bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepatitis B Virus (HBV) Surface Antigen Interacts with and Promotes Cyclophilin A Secretion: Possible Link to Pathogenesis of HBV Infection
Authors: Tian Xiaochen , Zhao Chao , Zhu Hongguang , She Weimin , Zhang Jiming , Liu Jing , Li Lanjuan , Zheng Shusen , Wen Yu-Mei , Xie Youhua 
Published: January 2010

ABSTRACT

Cyclophilin A (CypA), predominantly located intracellularly, is a multifunctional protein. We previously reported decreased CypA levels in hepatocytes of transgenic mice expressing hepatitis B virus (HBV) surface antigen (HBsAg). In this study, we found that expression of HBV small surface protein (SHBs) in human hepatoma cell lines specifically triggered CypA secretion, whereas SHBs added extracellularly to culture medium did not. Moreover, CypA secretion was not promoted by the expression of a secretion deficient SHBs mutant, suggesting a close association between secretion of CypA and SHBs. Interaction between CypA and SHBs was observed by using coimmunoprecipitation and glutathione
S
-transferase pull-down assays. Hydrodynamic injection of the SHBs expression construct into C57BL/6J mice resulted in increased serum CypA levels and ALT/AST levels, as well as the infiltration of inflammatory cells surrounding SHBs-positive hepatocytes. The inflammatory response and serum ALT/AST level were reduced when the chemotactic effect of CypA was inhibited by cyclosporine and anti-CD147 antibody. Furthermore, higher serum CypA levels were detected in chronic hepatitis B patients than in healthy individuals. In HBV patients who had received liver transplantation, serum CypA levels declined dramatically after the loss of HBsAg as a consequence of liver transplantation. Taken together, these results indicate that expression and secretion of SHBs can promote CypA secretion, which may contribute to the pathogenesis of HBV infection.
HIV-1 Vpr Induces the K48-Linked Polyubiquitination and Proteasomal Degradation of Target Cellular Proteins To Activate ATR and Promote G
2
Arrest
Authors: Belzile Jean-Philippe , Richard Jonathan , Rougeau Nicole , Xiao Yong , Cohen Éric A. 
Published: January 2010

ABSTRACT

HIV-1 viral protein R (Vpr) induces cell cycle arrest at the G
2
/M phase by a mechanism involving the activation of the DNA damage sensor ATR. We and others recently showed that Vpr performs this function by subverting the activity of the DDB1-CUL4A (VPRBP) E3 ubiquitin ligase. Vpr could thus act as a connector between the E3 ligase and an unknown cellular factor whose ubiquitination would induce G
2
arrest. While attractive, this model is based solely on the indirect observation that some mutants of Vpr retain their interaction with the E3 ligase but fail to induce G
2
arrest. Using a tandem affinity purification approach, we observed that Vpr interacts with ubiquitinated cellular proteins and that this association requires the recruitment of an active E3 ligase given that the depletion of VPRBP by RNA interference or the overexpression of a dominant negative mutant of CUL4A decreased this association. Importantly, G
2
-arrest-defective mutants of Vpr in the C-terminal putative substrate-interacting domain displayed a decreased association with ubiquitinated proteins. We also found that the inhibition of proteasomal activity increased this association and that the ubiquitin chains were at least in part constituted of classical K48 linkages. Interestingly, the inhibition of K48 polyubiquitination specifically impaired the Vpr-induced phosphorylation of H2AX, an early target of ATR, but did not affect UV-induced H2AX phosphorylation. Overall, our results provide direct evidence that the association of Vpr with the DDB1-CUL4A (VPRBP) E3 ubiquitin ligase induces the K48-linked polyubiquitination of as-yet-unknown cellular proteins, resulting in their proteasomal degradation and ultimately leading to the activation of ATR and G
2
arrest.
Virological Synapse-Mediated Spread of Human Immunodeficiency Virus Type 1 between T Cells Is Sensitive to Entry Inhibition
Authors: Martin Nicola , Welsch Sonja , Jolly Clare , Briggs John A. G. , Vaux David , Sattentau Quentin J. 
Published: January 2010

ABSTRACT

Human immunodeficiency virus type 1 (HIV-1) can disseminate between CD4
+
T cells via diffusion-limited cell-free viral spread or by directed cell-cell transfer using virally induced structures termed virological synapses. Although T-cell virological synapses have been well characterized, it is unclear whether this mode of viral spread is susceptible to inhibition by neutralizing antibodies and entry inhibitors. We show here that both cell-cell and cell-free viral spread are equivalently sensitive to entry inhibition. Fluorescence imaging analysis measuring virological synapse lifetimes and inhibitor time-of-addition studies implied that inhibitors can access preformed virological synapses and interfere with HIV-1 cell-cell infection. This concept was supported by electron tomography that revealed the T-cell virological synapse to be a relatively permeable structure. Virological synapse-mediated HIV-1 spread is thus efficient but is not an immune or entry inhibitor evasion mechanism, a result that is encouraging for vaccine and drug design.
Resistance of simple plant root systems to uplift loads
Authors: Mickovski S. B. , Bransby M. F. , Bengough A. G. , Davies M. C.R. , Hallett P. D. 
Published: January 2010

Plant root systems frequently permeate both natural and engineered soil slopes, influencing slope stability via mechanical reinforcement and soil drying. These root systems are often loaded by external forces during slope movements and when plant stems are subject to animal foraging or wind gusts. A series of physical model tests were conducted to examine how root geometries, root properties, and soil effective stress states affect the pullout capacity of simple unbranched model roots. Lengths of wood, rubber, and real roots were pulled from dry and partially saturated sand. The tests revealed the importance of the root to soil stiffness ratio during progressive failure, the mechanical properties of soil (and interfaces) at low effective stresses, the root diameter, and the tortuosity of the root material. Scaling issues due to shear banding are more important, and effective stresses under wet conditions are smaller than in conventional geotechnical practice because roots have a relatively small diameter (typically 10−4–10−1 m) and are at shallow depth (typically 0–2 m). After careful consideration of these effects, predictions were made for the pullout capacity of small root sections based on material data for willow roots (Salix viminalis) in sand.
Strong and Weak Convergence of the Modified Proximal Point Algorithms in Hilbert Space
Authors: Chai Xinkuan , Li Bo , Song Yisheng 
Published: January 2010

AbstractFor a monotone operator "Equation missing", we shall show weak convergence of Rockafellar's proximal point algorithm to some zero of "Equation missing" and strong convergence of the perturbed version of Rockafellar's to "Equation missing" under some relaxed conditions, where "Equation missing" is the metric projection from "Equation missing" onto "Equation missing". Moreover, our proof techniques are simpler than some existed results.
Differentiation of Bone Marrow Stromal Cells into Osteoblasts in a Self-assembling Peptide Hydrogel: In Vitro and In Vivo Studies
Authors: Ozeki Maho , Kuroda Shinji , Kon Kazuhiro , Kasugai Shohei 
Published: January 2010

A prerequisite of tissue engineering approaches with regard to autograft is a suitable scaffold that can harbor cells and signals. Conventionally, such scaffolds have been prepared as 3D scaffolds prefabricated from synthetic or natural biomaterials. RAD16 has been introduced as a new biomaterial, where synthetic peptides self-assemble to form a hydrogel. In this study, RAD16 was examined in terms of osteogenic efficacy and feasibility of ectopic mineralization. Two hundred and seventy-one RAD16 was cocultured with 1 × 106 bone marrow cells from the femurs of 6-week-old Wistar male rats in alpha minimum essential medium supplemented with or without dexamethasone. Second, the same volume of the RAD16 construct hosting the cells with or without hydroxyapatite (HA) particles was treated in the dexamethasone medium as well, prepared in a Teflon tube, and implanted subcutaneously. Cell proliferation was prominent in the RAD16 coculture with dexamethasone at 1 week and significantly decreased by 2 weeks, whereas the other combinations remained or inclined, and their osteogenic differentiation was accelerated up to 2 weeks, as seen in increasing alkaline phosphatase (ALP) activity and mRNAs of ALP, OPN, and OCN. The RAD16 implant prepared with HA particles allowed more osteoblast-like cells and blood cells to grow inside, which was accompanied by elevating OPN gene expression and the stronger peak of VEGF gene expression at 2 weeks. Furthermore, more OPN mRNA signal was detected around the RAD16 containing HA particles by 4 weeks. On the other hand, the RAD16 alone represented lower expression of OPN gene. During the experiment, however, no ectopic mineralization was observed in both groups. Conclusively, it was suggested that the RAD16 showed feasibility of serving as a matrix for osteogenic differentiation of cocultured bone marrow cells in vitro and in vivo. Proceeding of exploration and modification of RAD16 are continuously required for cell-based tissue engineering.
Identification of an alternative CD20 transcript variant in B-cell malignancies coding for a novel protein associated to rituximab resistance
Authors: Henry Carole , Deschamps Marina , Rohrlich Pierre-Simon , Pallandre Jean-René , Rémy-Martin Jean-Paul , Callanan Mary , Traverse-Glehen Alexandra , GrandClément Camille , Garnache-Ottou Francine , Gressin Remy , Deconinck Eric , Salles Gilles , Robinet Eric , Tiberghien Pierre , Borg Christophe , Ferrand Christophe 
Published: January 2010

AbstractHuman CD20 is a B-cell lineage–specific marker expressed by normal and leukemic B cells from the pre-B to the plasma-cell stages and is a target for rituximab (RTX) immunotherapy. A CD20 reverse transcriptase–polymerase chain reaction (PCR) on B-cell lines cDNA yielded a short PCR product (ΔCD20) corresponding to a spliced mRNA transcript linking the exon 3 and exon 7 ends. We established here that this novel, alternatively spliced CD20 transcript is expressed and detectable at various levels in leukemic B cells, lymphoma B cells, in vivo tonsil- or in vitro CD40L-activated B cells, and Epstein-Barr virus (EBV)–transformed B cells, but not in resting CD19+- or CD20+-sorted B cells from peripheral blood or bone marrow of healthy donors. The truncated CD20 sequence is within the reading frame, codes a protein of 130 amino acids (∼ 15-17 kDa) lacking large parts of the 4 transmembrane segments, suggesting that ΔCD20 is a nonanchored membrane protein. We demonstrated the translation into a ΔCD20 protein which is associated with the membrane CD20 protein and showed its involvement in RTX resistance. Study of patient samples before and after RTX resistance or escape confirms our in vitro findings.
CD44 activation in mature B-cell malignancies by a novel recurrent IGH translocation
Authors: Hu Xiao-Tong , Chen Yun-Wen , Liang Anthony C. T. , Au Wing-Yan , Wong Kai-Yau , Wan Thomas S. K. , Wong Michelle L. Y. , Shen Lijun , Chan Ka-Kui , Guo Tianhuan , Chu Kent-Man , Tao Qian , Chim Chor-Sang , Loong Florence , Choi William W. L. , Lu Liwei , So Chi-Chiu , Chan Li Chong , Kwong Yok-Lam , Liang Raymond H. S. , Srivastava Gopesh 
Published: January 2010

Abstract
Using inverse polymerase chain reaction, we identified CD44, located on chromosome 11p13, as a novel translocation partner of IGH in 9 of 114 cases of gastric, nongastric extranodal, follicular, and nodal diffuse large B-cell lymphoma (DLBCL). Notably, these translocations involving IGHSμ were detected in follicular lymphomas and exclusively in germinal center B cell-ike (GCB)–DLBCLs. CD44 is not expressed in reactive GC B cells. The IGHSμ/CD44 translocations substitute Sμ for the CD44 promoter and remove exon 1 of CD44, resulting in the overexpression of Iμ-CD44 hybrid mRNA transcripts activated from derivative 11 that encode a new CD44 variant lacking the leader peptide and with a unique C-terminus (CD44ΔEx1). When overexpressed in vitro in the CD44− GCB-DLBCL cell line BJAB, CD44ΔEx1–green fluorescent protein localized to the cytoplasm and nucleus, whereas CD44s–green fluorescent protein (standard form) localized to the plasma membrane. The ectopic expression of CD44ΔEx1 in BJAB cells enhanced their proliferation rate and clonogenic ability, indicating a possible pathogenic role of the translocation.
Nutritional control of gene expression in Drosophila larvae via TOR, Myc and a novel cis-regulatory element
Authors: Li Ling , Edgar Bruce A , Grewal Savraj S 
Published: January 2010

Abstract

Background
Nutrient availability is a key determinant of eukaryotic cell growth. In unicellular organisms many signaling and transcriptional networks link nutrient availability to the expression of metabolic genes required for growth. However, less is known about the corresponding mechanisms that operate in metazoans. We used gene expression profiling to explore this issue in developing Drosophila larvae.

Results
We found that starvation for dietary amino acids (AA's) leads to dynamic changes in transcript levels of many metabolic genes. The conserved insulin/PI3K and TOR signaling pathways mediate nutrition-dependent growth in Drosophila and other animals. We found that many AA starvation-responsive transcripts were also altered in TOR mutants. In contrast, although PI3K overexpression induced robust changes in the expression of many metabolic genes, these changes showed limited overlap with the AA starvation expression profile. We did however identify a strong overlap between genes regulated by the transcription factor, Myc, and AA starvation-responsive genes, particularly those involved in ribosome biogenesis, protein synthesis and mitochondrial function. The consensus Myc DNA binding site is enriched in promoters of these AA starvation genes, and we found that Myc overexpression could bypass dietary AA to induce expression of these genes. We also identified another sequence motif (Motif 1) enriched in the promoters of AA starvation-responsive genes. We showed that Motif 1 was both necessary and sufficient to mediate transcriptional responses to dietary AA in larvae.

Conclusions
Our data suggest that many of the transcriptional effects of amino acids are mediated via signaling through the TOR pathway in Drosophila larvae. We also find that these transcriptional effects are mediated through at least two mechanisms: via the transcription factor Myc, and via the Motif 1 cis-regulatory element. These studies begin to elucidate a nutrient-responsive signaling network that controls metabolic gene transcription in Drosophila.
F-Prostaglandin receptor regulates endothelial cell function via fibroblast growth factor-2
Authors: Keightley Margaret C , Brown Pamela , Jabbour Henry N , Sales Kurt J 
Published: January 2010

Abstract

Background
Prostaglandin (PG) F2α is a key regulator of endometrial function and exerts its biological action after coupling with its heptahelical G protein-coupled receptor (FP receptor). In endometrial adenocarcinoma the FP receptor expression is elevated. We have shown previously that PGF2α-FP receptor signalling in endometrial adenocarcinoma cells can upregulate several angiogenic factors including fibroblast growth factor-2 (FGF2). In the present study, we investigated the paracrine effect of conditioned medium produced via PGF2α-FP receptor signalling in endometrial adenocarcinoma cells stably expressing the FP receptor (Ishikawa FPS cells), on endothelial cell function.

Results
Conditioned medium (CM) was collected from FPS cells after 24 hrs treatment with either vehicle (V CM) or 100 nM PGF2α (P CM). Treatment of human umbilical vein endothelial cells (HUVECs) with P CM significantly enhanced endothelial cell differentiation (network formation) and proliferation. Using chemical inhibitors of intracellular signalling, we found that P CM-stimulated endothelial cell network formation was mediated by secretion of endothelial PGF2α and activation of endothelial FP receptors, following FGF2-FGFR1 signalling, phosphorylation of ERK1/2 and induction of COX-2. Whereas, P CM stimulation of endothelial cell proliferation occurred independently of PGF2α secretion via an FGF2-FGFR1-ERK1/2 dependent mechanism involving activation of the mTOR pathway.

Conclusions
Taken together, we have shown a novel mechanism whereby epithelial prostaglandin F2α-FP signalling regulates endothelial cell network formation and proliferation. In addition we provide novel in vitro evidence to suggest that prostaglandin F2α can directly regulate endothelial cell network formation but not endothelial cell proliferation. These findings have relevance for pathologies where the FP receptor is aberrantly expressed, such as endometrial adenocarcinoma, and provide in vitro evidence to suggest that targeting the FP receptor could provide an anti-angiogenic approach to reducing tumour vasculature and growth.
Cloning and expression of SOLD1 in ovine and caprine placenta, and their expected roles during the development of placentomes
Authors: Ushizawa Koichi , Takahashi Toru , Hosoe Misa , Kizaki Keiichiro , Hashizume Kazuyoshi 
Published: January 2010

Abstract

Background
The Ly-6 (Ly-6/uPAR) superfamily members share the Ly-6 domain defined by distinct disulfide bonding patterns between 8 or 10 cysteine residues. They comprise membrane- and secretory-type proteins. We recently reported the gene and protein characterization of the bovine secreted protein of Ly-6 domain 1 (SOLD1). Bovine SOLD1 is expressed in trophoblast mononucleate cells (TMCs) and is localized in the cotyledonary mesenchyme. Here, we compared the expression and functionality of SOLD1 among the ruminants. We examined mRNA expression by chorionic fibroblasts as a measure of one of the SOLD1 functions.

Results
Ovine and caprine SOLD1 mRNAs have 303 bp open reading frames and encode for deduced SOLD1 proteins with 100 amino acids, including a 22-aa-long signal peptide at the N-terminal. Both of the SOLD1 amino acid sequences have high similarities with the bovine sequence. Both SOLD1 mRNAs were also expressed in TMCs of cotyledons and intercotyledonary membranes. The mature SOLD1 proteins were localized in the mesenchymal villi of cotyledons after secretion. Bovine, ovine and caprine SOLD1 affected gene expression in mesenchymal fibroblasts in vitro; nucleoredoxin expression was upregulated and BCL2-like 13 was downregulated. Thus, we suggest that SOLD1 acts as a modulator of cell proliferation and apoptosis.

Conclusion
Expressing cells and protein localization of SOLD1 coincided among the three ruminants. SOLD1 participated in regulating nucleoredoxin and BCL2-like 13 expression in chorionic fibroblasts. SOLD1 is produced specifically in the cotyledons and intercotyledonary membranes in ruminants and appears to be involved in the construction of the ruminant placenta.
Identification and characterization of microRNAs and endogenous siRNAs in Schistosoma japonicum
Authors: Hao Lili , Cai Pengfei , Jiang Ning , Wang Heng , Chen Qijun 
Published: January 2010

Abstract

Background
Small endogenous non-coding RNAs (sncRNAs) such as small interfering RNA (siRNA), microRNA and other small RNA transcripts are derived from distinct loci in the genome and play critical roles in RNA-mediated gene silencing mechanisms in plants and metazoa. They are approximately 22 nucleotides long; regulate mRNA stability through perfect or imperfect match to the targets. The biological activities of sncRNAs have been related to many biological events, from resistance to microbe infections to cellular differentiation. The development of the zoonotic parasite Schistosoma japonicum parasite includes multiple steps of morphological alterations and biological differentiations, which provide a unique model for studies on the functions of small RNAs. Characterization of the genome-wide transcription of the sncRNAs will be a major step in understanding of the parasite biology. The objective of this study is to investigate the transcriptional profile and potential function of the small non-coding RNAs in the development of S. japanicum.

Results
The endogenous siRNAs were found mainly derived from transposable elements (TE) or transposons and the natural antisense transcripts (NAT). In contrast to other organisms, the TE-derived siRNAs in S. japonicum were more predominant than other sncRNAs including microRNAs (miRNAs). Further, there were distinct length and 3'end variations in the sncRNAs, which were associated with the developmental differentiation of the parasite. Among the identified miRNA transcripts, there were 38 unique to S. japonicum and 16 that belonged to 13 miRNA families are common to other metazoan lineages. These miRNAs were either ubiquitously expressed, or they exhibited specific expression patterns related to the developmental stages or sex. Genes that encoded miRNAs are mainly located in clusters within the genome of S. japonicum. However, genes within one cluster could be differentially transcribed, which suggested that individual genes might be regulated by distinct mechanisms during parasite development.

Conclusions
Many miRNA and endogenous siRNA transcripts were identified in S. japonicum and the amount of siRNA was at least 4.4 and 1.6 times more than that of miRNA in both schistosomulum and adult worm stages respectively. SiRNAs are mainly derived from transposable elements (or transposons); while natural antisense transcripts (NAT)-derived siRNAs were much less. A majority of miRNA transcripts identified in the parasite were species-specific and the expression of certain miRNAs was found developmentally regulated. Both miRNA and siRNAs are potentially important regulators in the development of schistosomal parasites.
Large effects on body mass index and insulin resistance of fat mass and obesity associated gene (FTO) variants in patients with polycystic ovary syndrome (PCOS)
Authors: Tan Susanne , Scherag André , Janssen Onno Eilard , Hahn Susanne , Lahner Harald , Dietz Tiina , Scherag Susann , Grallert Harald , Vogel Carla Ivane Ganz , Kimmig Rainer , Illig Thomas , Mann Klaus , Hebebrand Johannes , Hinney Anke 
Published: January 2010

AbstractBackgroundThe polycystic ovary syndrome (PCOS), a common endocrine disorder in women of child-bearing age, mainly characterised by chronic anovulation and hyperandrogenism, is often associated with insulin resistance (IR) and obesity. Its etiology and the role of IR and obesity in PCOS are not fully understood. We examined the influence of validated genetic variants conferring susceptibility to obesity and/or type 2 diabetes mellitus (T2DM) on metabolic and PCOS-specific traits in patients with PCOS.MethodsWe conducted an association study in 386 patients with PCOS (defined by the Rotterdam-criteria) using single nucleotide polymorphisms (SNPs) in or in proximity to the fat mass and obesity associated gene(FTO), insulin-induced gene-2 (INSIG2), transcription factor 7-like 2 gene (TCF7L2) and melanocortin 4 receptor gene (MC4R). To compare the effect ofFTOobesity risk alleles on BMI in patients with PCOS to unselected females of the same age range we genotyped 1,971 females from the population-based KORA-S4 study (Kooperative Gesundheitsforschung im Raum Augsburg, Survey 4).ResultsTheFTOrisk allele was associated with IR traits and measures of increased body weight. In addition, theTCF7L2SNP was associated with body weight traits. For the SNPs in the vicinity ofINSIG2andMC4Rand for the other examined phenotypes there was no evidence for an association. In PCOS the observed per risk allele effect ofFTOintron 1 SNP rs9939609 on BMI was +1.56 kg/m2, whereas it was +0.46 kg/m2in females of the same age range from the general population as shown previously.ConclusionThe stronger effect on body weight of theFTOSNP in PCOS might well have implications for the etiology of the disease.