bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of an intensive exercise programme on leg function in chronic stroke patients: a pilot study with one-year follow-up
Authors: Stock Roland , Mork Paul Jarle 
Published: June 2009

Objective: To investigate the effect of two weeks of intensive exercise on leg function in chronic stroke patients and to evaluate the feasibility of an intensive exercise programme in a group setting. Design: Pilot study with one-group pre-test post-test design with two pre-tests and one-year follow-up. Setting: Inpatient rehabilitation hospital. Subjects: Twelve hemiparetic patients completed the intervention. Ten patients participated at one-year follow-up. Intervention: Six hours of daily intensive exercise for two weeks with focus on weight-shifting towards the affected side and increased use of the affected extremity during functional activities. An insole with nubs in the shoe of the non-paretic limb was used to reinforce weight-shift toward the affected side. Main measures: Timed Up and Go, Four Square Step Test, gait velocity, gait symmetry and muscle strength in knee and ankle muscles. Results: Maximal gait velocity (P = 0.002) and performance time (seconds) on Timed Up and Go (mean, SD; 12.2, 3.8 vs. 9.4, 3.2) and Four Square Step Test improved from pre- to post-test (P = 0.005). Improvements remained significant at follow-up. Preferred gait velocity and gait symmetry remained unchanged. Knee extensor (P<50.009) and flexor (P<50.001) strength increased bilaterally from pre- to post-test but only knee flexor strength remained significant at follow-up. Ankle dorsi flexor (P = 0.02) and plantar flexor (P<0.001) strength increased on paretic side only (not tested at follow-up). Conclusion: Intensive exercise for lower extremity is feasible in a group setting and was effective in improving ambulatory function, maximal gait velocity and muscle strength in chronic stroke patients. Most improvements persisted at the one-year follow-up.
Comparison of Landing Biomechanics Between Male and Female Professional Dancers
Authors: Orishimo Karl F. , Kremenic Ian J. , Pappas Evangelos , Hagins Marshall , Liederbach Marijeanne 
Published: June 2009

Background The incidence of anterior cruciate ligament injuries among dancers is much lower than that among team sport athletes and no clear gender disparity has been reported in the dance population. Although numerous studies have observed differences in lower extremity landing biomechanics between male and female athletes, there is currently little research examining the landing biomechanics of male and female dancers. Comparing landing biomechanics within this population may help explain the lower overall anterior cruciate ligament injury rates and the lack of gender disparity. Hypothesis Due to the fact that dancers receive jump-specific and balance-specific training from a very young age, we hypothesized that there would be no gender differences in drop-landing biomechanics in professional dancers. Study Design Controlled laboratory study. Methods Kinematics and ground-reaction forces were recorded as 33 professional modern and ballet dancers (12 men and 21 women) performed single-legged drop landings from a 30-cm platform. Joint kinematics and kinetics were compared between genders. Results No gender differences in joint kinematics or kinetics were found during landings (multivariate analysis of variance: P = .490 and P = .175, respectively). A significant relationship was found between the age at which the dancers began training and the peak hip adduction angle during landing ( r = .358, P = .041). Conclusion In executing a 30-cm drop landing, male and female dancers exhibited similar landing strategies and avoided landing patterns previously associated with increased injury rates. Clinical Relevance Commonly reported biomechanical differences between men and women, as well as the gender disparity among athletes in the incidence of ACL injuries, may be the result of inadequate experience in proper balance and landing technique rather than intrinsic gender factors. Beginning jump-specific and balance-specific training at an early age may counteract the potentially harmful adaptations in landing biomechanics observed in female athletes after maturity.
Sex hormones, acting on the TERT gene, increase telomerase activity in human primary hematopoietic cells
Authors: Calado Rodrigo T. , Yewdell William T. , Wilkerson Keisha L. , Regal Joshua A. , Kajigaya Sachiko , Stratakis Constantine A. , Young Neal S. 
Published: June 2009

Abstract
Androgens have been used in the treatment of bone marrow failure syndromes without a clear understanding of their mechanism of action. Blood counts of patients with dyskeratosis congenita or aplastic anemia with mutations in telomerase genes can improve with androgen therapy. Here we observed that exposure in vitro of normal peripheral blood lymphocytes and human bone marrow–derived CD34+ cells to androgens increased telomerase activity, coincident with higher TERT mRNA levels. Cells from patients who were heterozygous for telomerase mutations had low baseline telomerase activity, which was restored to normal levels by exposure to androgens. Estradiol had an effect similar to androgens on TERT gene expression and telomerase enzymatic activity. Tamoxifen abolished the effects of both estradiol and androgens on telomerase function, and letrozole, an aromatase inhibitor, blocked androgen effects on telomerase activity. Conversely, flutamide, an androgen receptor antagonist, did not affect androgen stimulation of telomerase. Down-regulation by siRNA of estrogen receptor-α (ERα), but not ERβ, inhibited estrogen-stimulated telomerase function. Our results provide a mechanism for androgen therapy in bone marrow failure: androgens appear to regulate telomerase expression and activity mainly by aromatization and through ERα. These findings have potential implications for the choice of current androgenic compounds and the development of future agents for clinical use.
BIO5192, a small molecule inhibitor of VLA-4, mobilizes hematopoietic stem and progenitor cells
Authors: Ramirez Pablo , Rettig Michael P. , Uy Geoffrey L. , Deych Elena , Holt Matthew S. , Ritchey Julie K. , DiPersio John F. 
Published: July 2009

Abstract
Here we show that interruption of the VCAM-1/VLA-4 axis with a small molecule inhibitor of VLA-4, BIO5192, results in a 30-fold increase in mobilization of murine hematopoietic stem and progenitors (HSPCs) over basal levels. An additive affect on HSPC mobilization (3-fold) was observed when plerixafor (AMD3100), a small molecule inhibitor of the CXCR-4/SDF-1 axis, was combined with BIO5192. Furthermore, the combination of granulocyte colony-stimulating factor (G-CSF), BIO5192, and plerixafor enhanced mobilization by 17-fold compared with G-CSF alone. HSPCs mobilized by BIO5192 or the combination of BIO5192 and plerixafor mobilized long-term repopulating cells, which successfully engraft and expand in a multilineage fashion in secondary transplantation recipients. Splenectomy resulted in a dramatic enhancement of G-CSF–induced mobilization while decreasing both plerixafor- and BIO5192-induced mobilization of HSPCs. These data provide evidence for the utility of small molecule inhibitors of VLA-4 either alone or in combination with G-CSF or AMD3100 for mobilization of hematopoietic stem and progenitor cells.
Programming tumor-reactive effector memory CD8+ T cells in vitro obviates the requirement for in vivo vaccination
Authors: Klebanoff Christopher A. , Yu Zhiya , Hwang Leroy N. , Palmer Douglas C. , Gattinoni Luca , Restifo Nicholas P. 
Published: June 2009

AbstractNaive and memory CD8+ T cells can undergo programmed activation and expansion in response to a short T-cell receptor stimulus, but the extent to which in vitro programming can qualitatively substitute for an in vivo antigen stimulation remains unknown. We show that self-/tumor-reactive effector memory CD8+ T cells (TEM) programmed in vitro either with peptide-pulsed antigen-presenting cells or plate-bound anti-CD3/anti-CD28 embark on a highly stereotyped response of in vivo clonal expansion and tumor destruction nearly identical to that of vaccine-stimulated TEM cells. This programmed response was associated with an interval of antigen-independent interferon-γ (IFN-γ) release that facilitated the dynamic expression of the major histocompatibility complex class I restriction element H-2Db on responding tumor cells, leading to recognition and subsequent tumor lysis. Delaying cell transfer for more than 24 hours after stimulation or infusion of cells deficient in IFN-γ entirely abrogated the benefit of the programmed response, whereas transfer of cells unable to respond to IFN-γ had no detriment to antitumor immunity. These findings extend the phenomenon of a programmable effector response to memory CD8+ T cells and have major implications for the design of current adoptive-cell transfer trials.
Long-term outcome of patients with chronic myeloid leukemia treated with second-generation tyrosine kinase inhibitors after imatinib failure is predicted by the in vitro sensitivity of BCR-ABL kinase domain mutations
Authors: Jabbour Elias , Jones Daniel , Kantarjian Hagop M. , O'Brien Susan , Tam Constantine , Koller Charles , Burger Jan A. , Borthakur Gautam , Wierda William G. , Cortes Jorge 
Published: July 2009

AbstractSecondary imatinib resistance in chronic myeloid leukemia (CML) is associated in approximately 50% of cases with mutations in the BCR-ABL kinase domain, necessitating switch to one of several new tyrosine kinase inhibitors (TKIs) that act differentially on mutated BCR-ABL. We assess here whether scoring mutation based on in vitro inhibitory concentration of each TKI-mutation pair can predict long-term clinical outcome. Among 169 patients with CML after imatinib failure, mutations were detected before TKI switch in 41 (48%) treated with dasatinib and 45 (52%) treated with nilotinib. Inhibitory concentration values for each TKI-mutation pair were stratified into high (n = 42), intermediate (n = 25), low (T315I, n = 9), or unknown sensitivity (n = 10). Hematologic and cytogenetic response rates were similar for patients with or without mutations. For patients in chronic phase, hematologic and cytogenetic responses correlated with mutation score; tumors with low and intermediate scores had lower response rates than those with highly sensitive mutations, and worse event-free and overall survival. These correlations with overall survival were not seen for advanced phases. Mutation scoring can predict outcome in CML-chronic phase with imatinib failure treated with second-generation TKIs and can help in therapy selection. More complex prognostic models will be required for advanced stages of disease.
Generation and phenotypic analysis of protein S–deficient mice
Authors: Saller François , Brisset Anne C. , Tchaikovski Svetlana N. , Azevedo Monica , Chrast Roman , Fernández José A. , Schapira Marc , Hackeng Tilman M. , Griffin John H. , Angelillo-Scherrer Anne 
Published: July 2009

AbstractProtein S (PS) is an important natural anticoagulant with potentially multiple biologic functions. To investigate further the role of PS in vivo, we generated Pros+/− heterozygous mice. In the null (−) allele, the Pros exons 3 to 7 have been excised through conditional gene targeting. Pros+/− mice did not present any signs of spontaneous thrombosis and had reduced PS plasma levels and activated protein C cofactor activity in plasma coagulation and thrombin generation assays. Tissue factor pathway inhibitor cofactor activity of PS could not be demonstrated. Heterozygous Pros+/− mice exhibited a notable thrombotic phenotype in vivo when challenged in a tissue factor–induced thromboembolism model. No viable Pros−/− mice were obtained through mating of Pros+/− parents. Most E17.5 Pros−/− embryos were found dead with severe intracranial hemorrhages and most likely presented consumptive coagulopathy, as demonstrated by intravascular and interstitial fibrin deposition and an increased number of megakaryocytes in the liver, suggesting peripheral thrombocytopenia. A few E17.5 Pros−/− embryos had less severe phenotype, indicating that life-threatening manifestations might occur between E17.5 and the full term. Thus, similar to human phenotypes, mild heterozygous PS deficiency in mice was associated with a thrombotic phenotype, whereas total homozygous deficiency in PS was incompatible with life.
Phylogeography of the Alcippe morrisonia(Aves: Timaliidae): long population history beyond late Pleistocene glaciations
Authors: Song Gang , Qu Yanhua , Yin Zuohua , Li Shouhsien , Liu Naifa , Lei Fumin 
Published: June 2009

AbstractBackgroundThe role of Pleistocene glacial oscillations in current biodiversity and distribution patterns varies with latitude, physical topology and population life history and has long been a topic of discussion. However, there had been little phylogeographical research in south China, where the geophysical complexity is associated with great biodiversity. A bird endemic in Southeast Asia, the Grey-cheeked Fulvetta,Alcippe morrisonia, has been reported to show deep genetic divergences among its seven subspecies. In the present study, we investigated the phylogeography ofA. morrisoniato explore its population structure and evolutionary history, in order to gain insight into the effect of geological events on the speciation and diversity of birds endemic in south China.ResultsMitochondrial genes cytochrome b (Cytb) and cytochrome c oxidase I (COI) were represented by 1236 nucleotide sites from 151 individuals from 29 localities. Phylogenetic analysis showed seven monophyletic clades congruent with the geographically separated groups, which were identified as major sources of molecular variance (90.92%) by AMOVA. TCS analysis revealed four disconnected networks, and that no haplotype was shared among the geographical groups. The common ancestor of these populations was dated to 11.6 Mya and several divergence events were estimated along the population evolutionary history. Isolation by distance was inferred by NCPA to be responsible for the current intra-population genetic pattern and gene flow among geographical groups was interrupted. A late Pleistocene demographic expansion was detected in the eastern geographical groups, while the expansion time (0.2–0.4 Mya) was earlier than the Last Glacial Maximum.ConclusionIt is proposed that the complicated topology preserves high genetic diversity and ancient lineages for geographical groups ofA. morrisoniain China mainland and its two major islands, and restricts gene exchange during climate oscillations. Isolation by distance seems to be an important factor of genetic structure formation within geographical populations. Although glacial influence to population fluctuation was observed in late Pleistocene, it seems that populations in eastern China were more susceptible to climate change, and all geographical groups were growing stably through the Last Glacial Maximum. Coalescence analysis suggested that the ancestor ofA. morrisoniamight be traced back to the late Miocene, and the current phylogeographical structure ofA. morrisoniais more likely to be attributable to a series geological events than to Pleistocene glacial cycles.
Integration of Bayesian molecular clock methods and fossil-based soft bounds reveals early Cenozoic origin of African lacertid lizards
Authors: Hipsley Christy A , Himmelmann Lin , Metzler Dirk , Müller Johannes 
Published: July 2009

Abstract

Background
Although current molecular clock methods offer greater flexibility in modelling evolutionary events, calibration of the clock with dates from the fossil record is still problematic for many groups. Here we implement several new approaches in molecular dating to estimate the evolutionary ages of Lacertidae, an Old World family of lizards with a poor fossil record and uncertain phylogeny. Four different models of rate variation are tested in a new program for Bayesian phylogenetic analysis called TreeTime, based on a combination of mitochondrial and nuclear gene sequences. We incorporate paleontological uncertainty into divergence estimates by expressing multiple calibration dates as a range of probabilistic distributions. We also test the reliability of our proposed calibrations by exploring effects of individual priors on posterior estimates.

Results
According to the most reliable model, as indicated by Bayes factor comparison, modern lacertids arose shortly after the K/T transition and entered Africa about 45 million years ago, with the majority of their African radiation occurring in the Eocene and Oligocene. Our findings indicate much earlier origins for these clades than previously reported, and we discuss our results in light of paleogeographic trends during the Cenozoic.

Conclusion
This study represents the first attempt to estimate evolutionary ages of a specific group of reptiles exhibiting uncertain phylogenetic relationships, molecular rate variation and a poor fossil record. Our results emphasize the sensitivity of molecular divergence dates to fossil calibrations, and support the use of combined molecular data sets and multiple, well-spaced dates from the fossil record as minimum node constraints. The bioinformatics program used here, TreeTime, is publicly available, and we recommend its use for molecular dating of taxa faced with similar challenges.
Discovery of novel inhibitors of Streptococcus pneumoniae based on the virtual screening with the homology-modeled structure of histidine kinase (VicK)
Authors: Li Nan , Wang Fei , Niu Siqiang , Cao Ju , Wu Kaifeng , Li Youqiang , Yin Nanlin , Zhang Xuemei , Zhu Weiliang , Yin Yibing 
Published: June 2009

Abstract

Background
Due to the widespread abusage of antibiotics, antibiotic-resistance in Streptococcus pneumoniae (S. pneumoniae) has been increasing quickly in recent years, and it is obviously urgent to develop new types of antibiotics. Two-component systems (TCSs) are the major signal transduction pathways in bacteria and have emerged as potential targets for antibacterial drugs. Among the 13 pairs of TCSs proteins presenting in S. pneumoniae, VicR/K is the unique one essential for bacterium growth, and block agents to which, if can be found, may be developed as effective antibiotics against S. pneumoniae infection.

Results
Using a structure-based virtual screening (SBVS) method, 105 compounds were computationally identified as potential inhibitors of the histidine kinase (HK) VicK protein from the compound library SPECS. Six of them were then validated in vitro to be active in inhibiting the growth of S. pneumoniae without obvious cytotoxicity to Vero cell. In mouse sepsis models, these compounds are still able to decrease the mortality of the mice infected by S. pneumoniae and one compound even has significant therapeutic effect.

Conclusion
To our knowledge, these compounds are the first reported inhibitors of HK with antibacterial activity in vitro and in vivo, and are novel lead structures for developing new drugs to combat pneumococcal infection.
Contextual blending of ingroup/outgroup face stimuli and word valence: LPP modulation and convergence of measures
Authors: Hurtado Esteban , Haye Andrés , González Ramiro , Manes Facundo , Ibáñez Agustiń 
Published: June 2009

Abstract

Background
Several event related potential (ERP) studies have investigated the time course of different aspects of evaluative processing in social bias research. Various reports suggest that the late positive potential (LPP) is modulated by basic evaluative processes, and some reports suggest that in-/outgroup relative position affects ERP responses. In order to study possible LPP blending between facial race processing and semantic valence (positive or negative words), we recorded ERPs while indigenous and non-indigenous participants who were matched by age and gender performed an implicit association test (IAT). The task involved categorizing faces (ingroup and outgroup) and words (positive and negative). Since our paradigm implies an evaluative task with positive and negative valence association, a frontal distribution of LPPs similar to that found in previous reports was expected. At the same time, we predicted that LPP valence lateralization would be modulated not only by positive/negative associations but also by particular combinations of valence, face stimuli and participant relative position.

Results
Results showed that, during an IAT, indigenous participants with greater behavioral ingroup bias displayed a frontal LPP that was modulated in terms of complex contextual associations involving ethnic group and valence. The LPP was lateralized to the right for negative valence stimuli and to the left for positive valence stimuli. This valence lateralization was influenced by the combination of valence and membership type relevant to compatibility with prejudice toward a minority. Behavioral data from the IAT and an explicit attitudes questionnaire were used to clarify this finding and showed that ingroup bias plays an important role. Both ingroup favoritism and indigenous/non-indigenous differences were consistently present in the data.

Conclusion
Our results suggest that frontal LPP is elicited by contextual blending of evaluative judgments of in-/outgroup information and positive vs. negative valence association and confirm recent research relating in-/outgroup ERP modulation and frontal LPP. LPP modulation may cohere with implicit measures of attitudes. The convergence of measures that were observed supports the idea that racial and valence evaluations are strongly influenced by context. This result adds to a growing set of evidence concerning contextual sensitivity of different measures of prejudice.
Phylogenetic analysis and molecular evolution of the dormancy associated MADS-box genes from peach
Authors: Jiménez Sergio , Lawton-Rauh Amy L , Reighard Gregory L , Abbott Albert G , Bielenberg Douglas G 
Published: June 2009

Abstract

Background
Dormancy associated MADS-box (DAM) genes are candidates for the regulation of growth cessation and terminal bud formation in peach. These genes are not expressed in the peach mutant evergrowing, which fails to cease growth and enter dormancy under dormancy-inducing conditions. We analyzed the phylogenetic relationships among and the rates and patterns of molecular evolution within DAM genes in the phylogenetic context of the MADS-box gene family.

Results
The peach DAM genes grouped with the SVP/StMADS11 lineage of type II MIKCC MADS-box genes. Phylogenetic analyses suggest that the peach SVP/StMADS11-like gene family, which contains significantly more members than annual model plants, expanded through serial tandem gene duplication. We found evidence of strong purifying selection acting to constrain functional divergence among the peach DAM genes and only a single codon, located in the C-terminal region, under significant positive selection.

Conclusion
Because all DAM genes are expressed in peach and are subjected to strong purifying selection we suggest that the duplicated genes have been maintained by subfunctionalization and/or neofunctionalization. In addition, this pattern of selection suggests that the DAM genes are important for peach growth and development.