bluuebunny/crossref_metadata_2025_split huggingface dataset:
Caspase-3 Modulates Regenerative Response After Stroke
Authors: Fan Wenying , Dai Yiqin , Xu Haochen , Zhu Ximin , Cai Ping , Wang Lixiang , Sun Chungang , Hu Changlong , Zheng Ping , Zhao Bing–Qiao 
Published: August 2013

Abstract
Stroke is a leading cause of long-lasting disability in humans. However, currently there are still no effective therapies available for promoting stroke recovery. Recent studies have shown that the adult brain has the capacity to regenerate neurons after stroke. Although this neurogenic response may be functionally important for brain repair after injury, the mechanisms underlying stroke-induced neurogenesis are not known. Caspase-3 is a major executioner and has been identified as a key mediator of neuronal death in the acute stage of stroke. Recently, however, accumulating data indicate that caspase-3 also participates in various biological processes that do not cause cell death. Here, we show that cleaved caspase-3 was increased in newborn neuronal precursor cells (NPCs) in the subventricular zone (SVZ) and the dentate gyrus during the period of stroke recovery, with no evidence of apoptosis. We observed that cleaved caspase-3 was expressed by NPCs and limited its self-renewal without triggering apoptosis in cultured NPCs from the SVZ of ischemic mice. Moreover, we revealed that caspase-3 negatively regulated the proliferation of NPCs through reducing the phosphorylation of Akt. Importantly, we demonstrated that peptide inhibition of caspase-3 activity significantly promoted the proliferation and migration of SVZ NPCs and resulted in a significant increase in subsequent neuronal regeneration and functional recovery after stroke. Together, our data identify a previously unknown caspase-3-dependent mechanism that constrains stroke-induced endogenous neurogenesis and should revitalize interest in targeting caspase-3 for treatment of stroke. Stem Cells 2014;32:473–486
Human Mesenchymal Stem Cell Microvesicles for Treatment of Escherichia coli Endotoxin-Induced Acute Lung Injury in Mice
Authors: Zhu Ying-gang , Feng Xiao-mei , Abbott Jason , Fang Xiao-hui , Hao Qi , Monsel Antoine , Qu Jie-ming , Matthay Michael A. , Lee Jae W. 
Published: August 2013

Abstract
We previously found that human mesenchymal stem cells (MSC) or its conditioned medium restored lung protein permeability and reduced alveolar inflammation following Escherichia coli endotoxin-induced acute lung injury (ALI) in an ex vivo perfused human lung in part through the secretion of soluble factors such as keratinocyte growth factor (KGF). Recently, MSC were found to release microvesicles (MVs) that were biologically active because of the presence of mRNA or miRNA with reparative properties. MVs are circular fragments of membrane released from the endosomal compartment as exosomes or shed from the surface membranes. These studies were designed to determine if MVs released by human bone marrow derived MSCs would be effective in restoring lung protein permeability and reducing inflammation in E. coli endotoxin-induced ALI in C57BL/6 mice. The intratracheal instillation of MVs improved several indices of ALI at 48 hours. Compared to endotoxin-injured mice, MVs reduced extravascular lung water by 43% and reduced total protein levels in the bronchoalveolar lavage (BAL) fluid by 35%, demonstrating a reduction in pulmonary edema and lung protein permeability. MVs also reduced the influx of neutrophils and macrophage inflammatory protein-2 levels in the BAL fluid by 73% and 49%, respectively, demonstrating a reduction in inflammation. KGF siRNA-pretreatment of MSC partially eliminated the therapeutic effects of MVs released by MSCs, suggesting that KGF protein expression was important for the underlying mechanism. In summary, human MSC-derived MVs were therapeutically effective following E. coli endotoxin-induced ALI in mice in part through the expression of KGF mRNA in the injured alveolus. Stem Cells 2014;32:116–125
Transplants of Adult Mesenchymal and Neural Stem Cells Provide Neuroprotection and Behavioral Sparing in a Transgenic Rat Model of Huntington’s Disease
Authors: Rossignol Julien , Fink Kyle , Davis Kendra , Clerc Steven , Crane Andrew , Matchynski Jessica , Lowrance Steven , Bombard Matthew , DeKorver Nicholas , Lescaudron Laurent , Dunbar Gary L. 
Published: August 2013

Abstract
Stem cells have gained significant interest as a potential treatment of neurodegenerative diseases, including Huntington’s disease (HD). One source of these cells is adult neural stem cells (aNSCs), which differentiate easily into neuronal lineages. However, these cells are vulnerable to immune responses following transplantation. Another source is bone-marrow-derived mesenchymal stem cells (MSCs), which release neurotrophic factors and anti-inflammatory cytokines following transplantation, and are less vulnerable to rejection. The goal of this study was to compare the efficacy of transplants of MSCs, aNSCs, or cotransplants of MSCs and aNSCs for reducing deficits in a transgenic rat model of HD. HD rats received intrastriatal transplantations of 400,000 MSCs, aNSCs, or a combination of MSCs/aNSCs, while wild-type and HD controls were given vehicle. Rats were tested on the rotarod over the course of 20 weeks. The results indicated that transplants of: (a) aNSCs produced a strong immune response and conferred short-term behavioral benefits; (b) MSCs elicited a relatively weak immune response, and provided a longer term behavioral benefit; and (c) combined MSCs and aNSCs conferred long-term behavioral benefits and increased survival of the transplanted aNSCs. The finding that cotransplanting MSCs with aNSCs can prolong aNSC survival and provide greater behavioral sparing than when the transplants contains only aNSCs suggests that MSCs are capable of creating a more suitable microenvironment for aNSC survival. This cotransplantation strategy may be useful as a future therapeutic option for treating HD, especially if long-term survival of differentiated cells proves to be critically important for preserving lasting functional outcomes. Stem Cells 2014;32:500–509
Wnt5a Regulates Hematopoietic Stem Cell Proliferation and Repopulation Through the Ryk Receptor
Authors: Povinelli Benjamin J. , Nemeth Michael J. 
Published: August 2013

AbstractProper regulation of the balance between hematopoietic stem cell (HSC) proliferation, self-renewal, and differentiation is necessary to maintain hematopoiesis throughout life. The Wnt family of ligands has been implicated as critical regulators of these processes through a network of signaling pathways. Previously, we have demonstrated that the Wnt5a ligand can induce HSC quiescence through a noncanonical Wnt pathway, resulting in an increased ability to reconstitute hematopoiesis. In this study, we tested the hypothesis that the Ryk protein, a Wnt ligand receptor that can bind the Wnt5a ligand, regulated the response of HSCs to Wnt5a. We observed that inhibiting Ryk blocked the ability of Wnt5a to induce HSC quiescence and enhance short-term and long-term hematopoietic repopulation. We found that Wnt5a suppressed production of reactive oxygen species, a known inducer of HSC proliferation. The ability of Wnt5a to inhibit ROS production was also regulated by Ryk. From these data, we propose that Wnt5a regulates HSC quiescence and hematopoietic repopulation through the Ryk receptor and that this process is mediated by suppression of reactive oxygen species. Stem Cells 2014;32:105–115
FGFR1 Signaling Stimulates Proliferation of Human Mesenchymal Stem Cells by Inhibiting the Cyclin-Dependent Kinase Inhibitors p21Waf1 and p27Kip1
Authors: Dombrowski Christian , Helledie Torben , Ling Ling , Grünert Martin , Canning Claire A. , Jones C. Michael , Hui James H. , Nurcombe Victor , van Wijnen Andre J. , Cool Simon M. 
Published: August 2013

Abstract
Signaling through fibroblast growth factor receptor one (FGFR1) is a known inducer of proliferation in both embryonic and human adult mesenchymal stem cells (hMSCs) and positively regulates maintenance of stem cell viability. Leveraging the mitogenic potential of FGF2/FGFR1 signaling in stem cells for therapeutic applications necessitates a mechanistic understanding of how this receptor stimulates cell cycle progression. Using small interfering RNA (siRNA) depletion, antibody-inhibition, and small molecule inhibition, we establish that FGFR1 activity is rate limiting for self-renewal of hMSCs. We show that FGFR1 promotes stem cell proliferation through multiple mechanisms that unite to antagonize cyclin-dependent kinase (CDK) inhibitors. FGFR1 not only stimulates c-Myc to suppress transcription of the CDK inhibitors p21Waf1 and p27Kip1, thus promoting cell cycle progression but also increases the activity of protein kinase B (AKT) and the level of S-phase kinase-associated protein 2 (Skp2), resulting in the nuclear exclusion and reduction of p21Waf1. The in vivo importance of FGFR1 signaling for the control of proliferation in mesenchymal progenitor populations is underscored by defects in ventral mesoderm formation during development upon inhibition of its signaling. Collectively, these studies demonstrate that FGFR1 signaling mediates the continuation of MSC growth and establishes a receptor target for enhancing the expansion of mesenchymal progenitors while maintaining their multilineage potential. Stem Cells 2013;31:2724–2736
The Emerging Role of SOX2 in Cell Proliferation and Survival and Its Crosstalk with Oncogenic Signaling in Lung Cancer
Authors: Chou Yu-Ting , Lee Chih-Chan , Hsiao Shih-Hsin , Lin Sey-En , Lin Sheng-Chieh , Chung Chih-Hung , Chung Chi-Hsiu , Kao Yu-Rong , Wang Yuan-Hung , Chen Chien-Tsun , Wei Yau-Huei , Wu Cheng-Wen 
Published: August 2013

Abstract
Tumor cells have long been observed to share several biological characteristics with normal stem/progenitor cells; however, the oncogenic mechanisms underlying the lung stem/progenitor cell signaling remain elusive. Here, we report that SOX2, a self-renewal factor in lung stem/progenitor cells, is highly expressed in a subclass of lung cancer cells, the proliferation, survival, and chemoresistance of which are dependent on SOX2 signaling. Overexpression of SOX2 promotes oncogenic phenotypes in lung cancer cells; knockdown of SOX2 attenuated cell proliferation. We observed that SOX2 increased the expression of epidermal growth factor receptor (EGFR), and EGFR activation further upregulated SOX2 levels, forming a positive feedback loop. SOX2 expression promoted chemoresistance, and silencing of SOX2 perturbed mitochondrial function, causing marked apoptosis and autophagy. SOX2 induced BCL2L1, the ectopic expression of which rescued the effects of SOX2 silencing on apoptosis, autophagy, and mitochondrial function. SOX2 promoted tumor formation, along with increased cell proliferation in a xenograft mouse model. SOX2 expression is associated with poor prognosis in lung cancer patients; moreover, SOX2, EGFR, and BCL2L1 expression levels were significantly correlated in lung tumors. Our findings support the emerging role of SOX2 in cell proliferation and survival by eliciting oncogenic EGFR and BCL2L1 signaling with potential applications as a prognosis marker and a therapeutic target in lung cancer. Stem Cells 2013;31:2607–2619
Invertebrate learning and cognition: relating phenomena to neural substrate
Authors: Perry Clint J , Barron Andrew B , Cheng Ken 
Published: August 2013

Diverse invertebrate species have been used for studies of learning and comparative cognition. Although we have gained invaluable information from this, in this study we argue that our approach to comparative learning research is rather deficient. Generally invertebrate learning research has focused mainly on arthropods, and most of that within the Hymenoptera and Diptera. Any true comparative analysis of the distribution of comparative cognitive abilities across phyla is hampered by this bias, and more fundamentally by a reporting bias toward positive results. To understand the limits of learning and cognition for a species, knowing what animals cannot do is at least as important as reporting what they can. Finally, much more effort needs to be focused on the neurobiological analysis of different types of learning to truly understand the differences and similarities of learning types. In this review, we first give a brief overview of the various forms of learning in invertebrates. We also suggest areas where further study is needed for a more comparative understanding of learning. Finally, using what is known of learning in honeybees and the well‐studied honeybee brain, we present a model of how various complex forms of learning may be accounted for with the same neural circuitry required for so‐called simple learning types. At the neurobiological level, different learning phenomena are unlikely to be independent, and without considering this it is very difficult to correctly interpret the phylogenetic distribution of learning and cognitive abilities.WIREs Cogn Sci2013, 4:561–582. doi: 10.1002/wcs.1248This article is categorized under:Psychology > Comparative PsychologyPsychology > Learning
Access to a Simulator is Not Enough: The Benefits of Virtual Reality Training Based on Peer‐Group‐Derived Benchmarks—A Randomized Controlled Trial
Authors: von Websky Martin W. , Raptis Dimitri A. , Vitz Martina , Rosenthal Rachel , Clavien P. A. , Hahnloser Dieter 
Published: August 2013

AbstractBackgroundVirtual reality (VR) simulators are widely used to familiarize surgical novices with laparoscopy, but VR training methods differ in efficacy. In the present trial, self‐controlled basic VR training (SC‐training) was tested against training based on peer‐group‐derived benchmarks (PGD‐training).MethodsFirst, novice laparoscopic residents were randomized into a SC group (n = 34), and a group using PGD‐benchmarks (n = 34) for basic laparoscopic training. After completing basic training, both groups performed 60 VR laparoscopic cholecystectomies for performance analysis. Primary endpoints were simulator metrics; secondary endpoints were program adherence, trainee motivation, and training efficacy.ResultsAltogether, 66 residents completed basic training, and 3,837 of 3,960 (96.8 %) cholecystectomies were available for analysis. Course adherence was good, with only two dropouts, both in the SC‐group. The PGD‐group spent more time and repetitions in basic training until the benchmarks were reached and subsequently showed better performance in the readout cholecystectomies: Median time (gallbladder extraction) showed significant differences of 520 s (IQR 354–738 s) in SC‐training versus 390 s (IQR 278–536 s) in the PGD‐group (p < 0.001) and 215 s (IQR 175–276 s) in experts, respectively. Path length of the right instrument also showed significant differences, again with the PGD‐training group being more efficient.ConclusionsBasic VR laparoscopic training based on PGD benchmarks with external assessment is superior to SC training, resulting in higher trainee motivation and better performance in simulated laparoscopic cholecystectomies. We recommend such a basic course based on PGD benchmarks before advancing to more elaborate VR training.
Completely Removing Solitary Intraductal Papillomas Using the Mammotome System Guided by Ultrasonography Is Feasible and Safe
Authors: Yi Wenjun , Xu Feng , Zou Qiongyan , Tang Zhonghua 
Published: August 2013

AbstractBackground
Because of the potential for an intraductal papilloma to progress to malignancy and the likelihood of detecting unexpected coexisting malignant disease, complete removal of the intraductal papilloma is safer than merely sampling it. The purpose of this study was to estimate the feasibility and safety of excising a solitary intraductal papilloma using the Mammotome system guided by ultrasonography (US).Methods
We retrospectively reviewed the clinical information of 136 patients who underwent excision of solitary intraductal papillomas using the 8‐gauge probe with the US‐guided Mammotome system between December 2005 and December 2011 at our institution. Their lesions had been suspected preoperatively or were occasionally diagnosed postoperatively.ResultsThere were no local recurrences during the follow‐up period. Of the patients who showed atypia and underwent re‐excision, only 2 (6.1 %) had local ductal atypia. The patients with atypia were significantly older than the patients without atypia (p < 0.05).ConclusionsUsing the US‐guided 8‐gauge probe Mammotome system to completely remove a solitary intraductal papilloma is feasible and safe. Close follow‐up may be considered for those whose lesions exhibit atypia.
Seating
Authors: Strobl Walter Michael 
Published: August 2013

Introduction Patients with neuromuscular disorders are not able to adapt their sitting posture continuously. Seating devices, like seating orthoses, braces, seating shells, and custom-made cushions for wheelchairs, however may improve their quality of life by stabilizing their pelvis and trunk. Sitting should be regarded as a dynamic process regulated by motor reactions of trunk and pelvic muscles due to endogenic and exogenic influences. Methods Prerequisites for the indication of high-quality and cost effective seating devices are guidelines for planning and fitting which consider both pathomorphologic mechanisms and the patient's personality. In order to avoid functional problems and pain caused by an insufficient seating device it is necessary to pay attention to the exact indication, time, and combination of technical options. Planning within a seating clinic needs teamwork. Primarily the goal of treatment is defined; it depends on the functional deficit, on the daily living activities of the patient, and on the social environmental factors. Secondly, fitting of the devices follows defined treatment guidelines. Conclusion By examination of the sensor and musculoskeletal system, it is possible to classify the patient's sitting or seating ability for simplifying indication: three groups of ACTIVE sitters who are able to change position of trunk and pelvis actively are differentiated from three groups of PASSIVE sitters who have to be seated.
Acne severity and the Global Acne Grading System in polycystic ovary syndrome
Authors: Hacivelioglu Servet , Gungor Ayse Nur Cakir , Gencer Meryem , Uysal Ahmet , Hizli Deniz , Koc Evrim , Cosar Emine 
Published: August 2013

AbstractObjectiveTo evaluate the association between acne, quantified by the Global Acne Grading System (GAGS), and abnormal clinical and laboratory markers of androgen excess in patients with polycystic ovary syndrome (PCOS).MethodsThe retrospective study included 133 patients with PCOS. Acne severity was quantified with the GAGS score, alopecia was graded with the Ludwig classification, and hirsutism was quantified with a modified Ferriman–Gallwey (FG) score.ResultsThe mean GAGS score was significantly greater in younger women, those with a lower BMI, and those with a higher FG score. There was no relation between the mean GAGS score and waist circumference, waist/hip ratio, androgen hormone levels (free testosterone, total testosterone, or dehydroepiandrosterone sulfate), sex‐hormone‐binding globulin level, or menstrual irregularity. Alopecia was significantly associated with an increased waist/hip ratio; there was no relation between alopecia and age, waist circumference, body mass index, FG score, androgen hormone levels, or menstrual irregularity. A weak positive correlation was observed between the GAGS and FG scores.ConclusionThe GAGS may provide more precise and comprehensive information about acne severity in obese or hirsute patients with PCOS because this grading system includes evaluation of the type (comedones, papules, pustules, nodules) and location (anatomic area) of acne lesions.
Quantitative proteomics analysis of varicose veins: Identification of a set of differentially expressed proteins related to ATP generation and utilization
Authors: Kuo Chao‐Jen , Liang Shih‐Shin , Hsi Edward , Chiou Shyh‐Horng , Lin Sin‐Daw 
Published: August 2013

AbstractAlthough morphological and anatomical studies indicate that varicose veins are characterized by venous wall weakening and subendothelial fibrosis, the exact underlying biochemical mechanism of their development remains unknown. Additionally, no quantitative proteomic study of venous proteins leading to decreased contractility of varicose veins has been reported to date. Therefore, to elucidate the molecular mechanism of altered vascular contractility, this study performed shotgun proteomic analysis to obtain protein expression profiles in patients with varicose veins. Stable isotope dimethyl labeling coupled with nanoLC‐MS/MS revealed downregulation in 12 polypeptides, including myosin light chain kinase, creatine kinase B‐type, ATP synthase, phosphoglycerate kinase, and pyruvate kinase. However, analyses of protein species associated with cytoskeletal assembly or with cellular morphology showed no clear up‐ or down‐regulation. These results indicate that defects in ATP generation and utilization may account for the dysfunction of vascular smooth muscle following formation of varicose veins. Collectively, the severity of varicose veins depends on the regulatory roles of various protein factors in the metabolic coordination of physiological functions. This pilot study improves understanding of the pathogenesis of varicose veins and lays the foundation for further validation and clinical translation of biomarkers for targeted therapies in treating this disease.
EBV‐encoded small RNA1 and nonresolving inflammation in rheumatoid arthritis
Authors: Chiu Wen‐Chan , Chen Ching‐Mei , Cheng Tien‐Tsai , You Huey‐Ling , Yu Shan‐Fu , Weng Lin‐Hsiu , Huang Hsuan‐Ying , Huang Chao‐Cheng , Chen Chung‐Jen 
Published: August 2013

AbstractRheumatoid arthritis (RA) is a chronic autoimmune disease characterized by perpetuated inflammation in multiple joints. To date, there is no cure for RA, and the causal factor for non‐resolving inflammation in RA remains unclear. In this study, we initially observed expression of Epstein–Barr virus‐encoded small RNA1 (EBER1) in the synovial tissue of all five patients who showed nonresolving RA inflammation. By contrast, EBER1 was detected in the synovial tissue of only one out of seven patients with advanced osteoarthritis (OA; p < 0.01, Fisher's exact test). To confirm this finding, we conducted a second study on synovial tissue samples taken from 23 patients with nonresolving RA inflammation and 13 patients with OA. All synovial samples from patients with nonresolving inflammation of RA showed positive expression of EBER1 (23/23, 100%), whereas none of the synovial samples from patients with OA showed expression of EBER1 (0/13, 0%; p < 0.001, by Fisher's exact test). In vitro, transfection of RA synovial fibroblasts with EBER1 induced the production of interleukin‐6. Taken together, these data strongly suggest that nonresolving RA inflammation is strongly related to the presence of EBER1, which might be, at least partially, responsible for synovial fibroblast interleukin‐6 production.