of the 1968 riots and a time of deep doubt about the possibility of collective political action. For La Scala, 1978 was not only the tenth year under the bold musical directorship of Claudio Abbado, but also involved celebrations of the theatre's bicentenary. In this article we weave together the Left's crisis with a close reading of Fo's adaptation, using the notion of vocal address as an interpretative linchpin. By considering the myth of Risorgimento opera as vox populi, the figure of Stravinsky's songless soldier, the sound of babbling crowds and the recorded speaking voice of Antonio Negri, we offer a new exploration of the cross section of art and left-wing politics in the Italy of 1978.
Quality of life of community-based palliative care clients and their caregivers
Authors: Connell Tanya , Fernandez Ritin S. , Tran Duong , Griffiths Rhonda , Harlum Janeane , Agar Meera 
Published: October 2012

AbstractObjective:This study aimed to investigate health-related quality of life of palliative care (PC) clients and their caregivers, at baseline and follow-up, following a referral to a community PC service.Method:Quality of life of clients and their caregivers was respectively measured using the McGill Quality of Life instrument (MQoL) and the Caregiver Quality of Life Cancer Index (CQoLC) instruments. Participants were recruited from June 8 to October 27, 2006. This study was undertaken in one zone of an Area Health Service in New South Wales, which has a diverse socioeconomic population. The zone covers an area of 6237 km2 and is divided into five sectors, each with a PC service, all of which participated in this study.Results:Data were obtained from 49 clients and 43 caregivers at baseline, and 22 clients and 12 caregivers at 8 week follow-up. Twenty-one participants died and six moved out of the area during the study. At baseline, clients reported a low mean score for physical symptoms (3.3 ± 1.9) and a high score for support (8.7 ± 1.0). Caregivers scored a total CQoLC of 63.9 ± 21.4 and clients had a total QOL of 6.1 ± 1.3. At follow up, matched data for 22 clients and 13 caregivers demonstrated no statistical differences in quality of life.Significance of results:This study has provided evidence that health-related quality of life questionnaires show lower scores for physical health and higher scores for support, which can directly inform specific interventions targeted at the physical and support domains.
Setting priorities in and for end-of-life care: challenges in the application of economic evaluation
Authors: NORMAND CHARLES 
Published: October 2012

AbstractHealth technology assessment processes aim to provide evidence on the effectiveness and cost-effectiveness of different elements of health care to assist setting priorities. There is a risk that services that are difficult to evaluate, and for which there is limited evidence on cost-effectiveness, may lose out in the competition for resources to those with better evidence. It is argued here that end-of-life care provides particular challenges for evaluation. Outcomes are difficult to measure, can take place over short time scales, and services can be difficult to characterise as they are tailored to the specific needs of individuals. Tools commonly used to measure health care outcomes do not appear to discriminate well in the end-of-life care context. It is argued that the assumption that units of time of different quality of life can simply be added to assess the overall experience at the end of life may not apply, and that alternative perspectives, such as the Peak and End Rule, might offer useful perspectives.