bluuebunny/crossref_metadata_2025_split huggingface dataset:
A New Type of Dendritic [60]Fullerene–Metallo‐tetraphenylporphyrin Diads (M = Zn, Co)
Authors: Kovacs Christian , Hirsch Andreas 
Published: June 2006

AbstractThe synthesis of unsymmetrical malonates 19–23 terminated by a metallo‐tetraphenylporphyrin (M = ZnII, CoII, CoIII) and by Newkome‐type amide dendrons of generation two and three is reported. Cyclopropanation of C60 with the second‐generation dendrons 20 and 21 leads to the formation of fullerene monoadducts 24 and 25, representing a new type of dendritic diads. The establishment of Co in the oxidation sates of +II and +III was achieved by the treatment with Na2S2O4 or with O2 in the presence of CN– and SCN–, respectively, leading to the paramagnetic complex 26 and the diamagnetic axially coordinated complexes 27. Deprotection of the tert‐butyl groups terminating the dendritic branch of the diads 24 and 25 generates the corresponding water‐soluble systems 28 and 29. Due to their amphiphilic character micellar aggregates are formed in water. DOSY NMR measurements showed that the aggregates consisting of 28 have an average diameter of approximately 7 nm in a buffered D2O solution (pH = 7.2). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Large‐scale identification of cytosolic mouse brain proteins by chromatographic prefractionation
Authors: Shin Joo‐Ho , Krapfenbauer Kurt , Lubec Gert 
Published: June 2006

AbstractProteomic studies on mouse brain protein expression are still holding center stage as the generation of a reference database for the brain proteome, a need for designing expressional studies at the protein level. We therefore decided to extend the amount of identified brain proteins by the use of prefractionation. In order to reduce the complexity of mouse brain proteome we applied chromatographic prefractionations, ion‐exchange and hydrophobic interaction chromatography, prior to 2‐DE, followed by mass spectrometric identification (2‐DE MALDI‐MS). We analyzed about 17 000 protein spots in cytosolic fractions of mouse brain and identified about 10 000 spots. A total of 1841 proteins showing different pI or Mr, representing probably post‐translational modifications or splice variants, were products of 789 different genes. Numerous proteins were clearly identified as metabolic, antioxidant, cytoskeleton, signaling, transcription/translation, nucleic acid‐binding, proteolysis‐related proteins. We additionally provided evidence for the existence of hypothetical proteins predicted from nucleic acid sequences. Moreover, observed pIs of proteins are listed thus enabling localization of proteins in a gel, information that cannot be obtained from theoretical pI's in databases. The results represent so far the largest database of mouse brain proteins and provide valuable information for the design of proteomic studies in the mouse.
Neuroproteomics – the tasks lying ahead
Authors: Becker Michael , Schindler Jens , Nothwang Hans Gerd 
Published: June 2006

AbstractThe brain is unquestionably the most fascinating organ. Despite tremendous progress, current knowledge falls short of being able to explain its function. An emerging approach toward improved understanding of the molecular mechanisms underlying brain function is neuroproteomics. Today's neuroscientists have access to a battery of versatile technologies both in transcriptomics and proteomics. The challenge is to choose the right strategy in order to generate new hypotheses on how the brain works. The goal of this review is therefore two‐fold: first we recall the bewildering cellular, molecular, and functional complexity in the brain, as this knowledge is fundamental to any study design. In fact, an impressive complexity on the molecular level has recently re‐emerged as a central theme in large‐scale analyses. Then we review transcriptomics and proteomics technologies, as both are complementary. Finally, we comment on the most widely used proteomics techniques and their respective strengths and drawbacks. We conclude that for the time being, neuroproteomics should focus on its strengths, namely the identification of posttranslational modifications and protein–protein interactions, as well as the characterization of highly purified subproteomes. For global expression profiling, emphasis should be put on further development to significantly increase coverage.
Hydrogels as artificial matrices for human embryonic stem cell self‐renewal
Authors: Li Ying J. , Chung Eugene H. , Rodriguez Ryan T. , Firpo Meri T. , Healy Kevin E. 
Published: June 2006

AbstractHuman embryonic stem cells (hESCs) have the potential to differentiate into all cell types in the body and hold great promise for regenerative medicine; however, large‐scale expansion of undifferentiated hESCs remains a major challenge. Self‐renewal of hESCs requires culturing these cells on either mouse or human fibroblast cells (i.e., a feeder layer of cells), or on artificial extracellular matrices (ECMs) while supplementing the media with soluble growth factors. Here we report a completely synthetic ECM system composed of a semi‐interpenetrating polymer network (sIPN), a polymer hydrogel, which was designed to allow the independent manipulation of cell adhesion ligand presentation and matrix stiffness. In the short term, hESCs that were cultured on the sIPN adhered to the surface, remained viable, maintained the morphology, and expressed the markers of undifferentiated hESCs. This was the first demonstration that a completely synthetic ECM can support short‐term self‐renewal of hESCs. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
Increased osteoblast functions among nanophase titania/poly(lactide‐co‐glycolide) composites of the highest nanometer surface roughness
Authors: Liu Huinan , Slamovich Elliott B. , Webster Thomas J. 
Published: June 2006

AbstractCurrently, the scientific challenges for bone tissue engineering lie in the development of suitable scaffold materials that can improve bone cell adhesion, proliferation, and differentiation. The design of nanophase titania/poly(lactide‐co‐glycolide) (PLGA) composites offers an exciting approach to combine the advantages of a degradable polymer with nanosize ceramic particles to optimize the physical and biological properties necessary for bone regeneration. Moreover, because of the presence of nanosized ceramics, such composites can be formulated to match the surface roughness of bone. For these reasons, the objective of the present in vitro study was to investigate osteoblast (bone‐forming cell) adhesion and long‐term functions on nanophase titania/PLGA composites that mimic the surface roughness of bone. Various sonication powers were applied in this study to manipulate titania dispersions in PLGA and consequently control their surface roughness. Most importantly, results correlated better osteoblast adhesion and long‐term functions (such as collagen, alkaline phosphatase activity, and calcium‐containing mineral deposition) among nanophase titania/PLGA composites that had surface roughness values closer to natural bone. In this manner, this present study demonstrated that the nanophase titania/PLGA composites sonicated to have nanometer surface roughness values can improve osteoblast functions necessary for enhanced bone tissue engineering applications. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
Evidence that both 1α,25‐dihydroxyvitamin D3 and 24‐hydroxylated D3 enhance human osteoblast differentiation and mineralization
Authors: van Driel M. , Koedam M. , Buurman C.J. , Roelse M. , Weyts F. , Chiba H. , Uitterlinden A.G. , Pols H.A.P. , van Leeuwen J.P.T.M. 
Published: June 2006

AbstractVitamin D plays a major role in the regulation of mineral homeostasis and affects bone metabolism. So far, detailed knowledge on the vitamin D endocrine system in human bone cells is limited. Here we investigated the direct effects of 1α,25‐(OH)2D3 on osteoblast differentiation and mineralization. Also, we studied the impact of 24‐hydroxylation, generally considered as the first step in the degradation pathway of vitamin D, as well as the role of the nuclear and presumed membrane vitamin D receptor (VDR). For this we used a human osteoblast cell line (SV‐HFO) that has the potency to differentiate during culture forming a mineralized extracellular matrix in a 3‐week period. Transcriptional analyses demonstrated that both 1α,25‐(OH)2D3 and the 24‐hydroxylated metabolites 24R,25‐(OH)2D3 and 1α,24R,25‐(OH)3D3 induced gene transcription. All metabolites dose‐dependently increased alkaline phosphatase (ALP) activity and osteocalcin (OC) production (protein and RNA), and directly enhanced mineralization. 1α,24R,25‐(OH)3D3 stimulated ALP activity and OC production most potently, while for mineralization it was equipotent to 1α,25‐(OH)2D3. The nuclear VDR antagonist ZK159222 almost completely blocked the effects of all metabolites. Interestingly, 1β,25‐(OH)2D3, an inhibitor of membrane effects of 1α,25‐(OH)2D3 in the intestine, induced gene transcription and increased ALP activity, OC expression and mineralization. In conclusion, not only 1α,25‐(OH)2D3, but also the presumed 24‐hydroxylated “degradation” products stimulate differentiation of human osteoblasts. 1α,25‐(OH)2D3 as well as the 24‐hydroxylated metabolites directly enhance mineralization, with the nuclear VDR playing a central role. The intestinal antagonist 1β,25‐(OH)2D3 acts in bone as an agonist and directly stimulates mineralization in a nuclear VDR‐dependent way. J. Cell. Biochem. 99: 922–935, 2006. © 2006 Wiley‐Liss, Inc.
Multifaceted interaction between the androgen and Wnt signaling pathways and the implication for prostate cancer
Authors: Terry Stéphane , Yang Xuezhen , Chen Min‐Wei , Vacherot Francis , Buttyan Ralph 
Published: June 2006

AbstractAndrogen action in prostate and prostate cancer cells is dependent upon the androgen receptor (AR) protein that transcriptionally regulates the expression of androgen‐dependent genes in the presence of a steroid ligand. Whereas the overall schema of androgen action mediated by this receptor protein appears to be relatively simple, androgen signaling is now known to be influenced by several other cell signal transduction pathways and here we review the evidence that the canonical Wnt signaling pathway also modulates androgen signaling at multiple levels. Wnt is a complex signaling pathway whose endpoint involves activation of transcription from LEF‐1/TCF transcription factors and it is known to be involved in the development and progression of numerous human epithelial tumors including prostate cancer. β‐catenin protein, a particularly critical molecular component of canonical Wnt signaling is now known to promote androgen signaling through its ability to bind to the AR protein in a ligand‐dependent fashion and to enhance the ability of liganded AR to activate transcription of androgen‐regulated genes. Under certain conditions, glycogen synthase kinase‐3β (GSK‐3β), a protein serine/threonine kinase that regulates β‐catenin degradation within the Wnt signaling pathway, can also phosphorylate AR and suppress its ability to activate transcription. Finally, it was recently found that the human AR gene itself is a target of LEF‐1/TCF‐mediated transcription and that AR mRNA is highly upregulated by activation of Wnt signaling in prostate cancer cells. Paradoxically, Wnt activation also appears to stimulate Akt activity promoting an MDM‐2‐mediated degradation process that reduces AR protein levels in Wnt‐stimulated prostate cancer cells. Collectively, this information indicates that the multifaceted nature of the interaction between the Wnt and the androgen signaling pathways likely has numerous consequences for the development, growth, and progression of prostate cancer. J. Cell. Biochem. 99: 402–410, 2006. © 2006 Wiley‐Liss, Inc.
Regulation of osteoblast differentiation by Nurr1 in MC3T3‐E1 cell line and mouse calvarial osteoblasts
Authors: Lee Mi Kyeong , Choi Hosoon , Gil Minchan , Nikodem Vera M. 
Published: June 2006

AbstractThe orphan nuclear receptor Nurr1 is primarily expressed in the central nervous system. It has been shown that Nurr1 is necessary for terminal differentiation of dopaminergic (DA) neurons in ventral midbrain. The receptor, however, is also expressed in other organs including bone, even though the role of Nurr1 is not yet understood. Therefore, we investigated the role of Nurr1 in osteoblast differentiation in MC3T3‐E1 cells and calvarial osteoblasts derived from Nurr1 null newborn pups. Our results revealed that reduced Nurr1 expression, using Nurr1 siRNA in MC3T3‐E1 cells, affected the expression of osteoblast differentiation marker genes, osteocalcin (OCN) and collagen type I alpha 1 (COL1A1), as measured by quantitative real‐time PCR. The activity of alkaline phosphatase (ALP), another osteoblast differentiation marker gene, was also decreased in Nurr1 siRNA‐treated MC3T3‐E1 cells. In addition, Nurr1 overexpression increased OCN and COL1A1 expression. Furthermore, consistent with these results, during osteoblast differentiation, the expression of osteoblast marker genes was decreased in primary cultured mouse calvarial osteoblasts derived from Nurr1 null mice. Collectively, our results suggest that Nurr1 is important for osteoblast differentiation. J. Cell. Biochem. 99: 986–994, 2006. © 2006 Wiley‐Liss, Inc.
PGE2 amplifies the effects of IL‐1β on vascular smooth muscle cell de‐differentiation: A consequence of the versatility of PGE2 receptors 3 due to the emerging expression of adenylyl cyclase 8
Authors: Clément Nathalie , Glorian Martine , Raymondjean Michel , Andréani Marise , Limon Isabelle 
Published: June 2006

AbstractTransition of vascular smooth muscle cells from a contractile/quiescent to a secretory/proliferative phenotype is one of the critical steps in atherosclerosis and is instigated by pro‐inflammatory cytokines released from macrophages that have infiltrated into the vascular wall. In most inflammatory diseases, cell activation induced by these compounds leads to a massive production of type E2 prostaglandin (PGE2) which often takes over and even potentiates the pro‐inflammatory cytokine‐related effects. To evaluate PGE2 incidence on atheroma plaque development, we investigated whether and how this compound could enhance the de‐differentiation of smooth muscle cells initially induced by interleukin‐1β (IL‐1β). To address this issue, we took advantage of vascular smooth muscle cells in primary culture and tracked two markers: PLA2 secretion and α‐actin filament disorganization. In such a context, we found that PGE2 synergizes with IL‐1β to further enhance the phenotype transition of smooth muscle cells, through cAMP‐protein kinase A. As indicated by pharmacological studies, the full PGE2‐dependent potentiation of IL‐1β induced PLA2 secretion is associated with a change of regulation exerted by the subtypes 3 Gi‐coupled PGE2 receptors toward adenylyl cyclase(s) activated by the subtype 4 Gs‐linked PGE2 receptor. Whereas on contractile cells, stimulated subtypes 3 inhibit type 4‐dependent PLA2 secretion, this negative regulation is switched to positive on IL‐1β‐treated cells. Using real time PCR, pharmacological tools and small interfering RNA (siRNA), we demonstrated that the different integration of PGE2 signals depends on the upregulation of calcium/calmodulin stimulable adenylyl cyclase 8. J. Cell. Physiol. 208: 495–505, 2006. © 2006 Wiley‐Liss, Inc.
Dysregulation of NGF‐signaling and Egr‐1 expression by Tat in neuronal cell culture
Authors: Darbinian‐Sarkissian Nune , Czernik Marta , Peruzzi Francesca , Gordon Jennifer , Rappaport Jay , Reiss Krzysztof , Khalili Kamel , Amini Shohreh 
Published: June 2006

AbstractExamination of signal transduction pathways that modulate neuronal cell differentiation and protection against apoptosis has revealed a central role for the MAPK/Erk cascade. The activation of MAPK/Erk through the TrkA NGF signaling pathway is critical for growth and survival of neuronal cells. Here, we investigate the impact of HIV‐1 Tat on the NGF‐signaling pathway in SK‐N‐MC neuroblastoma cells. Expression of Tat decreased cell growth and induced apoptosis. Our results revealed dysregulation of various steps involved in the NGF pathway including suppression of MAPK, and inhibition of the promoter activity of Egr‐1, a key pleiotropic mediator of the expression of genes involved in cell growth upon expression of Tat in SK‐N‐MC cells. Similarly, exposure of SK‐N‐MC to conditioned media derived from cells expressing Tat decreased phosphorylation of MAPK and reduced the level of Egr‐1 protein expression in SK‐N‐MC cells. Furthermore, MAPK was able to phosphorylate Purα, a cellular protein that plays an important role in neuronal cell function and differentiation, and this was inhibited by Tat. The ability of Purα to interact with a GA/GC‐rich sequence positioned upstream from the transcription start site of the Egr‐1 promoter provided a rationale to examine Egr‐1 expression. Expression of Tat decreased NGF‐induced Egr‐1 levels in SK‐N‐MC cells and reduced binding of Purα to the Egr‐1 promoter. All of these observations support a model where the interplay between Tat and Purα dysregulates the NGF pathway including the MAPK/Erk network, resulting in reduced expression and activity of Egr‐1 in neuronal cells. J. Cell. Physiol. 208: 506–515, 2006. © 2006 Wiley‐Liss, Inc.
Superoxide dismutase 1 protects retinal cells from oxidative damage
Authors: Dong Aling , Shen JiKui , Krause Melissa , Akiyama Hideo , Hackett Sean F. , Lai Hong , Campochiaro Peter A. 
Published: June 2006

AbstractBolstering the endogenous oxidative damage defense system is a good strategy for development of treatments to combat neurodegenerative diseases in which oxidative damage plays a role. A first step in such treatment development is to determine the role of various components of the defense system in cells that degenerate. In this study, we sought to determine the role of superoxide dismutase 1 (SOD1) in two models of oxidative damage‐induced retinal degeneration. In one model, paraquat is injected into the vitreous cavity and then enters retinal cells and generates reactive oxygen species (ROS) that cause progressive retinal damage. Assessment of retinal function with serial electroretinograms (ERGs) showed that sod1−/− mice were much more sensitive than sod1+/+ mice to the damaging effects of paraquat, while sod1+/− mice showed intermediate sensitivity. Compared to sod1+/+ mice, sod1−/− mice showed greater paraquat‐induced oxidative damage and apoptosis. In the second model, mice were exposed to hyperoxia for several weeks, and sod1−/− mice showed significantly greater reductions in ERG amplitudes than sod1+/+ mice. In both of these models, transgenic mice carrying a sod1 transgene driven by a β‐actin promoter showed less oxidative stress‐induced reduction in ERG amplitudes. These data demonstrate that SOD1 protects retinal cells against paraquat‐ and hyperoxia‐induced oxidative damage and suggest that overexpression of SOD1 should be considered as one component of ocular gene therapy to prevent oxidative damage‐induced retinal degeneration. J. Cell. Physiol. 208: 516–526, 2006. © 2006 Wiley‐Liss, Inc.
The p53 tumor suppressor participates in multiple cell cycle checkpoints
Authors: Giono Luciana E. , Manfredi James J. 
Published: June 2006

AbstractThe process of cell division is highly ordered and regulated. Checkpoints exist to delay progression into the next cell cycle phase only when the previous step is fully completed. The ultimate goal is to guarantee that the two daughter cells inherit a complete and faithful copy of the genome. Checkpoints can become activated due to DNA damage, exogenous stress signals, defects during the replication of DNA, or failure of chromosomes to attach to the mitotic spindle. Abrogation of cell cycle checkpoints can result in death for a unicellular organism or uncontrolled proliferation and tumorigenesis in metazoans (Nyberg et al., 2002). The tumor suppressor p53 plays a critical role in each of these cell cycle checkpoints and is reviewed here. J. Cell. Physiol. 209: 13–20, 2006. © 2006 Wiley‐Liss, Inc.
Leukemogenic AML1‐ETO fusion protein upregulates expression of connexin 43: The role in AML1‐ETO‐induced growth arrest in leukemic cells
Authors: Li Xi , Xu Ya‐Bei , Wang Qiong , Lu Ying , Zheng Ying , Wang Ying‐Chao , Lübbert Michael , Zhao Ke‐Wen , Chen Guo‐Qiang 
Published: June 2006

AbstractAML1‐ETO, a fusion protein generated by the chromosomal translocation t(8;21), is frequently associated with acute myeloid leukemia (AML). In addition to blocking differentiation, AML1‐ETO is also shown to induce growth arrest in AML cells, which is unfavorable for leukemogenesis harboring the t(8;21) translocation. However, its precise mechanism is still unclear. Here we provide the first demonstration that the conditional expression of AML1‐ETO by the ecdysone‐inducible system dramatically increases the expression of connexin 43 (CX43), together with growth arrest at G1 phase in leukemic U937 cells. We also show that the CX43 induction inhibits the proliferation of U937 cells at G1 phase, while the suppression of CX43 expression by small interfering RNA (siRNA) effectively overcomes the growth‐inhibitory effect of AML1‐ETO in leukemic cells. Furthermore, either AML1‐ETO or CX43 induction elevates cell‐cycle negative regulator P27kip1 protein by inhibiting its degradation, which is antagonized by siRNA against CX43. Taken together, our data indicate that CX43 plays a role in AML1‐ETO‐induced growth arrest possibly through the accumulation of P27kip1 protein. The potential mutation or/and epigenetic alterations of CX43 and its related gene(s) deserve to be explored in AML1‐ETO‐positive AML patients. J. Cell. Physiol. 208: 594–601, 2006. © 2006 Wiley‐Liss, Inc.
Cdk9 phosphorylates p53 on serine 392 independently of CKII
Authors: Claudio Pier Paolo , Cui Jianqi , Ghafouri Mohammad , Mariano Chiara , White Martyn K. , Safak Mahmut , Sheffield Joel B. , Giordano Antonio , Khalili Kamel , Amini Shohreh , Sawaya Bassel E. 
Published: June 2006

AbstractThe tumor suppressor p53 is an important cellular protein, which controls cell cycle progression. Phosphorylation is one of the mechanisms by which p53 is regulated. Here we report the interaction of p53 with another key regulator, cdk9, which together with cyclin T1 forms the positive transcription elongation complex, p‐TEFb. This complex cooperates with the HIV‐1 Tat protein to cause the phosphorylation of the carboxyl terminal domain (CTD) of RNA polymerase II and this facilitates the elongation of HIV‐1 transcription. We demonstrate that cdk9 phosphorylates p53 on serine 392 through their direct physical interaction. Results from protein–protein interaction assays revealed that cdk9 interacts with the C‐terminal domain (aa 361–393) of p53, while p53 interacts with the N‐terminal domain of cdk9. Transfection and protein binding assays (EMSA and ChIP) demonstrated the ability of p53 to bind and activate the cdk9 promoter. Interestingly, cdk9 phosphorylates serine 392 of p53, which could be also phosphorylated by casein kinase II. Kinase assays demonstrated that cdk9 phosphorylates p53 independently of CKII. These studies demonstrate the existence of a feedback‐loop between p53 and cdk9, pinpointing a novel mechanism by which p53 regulates the basal transcriptional machinery. J. Cell. Physiol. 208: 602–612, 2006. © 2006 Wiley‐Liss, Inc.