bluuebunny/crossref_metadata_2025_split huggingface dataset:
The spatio‐temporal expression of ProSAP/shank family members and their interaction partner LAPSER1 during Xenopus laevis development
Authors: Gessert Susanne , Schmeisser Michael J. , Tao Si , Boeckers Tobias M. , Kühl Michael 
Published: March 2011

AbstractMembers of the ProSAP/Shank family are important scaffolding proteins of the postsynaptic density (PSD). We investigated for the first time the expression of the three family members named Shank1, ProSAP1/Shank2, and ProSAP2/Shank3 during Xenopus laevis development. Shank1 is expressed in the neural tube, the retina, and the cranial ganglions. In contrast, ProSAP1/Shank2 transcripts could be visualized in the otic vesicle, the pronephros, the liver, the neural tube, and the retina. ProSAP2/Shank3 could be detected in the cardiovascular network, the neural tube, the pronephros, and the retina. Furthermore, we showed that LAPSER1 interacts with all three ProSAP/Shank family members in Xenopus embryos and co‐localizes with ProSAP/Shank in a cell‐based assay. In Xenopus, LAPSER1 is expressed in somites, brain, proctodeum, pronephros, and in some cranial ganglions. Thus, we suggest that members of the ProSAP/Shank family and LAPSER1 not only play a role in PSD formation and plasticity, but also during embryonic development. Developmental Dynamics 240:1528–1536, 2011. © 2011 Wiley‐Liss, Inc.
Hydrogeomorphic processes and vegetation: disturbance, process histories, dependencies and interactions
Authors: Stoffel Markus , Wilford David J. 
Published: March 2011

ABSTRACTRiparian vegetation and hydrogeomorphic processes are intimately connected parts of upland catchment and fan environments. Trees, shrubs and grasses and hydrogeomorphic processes interact and depend on each other in complex ways on the hillslopes, channels and cone‐shaped fans of torrential watersheds. While the presence and density of vegetation have a profound influence on hydrogeomorphic processes, the occurrence of the latter will also exert control on the presence, vitality, species, and age distribution of vegetation. This contribution aims at providing a review of foundational and more recent work on the dependencies and interactions between hydrogeomorphic processes and vegetation. In particular, we address the role of vegetation in the initiation of hydrogeomorphic processes and its impact on stream morphology as well as immediate and long‐term effects of hydrogeomorphic disturbance on vegetation. Copyright © 2011 John Wiley & Sons, Ltd.
Olig1 is expressed in human oligodendrocytes during maturation and regeneration
Authors: Othman Ahmad , Frim David M. , Polak Paul , Vujicic Snezana , Arnason Barry G. W. , Boullerne Anne I. 
Published: March 2011

AbstractMyelin repair is inhibited in multiple sclerosis (MS), ultimately leading to axonal damage and disability. We aimed to understand the transcriptional mechanisms of regeneration in primary human oligodendrocyte cultures isolated from white matter of medically intractable epilepsy patients. Cultures at isolation contained 84% mature oligodendrocytes and 16% oligodendrocyte progenitor cells (OPC). The two populations showed a protracted regeneration of membranes expressing myelin proteins after 2–3 weeks in culture, and were kept long‐term to study membranes maintenance. We profiled by quantitative PCR (qPCR) the sequential mRNA expression of transcription factors Olig1, Olig2, Nkx2.2, Sox10, PPARδ, PPARγ, cyclic nucleotide phosphodiesterase (CNP), myelin basic protein (MBP), myelin‐associated glycoprotein (MAG) and myelin oligodendrocyte glycoprotein (MOG). In summary, Olig1 was not expressed in freshly isolated oligodendrocytes, but was expressed from the beginning of process extension until membranes maintenance. In contrast, Olig2 expression was restricted to isolation and during membranes production. We show for the first time PPARδ expression and absence of PPARγ in human oligodendrocytes. Nkx2.2, Sox10, PPARδ, CNP, MBP and MOG messengers were expressed at any time, while MAG messenger was expressed at mature stage only. Myelin proteins CNP, MBP, MAG, and MOG were confirmed by immunocytochemistry. Our findings point to different roles of Olig1 and Olig2 in regeneration of cultured adult human oligodendrocytes. Noticeably, the transcriptional profiles found in cultured neonatal rodent OPC are different. More studies are necessary to elucidate myelin repair in the adult human brain. © 2011 Wiley‐Liss, Inc.
H‐ferritin is the major source of iron for oligodendrocytes
Authors: Todorich Bozho , Zhang Xuesheng , Connor James R. 
Published: March 2011

AbstractThere is a critical relationship between oligodendrocyte development, myelin production, and iron bioavailability. Iron deficiency leads to hypomyelination both in humans and animal models, and the neurological sequelae of hypomyelination are significant. Therefore, understanding molecular mechanisms of iron import into oligodendrocytes is necessary for devising effective strategies for iron supplementation. Although transferrin has been considered as an essential component of oligodendrocyte media in culture, oligodendrocytes in vivo lack transferrin receptors. We have established that receptors for H‐ferritin (HF) exist on cells of oligodendroglial lineage and that uptake of extracellular HF by oligodendrocyte progenitors is via receptor mediated endocytosis. These data strongly argue that ferritin is a major source of iron for oligodendrocytes. In this study, we demonstrate that media deficient in transferrin results in loss of viability of oligodendrocyte progenitors in culture. Cell loss could be prevented by supplementing the media with HF. Moreover, the addition of extracellular HF stimulates development of oligodendrocyte progenitor cells (OPCs) by increasing expression of myelin basic protein (MBP) and olig2 proteins without increasing their proliferation. The effect of HF on the OPCs could be mimicked by addition of membrane permeable 3,5,5‐trimethylhexanoyl ferrocene (TMH‐Fe) as an iron source to the media, but not membrane‐impermeable ferric ammonium citrate. Overall, therefore, our results demonstrate the importance of iron for OPCs viability and differentiation and identify extracellular HF as a critical source of iron for oligodendrocytes. Given that ferritin receptors, but not transferrin receptors can be demonstrated on oligodendrocytes in vivo, the delivery of iron to oligodendrocytes viaferritin may be the more biological relevant delivery system. © 2011 Wiley‐Liss, Inc.
Regenerating islet‐derived family member, 4 modulates multiple receptor tyrosine kinases and mediators of drug resistance in cancer
Authors: Vanderlaag Kathryn , Wang Wei , Fayadat‐Dilman Laurence , Wagner Janet , Bald Laura , Grein Jeff , Janatpour Mary J. 
Published: March 2011

AbstractRegenerating islet‐derived family member, 4 (Reg IV) is a secreted protein and member of the C‐type lectin superfamily. Expression analyses have characterized Reg IV as a prognostic marker for certain cancers; however, the functional role of Reg IV in cancer, including downstream signaling, has only begun to be elucidated. To investigate the biological role of Reg IV in cancer, phosphorylation events were studied in cancer cell lines in the context of either Reg IV stimulation (HCT116 cells) or knockdown of endogenous Reg IV (PC3 and KM12 cells). In addition to the previously observed impact on epidermal growth factor receptor and Akt phosphorylation, we observed modulation in the phosphorylation of multiple additional receptor tyrosine kinases (RTKs), including insulin receptor, insulin‐like growth factor receptor as well as their downstream effectors, mitogen‐activated protein kinase and phosphatidylinositol‐3‐kinase pathways. Furthermore, knockdown of Reg IV impacted the ability of insulin and EGF to stimulate downstream tyrosine phosphorylation. Knockdown of Reg IV in cancer cell lines inhibited anchorage‐dependent and anchorage‐independent (both soft‐agar and spheroid assays) cell growth and induced cell cycle arrest. This was accompanied by upregulation of p21 and p27. Transiently silencing Reg IV in cancer cells induced apoptosis and downregulated Bcl‐2. Conversely, stimulation of HCT116 cells with recombinant Reg IV induced Bcl‐2. Hsp27, a molecule implicated in drug resistance, was similarly modulated by Reg IV. Consistent with our observations with Reg IV siRNA‐mediated knockdown, monoclonal antibodies directed against Reg IV inhibited PC3 and KM12 cell growth. Collectively, Reg IV plays an important role in cancer by modulation of key signaling molecules including Hsp27, Bcl‐2 and multiple RTKs.
Human melanoma cells express FGFR/Src/Rho signaling that entails an adhesion‐independent caveolin‐1 membrane association
Authors: Fecchi Katia , Travaglione Sara , Spadaro Francesca , Quattrini Adriano , Parolini Isabella , Piccaro Giovanni , Raggi Carla , Fabbri Alessia , Felicetti Federica , Carè Alessandra , Fiorentini Carla , Sargiacomo Massimo 
Published: March 2011

AbstractCaveolae have been indicated as a center of cytoskeleton regulation for Src kinase/Rho GTPase signaling. In addition, Src recruitment on intact cortical actin cytoskeleton appears to be required for bFGF/FGFR signal activation. Recently, we established a relationship between caveolin‐1 (Cav‐1) expression and cell migration in human malignant melanoma, constitutively activated by a bFGF autoregulatory loop. This work intends to investigate whether caveolae's asset, through bFGF/FGFR/c‐Src/Rho signaling, could be related to melanoma cell anchorage. Accordingly, we revealed the existence of a FGFR/Src kinase pathway in Cav‐1 enriched detergent‐resistant membranes (DRMs) of Me665/1 metastatic melanoma cells, as confirmed by FGFR silencing. Moreover, we determined the expression and phosphorylation levels of Cav‐1/Src/Erk signal pathway as a function of FGFR activation and cell density. A sucrose density gradient ultracentrifugation was employed to monitor Cav‐1 membrane association and buoyancy in Me665/1 cells treated for actin fragmentation or for altered phosphorylation signals. As a result, melanoma cells show remarkable resistance to Cav‐1 disassembly, together with persisting cell signal activity, being Src and Cav‐1 crucial modulators of Rho GTPases. In conclusion, our study primarily highlights, in a metastatic melanoma cell line expressing caveolin, the circumstances whereby caveola structural and functional endurance enables the FGFR/Src/Rho GTPases pathway to keep on cell progression.
Long‐term exposure of gastrointestinal stromal tumor cells to sunitinib induces epigenetic silencing of the PTEN gene
Authors: Yang Jing , Ikezoe Takayuki , Nishioka Chie , Takezaki Yuka , Hanazaki Kazuhiro , Taguchi Takahiro , Yokoyama Akihito 
Published: March 2011

AbstractAlthough sunitinib possesses significant clinical effects on imatinib‐resistant gastrointestinal stromal tumors (GISTs), the individuals with GIST eventually become resistant to treatment with this tyrosine kinase inhibitor. The mechanism of resistance to sunitinib is still under investigation. To address this issue, we have established sunitinib‐resistant GIST‐T1 sublines (designated as GIST‐T1R) by culturing cells with increasing concentrations of sunitinib. GIST‐T1R cells were also resistant to imatinib‐mediated growth inhibition. Examination of intracellular signaling found that Akt/ mammalian target of rapamycin (mTOR) signaling remained activated in GIST‐T1R but not in parental GIST‐T1 cells, after exposure of these cells to sunitinib, as measured by immunoblotting. Further study found that the phosphatase and tensin homolog deleted on chromosome ten (PTEN) gene was silenced by methylation of the promoter region of the gene. Notably, forced‐expression of PTEN in GIST‐T1R cells negatively regulated the Akt/mTOR pathways and sensitized these cells to sunitinib‐mediated growth arrest and apoptosis. Taken together, epigenetic silence of PTEN might be one of the mechanisms which cause drug‐resistance in individuals with GIST after exposure to tyrosine kinase inhibitors. Blockade of the PI3K/Akt signaling with the specific inhibitors could be useful in such a case.
Inhibition of activated receptor tyrosine kinases by Sunitinib induces growth arrest and sensitizes melanoma cells to Bortezomib by blocking Akt pathway
Authors: Yeramian Andree , Sorolla Anabel , Velasco Ana , Santacana Maria , Dolcet Xavier , Valls Joan , Abal Leandre , Moreno Sara , Egido Ramón , Casanova Josep M. , Puig Susana , Vilella Ramón , Llombart‐Cussac Antonio , Matias‐Guiu Xavier , Martí Rosa M. 
Published: March 2011

AbstractDespite the use of multiple therapeutic strategies, metastatic melanoma remains a challenge for oncologists. Thus, new approaches using combinational treatment may be used to try to improve the prognosis of this disease. In this report, we have analyzed the expression of receptor tyrosine kinases (RTKs) in melanoma specimens and in four metastatic melanoma cell lines. Both melanoma specimens and cell lines expressed RTKs, suggesting that they may represent eventual targets for multitargeted tyrosine kinase inhibitor, Suntinib. Sunitinib reduced the proliferation of two melanoma cell lines (M16 and M17) and increased apoptosis in one of them (M16). Moreover, the two metastatic melanoma cell lines harbored an activated receptor (PDGFRα and VEGFR, respectively), and Sunitinib suppressed the phosphorylation of the RTKs and their downstream targets Akt and ribosomal protein S6, in these two cell lines. Similar results were obtained when either PDGFRα or VEGFR2 expression was silenced by lentiviral‐mediated short‐hairpin RNA delivery in M16 and M17, respectively. To evaluate the interaction between Sunitinib and Bortezomib, median dose effect analysis using MTT assay was performed, and combination index was calculated. Bortezomib synergistically enhanced the Sunitinib‐induced growth arrest in Sunitinib‐sensitive cells (combination index < 1). Moreover, LY294002, a PI3K inhibitor, sensitized melanoma cells to Bortezomib treatment, suggesting that downregulation of phospho‐Akt by Sunitinib mediates the synergy obtained by Bortezomib + Sunitinib cotreatment. Altogether, our results suggest that melanoma cells harboring an activated RTK may be clinically responsive to pharmacologic RTK inhibition by Sunitinib, and a strategy combining Sunitinib and Bortezomib, may provide therapeutic benefit.
Downregulation of zinc finger protein 132 in prostate cancer is associated with aberrant promoter hypermethylation and poor prognosis
Authors: Abildgaard Mette Opstrup , Borre Michael , Mortensen Martin Mørck , Ulhøi Benedicte P. , Tørring Niels , Wild Peter , Kristensen Helle , Mansilla Francisco , Ottosen Peter D. , Dyrskjøt Lars , Ørntoft Torben F. , Sørensen Karina Dalsgaard 
Published: March 2011

AbstractThis study investigates the expression and biomarker potential of zinc finger protein 132 (ZNF132) in prostate cancer (PC) by transcriptional profiling and immunohistochemical analysis of tissue microarrays, including tumor specimens from 615 radical prostatectomy (RP) patients and 199 conservatively treated patients. Primary clinical endpoints were time to PSA recurrence and cancer‐specific death, respectively. Compared to normal prostate epithelial cells from men without PC, ZNF132 transcript levels were significantly reduced in PC cells from patients with localized PC and further downregulated in metastatic PC. Likewise, ZNF132 protein expression was significantly lower in primary tumors from patients with metastatic compared to localized PC and further reduced in castrate‐refractory PC, indicating that ZNF132 downregulation correlates with disease progression. Reduced ZNF132 immunoreactivity was significantly associated with high Gleason score and advanced T stage in both PC patient cohorts. By univariate analysis, no/weak ZNF132 staining was a significant adverse predictor of PSA recurrence after RP (p = 0.024) and cancer‐specific death following conservative treatment (p = 0.009). In multivariate models, however, ZNF132 did not add significant independent value to established prognostic factors. Finally, bisulfite sequencing revealed frequent promoter hypermethylation of ZNF132 in both PC cell lines and PC tissue samples, indicating that ZNF132 is epigenetically silenced in PC. In summary, our results show that downregulation of ZNF132 is associated with aggressive PC and furthermore identify ZNF132 as a new candidate methylation marker for PC.
Ligand migration in human indoleamine‐2,3 dioxygenase
Authors: Nienhaus Karin , Nickel Elena , Lu Changyuan , Yeh Syun‐Ru , Nienhaus G. Ulrich 
Published: March 2011

AbstractHuman indoleamine 2,3‐dioxygenase (hIDO), a monomeric heme enzyme, catalyzes the oxidative degradation of L‐tryptophan (L‐Trp) and other indoleamine derivatives. Its activity follows typical Michaelis–Menten behavior only for L‐Trp concentrations up to 50 μM; a further increase in the concentration of L‐Trp causes a decrease in the activity. This substrate inhibition of hIDO is a result of the binding of a second L‐Trp molecule in an inhibitory substrate binding site of the enzyme. The molecular details of the reaction and the inhibition are not yet known. In the following, we summarize the present knowledge about this heme enzyme. © 2011 IUBMB IUBMB Life, 63(3): 153–159, 2011
Ligand migration in the truncated hemoglobin of Mycobacterium tuberculosis
Authors: Heroux Maxime S. , Mohan Anne D. , Olsen Kenneth W. 
Published: March 2011

AbstractThe truncated hemoglobin of Mycobacterium tuberculosis (Mt‐trHbO) is a small heme protein belonging to the hemoglobin superfamily. Truncated hemoglobins (trHbs) are believed to have functional roles such as terminal oxidases and oxygen sensors involved in the response to oxidative and nitrosative stress, nitric oxide (NO) detoxification, O2/NO chemistry, O2 delivery under hypoxic conditions, and long‐term ligand storage. Based on sequence similarities, they are classified into three groups. Experimental studies revealed that all trHbs display a 2‐on‐2 α‐helical sandwich fold rather than the 3‐on‐3 α‐helical sandwich fold of the classical hemoglobin fold. Using locally enhanced sampling (LESMD) molecular dynamics, the ligand‐binding escape pathways from the distal heme binding cavity of Mt‐trHbO were determined to better understand how this protein functions. The importance of specific residues, such as the group II and III invariant W(G8) residue, can be seen in terms of ligand diffusion pathways and ligand dynamics. LESMD simulations show that the wild‐type Mt‐trHbO has three diffusion pathways while the W(G8)F Mt‐trHbO mutant has only two. The W(G8) residue plays a critical role in ligand binding and stabilization and helps regulate the rate of ligand escape from the distal heme pocket. Thus, this invariant residue is important in creating ligand diffusion pathways and possibly in the enzymatic functions of this protein. © 2011 IUBMB IUBMB Life, 63(3): 214–220, 2011
Cardiolipin drives cytochrome c proapoptotic and antiapoptotic actions
Authors: Ascenzi Paolo , Polticelli Fabio , Marino Maria , Santucci Roberto , Coletta Massimo 
Published: March 2011

AbstractCytochrome c (cytc) is pivotal in mitochondrial respiration and apoptosis. The heme‐Fe‐atom of native hexacoordinated horse heart cytc (hhcytc) displays a very low reactivity toward ligands and does not exhibit catalytic properties. However, on interaction with cardiolipin (CL), hhcytc changes its tertiary structure disrupting the heme‐Fe‐Met80 distal bond. The CL‐hhcytc complex displays a very low midpoint potential, out of the range required for its physiological role, binds CO and NO with high affinity, facilitates peroxynitrite isomerization to NO3−, and displays peroxidase activity. As a whole, the CL‐hhcytc complex could play either proapoptotic effects, catalyzing lipid peroxidation and the subsequent hhcytc release into the cytoplasm, orantiapoptotic actions, such as scavenging peroxynitrite (i.e., protecting the mitochondrion from reactive nitrogen and oxygen species), and binding of CO and NO (i.e., inhibiting lipid peroxidation and hhcytc traslocation). Here, the CL‐driven allosteric modulation of hhcytc properties is reviewed, highlighting proapoptotic and antiapoptotic actions. © 2011 IUBMB IUBMB Life, 63(3): 160–165, 2011
Changes in hip fracture rates in southeastern Australia spanning the period 1994–2007
Authors: Pasco Julie A , Brennan Sharon L , Henry Margaret J , Nicholson Geoffrey C , Sanders Kerrie M , Zhang Yu , Kotowicz Mark A 
Published: March 2011

Abstract
Hip fracture incidence rates appear to be declining in Western populations. Utilizing comprehensive incident hip fracture data from radiology reports, we determined changes in hip fracture rates in southeastern Australia between 1994–1996 and 2006–2007 for residents aged 55 years or older. During this period, the population at risk increased by 47% for men and 40% for women. Although the absolute number of hip fractures increased by 53% in men and 4.4% in women, standardized hip fracture ratios were 0.92 [95% confidence interval (CI) 0.79–1.08] and 0.69 (95% CI 0.62–0.77), respectively. Marked reductions in hip fracture rates were observed for women: 32% for ages 75 to 84 years and 29% for ages 85 years or older. Data from the Geelong Osteoporosis Study were used to identify changes in body composition and lifestyle that might have influenced hip fracture risk in women during this period. Between 1993–1997 and 2004–2008, there was an increase in adiposity, bone mineral density (BMD), healthy lifestyles, and exposure to bone-active drugs; use of hormone therapy declined. Thus hip fracture incidence rates have decreased from the mid-1990 s to the mid-2000 s, the effect being greater among women. Our data also suggest that the recent increase in adiposity and consequent increase in BMD at the hip may have contributed to this decline. However, improved efficacy and increased uptake of antifracture drug treatments, other cohort effects, or other environmental influences cannot be excluded. © 2011 American Society for Bone and Mineral Research.
Differential expression of complement proteins in cerebrospinal fluid from active multiple sclerosis patients
Authors: Li Yun , Qin Zhaoyu , Yang Mingchong , Qin Yanjiang , Lin Chengzhao , Liu Shilian 
Published: March 2011

AbstractMultiple sclerosis (MS) is a demyelinating disease of the central nervous system with complex immunopathogenesis. Using the 2‐D DIGE technology, we separate CSF proteins from patients with active MS and control subjects. Three of the seven differential proteins identified were related with complement system, and the network analysis of the differential proteins revealed complement activation involvement in active MS. Complement C4b (gamma chain) was confirmed elevated by performing western blotting analysis (P < 0.01). The present results are an independent quantitative proteomic measure in CSF from active MS patients. The differential expression of the complement C4b and related proteins in CSF provides potential biomarkers as well as evidence for the involvement of complement activation in the pathogenesis of MS disease. J. Cell. Biochem. 112: 1930–1937, 2011. © 2011 Wiley‐Liss, Inc.