bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of RBM5‐related factors in primary breast tissue
Authors: Rintala‐Maki Nina D. , Goard Carolyn A. , Langdon Colleen E. , Wall Vanessa E. , Traulsen Kathryn E.A. , Morin Cory D. , Bonin Michel , Sutherland Leslie C. 
Published: November 2006

AbstractThe aim of this study was to examine the expression of the RBM5 tumor suppressor, in relation to RBM6 and RBM10, to obtain a better understanding of the potential role played by these RBM5‐related factors in the regulation of RBM5 tumor‐suppressor activity. Paired non‐tumor and tumor samples were obtained from 73 breast cancer patients. RNA and protein expression were examined by semi‐quantitative reverse transcription‐polymerase chain reaction and immunoblot, respectively. Data were analyzed using various statistical methods to test for correlations amongst the RBM5‐related factors, and between the factors and various pathological parameters. Most notably, RBM5, RBM10v1, and HER2 protein expression levels were elevated in tumor tissue (P < 0.0001). RBM5 and RBM10v1 protein expression were significantly positively correlated (P < 0.001), as were RBM5 and HER2 protein expression (P < 0.01), in both non‐tumor and tumor tissue, whereas RBM10v1 and HER2 protein expression were only marginally correlated, in non‐tumor tissue (P < 0.05). Interestingly, RBM5 and RBM10v1 protein expression were both deregulated in relation to RNA expression in tumor tissue. RBM10v2 and RBM6 RNA were highly significantly positively correlated in relation to various factors relating to poor prognosis (P < 0.0001). To our knowledge, this study is the first to examine RBM5 expression at both the RNA and protein level in primary breast tumor tissue, and the first to examine expression of all RBM5‐related factors in a comprehensive manner. The results provide a graphic illustration that RBM5‐related factors are significantly differentially expressed in breast cancer, and suggest complex inter‐related regulatory networks involving alternative splicing, oncogenic expression, and tissue‐specific function. J. Cell. Biochem. 100: 1440–1458, 2007. © 2006 Wiley‐Liss, Inc.
Impact of silencing HO‐2 on EC‐SOD and the mitochondrial signaling pathway
Authors: Turkseven S. , Drummond G. , Rezzani R. , Rodella L. , Quan S. , Ikehara S. , Abraham N.G. 
Published: November 2006

AbstractThe contribution of heme oxygenase HO‐2, the primary source of bilirubin and carbon monoxide (CO) under physiological conditions, to the regulation of vascular function has remained largely unexplored. Using siRNA HO‐2, we examined the effect of suppressed levels of HO‐2 on vascular antioxidant and survival proteins. In vivo HO‐2 siRNA treatment decreased the basal levels of EC‐SOD, pAKT proteins (serine‐473 and threonine‐308), without changing Akt protein expression. HO‐2 siRNA treatment increased 3‐nitrotyrosine (3‐NT) and apoptotic signaling kinase‐1 (ASK‐1) (P < 0.01). HO activity was decreased by the use of siRNA HO‐2. We extended these studies to the mitochondria, examining for the presence of HO‐1 and its role in the regulation of pro‐ and anti‐apoptotic proteins. HO activity was increased by the administration of CoPP resulting in the translocation of HO‐1 into the mitochondria, mainly to the inner face of the mitochondrial inner membrane. These findings suggest that HO‐2 is critical in the maintenance of heme homeostasis and also the regulation of apoptosis by controlling levels of EC‐SOD, Akt, 3‐NT, and ASK‐1. In addition, localization of HO‐1 in the mitochondrial compartment plays a critical role in mitochondria‐mediated apoptosis. J. Cell. Biochem. 100: 815–823, 2007. © 2006 Wiley‐Liss, Inc.
Differential signal transduction of alternatively spliced FGFR2 variants expressed in human mammary epithelial cells
Authors: Moffa Allison B. , Ethier Stephen P. 
Published: November 2006

AbstractGene amplification and protein overexpression of fibroblast growth factor receptor 2 (FGFR2) characterize the SUM‐52 breast cancer cell line developed in our laboratory. SUM‐52 cells express nine distinct alternatively spliced isoforms of FGFR2. Among these isoforms are two otherwise identical FGFR2 variants that express either the C1 or C3 carboxyl terminus. FGFR2‐C3 variants are not normally expressed by human mammary epithelial (HME) cells, and we have shown that overexpression of FGFR2‐C3 in HME cells results in potent transformation. In particular, FGFR2‐C3 expression leads to robust levels of constitutively tyrosine phosphorylated FRS2 in the absence of ligand stimulation. In contrast, overexpressed FGFR2‐C1 requires constant stimulation with exogenous keratinocyte growth factor (KGF) to mimic the signaling capability of FGFR2‐C3. However, activation of FRS2 that results from KGF‐stimulated FGFR2‐C1 signaling is transient and is associated with a mobility shift of FRS2 not observed when this signaling molecule is activated by the C3 isoform of FGFR2. Mutation of the only tyrosine phosphorylated site present in the C1 terminus and absent from C3, Tyr769, did not yield a receptor that rivaled the potent signaling of FGFR2‐C3. We therefore conclude that aberrant expression of alternatively spliced isoforms of FGFR2 with the C3 carboxyl terminus in the SUM‐52 breast cancer cells results in sustained activation of signal transduction leading to transformation. J. Cell. Physiol. 210: 720–731, 2007. © 2006 Wiley‐Liss, Inc.
ERK1/2‐driven and MKP‐mediated inhibition of EGF‐induced ERK5 signaling in human proximal tubular cells
Authors: Sarközi Rita , Miller Bradley , Pollack Verena , Feifel Elisabeth , Mayer Gert , Sorokin Andrey , Schramek Herbert 
Published: November 2006

AbstractThe MEK1‐ERK1/2 signaling pathway has been implicated in the regulation of renal epithelial cell proliferation, epithelial‐to‐mesenchymal transition and the induction of an invasive cell phenotype. Much less information is available about the MEK5‐ERK5 module and its role in renal epithelial cell proliferation and differentiation. In the present study we have investigated the regulation of these two families of extracellular signal‐regulated kinases in epidermal growth factor (EGF)‐stimulated human kidney‐2 (HK‐2) cells and a possible interaction between ERK1/2 and ERK5. Here we report that 5 ng/ml EGF led to a strong stimulation of HK‐2 cell proliferation, which was largely U0126‐sensitive. Both synthetic MEK1/2 inhibitors U0126 and Cl‐1040, when used at 10 and 1 µM, respectively, inhibited basal and EGF‐induced ERK1/2 phosphorylation but not ERK5 phosphorylation. Long‐term inhibition of MEK1/2‐ERK1/2 signaling and/or vanadate‐sensitive protein phosphatases enhanced and prolonged EGF‐induced ERK5 phosphorylation, while transient expression of an adenoviral constitutively active MEK1 (Ad‐caMEK1) construct completely blocked EGF‐induced ERK5 phosphorylation. Expression of Ad‐caMEK1 in HK‐2 cells resulted in the upregulation of the dual‐specificity phosphatases MKP‐3/DUSP6, MKP‐1/DUSP1, and DUSP5. The EGF‐mediated time‐dependent induction of MKP‐3, MKP‐1 and DUSP5 mRNA levels was U0126‐sensitive at a concentration, which blocked EGF‐mediated ERK1/2 phosphorylation but not ERK5 phosphorylation. Furthermore, U0126 inhibited EGF‐induced MKP‐3 and MKP‐1 protein expression. Both MKP‐3 and MKP‐1 co‐immunoprecipitated with ERK5 in unstimulated as well as in EGF‐stimulated HK‐2 cells. These results suggest the existence of an ERK1/2‐driven negative feed‐back regulation of ERK5 signaling in EGF‐stimulated HK‐2 cells, which is mediated by MKP‐3, DUSP5 and/or MKP‐1. J. Cell. Physiol. 211: 88–100, 2007. © 2006 Wiley‐Liss, Inc.
Granulocyte colony‐stimulating factor promotes the translocation of protein kinase Cι in neutrophilic differentiation cells
Authors: Kanayasu‐Toyoda Toshie , Suzuki Takayoshi , Oshizawa Tadashi , Uchida Eriko , Hayakawa Takao , Yamaguchi Teruhide 
Published: November 2006

AbstractPreviously, we suggested that the phosphatidylinositol 3‐kinase (PI3K)‐p70 S6 kinase (p70 S6K) pathway plays an important role in granulocyte colony‐stimulating factor (G‐CSF)‐dependent enhancement of the neutrophilic differentiation and proliferation of HL‐60 cells. While atypical protein kinase C (PKC) has been reported to be a regulator of p70 S6K, abundant expression of PKCι was observed in myeloid and lymphoid cells. Therefore, we analyzed the participation of PKCι in G‐CSF‐dependent proliferation. The maximum stimulation of PKCι was observed from 15 to 30 min after the addition of G‐CSF. From 5 to 15 min into this lag time, PKCι was found to translocate from the nucleus to the membrane. At 30 min it re‐translocated to the cytosol. This dynamic translocation of PKCι was also observed in G‐CSF‐stimulated myeloperoxidase‐positive cells differentiated from cord blood cells. Small interfering RNA for PKCι inhibited G‐CSF‐induced proliferation and the promotion of neutrophilic differentiation of HL‐60 cells. These data indicate that the G‐CSF‐induced dynamic translocation and activation processes of PKCι are important to neutrophilic proliferation. J. Cell. Physiol. 211: 189–196, 2007. © 2006 Wiley‐Liss, Inc.
X‐ray microanalysis of biological material in the frozen‐hydrated state by PIXE
Authors: Tylko Grzegorz , Mesjasz‐Przybyłowicz Jolanta , Przybyłowicz Wojciech J. 
Published: November 2006

AbstractElemental microanalysis of biological material in the frozen‐hydrated state using in‐vacuum proton induced X‐ray emission is described for the first time. For this purpose, a commercially available cryotransfer system was modified and coupled to the experimental chamber of the nuclear microprobe (NMP). The analyzed material was frozen in propane cooled by liquid nitrogen, fractured, carbon coated, and transferred onto the cold stage (100 K) of the nuclear microprobe chamber. Micro‐PIXE and simultaneous proton backscattering was performed using a 3 MeV proton beam. Quantitative results were obtained by the standardless method, and tested using 20% gelatin standards. Monitoring of the gas composition inside the system by means of mass spectrometry performed before, during, and after proton bombardment showed good stability of the analyzed material for proton currents not exceeding 150 pA. Average concentrations of light elements (C, N, O, and indirectly H) were also obtained by the proton backscattering technique. No losses of elements measurable by particle‐induced X‐ray emission (PIXE) during proton irradiation were found during repetitive, short analyses of the same micro areas of gelatin standards. Measurements of thick sections of selected plant and animal material in the frozen‐hydrated state–leaf sections of the plant Senecio anomalochrous Hilliard (Asteraceae) and larvae of Chysolina pardalina Fabricius (Chrysomelidae)–showed very good preservation of morphology and elemental distribution. Limits of detection of the order of a few μg g−1 were obtained for most elements. Microsc. Res. Tech., 2007. © 2006 Wiley‐Liss, Inc.
Heterogeneity in informal sector mitigation of micro‐enterprise credit rationing
Authors: Mushinski David W. , Pickering Kathleen A. 
Published: November 2006

AbstractEconomists have observed that informal credit markets may mitigate micro‐entrepreneurial rationing in formal credit markets. While informal credit markets may have that effect, the uniformity and magnitude of the mitigation is not apparent. We analyse micro‐enterprise credit rationing on the Pine Ridge Indian Reservation in the United States. We find that micro‐entrepreneurs have virtually no access to formal credit markets and that informal credit markets have differential impacts on micro‐entrepreneurs' rationing in formal credit markets. Informal markets appear to ease credit rationing the most for the mid‐size micro‐enterprises in our sample, with the smallest and largest micro‐enterprises still facing severe rationing constraints. We also find that micro‐enterprises of all sizes face a positive probability of credit rationing. Copyright © 2006 John Wiley & Sons, Ltd.
Progression towards AIDS leads to increased torque teno virus and torque teno minivirus titers in tissues of HIV infected individuals
Authors: Thom K. , Petrik J. 
Published: November 2006

AbstractTorque teno virus (TTV) and Torque teno minivirus (TTMV) are highly prevalent in the general population and although no disease has been associated with these viruses yet, co‐infections with other pathological viruses are frequent. Both viruses are extremely heterogeneous, especially for DNA viruses, and the role of the immune system in controlling the infections has yet to be established. In this study the TTV/TTMV viral loads in HIV positive tissues have been investigated for the first time. The titers of both TTV and TTMV were compared in the bone marrow and spleen tissues from three groups: HIV negative individuals, HIV positive individuals and HIV positive individuals who had progressed to AIDS, leading to immunosuppression. Limiting dilution PCR using primers situated in the UTR region of the genome were used to semi‐quantitate the virus, and TTV and TTMV were differentiated using melting curve analysis of the PCR product. The AIDS group had significantly higher titers compared with both the HIV positive and negative groups for both bone marrow (AIDS vs. HIV positive P = 0.006, AIDS vs. HIV negative P < 0.001) and spleen (AIDS vs. HIV positive P = 0.022, AIDS vs. HIV negative P < 0.001). Analysis of TTV/TTMV titer with CD4 T lymphocyte count showed a significant inverse correlation however neither HCV co‐infection or type of Anellovirus infection (single TTV or TTMV, or mixed TTV/TTMV) showed any significant correlation with virus titer. The results show a link between deterioration of the immune system and increased the viral loads in studied tissues. J. Med. Virol. 79:1–7, 2007. © 2006 Wiley‐Liss, Inc.
Comparison of hepatitis A and E virus infections among healthy children in Mongolia: Evidence for infection with a subgenotype IA HAV in children
Authors: Tsatsralt‐Od Bira , Takahashi Masaharu , Endo Kazunori , Agiimaa Dondog , Buyankhuu Osorjin , Okamoto Hiroaki 
Published: November 2006

AbstractTo compare the epidemiologic profiles of hepatitis A virus (HAV) and hepatitis E virus (HEV) infections in children in Mongolia, the prevalence of HAV and HEV infections was investigated serologically and molecularly among 717 apparently healthy individuals of 0–20 years of age (mean ± standard deviation, 8.6 ± 4.9 years) using serum samples obtained between October 2005 and January 2006. Total antibody against HAV (anti‐HAV [total]) was detected in 494 (68.9%) of the 717 subjects, while IgG antibody against HEV (anti‐HEV IgG) was detected in only five subjects (0.7%) (P < 0.0001). All five subjects who had anti‐HEV IgG, were negative for anti‐HEV IgM and HEV RNA. Anti‐HAV was detectable in 24 (75.0%) of the 32 infants aged 7 days to 6 months, but not in any of the 8 infants aged 7 to <12 months. The prevalence of anti‐HAV was 19.5% (17/87) in the age group of 1–3 years, and it increased to 50.0% (69/138) in the age group of 4–6 years, and further to 81.4% (105/129) in the age group of 7–9 years. Of note, 97.2% of the subjects in the age group of 16–20 years had anti‐HAV. The presence of HAV RNA was tested in all 717 subjects, and three children of 1, 4, or 8 years of age were found to have detectable HAV RNA (subgenotype IA). No subject had a history of hepatitis or jaundice. In conclusion, HEV infection was uncommon, but HAV infection lacking overt clinical features was prevalent among children in Mongolia. J. Med. Virol. 79:18–25, 2007. © 2006 Wiley‐Liss, Inc.
Genetic diversity of HCV genotype 2 strains in South Western France
Authors: Thomas Fabienne , Nicot Florence , Sandres‐Sauné Karine , Dubois Martine , Legrand‐Abravanel Florence , Alric Laurent , Peron Jean‐Marie , Pasquier Christophe , Izopet Jacques 
Published: November 2006

AbstractHepatitis C virus (HCV) is a major cause of chronic hepatitis and liver disease worldwide. The genetic heterogeneity of HCV and its spread among infected patients can be examined accurately by nucleotide sequencing. The diversity of HCV genotype 2 strains (HCV‐2) was studied in a large cohort of patients in the Midi Pyrénées area of southern France. Phylogenetic analysis was performed on 344 NS5B sequences from patients infected with HCV‐2. These included 145 strains whose E2 region was also analyzed, and epidemiological data were collected for the corresponding patients. HCV‐2 accounts for 11.3% of HCV infections in this area. Phylogenetic analysis of NS5B sequences revealed eight subtypes, while that of the E2 region provided congruent results for 100% of strains. The most frequent subtypes were 2i (24.7%), 2k (22.4%) 2c (17.4%), and 2a (10.8%). The mean age of HCV‐2‐infected patients was 55.5 years. Epidemiological data showed that blood transfusion is the major route of infection, but it was not associated with any particular subtype. By contrast, intravenous drug users were infected predominantly with genotype 2a. HCV‐2a‐infected patients were younger than patients infected with other subtypes (48 vs. 56.5 years, P < 0.01). This study shows substantial genetic diversity of HCV‐2 subtypes in the south of France and the spread of 2a strains via intravenous drug users. J. Med. Virol. 79:26–34, 2007. © 2006 Wiley‐Liss, Inc.
A mutation in the interferon sensitivity‐determining region is associated with responsiveness to interferon‐ribavirin combination therapy in chronic hepatitis patients infected with a Japan‐specific subtype of hepatitis C virus genotype 1b
Authors: Murayama Mutsumi , Katano Yoshiaki , Nakano Isao , Ishigami Masatoshi , Hayashi Kazuhiko , Honda Takashi , Hirooka Yoshiki , Itoh Akihiro , Goto Hidemi 
Published: November 2006

AbstractThe interferon sensitivity‐determining region (ISDR) is useful as a predictive marker of the response to interferon (IFN) therapy for chronic hepatitis patients with a Japan‐specific subtype (J‐type) of hepatitis C virus (HCV) genotype 1b. This marker is not useful for predicting responsiveness of a worldwide subtype (W‐type) of HCV 1b, which could explain the restricted usefulness of this system only to Japan. In the present study, we examined the predictive value of the ISDR for ribavirin combination therapy. A total of 79 patients with HCV 1b comprising 35 patients with J‐type and 44 patients with W‐type were treated with IFN in combination with ribavirin for more than 48 weeks. Mutations in the ISDR were detected more frequently often seen in J‐type HCV 1b than in W‐type; however, the sustained virological response (SVR) rate for the combination therapy was similar between the two subtypes. Multivariate analysis revealed that factors associated with SVR were IFN dose and the number of amino acid substitutions in ISDR but not with subtypes J and W. The correlation between the number of substitutions in ISDR and responses to IFN‐ribavirin combination therapy was restricted to patients with J‐type HCV 1b. The ISDR is a useful predictive marker for response to IFN‐ribavirin combination therapy in J‐type HCV. J. Med. Virol. 79:35–40, 2007. © 2006 Wiley‐Liss, Inc.
Injury‐induced Janus kinase/protein kinase C‐dependent phosphorylation of growth‐associated protein 43 and signal transducer and activator of transcription 3 for neurite growth in dorsal root ganglion
Authors: Tsai Shih‐Ying , Yang Liang‐Yo , Wu Chin‐Hsiang , Chang Shwu‐Fen , Hsu Chung Y. , Wei Chi‐Peng , Leu Sy‐Jye , Liaw Jiahorng , Lee Yi‐Hsuan , Tsai Ming‐Dar 
Published: November 2006

AbstractElevation of corticosteroids and excessive glutamate release are the two major stress responses that occur sequentially during traumatic CNS injury. We have previously reported that sequential application of corticosterone and kainic acid (CORT + KA) mimicking the nerve injury condition results in synergistic enhancement of neurite outgrowth and expression of growth‐associated protein 43 (GAP‐43) in cultured dorsal root ganglion (DRG). GAP‐43 is known to promote neurite extension when phosphorylated by protein kinase C (PKC). In addition, PKC can phosphorylate the signal transducer and activator of transcription 3 (STAT3) at Ser727, which is phosphorylated primarily by Janus kinase (JAK) at Tyr705. In this study, we further examine the role of PKC in this stress‐induced growth‐promoting effect. In the cultured DRG neurons, the JAK inhibitor AG‐490 and the PKC inhibitor Ro‐318220 reduced the CORT + KA‐enhanced neurite growth effect when applied prior to CORT and KA treatment, respectively. Both AG‐490 and Ro‐318220 diminished the CORT + KA‐enhanced GAP‐43 expression, phosphorylation, and axonal localization. Furthermore, CORT + KA treatment synergistically phosphorylated STAT3 at Ser727 but not at Tyr705. Similar phenomena were observed in an animal model of acute spinal cord injury (SCI), in which phosphorylation of GAP‐43 and phospho‐Ser727‐STAT3 was elevated in the injured DRG 4 hr after the impact injury. Further treatment with the therapeutic glucocorticoid methylprednisolone enhanced the phosphorylation of GAP‐43 in both the DRG and the spinal cord of SCI rats. These results suggest that elevated glucocorticoids and overexcitation following CNS injury contribute to nerve regeneration via induction of JAK/PKC‐mediated GAP‐43 and STAT3 activities. © 2006 Wiley‐Liss, Inc.
RNA interference‐mediated knockdown of α‐synuclein protects human dopaminergic neuroblastoma cells from MPP+ toxicity and reduces dopamine transport
Authors: Fountaine Timothy M. , Wade‐Martins Richard 
Published: November 2006

AbstractThe critical observation in the pathology of Parkinson's disease (PD) is that neurodegeneration is largely restricted to dopaminergic neurons that develop cytoplasmic inclusions called Lewy bodies. These aggregations contain the protein α‐synuclein. Furthermore, it is becoming apparent that α‐synuclein expression levels are a major factor in PD pathogenesis. Patients with additional copies of the α‐synuclein gene develop PD with a severity proportional to levels of α‐synuclein overexpression. Similarly, overexpression of α‐synuclein in in vitro and in vivo models has been shown to be toxic. However, little is known about the effects of reducing α‐synuclein expression in human neurons. To investigate this, we have developed a system in which levels of α‐synuclein can be acutely suppressed by using RNA interference (RNAi) in a physiologically relevant human dopaminergic cellular model. By using small interfering RNA (siRNA) molecules targeted to endogenous α‐synuclein, we achieved 80% protein knockdown. We show that α‐synuclein knockdown has no effect on cellular survival either under normal growth conditions over 5 days or in the presence of the mitochondrial inhibitor rotenone. Knockdown does, however, confer resistance to the dopamine transporter (DAT)‐dependent neurotoxin N‐methyl‐4‐phenylpyridinium (MPP+). We then demonstrate for the first time that α‐synuclein suppression decreases dopamine transport in human cells, reducing the maximal uptake velocity (Vmax) of dopamine and the surface density of its transporter by up to 50%. These results show that RNAi‐mediated α‐synuclein knockdown alters cellular dopamine homeostasis in human cells and may suggest a mechanism for the increased survival in the presence of MPP+, a toxin used extensively to model Parkinson's disease. © 2006 Wiley‐Liss, Inc.