bluuebunny/crossref_metadata_2025_split huggingface dataset:
Capacitation suppression by mouse seminal vesicle autoantigen involves a decrease in plasma membrane Ca2+‐ATPase (PMCA)‐mediated intracellular calcium
Authors: Lu Shing‐Hwa , Yen Yuan‐Kuei , Ling Thai‐Yen , Cheng Kur‐Ta , Shu Jye‐An , Au Heng‐Kien , Huang Yen‐Hua 
Published: August 2010

AbstractSuccessful fertilization is tightly regulated by capacitation and decapacitation processes. Without appropriate decapacitation regulation, sperm would undergo a spontaneous acrosome reaction which leads to loss of fertilization ability. Seminal plasma is known to negatively regulate sperm capacitation. However, the suppressive mechanisms still remain unclear. In this study, we demonstrate the decapacitation mechanism of mouse seminal vesicle autoantigen (SVA) might target membrane sphingomyelin (SPM) and regulate plasma membrane Ca2+‐ATPase (PMCA) activity. The SVA was shown to suppress sperm capacitation induced by a broad panel of capacitation factors (bovine serum albumin (BSA), PAF, and cyclodextrin (CD)). Furthermore, SVA significantly decreased [Ca2+]i and NaHCO3‐induced [cAMP]i. Cyclic AMP agonists bypassed the SVA's suppressive ability. Importantly, the SVA may regulate PMCA activity which was evidenced by the fact that the SVA decreased the [Ca2+]i and intracellular pH (pHi) of sperm; meanwhile, a PMCA inhibitor (carboxyeosin) could reverse SVA's suppression of [Ca2+]i. The potential target of the SVA on membrane SPM/lipid rafts was highlighted by the high binding affinity of SPM–SVA (with a Kd of ∼3 µM) which was close to the IC50 of SVA's suppressive activity. Additionally, treatment of mink lung epithelial cells with the SVA enhanced plasminogen activator inhibitor (PAI)‐1 expression stimulated by tumor growth factor (TGF)‐β and CD. These observations supported the membrane lipid‐raft targeting of SVA. In summary, in this paper, we demonstrate that the decapacitation mechanism of the SVA might target membrane sphingolipid SPM and regulate PMCA activity to lower [Ca2+]i, thereby decreasing the [cAMP]i level and preventing sperm pre‐capacitation. J. Cell. Biochem. 111: 1188–1198, 2010. © 2010 Wiley‐Liss, Inc.
Hedgehog signaling and osteogenic differentiation in multipotent bone marrow stromal cells are inhibited by oxidative stress
Authors: Kim Woo‐Kyun , Meliton Vicente , Bourquard Noam , Hahn Theodore J. , Parhami Farhad 
Published: August 2010

AbstractOxidative stress may play a major role in age‐related osteoporosis in part by inhibiting osteoblast generation from osteoprogenitors cells. In the present study, we hypothesized that oxidative stress may inhibit the osteogenic differentiation of bone marrow stromal cells (MSC) in part by inhibiting the Hedgehog (Hh) signaling pathway, which is essential for bone development and maintenance and induces osteogenic differentiation of osteoprogenitor cells. To test this hypothesis, we examined the effects of oxidative stress on Sonic Hh (Shh)‐induced osteogenic differentiation and signaling in M2‐10B4 (M2) MSC, C3H10T1/2 embryonic fibroblasts, and mouse primary MSC. Treatment of cells with H2O2 inhibited Shh‐induced osteogenic differentiation determined by the inhibition of Shh‐induced expression of osteogenic differentiation markers alkaline phosphatase (ALP), osterix (OSX), and bone sialoprotein (BSP). Similar effects were found when oxidative stress was induced by xanthine/xanthine oxidase (XXO) or minimally oxidized LDL (MM‐LDL). H2O2, XXO, and MM‐LDL treatment inhibited Shh‐induced expression of the Hh target genes Gli1 and Patched1 as well as Gli‐dependent transcriptional activity in M2 cells. H2O2 treatment also inhibited Hh signaling induced by the direct activation of Smoothened by purmorphamine (PM), but not by Gli1 overexpression. This suggests that oxidative stress may inhibit Hh signaling upstream of Gli activation and Gli‐induced gene expression. These findings demonstrate for the first time that oxidative stress inhibits Hh signaling associated with osteogenic differentiation. Inhibition of Hh signaling‐mediated osteogenic differentiation of osteoprogenitor cells may in part explain the inhibitory effects of oxidative stress on osteoblast development, differentiation, and maintenance in aging. J. Cell. Biochem. 111: 1199–1209, 2010. © 2010 Wiley‐Liss, Inc.
Nucleic acid sequence design via efficient ensemble defect optimization
Authors: Zadeh Joseph N. , Wolfe Brian R. , Pierce Niles A. 
Published: August 2010

AbstractWe describe an algorithm for designing the sequence of one or more interacting nucleic acid strands intended to adopt a target secondary structure at equilibrium. Sequence design is formulated as an optimization problem with the goal of reducing the ensemble defect below a user‐specified stop condition. For a candidate sequence and a given target secondary structure, the ensemble defect is the average number of incorrectly paired nucleotides at equilibrium evaluated over the ensemble of unpseudoknotted secondary structures. To reduce the computational cost of accepting or rejecting mutations to a random initial sequence, candidate mutations are evaluated on the leaf nodes of a tree‐decomposition of the target structure. During leaf optimization, defect‐weighted mutation sampling is used to select each candidate mutation position with probability proportional to its contribution to the ensemble defect of the leaf. As subsequences are merged moving up the tree, emergent structural defects resulting from crosstalk between sibling sequences are eliminated via reoptimization within the defective subtree starting from new random subsequences. Using a Θ(N3) dynamic program to evaluate the ensemble defect of a target structure with N nucleotides, this hierarchical approach implies an asymptotic optimality bound on design time: for sufficiently large N, the cost of sequence design is bounded below by 4/3 the cost of a single evaluation of the ensemble defect for the full sequence. Hence, the design algorithm has time complexity Ω(N3). For target structures containing N ∈{100,200,400,800,1600,3200} nucleotides and duplex stems ranging from 1 to 30 base pairs, RNA sequence designs at 37°C typically succeed in satisfying a stop condition with ensemble defect less than N/100. Empirically, the sequence design algorithm exhibits asymptotic optimality and the exponent in the time complexity bound is sharp. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2011
Bcr‐Abl‐induced tyrosine phosphorylation of Emi1 to stabilize Skp2 protein via inhibition of ubiquitination in chronic myeloid leukemia cells
Authors: Chen Jing‐Yi , Wang Ming‐Chung , Hung Wen‐Chun 
Published: August 2010

AbstractOur previous study demonstrates that Bcr‐Abl fusion oncogene frequently found in chronic myeloid leukemia (CML) cells can up‐regulate Skp2 expression via transcriptional activation. However, Bcr‐Abl also modulates Skp2 protein stability in these cells. Treatment of Bcr‐Abl kinase inhibitor imatinib led to G1 growth arrest accompanied with reduced Skp2 expression. Interestingly, reduction of Skp2 protein occurred prior to down‐regulation of Skp2 mRNA suggesting a post‐translational control. The half‐life of Skp2 protein was significantly attenuated in imatinib‐treated cells. These effects are not cell line specific because similar results were also found in CML cells obtained from patients. Knockdown of Bcr‐Abl similarly caused Skp2 protein instability. The decrease of Skp2 was induced by increased protein degradation through the ubiquitin/proteasome pathway. Imatinib treatment or Bcr‐Abl knockdown reduced Emi1, an endogenous inhibitor of the E3 ligase APC/Cdh1 which mediated Skp2 degradation. We found that Emi1 stability was regulated by phosphorylation and mutation of tyrosine 142 reduced the stability. Our data suggested Bcr‐Abl‐induced Emi1 phosphorylation might be mediated by Src kinase. Firstly, Src inhibitor SU6656 inhibited Emi1 tyrosine phosphorylation in K562 cells. Secondly, transfection of v‐Src rescued the reduction of Emi1 by imatinib. Thirdly, mutation of tyrosine 142 to phenylalanine (Y142F) abolished the phosphorylation of Emi1 by recombinant Src kinase. In addition, ectopic expression of wild type but not Y142F mutant Emi1 counteracted imatinib‐caused growth arrest. Collectively, our results suggest that Bcr‐Abl increases Emi1 phosphorylation and stability to prevent Skp2 protein degradation via APC/Cdh1‐induced ubiquitination and to enhance proliferation of CML cells. J. Cell. Physiol. 226: 407–413, 2011. © 2010 Wiley‐Liss, Inc.
Altered intracellular calcium fluxes in pancreatic cancer induced diabetes mellitus: Relevance of the S100A8 N‐terminal peptide (NT‐S100A8)
Authors: Basso Daniela , Greco Eliana , Padoan Andrea , Fogar Paola , Scorzeto Michele , Fadi Elisa , Bozzato Dania , Moz Stefania , Navaglia Filippo , Zambon Carlo‐Federico , Seraglia Roberta , De Carlo Eugenio , Valerio Anna , Reggiani Carlo , Pedrazzoli Sergio , Plebani Mario 
Published: August 2010

AbstractAfter isolating NT‐S100A8 from pancreatic cancer (PC) tissue of diabetic patients, we verified whether this peptide alters PC cell growth and invasion and/or insulin release and [Ca2+]i oscillations of insulin secreting cells and/or insulin signaling. BxPC3, Capan1, MiaPaCa2, Panc1 (PC cell lines) cell growth, and invasion were assessed in the absence or presence of 50, 200, and 500 nM NT‐S100A8. In NT‐S100A8 stimulated β‐TC6 (insulinoma cell line) culture medium, insulin and [Ca2+] were measured at 2, 3, 5, 10, 15, 30, and 60 min, and [Ca2+]i oscillations were monitored (epifluorescence) for 3 min. Five hundred nanomolars NT‐S100A8 stimulated BxPC3 cell growth only and dose dependently reduced MiaPaCa2 and Panc1 invasion. Five hundred nanomolars NT‐S100A8 induced a rapid insulin release and enhanced β‐TC6 [Ca2+]i oscillations after both one (F = 6.05, P < 0.01) and 2 min (F = 7.42, P < 0.01). In the presence of NT‐S100A8, [Ca2+] in β‐TC6 culture medium significantly decreased with respect to control cells (F = 6.3, P < 0.01). NT‐S100A8 did not counteract insulin induced phosphorylation of the insulin receptor, Akt and IκB‐α, but it independently activated Akt and NF‐κB signaling in PC cells. In conclusion, NT‐S100A8 exerts a mild effect on PC cell growth, while it reduces PC cell invasion, possibly by Akt and NF‐κB signaling, NT‐S100A8 enhances [Ca2+]i oscillations and insulin release, probably by inducing Ca2+ influx from the extracellular space, but it does not interfere with insulin signaling. J. Cell. Physiol. 226: 456–468, 2011. © 2010 Wiley‐Liss, Inc.
Physiological implications of adenosine receptor‐mediated platelet aggregation
Authors: Johnston‐Cox Hillary A. , Yang Dan , Ravid Katya 
Published: August 2010

AbstractAdenosine is an important mediator of inhibition of platelet activation. This metabolite is released from various cells, as well as generated via activity of ecto‐enzymes on the cell surface. Binding of adenosine to A2subtypes (A2Aor A2B), G‐protein coupled adenosine receptors, results in increased levels of intracellular cyclic adenosine monophosphate (cAMP), a strong inhibitor of platelet activation. The role and importance of adenosine and its receptors in platelet physiology are addressed in this review, including recently identified roles for the A2Badenosine receptor as a modulator of platelet activation through its newly described role in the control of expression of adenosine diphosphate (ADP) receptors. J. Cell. Physiol. 226: 46–51, 2010. © 2010 Wiley‐Liss, Inc.
Forced activation of Stat5 subjects mammary epithelial cells to DNA damage and preferential induction of the cellular response mechanism during proliferation
Authors: Eilon Tali , Barash Itamar 
Published: August 2010

AbstractParity‐dependent adenocarcinoma tumors developed in postestropausal transgenic mice expressing a constitutively active Stat5 variant (STAT5ca) in their mammary gland. These tumors maintained elevated expression levels of genes regulating the cellular DNA damage response (DDR) mechanism, compared to the intact gland. No correlation with STAT5ca expression was observed for these genes in the established tumors. However, activated Stat5a in individual cells of the rarely and earlier developed hyperplasia was associated with induced Chk2 activity. Deregulated Stat5 may already cause DNA damage during the fertile period. This hypothesis and the specific vulnerable stage were further studied in mammary epithelial cells that were stably transfected with β‐lactoglobulin (BLG)/STAT5ca and exposed to a reproduced reproductive cycle. During the pregnancy‐like proliferative state, STAT5ca expression was induced by the added lactogenic hormones. Production of reactive oxygen species, rather than proliferation, served as the primary mediator of DNA damage and cellular DDR. Differentiated cells expressed higher levels of STAT5ca and retained the DNA nicks. However, the elevated expression of the genes involved in DDR was downregulated. Higher levels of DNA damage were also detected in the mammary gland of transgenic mice expressing the BLG/STAT5ca during pregnancy and lactation. However, the relative number of damaged cells was much lower than that in the reproduced in vitro stages and the insults were generally associated with apoptosis and DDR. This study implicates pregnancy as the vulnerable stage for deregulated Stat5 activity, and demonstrates that DNA insults in viable differentiated mammary epithelial cells are ignored by the DDR mechanism. J. Cell. Physiol. 226: 616–626, 2011. © 2010 Wiley‐Liss, Inc.
Exceptional structural and mechanical flexibility of the nuclear pore complex
Authors: Liashkovich Ivan , Meyring Anne , Kramer Armin , Shahin Victor 
Published: August 2010

AbstractNuclear pore complexes (NPCs) mediate all transport between the cytosol and the nucleus and therefore take centre stage in physiology. While transport through NPCs has been extensively investigated little is known about their structural and barley anything about their mechanical flexibility. Structural and mechanical flexibility of NPCs, however, are presumably of key importance. Like the cell and the cell nucleus, NPCs themselves are regularly exposed to physiological mechanical forces. Besides, NPCs reveal striking transport properties which are likely to require fairly high structural flexibility. The NPC transports up to 1,000 molecules per second through a physically 9 nm wide channel which repeatedly opens to accommodate macromolecules significantly larger than its physical diameter. We hypothesised that NPCs possess remarkable structural and mechanical stability. Here, we tested this hypothesis at the single NPC level using the nano‐imaging and probing approach atomic force microscopy (AFM). AFM presents the NPC as a highly flexible structure. The NPC channel dilates by striking 35% on exposure to trans‐cyclohexane‐1,2‐diol (TCHD), which is known to transiently collapse the hydrophobic phase in the NPC channel like receptor–cargo complexes do in transit. It constricts again to its initial size after TCHD removal. AFM‐based nano‐indentation measurements show that the 50 nm long NPC basket can astonishingly be squeezed completely into the NPC channel on exposure to incremental mechanical loads but recovers its original vertical position within the nuclear envelope plane when relieved. We conclude that the NPC possesses exceptional structural and mechanical flexibility which is important to fulfilling its functions. J. Cell. Physiol. 226: 675–682, 2011. © 2010 Wiley‐Liss, Inc.
Decrease in claudin‐2 expression enhances cell migration in renal epithelial madin–darby canine kidney cells
Authors: Ikari Akira , Takiguchi Ayumi , Atomi Kosuke , Sato Tomonari , Sugatani Junko 
Published: August 2010

AbstractMigration of renal epithelial cells increases after renal tubular damage, but its mechanism has not been clarified in detail. Hyperosmotic stress increased a cellular injury concomitant with a decrease in mRNA and protein expression of claudin‐2 in renal tubular epithelial Madin–Darby canine kidney cells. We hypothesized that claudin‐2 is involved in the regulation of cell migration. To knockdown claudin‐2 expression, we made the cells expressing doxycycline‐inducible claudin‐2 shRNA vector. Claudin‐2 knockdown affected neither the endogenous expression levels of claudin‐1, ‐3, ‐4, and ‐7 nor the Triton X‐100 solubility of these claudins. Transepithelial electrical resistance was increased by claudin‐2 knockdown without affecting permeability to FITC‐dextran (4,000 Da). BrdU incorporation assay and cell counting revealed that cell proliferation and viability are unaffected by claudin‐2 knockdown. In the wound‐healing assay, the recovery rate of wound area was increased by claudin‐2 knockdown. The mRNA expression and activity of matrix metalloproteinase‐9 (MMP‐9) were increased by claudin‐2 knockdown. A selective MMP‐9 inhibitor suppressed cell migration in the claudin‐2 knockdown cells. Hyperosmotic stress increased the expression and activity of MMP‐9, which were inhibited by claudin‐2 overexpression. These results suggest that the decrease in claudin‐2 expression enhances cell migration mediated by the increase in the expression and activity of MMP‐9. J. Cell. Physiol. 226: 1471–1478, 2011. © 2010 Wiley‐Liss, Inc.
Development of microfluidic devices for biomedical and clinical application
Authors: Webster Abigail , Greenman John , Haswell Stephen J. 
Published: August 2010

AbstractThis review focuses on the development and use of microfluidic devices within a clinical setting. The underlying theoretical background of microfluidics is briefly elucidated. The materials and techniques used to fabricate the devices and their applicability to the clinical environment are described. The current research in this area is appraised and projections for future applications are discussed. Copyright © 2010 Society of Chemical Industry
Piscine aquaporins: an overview of recent advances
Authors: Cerdà Joan , Finn Roderick Nigel 
Published: August 2010

AbstractAquaporins are a superfamily of integral membrane proteins that facilitate the rapid and yet highly selective flux of water and other small solutes across biological membranes. Since their discovery, they have been documented throughout the living biota, with the majority of research focusing on mammals and plants. Here, we review available data for piscine aquaporins, including Agnatha (jawless fish), Chondrichthyes (chimaeras, sharks, and rays), Dipnoi (lungfishes), and Teleostei (ray‐finned bony fishes). Recent evidence suggests that the aquaporin superfamily has specifically expanded in the chordate lineage consequent to serial rounds of whole genome duplication, with teleost genomes harboring the largest number of paralogs. The selective retention and dichotomous clustering of most duplicated paralogs in Teleostei, with differential tissue expression profiles, implies that novel or specialized physiological functions may have evolved in this clade. The recently proposed new nomenclature of the piscine aquaporin superfamily is discussed in relation to the phylogenetic signal and genomic synteny, with the teleost aquaporin‐8 paralogs used as a case study to illustrate disparities between the underlying codons, molecular phylogeny, and physical locus. Structural data indicate that piscine aquaporins display similar channel restriction residues found in the tetrapod counterparts, and hence their functional properties seem to be conserved. However, emerging evidence suggests that regulation of aquaporin function in teleosts may have diverged in some cases. Cell localization and experimental studies imply that the physiological roles of piscine aquaporins extend at least to osmoregulation, reproduction, and early development, although in most cases their specific functions remain to be elucidated.J. Exp. Zool. 313A:623–650, 2010. © 2010 Wiley‐Liss, Inc.
Ross Granville Harrison (1870–1959) and perspectives on regeneration
Authors: Maienschein Jane 
Published: August 2010

AbstractHistorical case studies can serve as cautionary tales, reminding us to reflect on underlying assumptions and on limitations of any particular approach. Ross Harrison's work recorded at the beginning and end of his career in the Journal of Experimental Zoology reveal his own morphological and experimental convictions, as they played out in his studies of regeneration. A closer look at this particular example of Harrison's contributions offers a perspective from which to view current studies of regenerative phenomena and assumptions about appropriate research approaches and the driving questions involved. J. Exp. Zool. (Mol. Dev. Evol.) 314B:607–615, 2010. © 2010 Wiley‐Liss, Inc.
Implementation of a hospitalist‐run observation unit and impact on length of stay (LOS): A brief report
Authors: Leykum Luci K. , Huerta Vincent , Mortensen Eric 
Published: August 2010

AbstractBACKGROUND:While the impact of hospitalists on length of stay (LOS) for inpatient medicine services has been studied, there has been little work on the impact of hospitalist involvement in short‐stay or observation units.OBJECTIVE:The primary objective was to examine the impact of a hospitalist‐run observation unit on LOS. The secondary objective was to assess utilization of the unit through examining case‐weight and LOS.DESIGN:Retrospective cohort study with a preimplementation/postimplementation analysis.SETTING:University Hospital, the 604‐bed teaching hospital for Bexar County, San Antonio, Texas.PATIENTS:All patients discharged from the inpatient medicine and observation units with diagnoses of chest pain, asthma, syncope, cellulitis, and pyelonephritis.INTERVENTION:Creation of a hospitalist‐run, nonteaching, 10‐bed “Clinical Decision Unit” (CDU).MEASUREMENTS:The overall LOS of the “top 5” most common diagnoses was compared for the 12 months preimplementation and postimplementation of the unit.RESULTS:The overall LOS for all patients decreased from 2.4 to 2.2 days (P = 0.05) between the 12 months preimplementation and postimplementation. The greatest decreases were seen for cellulitis (2.4‐1.9 days; P < 0.001) and asthma (2.2‐1.2 days; P < 0.001).CONCLUSIONS:Implementation of a hospitalist‐run observation unit was associated with a significantly decreased LOS for all patients regardless of location, suggesting that the unit has led to more efficient care. Journal of Hospital Medicine 2010; © 2010 Society of Hospital Medicine.