bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of DOCK4 and its splicing variant as PIP3 binding proteins
Authors: Kanai Akinori , Ihara Sayoko , Ohdaira Tsutomu , Shinohara‐Kanda Azusa , Iwamatsu Akihiro , Fukui Yasuhisa 
Published: May 2008

AbstractDOCK4, a member of DOCK180 family proteins, was originally identified as a product of a gene deleted during tumor progression. Although its tumor suppression properties have been reported, the regulation mechanism of this protein has not been fully elucidated. DOCK4 shares two conserved domains called as DHR‐1 and DHR‐2 domain as other members including DOCK180. Although DHR‐1 in DOCK180 is reported to bind to PIP3, whether that of DOCK4 exhibits similar function has yet not been examined. In a search for novel PIP3 binding proteins by the PIP3 analog beads binding assay, we found that DOCK4 and its novel splicing variant, whose exon1 and exon52 are different from the known one, bind to PIP3. Binding assay using deletion mutants of DOCK4 revealed that the binding region falls into the DHR‐1 domain. These results raise the possibility that DOCK4 may be regulated by PIP3 to exert its function. © 2008 IUBMB IUBMB Life, 60(7): 467–472, 2008
Inhibition of histone acetyltransferase by glycosaminoglycans
Authors: Buczek‐Thomas Jo Ann , Hsia Edward , Rich Celeste B. , Foster Judith A. , Nugent Matthew A. 
Published: May 2008

AbstractHistone acetyltransferases (HATs) are a class of enzymes that participate in modulating chromatin structure and gene expression. Altered HAT activity has been implicated in a number of diseases, yet little is known about the regulation of HATs. In this study, we report that glycosaminoglycans (GAGs) are potent inhibitors of p300 and pCAF HAT activities in vitro, with heparin and heparan sulfate proteoglycans (HSPGs) being the most potent inhibitors. The mechanism of inhibition by heparin was investigated. The ability of heparin to inhibit HAT activity was in part dependent upon its size and structure, as small heparin‐derived oligosaccharides (>8 sugars) and N‐desulfated or O‐desulfated heparin showed reduced inhibitory activity. Heparin was shown to bind to pCAF; and enzyme assays indicated that heparin shows the characteristics of a competitive‐like inhibitor causing an ∼50‐fold increase in the apparent Km of pCAF for histone H4. HSPGs isolated from corneal and pulmonary fibroblasts inhibited HAT activity with similar effectiveness as heparin. As evidence that endogenous GAGs might be involved in modulating histone acetylation, the direct addition of heparin to pulmonary fibroblasts resulted in an ∼50% reduction of histone H3 acetylation after 6 h of treatment. In addition, Chinese hamster ovary cells deficient in GAG synthesis showed increased levels of acetylated histone H3 compared to wild‐type parent cells. GAGs represent a new class of HAT inhibitors that might participate in modulating cell function by regulating histone acetylation. J. Cell. Biochem. 105: 108–120, 2008. © 2008 Wiley‐Liss, Inc.
Modulation of cyclooxygenase in endothelial cells by fibronectin: Relevance to angiogenesis
Authors: Viji R.I. , Kumar V.B. Sameer , Kiran M.S. , Sudhakaran P.R. 
Published: May 2008

AbstractCyclooxygenases (COX), which catalyze the formation of prostaglandins (PGs), have been implicated in angiogenesis. Adhesion of endothelial cells (ECs) to extracellular matrix (ECM) induces the expression of COX‐2 and PG production. The present study was carried out to analyze the influence of the adhesive ECM protein, fibronectin (FN), in modulating COX expression and its implications to angiogenesis using in vitro cultures of human umbilical vein ECs. RT‐PCR analysis showed that the level of COX‐2 mRNA was significantly high while that of COX‐1 decreased in ECs maintained on FN. On treatment with p38 MAPK inhibitor and anti‐α5β1integrin antibody, FN dependent effect on COX expression was not observed. Analysis by ELISA and immunoblotting confirmed FN‐dependent upregulation of COX‐2 protein. The ratio of PG E2:PG D2was significantly high in cells maintained on FN and on treatment with p38 MAPK inhibitor, the relative level of PG D2increased and that of PG E2decreased. Concomitant with the modulation of COX‐2 and changes in PGs, ECs maintained on FN showed angiogenic response in an α5β1integrin/p38 MAPK dependent manner as evidenced by the expression of angiogenic markers, CD 31 and E‐selectin. These results suggest a FN‐α5β1/FAK/p38 MAPK dependent upregulation of COX‐2 causing a shift in the relative levels of PGs in HUVECs which contributes to the angiogenic effect of FN. J. Cell. Biochem. 105: 158–166, 2008. © 2008 Wiley‐Liss, Inc.
The use of symptom severity measured just before termination to predict child treatment dropout
Authors: Chasson Gregory S. , Vincent John P. , Harris Gerald E. 
Published: May 2008

AbstractThe current study examined indices of trauma‐related symptom severity as predictors of dropout from exposure‐based cognitive behavioral therapy in a sample of 99 child and adolescent trauma victims. The investigation incorporated measures of symptom severity at two time points: pretreatment and just before termination. The results indicated that a model with symptom severity measured just before termination was significantly associated with the number of attended sessions; however, a model with the symptom‐severity indices measured at pretreatment was nonsignificant. In addition, a significant main effect indicated that increased avoidance behavior measured just before termination was related to fewer treatment sessions. Further analyses also suggested that higher severity of intrusion and depression measured just before termination was correlated with fewer treatment sessions. The results support the idea that more immediate distress may be related to treatment dropout. Implications for the research and practice of exposure therapy for child trauma are discussed. © 2008 Wiley Periodicals, Inc. J Clin Psychol/In Session 64: 1–14, 2008.
Meditation with yoga, group therapy with hypnosis, and psychoeducation for long‐term depressed mood: a randomized pilot trial
Authors: Butler Lisa D. , Waelde Lynn C. , Hastings T. Andrew , Chen Xin‐Hua , Symons Barbara , Marshall Jonathan , Kaufman Adam , Nagy Thomas F. , Blasey Christine M. , Seibert Elizabeth O. , Spiegel David 
Published: May 2008

AbstractThis randomized pilot study investigated the effects of meditation with yoga (and psychoeducation) versus group therapy with hypnosis (and psychoeducation) versus psychoeducation alone on diagnostic status and symptom levels among 46 individuals with long‐term depressive disorders. Results indicate that significantly more meditation group participants experienced a remission than did controls at 9‐month follow‐up. Eight hypnosis group participants also experienced a remission, but the difference from controls was not statistically significant. Three control participants, but no meditation or hypnosis participants, developed a new depressive episode during the study, though this difference did not reach statistical significance in any case. Although all groups reported some reduction in symptom levels, they did not differ significantly in that outcome. Overall, these results suggest that these two interventions show promise for treating low‐ to moderate‐level depression. © 2008 Wiley Periodicals, Inc. J Clin Psychol 64(7): 1–15, 2008.
Haploinsufficiency of Runx2 results in bone formation decrease and different BSP expression pattern changes in two transgenic mouse models
Authors: Tu Qisheng , Zhang Jin , Paz Jeff , Wade Katherine , Yang Pishan , Chen Jake 
Published: May 2008

AbstractRunx2 has been identified as “a master gene” for the differentiation of osteoblasts and Runx2‐deficient mice has demonstrated a complete absence of mature osteoblast and ossification. To further characterize the Runx2 responsive elements within the bone sialoprotein (BSP) promoter and further investigate into the role of Runx2 haploinsufficiency in osteoblast differentiation, mBSP9.0Luc mice and mBSP4.8Luc mice were crossed with Runx2‐deficient mice respectively. Luciferase assay, micro CT scan, and histological analysis were performed using tissues isolated from mBSP9.0luc/Runx2+/− mice, mBSP4.8luc/Runx2+/− mice and their corresponding Runx2+/+ littermates. Alkaline phosphatase activity, mineralization assays and RT‐PCR analysis using calvarial osteoblasts isolated from these transgenic mice were also performed. Luciferase assay demonstrated an early increase in luciferase expression in mBSP9.0luc/Runx2+/− mice before the expression level of luciferase dramatically decreased and turned lower than that in their control littermates in later stages. In contrast, luciferase expression in mBSP4.8luc/Runx2+/− failed to show such an early increase. Micro CT scan and histological analysis showed that BMD and trabecular bone volume were decreased and bone formation was delayed in Runx2+/− mice. Furthermore, mineralization assay and semi‐quantitative RT‐PCR assay demonstrated a gene‐dose‐dependent decrease in bone nodule formation and bone marker genes expression levels in cultured calvarial osteoblasts derived from Runx2 knockout mice. Reconstitution of Runx2‐null cells with Runx2 vector partially rescued the osteoblast function defects. In conclusion, the 9.0 kb BSP promoter demonstrated a higher tissue‐specific regulation of the BSP gene by Runx2 in vivo and full Runx2 gene dose is essential for osteoblast differentiation and normal bone formation. J. Cell. Physiol. 217: 40–47, 2008. © 2008 Wiley‐Liss, Inc.
Stem cells: The root of prostate cancer?
Authors: Kasper Susan 
Published: May 2008

AbstractThe cancer stem cell (CSC) model states that tumors contain a reservoir of self‐renewing cells that maintain the heterogeneous cell population of the tumor. These cells appear to be resistant to therapy and can therefore survive to repopulate the tumor during progression to therapy resistant disease. The biology of CSCs is still not definitive since it is difficult to isolate them from solid tumors and analyze their characteristics in vitro. Another challenge is to correlate these characteristics with tumor development and progression in vivo. Using the prostate CSC as a model, this review presents the CSC hypothesis, reviews the origin, identification and functions of prostate CSCs, and discusses the clinical implications and therapeutic challenges CSCs have for cancer therapy. J. Cell. Physiol. 216: 332–336, 2008. © 2008 Wiley‐Liss, Inc.
Novel expression of PINCH in the central nervous system and its potential as a biomarker for human immunodeficiency virus‐associated neurodegeneration
Authors: Rearden Ann , Hurford Rosemary , Luu Nhan , Kieu Emily , Sandoval Melissa , Perez‐Liz Georgina , Del Valle Luis , Powell Henry , Langford T. Dianne 
Published: May 2008

AbstractParticularly interesting cysteine histidine‐rich (PINCH) protein functions as a shuttling protein in Schwann cells after peripheral nerve damage, during repair and remodeling, and in maintaining neuronal polarity. However, the presence of PINCH in the human CNS during disease has not been addressed. Because HIV‐associated damage to cells of the CNS involves dysregulation of neuronal signaling and white matter damage, we hypothesized that PINCH may play a role in neuropathological processes during the course of HIV infection. To determine the expression of PINCH in the CNS, brain, and cerebrospinal fluid (CSF) obtained at autopsy from HIV patients with no CNS alterations, HIV encephalitic (HIVE) patients, and HIV‐negative individuals with no CNS alterations were examined for PINCH immunoreactivity. Our results show that PINCH is expressed robustly in the brains and CSF of HIV patients, but is nearly undetectable in HIV‐negative individuals. However, HIVE patients' CSF contained significantly less PINCH than HIV patients with no CNS alterations. PINCH immunolabeling was significantly more intense in the white matter than in the grey matter and was associated exclusively with neuronal cell bodies or processes, or with the extracellular matrix. Given the recently discovered importance of PINCH in maintaining neuronal fitness, our observations that PINCH is robustly expressed in the CNS of HIV patients suggests an important role for PINCH in HIV‐associated neurodegenerative processes. Understanding mechanisms by which PINCH functions during HIV‐associated CNS alterations will provide new insight into potential treatments to limit neurological alterations in HIV. © 2008 Wiley‐Liss, Inc.
p53 cooperates berberine‐induced growth inhibition and apoptosis of non‐small cell human lung cancer cells in vitro and tumor xenograft growth in vivo
Authors: Katiyar Santosh K. , Meeran Syed M. , Katiyar Nandan , Akhtar Suhail 
Published: May 2008

AbstractBerberine has been shown to have anti‐carcinogenic effects. Since p53 is the most commonly mutated tumor suppressor gene, and a lack of functional p53 is associated with an increased risk of cancer development, we examined the effects of berberine on p53‐positive and p53‐deficient non‐small cell human lung cancer cells in vitro and in vivo. Treatment of A549, which express wild‐type p53, and H1299, which are p53‐deficient, human lung cancer cells with berberine resulted in inhibition of cell proliferation and an increase in apoptotic cell death; however, A549 cells were more sensitive to the berberine‐induced cytotoxic effects than H1299 cells. Further, the treatment of A549 cells with pifithrin‐α, a specific inhibitor of p53, or transfection of A549 cells with a p53 antisense oligodeoxynucleotide resulted in a reduction in the berberine‐induced inhibition of cell proliferation and apoptosis. The berberine‐induced apoptosis of both the A549 and H1299 human lung cancer cells was associated with the disruption of mitochondrial membrane potential, reduction in the levels of Bcl‐2, Bcl‐xl while increase in Bax, Bak, and activation of caspase‐3. Treatment of the cells with pan‐caspase inhibitor (z‐VAD‐fmk) or caspase‐3 inhibitor (z‐DEVD‐fmk) inhibited berberine‐induced apoptosis, thus suggesting the role of caspase‐3. Further, the administration of berberine by oral gavage inhibited the growth of s.c. A549 and H1299 lung tumor xenografts in athymic nude mice, however, the growth of tumor xenograft of H1299 cells was faster than A549 cells in mice and the chemotherapeutic effect of berberine was more pronounced in the p53‐positive‐A549 tumor xenograft than p53‐deficient‐H1299 tumor xenograft. © 2008 Wiley‐Liss, Inc.
Structure, physiological role, and specific inhibitors of human thymidine kinase 2 (TK2): Present and future
Authors: Pérez‐Pérez María‐Jesús , Priego Eva‐María , Hernández Ana‐Isabel , Familiar Olga , Camarasa María‐José , Negri Ana , Gago Federico , Balzarini Jan 
Published: May 2008

AbstractHuman mitochondrial thymidine kinase (TK2) is a pyrimidine deoxynucleoside kinase (dNK) that catalyzes the phosphorylation of pyrimidine deoxynucleosides to their corresponding deoxynucleoside 5′‐monophosphates by γ‐phosphoryl transfer from ATP. In resting cells, TK2 is suggested to play a key role in the mitochondrial salvage pathway to provide pyrimidine nucleotides for mitochondrial DNA (mtDNA) synthesis and maintenance. However, recently the physiological role of TK2turned out to have direct clinical relevance as well. Point mutations in the gene encoding TK2 have been correlated to mtDNA disorders in a heterogeneous group of patients suffering from the so‐called mtDNA depletion syndrome (MDS). TK2 activity could also be involved in mitochondrial toxicity associated to prolonged treatment with antiviral nucleoside analogues like AZT and FIAU. Therefore, TK2 inhibitors can be considered as valuable tools to unravel the role of TK2 in the maintenance and homeostasis of mitochondrial nucleotide pools and mtDNA, and to clarify the contribution of TK2 activity to mitochondrial toxicity of certain antivirals. Highly selective TK‐2 inhibitors having an acyclic nucleoside structure and efficiently discriminating between TK‐2 and the closely related TK‐1 have already been reported. It is actually unclear whether these agents efficiently reach the inner mitochondrial compartment. In the present review article,structural features of TK2, MDS‐related mutations observed in TK2 and their role in MDS will be discussed. Also, an update on novel and selective TK2 inhibitors will be provided. © 2008 Wiley Periodicals, Inc. Med Res Rev, 28, No. 5, 797–820, 2008
Revenue sharing contracts in a supply chain with uncontractible actions
Authors: Ha Albert Y. , Tong Shilu 
Published: May 2008

AbstractWe consider a supplier–customer relationship where the customer faces a typical Newsvendor problem of determining perishable capacity to meet uncertain demand. The customer outsources a critical, demand‐enhancing service to an outside supplier, who receives a fixed share of the revenue from the customer. Given such a linear sharing contract, the customer chooses capacity and the service supplier chooses service effort level before demand is realized. We consider the two cases when these decisions are made simultaneously (simultaneous game) or sequentially (sequential game). For each game, we analyze how the equilibrium solutions vary with the parameters of the problem. We show that in the equilibrium, it is possible that either the customer's capacity increases or the service supplier's effort level decreases when the supplier receives a larger share of the revenue. We also show that given the same sharing contract, the sequential game always induces a higher capacity and more effort. For the case of additive effort effect and uniform demand distribution, we consider the customer's problem of designing the optimal contract with or without a fixed payment in the contract, and obtain sensitivity results on how the optimal contract depends on the problem parameters. For the case of fixed payment, it is optimal to allocate more revenue to the supplier to induce more service effort when the profit margin is higher, the cost of effort is lower, effort is more effective in stimulating demand, the variability of demand is smaller or the supplier makes the first move in the sequential game. For the case of no fixed payment, however, it is optimal to allocate more revenue to the supplier when the variability of demand is larger or its mean is smaller. Numerical examples are analyzed to validate the sensitivity results for the case of normal demand distribution and to provide more managerial insights. © 2008 Wiley Periodicals, Inc. Naval Research Logistics, 2008
Preparation of photodegradable polypropylene/clay composites based on nanoscaled TiO2 immobilized organoclay
Authors: Meng Xiangfu , Wang Haitao , Qian Zhongzhong , Gao Xiaowei , Yi Qingfeng , Zhang Shimin , Yang Mingshu 
Published: May 2008

AbstractPhotodegradable polypropylene (PP) composites were prepared via melting blending using PP and titanium dioxide (TiO2) immobilized organically modified montmorillonite (organoclay). TiO2 immobilized organoclay (TiO2‐OMT) was synthesized by immobilizing anatase TiO2 nanoparticles on organically modified clay via sol–gel method. The structure and morphology of TiO2‐OMT were characterized by XRD and scanning electron microscope (SEM), which showed that anatase TiO2 nanoparticles with the size range of 8–12 nm were uniformly immobilized on the surface of organoclay layers. Diffuse reflection UV–vis spectra revealed TiO2‐OMT had similar absorbance characters to that of commercial photocatalyst, Degussa P25. The solid‐phase photocatalytic degradation of PP/TiO2‐OMT composites was investigated by FTIR, DSC, GPC and SEM. The results indicated that TiO2‐OMT enhanced the photodegradation rate of PP under UV irradiation. This was due to that immobilization of TiO2 nanoparticles on organoclay effectively avoided the formation of aggregation, and thereby increased the interface between PP and TiO2 nanoparticles. After 300 h irradiation, the average molecular weight was reduced by two orders of magnitude. This work presented a promising method for preparation of environment‐friendly polymer nanocomposites. POLYM. COMPOS., 2009. © 2008 Society of Plastics Engineers.
p300 (histone acetyltransferase) biomarker predicts prostate cancer biochemical recurrence and correlates with changes in epithelia nuclear size and shape
Authors: Isharwal Sumit , Miller Michael C. , Marlow Cameron , Makarov Danil V. , Partin Alan W. , Veltri Robert W. 
Published: May 2008

AbstractBACKGROUNDp300 impacts the transcription of several genes involved in key pathways critical to PCa progression. Therefore, we evaluated the prognostic value of p300 expression and its correlation with nuclear alterations seen in tumor cells in men with long‐term follow‐up after radical prostatectomy (RP).METHODSNCI Cooperative Prostate Cancer Tissue Resource tissue microarray cores of 92 RP cases (56 non‐recurrences and 36 PSA recurrences) were utilized for the study. p300 expression was assessed by quantitative immunohistochemistry and nuclear alterations in Feulgen‐stained nuclei were evaluated by digital image analysis using the AutoCyte™ Pathology Workstation. Cox proportional hazards regression, Spearman's rank correlation, and Kaplan–Meier plots were employed to analyze the data.RESULTSp300 expression significantly correlated with nuclear alterations seen in tumor cells; specifically with circular form factor (P = 0.012) and minimum feret (P = 0.048). p300 expression in high grade tumors (Gleason score ≥7) was significantly higher compared to low grade tumors (Gleason score <7) [17.7% versus 13.7%, respectively, P = 0.03]. TNM stage, Gleason score, and p300 expression were univariately significant in the prediction of PCa biochemical recurrence‐free survival (P ≤ 0.05). p300 expression remained significant in the multivariate model (P = 0.03) while Gleason score showed a trend toward significance (P = 0.06). Patients with a Gleason score ≥7 and p300 expression >24% showed the highest risk for PCa biochemical recurrence (P = 0.002).CONCLUSIONSp300 expression correlates with nuclear alterations seen in tumor cells and has prognostic value in predicting long‐term PCa biochemical recurrence‐free survival. Prostate 68:1097–1104, 2008. © 2008 Wiley‐Liss, Inc.
Alterations in β‐catenin expression and localization in prostate cancer
Authors: Whitaker Hayley C. , Girling Joanne , Warren Anne Y. , Leung Hing , Mills Ian G. , Neal David E. 
Published: May 2008

AbstractBackgroundWnt signaling is thought to be important in prostate cancer, in part because proteins such as β‐catenin can also affect androgen receptor signaling. β‐Catenin forms a cell adhesion complex with E‐cadherin raising the possibility that loss of expression or a change in β‐catenin distribution in the cell could also alter downstream signaling, decreased inter‐cellular adhesion and the promotion of metastasis. A number of studies have reported the altered expression and/or localization of β‐catenin as a biomarker in prostate cancer.MethodsTissue microarrays comprised of BPH and low, moderate and high‐grade prostate cancer (n = 77) were assessed for β‐catenin expression and distribution using immunohistochemistry. Staining was also performed on a tissue microarray containing tissue from patients before and after hormone manipulation. The effects of fixation and different antibodies was assessed on fixed LNCaP cell pellets and small prostate tissue microarrays.ResultsWe have observed increased β‐catenin expression in only high Gleason score (>7) prostate cancer. A nuclear re‐distribution of β‐catenin has previously been reported. We noted nuclear β‐catenin in benign prostatic hyperplasia and a gradual loss in nuclear distribution with increasing Gleason grade. We found no evidence for an alteration in β‐catenin expression or re‐distribution with hormone ablation. Altered fixation, antibodies and antibody concentration did affect the intensity and specificity of staining.ConclusionsA loss of nuclear β‐catenin is the most consistent feature in prostate cancer rather than absolute levels of expression. We also suggest that variation in immunohistochemical protocols may explain variations in the reported literature. Prostate 68: 1196–1205, 2008. © 2008 Wiley‐Liss, Inc.