bluuebunny/crossref_metadata_2025_split huggingface dataset:
The response of early neural genes to FGF signaling or inhibition of BMP indicate the absence of a conserved neural induction module
Authors: Rogers Crystal D , Ferzli George S , Casey Elena S 
Published: December 2011

Abstract

Background
The molecular mechanism that initiates the formation of the vertebrate central nervous system has long been debated. Studies in Xenopus and mouse demonstrate that inhibition of BMP signaling is sufficient to induce neural tissue in explants or ES cells respectively, whereas studies in chick argue that instructive FGF signaling is also required for the expression of neural genes. Although additional signals may be involved in neural induction and patterning, here we focus on the roles of BMP inhibition and FGF8a.

Results
To address the question of necessity and sufficiency of BMP inhibition and FGF signaling, we compared the temporal expression of the five earliest genes expressed in the neuroectoderm and determined their requirements for induction at the onset of neural plate formation in Xenopus. Our results demonstrate that the onset and peak of expression of the genes vary and that they have different regulatory requirements and are therefore unlikely to share a conserved neural induction regulatory module. Even though all require inhibition of BMP for expression, some also require FGF signaling; expression of the early-onset pan-neural genes sox2 and foxd5α requires FGF signaling while other early genes, sox3, geminin and zicr1 are induced by BMP inhibition alone.

Conclusions
We demonstrate that BMP inhibition and FGF signaling induce neural genes independently of each other. Together our data indicate that although the spatiotemporal expression patterns of early neural genes are similar, the mechanisms involved in their expression are distinct and there are different signaling requirements for the expression of each gene.
The mosquito Aedes aegypti has a large genome size and high transposable element load but contains a low proportion of transposon-specific piRNAs
Authors: Arensburger Peter , Hice Robert H , Wright Jennifer A , Craig Nancy L , Atkinson Peter W 
Published: December 2011

Abstract

Background
The piRNA pathway has been shown in model organisms to be involved in silencing of transposons thereby providing genome stability. In D. melanogaster the majority of piRNAs map to these sequences. The medically important mosquito species Aedes aegypti has a large genome size, a high transposon load which includes Miniature Inverted repeat Transposable Elements (MITES) and an expansion of the piRNA biogenesis genes. Studies of transgenic lines of Ae. aegypti have indicated that introduced transposons are poorly remobilized and we sought to explore the basis of this. We wished to analyze the piRNA profile of Ae. aegypti and thereby determine if it is responsible for transposon silencing in this mosquito.

Results
Estimated piRNA sequence diversity was comparable between Ae. aegypti and D. melanogaster, but surprisingly only 19% of mosquito piRNAs mapped to transposons compared to 51% for D. melanogaster. Ae. aegypti piRNA clusters made up a larger percentage of the total genome than those of D. melanogaster but did not contain significantly higher percentages of transposon derived sequences than other regions of the genome. Ae. aegypti contains a number of protein coding genes that may be sources of piRNA biogenesis with two, traffic jam and maelstrom, implicated in this process in model organisms. Several genes of viral origin were also targeted by piRNAs. Examination of six mosquito libraries that had previously been transformed with transposon derived sequence revealed that new piRNA sequences had been generated to the transformed sequences, suggesting that they may have stimulated a transposon inactivation mechanism.

Conclusions

Ae. aegypti has a large piRNA complement that maps to transposons but primarily gene sequences, including many viral-derived sequences. This, together the more uniform distribution of piRNA clusters throughout its genome, suggest that some aspects of the piRNA system differ between Ae. aegypti and D. melanogaster.
Development and characterization of a novel C-terminal inhibitor of Hsp90 in androgen dependent and independent prostate cancer cells
Authors: Eskew Jeffery D , Sadikot Takrima , Morales Pedro , Duren Alicia , Dunwiddie Irene , Swink Megan , Zhang Xiaoying , Hembruff Stacey , Donnelly Alison , Rajewski Roger A , Blagg Brian SJ , Manjarrez Jacob R , Matts Robert L , Holzbeierlein Jeffrey M , Vielhauer George A 
Published: December 2011

Abstract

Background
The molecular chaperone, heat shock protein 90 (Hsp90) has been shown to be overexpressed in a number of cancers, including prostate cancer, making it an important target for drug discovery. Unfortunately, results with N-terminal inhibitors from initial clinical trials have been disappointing, as toxicity and resistance resulting from induction of the heat shock response (HSR) has led to both scheduling and administration concerns. Therefore, Hsp90 inhibitors that do not induce the heat shock response represent a promising new direction for the treatment of prostate cancer. Herein, the development of a C-terminal Hsp90 inhibitor, KU174, is described, which demonstrates anti-cancer activity in prostate cancer cells in the absence of a HSR and describe a novel approach to characterize Hsp90 inhibition in cancer cells.

Methods
PC3-MM2 and LNCaP-LN3 cells were used in both direct and indirect in vitro Hsp90 inhibition assays (DARTS, Surface Plasmon Resonance, co-immunoprecipitation, luciferase, Western blot, anti-proliferative, cytotoxicity and size exclusion chromatography) to characterize the effects of KU174 in prostate cancer cells. Pilot in vivo efficacy studies were also conducted with KU174 in PC3-MM2 xenograft studies.

Results
KU174 exhibits robust anti-proliferative and cytotoxic activity along with client protein degradation and disruption of Hsp90 native complexes without induction of a HSR. Furthermore, KU174 demonstrates direct binding to the Hsp90 protein and Hsp90 complexes in cancer cells. In addition, in pilot in-vivo proof-of-concept studies KU174 demonstrates efficacy at 75 mg/kg in a PC3-MM2 rat tumor model.

Conclusions
Overall, these findings suggest C-terminal Hsp90 inhibitors have potential as therapeutic agents for the treatment of prostate cancer.
Production in yeast of pseudotype virus-like particles harboring functionally active antibody fragments neutralizing the cytolytic activity of vaginolysin
Authors: Pleckaityte Milda , Zvirbliene Aurelija , Sezaite Indre , Gedvilaite Alma 
Published: December 2011

AbstractBackgroundRecombinant antibodies can be produced in different formats and different expression systems. Single chain variable fragments (scFvs) represent an attractive alternative to full-length antibodies and they can be easily produced in bacteria or yeast. However, the scFvs exhibit monovalent antigen-binding properties and short serum half-lives. The stability and avidity of the scFvs can be improved by their multimerization or fusion with IgG Fc domain. The aim of the current study was to investigate the possibilities to produce in yeast high-affinity scFv-Fc proteins neutralizing the cytolytic activity of vaginolysin (VLY), the main virulence factor ofGardnerella vaginalis.ResultsThe scFv protein derived from hybridoma cell line producing high-affinity neutralizing antibodies against VLY was fused with human IgG1 Fc domain. Four different variants of anti-VLY scFv-Fc fusion proteins were constructed and produced in yeastSaccharomyces cerevisiae. The non-tagged scFv-Fc and hexahistidine-tagged scFv-Fc proteins were found predominantly as insoluble aggregates and therefore were not suitable for further purification and activity testing. The addition of yeast α-factor signal sequence did not support secretion of anti-VLY scFv-Fc but increased the amount of its intracellular soluble form. However, the purified protein showed a weak VLY-neutralizing capability. In contrast, the fusion of anti-VLY scFv-Fc molecules with hamster polyomavirus-derived VP2 protein and its co-expression with VP1 protein resulted in an effective production of pseudotype virus-like particles (VLPs) that exhibited strong VLY-binding activity. Recombinant scFv-Fc molecules displayed on the surface of VLPs neutralized VLY-mediated lysis of human erythrocytes and HeLa cells with high potency comparable to that of full-length antibody.ConclusionsRecombinant scFv-Fc proteins were expressed in yeast with low efficiency. New approach to display the scFv-Fc molecules on the surface of pseudotype VLPs was successful and allowed generation of multivalent scFv-Fc proteins with high VLY-neutralizing potency. Our study demonstrated for the first time that large recombinant antibody molecule fused with hamster polyomavirus VP2 protein and co-expressed with VP1 protein in the form of pseudotype VLPs was properly folded and exhibited strong antigen-binding activity. The current study broadens the potential of recombinant VLPs as a highly efficient carrier for functionally active complex proteins.
Granulocyte colony-stimulating factor affects the distribution and clonality of TRGV and TRDV repertoire of T cells and graft-versus-host disease
Authors: Xuan Li , Wu Xiuli , Zhang Yu , Fan Zhiping , Ling Yiwen , Huang Fen , Zhang Fuhua , Zhai Xiao , Liu Qifa 
Published: December 2011

AbstractBackgroundThe immune modulatory effect of granulocyte colony-stimulating factor (G-CSF) on T cells resulted in an unexpected low incidence of graft-versus-host disease (GVHD) in allogeneic peripheral blood stem cell transplantation (allo-PBSCT). Recent data indicated that gamma delta+T cells might participate in mediating graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effect after allogeneic hematopoietic stem cell transplantation. However, whether G-CSF could influence the T cell receptors (TCR) of gamma delta+T cells (TRGVandTRDVrepertoire) remains unclear. To further characterize this feature, we compared the distribution and clonality ofTRGVandTRDVrepertoire of T cells before and after G-CSF mobilization and investigated the association between the changes of TCR repertoire and GVHD in patients undergoing G-CSF mobilized allo-PBSCT.MethodsThe complementarity-determining region 3 (CDR3) sizes of threeTRGVand eightTRDVsubfamily genes were analyzed in peripheral blood mononuclear cells (PBMCs) from 20 donors before and after G-CSF mobilization, using RT-PCR and genescan technique. To determine the expression levels ofTRGVsubfamily genes, we performed quantitative analysis ofTRGVI~III subfamilies by real-time PCR.ResultsThe expression levels of threeTRGVsubfamilies were significantly decreased after G-CSF mobilization (P= 0.015, 0.009 and 0.006, respectively). The pattern ofTRGVsubfamily expression levels wasTRGVII >TRGVI >TRGVIII before mobilization, and changed toTRGVI >TRGVII >TRGVIII after G-CSF mobilization. The expression frequencies ofTRGVandTRDVsubfamilies changed at different levels after G-CSF mobilization. MostTRGVandTRDVsubfamilies revealed polyclonality from pre-G-CSF-mobilized and G-CSF-mobilized samples. Oligoclonality was detected inTRGVandTRDVsubfamilies in 3 donors before mobilization and in another 4 donors after G-CSF mobilization, distributed inTRGVII,TRDV1,TRDV3 andTRDV6, respectively. Significant positive association was observed between the invariable clonality ofTRDV1 gene repertoire after G-CSF mobilization and low incidence of GVHD in recipients (P= 0.015,OR= 0.047).ConclusionsG-CSF mobilization not only influences the distribution and expression levels ofTRGVandTRDVrepertoire, but also changes the clonality of gamma delta+T cells. This alteration ofTRGVandTRDVrepertoire might play a role in mediating GVHD in G-CSF mobilized allo-PBSCT.
HIV-1 and IL-1β regulate astrocytic CD38 through mitogen-activated protein kinases and nuclear factor-κB signaling mechanisms
Authors: Mamik Manmeet K , Banerjee Sugato , Walseth Timothy F , Hirte Renee , Tang Lin , Borgmann Kathleen , Ghorpade Anuja 
Published: December 2011

AbstractBackgroundInfection with human immunodeficiency virus type-1 (HIV)-1 leads to some form of HIV-1-associated neurocognitive disorders (HAND) in approximately half of the cases. The mechanisms by which astrocytes contribute to HIV-1-associated dementia (HAD), the most severe form of HAND, still remain unresolved. HIV-1-encephalitis (HIVE), a pathological correlate of HAD, affects an estimated 9-11% of the HIV-1-infected population. Our laboratory has previously demonstrated that HIVE brain tissues show significant upregulation of CD38, an enzyme involved in calcium signaling, in astrocytes. We also reported an increase in CD38 expression in interleukin (IL)-1β-activated astrocytes. In the present investigation, we studied regulatory mechanisms of CD38 gene expression in astrocytes activated with HIV-1-relevant stimuli. We also investigated the role of mitogen-activated protein kinases (MAPKs) and nuclear factor (NF)-κB in astrocyte CD38 regulation.MethodsCultured human astrocytes were transfected with HIV-1YU-2proviral clone and levels of CD38 mRNA and protein were measured by real-time PCR gene expression assay, western blot analysis and immunostaining. Astrocyte activation by viral transfection was determined by analyzing proinflammatory chemokine levels using ELISA. To evaluate the roles of MAPKs and NF-κB in CD38 regulation, astrocytes were treated with MAPK inhibitors (SB203580, SP600125, U0126), NF-κB interfering peptide (SN50) or transfected with dominant negative IκBα mutant (IκBαM) prior to IL-1β activation. CD38 gene expression and CD38 ADP-ribosyl cyclase activity assays were performed to analyze alterations in CD38 levels and function, respectively.ResultsHIV-1YU-2-transfection significantly increased CD38 mRNA and protein expression in astrocytes (p < 0.01) in a dose-dependent manner and induced astrocyte activation. IL-β-activation of HIV-1YU-2-transfected astrocytes significantly increased HIV-1 gene expression (p < 0.001). Treatment with MAPK inhibitors or NF-κB inhibitor SN50 abrogated IL-1β-induced CD38 expression and activity in astrocytes without altering basal CD38 levels (p < 0.001). IκBαM transfection also significantly inhibited IL-1β-mediated increases in CD38 expression and activity in astrocytes (p < 0.001).ConclusionThe present findings demonstrate a direct involvement of HIV-1 and virus-induced proinflammatory stimuli in regulating astrocyte-CD38 levels. HIV-1YU-2-transfection effectively induced HIV-1p24 protein expression and activated astrocytes to upregulate CCL2, CXCL8 and CD38. In astrocytes, IL-1β-induced increases in CD38 levels were regulated through the MAPK signaling pathway and by the transcription factor NF-κB. Future studies may be directed towards understanding the role of CD38 in response to infection and thus its role in HAND.
Effects of Sound on Postural Stability during Quiet Standing
Authors: Park Sung Ha , Lee Kichol , Lockhart Thurmon , Kim Sukwon 
Published: December 2011

Abstract
Loss of postural stability can increase the likelihood of slips and falls in workplaces. The present study intended to extend understanding of the effects of frequency and pressure level of sound on postural stability during standing. Eleven male subjects participated. Standing on a force platform, the subjects' center of pressures were measured under different combinations of pressure level and frequency of the sound. Variables such as the position variability of COP and the length of postural sway path in anterior-posterior (AP) and medio-lateral (ML) direction were evaluated. Subjective ratings of perceived disturbance at each experimental condition were also obtained using a 7-point rating scale. Results showed that the length of sway path and the position variability of COP increased as the frequency of sound increased in posterior-anterior axis. The effect of sound pressure level, however, was not significant on both the postural sway length and the position variability of COP. These results suggested substantial disturbance of standing balance system among subjects exposed to high frequency noise. The results implied that physical workers should be alerted that their abilities of postural balance could be degraded significantly as disturbance caused by a sound existed.
Prevalence of porcine circovirus-like agent P1 in Jiangsu, China
Authors: Wen Libin , He Kongwang , Yang Hanchun , Yu Zhengyu , Mao Aihua , Zhong Shulin , Ni Yanxiu , Zhang Xuehan , Li Bin , Wang Xiaomin , Zhou Junming , Guo Rongli , Lv Lixin , Jiang Jieyuan 
Published: December 2011

Abstract
Recently, we identified a novel porcine circovirus type 2-like agent P1 isolate from swine. The present study represents the first survey of P1 prevalence in swine herds from Jiangsu, China, by using PCR targeting the complete genome of P1. Prevalences of 50% and 19% were found among 6 herds and 248 animals, respectively. The results indicate a high prevalence of P1 in China pig populations.
Histopathological investigation in porcine infected with torque teno sus virus type 2 by inoculation
Authors: Mei Miao , Zhu Ling , Wang Yun , Xu Zhiwen , Zhao Ling , Peng Xi , Wu Yunfei , Li Song , Guo Wanzhu 
Published: December 2011

Abstract

Background
Porcine torque teno sus virus (TTSuV) is a small icosahedral and non-enveloped virus which contains a single-stranded (ssDNA), circular and negative DNA genome and infects mainly vertebrates and is currently classified into the 'floating' genus Anellovirus of Circoviridae with two species. Viral DNA of both porcine TTSuV species has a high prevalence in both healthy and diseased pigs worldwide and multiple infections of TTSuV with distinct genotypes or subtypes of the same species has been documented in the United States, Europe and Asia. However, there exists no information about histopathological lesions caused by infection with porcine TTSuV2.

Methods
Porcine liver tissue homogenate with 1 ml of 6.91 × 107genomic copies viral loads of porcine TTSuV2 that had positive result for torque teno sus virus type 2 and negative result for torque teno sus virus type 1 and porcine pseudorabies virus type 2 were used to inoculate specific pathogen-free piglets by intramuscular route and humanely killed at 3,7,10,14,17,21 and 24 days post inoculation (dpi), the control pigs were injected intramuscularly with 1 ml of sterile DMEM and humanely killed the end of the study for histopathological examination routinely processed, respectively.

Results
All porcine TTSuV2 inoculated piglets were clinic asymptomatic but developed myocardial fibroklasts and endocardium, interstitial pneumonia, membranous glomerular nephropathy, and modest inflammatory cells infiltration in portal areas in the liver, foci of hemorrhage in some pancreas islet, a tiny amount red blood cells in venule of muscularis mucosae and outer longitudinal muscle, rarely red blood cells in the microvasculation and infiltration of inflammatory cells (lymphocytes and eosinophils) of tonsil and hilar lymph nodes, infiltration of inflammatory lymphocytes and necrosis or degeneration and focal gliosis of lymphocytes in the paracortical zone after inoculation with porcine TTSuV2-containing tissue homogenate.

Conclusions
Analysis of these presentations revealed that porcine TTSuV2 was readily transmitted to TTSuV-negative swine and that infection was associated with characteristic pathologic changes in specific pathogen-free piglets inoculated with porcine TTSuV2. Those results indicated no markedly histopathological changes happened in those parenchymatous organs, especially the digestive system and immune system when the specific pathogen-free pigs were infected with porcine TTSuV2, hence, to some extent, it was not remarkable pathological agent for domestic pigs at least. So, porcine TTSuV2 could be an unrecognized pathogenic viral infectious etiology of swine. This study indicated a directly related description of lesions responsible for TTSuV2 infection in swine.
Reproducible computational biology experiments with SED-ML - The Simulation Experiment Description Markup Language
Authors: Waltemath Dagmar , Adams Richard , Bergmann Frank T , Hucka Michael , Kolpakov Fedor , Miller Andrew K , Moraru Ion I , Nickerson David , Sahle Sven , Snoep Jacky L , Le Novère Nicolas 
Published: December 2011

Abstract

Background
The increasing use of computational simulation experiments to inform modern biological research creates new challenges to annotate, archive, share and reproduce such experiments. The recently published Minimum Information About a Simulation Experiment (MIASE) proposes a minimal set of information that should be provided to allow the reproduction of simulation experiments among users and software tools.

Results
In this article, we present the Simulation Experiment Description Markup Language (SED-ML). SED-ML encodes in a computer-readable exchange format the information required by MIASE to enable reproduction of simulation experiments. It has been developed as a community project and it is defined in a detailed technical specification and additionally provides an XML schema. The version of SED-ML described in this publication is Level 1 Version 1. It covers the description of the most frequent type of simulation experiments in the area, namely time course simulations. SED-ML documents specify which models to use in an experiment, modifications to apply on the models before using them, which simulation procedures to run on each model, what analysis results to output, and how the results should be presented. These descriptions are independent of the underlying model implementation. SED-ML is a software-independent format for encoding the description of simulation experiments; it is not specific to particular simulation tools. Here, we demonstrate that with the growing software support for SED-ML we can effectively exchange executable simulation descriptions.

Conclusions
With SED-ML, software can exchange simulation experiment descriptions, enabling the validation and reuse of simulation experiments in different tools. Authors of papers reporting simulation experiments can make their simulation protocols available for other scientists to reproduce the results. Because SED-ML is agnostic about exact modeling language(s) used, experiments covering models from different fields of research can be accurately described and combined.