bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reciprocal Relationship Between Cytosolic NADH and ENOX2 Inhibition Triggers Sphingolipid‐Induced Apoptosis in HeLa Cells
Authors: De Luca Thomas , Morré Dorothy M. , Morré D. James 
Published: June 2010

AbstractENOX2 (tNOX), a tumor‐associated cell surface ubiquinol (NADH) oxidase, functions as an alternative terminal oxidase for plasma membrane electron transport. Ubiquitous in all cancer cell lines studied thus far, ENOX2 expression correlates with the abnormal growth and division associated with the malignant phenotype. ENOX2 has been proposed as the cellular target for various quinone site inhibitors that demonstrate anticancer activity such as the green tea constituent epigallocatechin‐3‐gallate (EGCg) and the isoflavene phenoxodiol (PXD). Here we present a possible mechanism that explains how these substances result in apoptosis in cancer cells by ENOX2‐mediated alterations of cytosolic amounts of NAD+ and NADH. When ENOX2 is inhibited, plasma membrane electron transport is diminished, and cytosolic NADH accumulates. We show in HeLa cells that NADH levels modulate the activities of two pivotal enzymes of sphingolipid metabolism: sphingosine kinase 1 (SK1) and neutral sphingomyelinase (nSMase). Their respective products sphingosine 1‐phosphate (S1P) and ceramide (Cer) are key determinants of cell fate. S1P promotes cell survival and Cer promotes apoptosis. Using plasma membranes isolated from cervical adenocarcinoma (HeLa) cells as well as purified proteins of both bacterial and human origin, we demonstrate that NADH inhibits SK1 and stimulates nSMase, while NAD+ inhibits nSMase and has no effect on SK1. Additionally, intact HeLa cells treated with ENOX2 inhibitors exhibit an increase in Cer and a decrease in S1P. Treatments that stimulate cytosolic NADH production potentiate the antiproliferative effects of ENOX2 inhibitors while those that attenuate NADH production or stimulate plasma membrane electron transport confer a survival advantage. J. Cell. Biochem. 110: 1504–1511, 2010. © 2010 Wiley‐Liss, Inc.
Pharmacophore alignment search tool: Influence of canonical atom labeling on similarity searching
Authors: Hähnke Volker , Rupp Matthias , Krier Mireille , Rippmann Friedrich , Schneider Gisbert 
Published: June 2010

AbstractPreviously, (Hähnke et al., J Comput Chem 2009, 30, 761) we presented the Pharmacophore Alignment Search Tool (PhAST), a ligand‐based virtual screening technique representing molecules as strings coding pharmacophoric features and comparing them by global pairwise sequence alignment. To guarantee unambiguity during the reduction of two‐dimensional molecular graphs to one‐dimensional strings, PhAST employs a graph canonization step. Here, we present the results of the comparison of 11 different algorithms for graph canonization with respect to their impact on virtual screening. Retrospective screenings of a drug‐like data set were evaluated using the BEDROC metric, which yielded averaged values between 0.4 and 0.14 for the best‐performing and worst‐performing canonization technique. We compared five scoring schemes for the alignments and found preferred combinations of canonization algorithms and scoring functions. Finally, we introduce a performance index that helps prioritize canonization approaches without the need for extensive retrospective evaluation. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2010
Coriolis coupling and nonadiabaticity in chemical reaction dynamics
Authors: Wu Emilia L. 
Published: June 2010

AbstractThe nonadiabatic quantum dynamics and Coriolis coupling effect in chemical reaction have been reviewed, with emphasis on recent progress in using the time‐dependent wave packet approach to study the Coriolis coupling and nonadiabatic effects, which was done by K. L. Han and his group. Several typical chemical reactions, for example, H+D2, F+H2/D2/HD, D++H2, O+H2, and He+H2+, have been discussed. One can find that there is a significant role of Coriolis coupling in reaction dynamics for the ion‐molecule collisions of D++H2, Ne+H, and He+H2+ in both adiabatic and nonadiabatic context. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2010
Depression anxiety stress scale: is it valid for children and adolescents?
Authors: Patrick Jeff , Dyck Murray , Bramston Paul 
Published: June 2010

AbstractThe Depression Anxiety Stress Scale (Lovibond & Lovibond, 1995) is used to assess the severity of symptoms in child and adolescent samples although its validity in these populations has not been demonstrated. The authors assessed the latent structure of the 21‐item version of the scale in samples of 425 and 285 children and adolescents on two occasions, one year apart. On each occasion, parallel analyses suggested that only one component should be extracted, indicating that the test does not differentiate depression, anxiety, and stress in children and adolescents. The results provide additional evidence that adult models of depression do not describe the experience of depression in children and adolescents. © 2010 Wiley Periodicals, Inc. J Clin Psychol: 66:1–12, 2010.
Generation of life events in bipolar spectrum disorders: A re‐examination and extension of the stress generation theory
Authors: Bender Rachel E. , Alloy Lauren B. , Sylvia Louisa G. , Uroševic Snezana , Abramson Lyn Y. 
Published: June 2010

AbstractThe extent to which stress generation occurs in bipolar spectrum disorders (BSD) is not well understood. The present study examined whether 75 BSD participants experienced elevated rates of behavior‐dependent life events, as compared with 38 normal control participants. Within the BSD group, we also examined whether depressive or hypomanic symptoms prospectively predicted increases in various types of negative and positive life events. Results indicated that BSD participants experienced overall increases in behavior‐dependent events over the follow‐up, as compared with normal controls. At the symptom level, the event generation process occurred in more specific event domains. Results suggest that the stress generation theory of unipolar depression can be extended to BSD and that the type of generated events may be polarity‐specific. © 2010 Wiley Periodicals, Inc. J Clin Psychol: 66: 1–20, 2010.
Does the perceived neighborhood reputation contribute to neighborhood differences in social trust and residential wellbeing?
Authors: Kullberg Agneta , Timpka Toomas , Svensson Tommy , Karlsson Nadine , Lindqvist Kent 
Published: June 2010

AbstractThe authors used a mixed methods approach to examine if the reputation of a housing area has bearing on residential wellbeing and social trust in three pairs of socioeconomically contrasting neighborhoods in a Swedish urban municipality. Multilevel logistic regression analyses were performed to examine associations between area reputation and residential wellbeing and social trust, controlling for the random effect of neighborhood and individual level sociodemographic factors. Qualitative data were analyzed to identify mechanisms of how neighborhood reputations were established. The housing area reputation was found to be strongly associated with wellbeing and social trust. The area reputation also seemed to be a determinant of position in the local social structure; residents were found to position themselves in a rank order. The results suggest that area reputation is an important and probably underestimated dimension in the development of residential wellbeing and social trust in housing. © 2010 Wiley Periodicals, Inc.
Community attachment and satisfaction: the role of a community's social network structure
Authors: Crowe Jessica 
Published: June 2010

AbstractThis paper links the micro and macro levels of analysis by examining how different aspects of community sentiment are affected by one's personal ties to the community compared with the organizational network structure of the community. Using data collected from residents of six communities in Washington State, network analysis combined with negative binomial regression is used to determine the effect of personal networks and community networks on community attachment and satisfaction. Findings suggest that while individual‐level variables, such as length of residence and individual ties, affect one's attachment to community, a community's network structure does not significantly affect community attachment. However, a community's network structure significantly affects one's evaluation of community. Regardless of one's ties to the community, residents of cohesive communities are more likely to evaluate the community's social and physical environments more positively. © 2010 Wiley Periodicals, Inc.
PRAS40 acts as a nodal regulator of high glucose‐induced TORC1 activation in glomerular mesangial cell hypertrophy
Authors: Dey Nirmalya , Ghosh‐Choudhury Nandini , Das Falguni , Li Xiaonan , Venkatesan Balachandar , Barnes Jeffrey L. , Kasinath Balakuntalam S. , Ghosh Choudhury Goutam 
Published: June 2010

AbstractDiabetic nephropathy manifests aberrant activation of TORC1, which senses key signals to modulate protein synthesis and renal hypertrophy. PRAS40 has recently been identified as a raptor‐interacting protein and is a component and a constitutive inhibitor of TORC1. The mechanism by which high glucose stimulates TORC1 activity is not known. PRAS40 was identified in the mesangial cells in renal glomeruli and in tubulointerstitium of rat kidney. Streptozotocin‐induced diabetic renal hypertrophy was associated with phosphorylation of PRAS40 in the cortex and glomeruli. In vitro, high glucose concentration increased PRAS40 phosphorylation in a PI 3 kinase‐ and Akt‐dependent manner, resulting in dissociation of raptor–PRAS40 complex in mesangial cells. High glucose augmented the inactivating and activating phosphorylation of 4EBP‐1 and S6 kinase, respectively, with concomitant induction of protein synthesis and hypertrophy. Expression of TORC1‐nonphosphorylatable mutant of 4EBP‐1 and dominant‐negative S6 kinase significantly inhibited high glucose‐induced protein synthesis and hypertrophy. PRAS40 knockdown mimicked the effect of high glucose on phosphorylation of 4EBP‐1 and S6 kinase, protein synthesis, and hypertrophy. To elucidate the role of PRAS40 phosphorylation, we used phosphorylation‐deficient mutant of PRAS40, which in contrast to PRAS40 knockdown inhibited phosphorylation of 4EBP‐1 and S6 kinase, leading to reduced mesangial cell hypertrophy. Thus, our data identify high glucose‐induced phosphorylation and inactivation of PRAS40 as a central node for mesangial cell hypertrophy in diabetic nephropathy. J. Cell. Physiol. 225: 27–41, 2010. � 2010 Wiley‐Liss, Inc.
Porphyromonas gingivalis lipopolysaccharide inhibits the osteoblastic differentiation of preosteoblasts by activating Notch1 signaling
Authors: Xing Quan , Ye Qingsong , Fan Mingwen , Zhou Yi , Xu Qiang , Sandham Andrew 
Published: June 2010

AbstractAlthough Porphyromonas gingivalis lipopolysaccharide (P‐LPS) is known to inhibit osteoblast differentiation, the exact molecular mechanisms underlying this phenomenon remain unclear. Here, we investigated the role of Notch signaling in the osteoblastic differentiation of both MC3T3E‐1 cells and primary mouse bone marrow stromal cells (BMSCs). P‐LPS stimulation activated the Notch1 signaling cascade and increased expression of the Notch target genes HES1 and HEY1. P‐LPS can also act as an inhibitor because it is capable of suppressing Wnt/β‐catenin signaling in preosteoblasts by decreasing both glycogen synthase kinase‐3β (GSK‐3β) phosphorylation and the expression of nuclear β‐catenin. These effects were rescued, however, by inhibiting Notch1 signaling. Furthermore, P‐LPS treatment inhibited osteoblast differentiation in preosteoblasts as demonstrated by reductions in alkaline phosphatase activity, osteoblast gene expression, and mineralization, all of which were rescued by suppression of Notch1 signaling. Moreover, inhibition of GSK‐3β, HES1, or HEY1 partially reversed the P‐LPS‐induced inhibition of osteoblast differentiation. Together, these findings suggest that P‐LPS inhibits osteoblast differentiation by promoting the expression of Notch target genes and suppressing canonical Wnt/β‐catenin signaling. J. Cell. Physiol. 225: 106–114, 2010. © 2010 Wiley‐Liss, Inc.
Dynamic distribution of spindlin in nucleoli, nucleoplasm and spindle from primary oocytes to mature eggs and its critical function for oocyte‐to‐embryo transition in gibel carp
Authors: Sun Min , Li Zhi , Gui Jian‐Fang 
Published: June 2010

AbstractSpindlin (Spin) was thought as a maternal‐effect factor associated with meiotic spindle. Its role for the oocyte‐to‐embryo transition was suggested in mouse, but its direct evidence for the function had been not obtained in other vertebrates. In this study, we used the CagSpin‐specific antibody to investigate CagSpin expression pattern and distribution during oogenesis of gibel carp (Carassius auratus gibelio). First, the oocyte‐specific expression pattern and dynamic distribution was revealed in nucleoli, nucleoplasm, and spindle from primary oocytes to mature eggs by immunofluorescence localization. In primary oocytes and growth stage oocytes, CagSpin accumulates in nucleoli in increasing numbers along with the oocyte growth, and its disassembly occurs in vitellogenic oocytes, which implicates that CagSpin may be a major component of a large number of nucleoli in fish growth oocytes. Then, co‐localization of CagSpin and β‐tubulin was revealed in meiotic spindle of mature egg, indicating that CagSpin is one spindle‐associated factor. Moreover, microinjection of CagSpin‐specific antibody into the fertilized eggs blocked the first cleavage, and found that the CagSpin depletion resulted in spindle assembly disturbance. Thereby, our study provided the first direct evidence for the critical oocyte‐to‐embryo transition function of Spin in vertebrates, and confirmed that Spin is one important maternal‐effect factor that participates in oocyte growth, oocyte maturation, and oocyte‐to‐embryo transition. J. Exp. Zool. 313A:461–473, 2010. © 2010 Wiley‐Liss, Inc.
Effect of climatic variables on seasonal morphological changes in the testis and epididymis in the wild rodent Microcavia australis from the andes mountains, Argentina
Authors: Velez Silvina , Sassi Paola L. , Borghi Carlos E. , Monclus María A. , Fornés Miguel W. 
Published: June 2010

AbstractIt has been shown that seasonal changes, especially in arid areas have a large influence on gonadal changes of the species that inhabit these areas. We studied a wild hystricomorph Microcavia australis in its natural habitat in the arid Andes Mountains. Sampling of adult males was carried out every 2 months. After autopsy, testes and epididymides were weighed and processed to obtain histological samples. Testes were analyzed with a microscope to measure seminiferous tubule area and diameter for each sampled month. Epididymides were used to determine spermatozoon storage in the cauda region. Results illustrate morphological changes in the testis and epididymis along the year. A high output of sperm cells was detected from middle winter to middle summer and a complete shutdown of spermatogenesis at the end of summer. The initiation of testicular activity coincided with month with the shortest day length, in dry season and very low temperature. On the other hand, gonadal regression started in the middle of summer with long day length, in the wet season, and high temperatures. Rainfall, temperature, and day length seem to be important for the testis cycle. We suggest that photoperiod could be a good predictor for an oncoming period suitable for breeding, and males may probably use it as a signal to regulate gonadal activity. J. Exp. Zool. 313A:474–483, 2010. © 2010 Wiley‐Liss, Inc.
Variation in the hormonal stress response among larvae of three amphibian species
Authors: Belden Lisa K. , Wingfield John C. , Kiesecker Joseph M. 
Published: June 2010

AbstractIn a series of studies, we examined how larval corticosterone treatment for several species of amphibians can impact fitness parameters both during exposure and after metamorphosis. We completed confinement stress series on larvae of three species in natural/semi‐natural conditions: wood frogs (Rana sylvatica), Jefferson salamanders (Ambystoma jeffersonianum), and Eastern spadefoot toads (Scaphiopus holbrooki). Two of the species had a typical vertebrate response of increasing corticosterone with confinement. However, Eastern spadefoot toads, which have a very short developmental period before metamorphosis, did not show any increase in corticosterone in response to confinement. In a second study, we treated the three species with a low and a high concentration of corticosterone (0.001 and 0.01 µM dissolved in tank water) in the laboratory and examined effects on growth. Although we were successful in raising baseline corticosterone levels with our high corticosterone concentrations, this did not translate into changes in mean larval growth for any of the three species. The larval treatments also did not appear to translate into differences in the juvenile response to confinement stress after metamorphosis. Although juvenile wood frogs did respond to confinement with increasing corticosterone, there was no variation based on larval treatment. As with the larval responses, the juvenile Eastern spadefoot toads did not have a hormonal response to confinement. In summary, while our larval corticosterone exposures did elevate baseline corticosterone levels, we did not see effects of exposure on growth or any latent effects of larval exposure on juvenile responses to confinement. J. Exp. Zool. 313A:524–531, 2010. © 2010 Wiley‐Liss, Inc.
Cationic and anionic lipoplexes inhibit gene transfection by electroporation in vivo
Authors: Mignet Nathalie , Vandermeulen Gaëlle , Pembouong Gaëlle , Largeau Céline , Thompson Betty , Spanedda Maria‐Vittoria , Wasungu Luc , Rols Marie‐Pierre , Bessodes Michel , Bureau Michel F. , Préat Véronique , Scherman Daniel 
Published: June 2010

AbstractBackgroundNonviral gene therapy still suffers from low efficiency. Methods that would lead to higher gene expression level of longer duration would be a major advance in this field. Lipidic vectors and physical methods have been investigated separately, and both induced gene expression improvement.MethodsWe sought to combine both chemical and physical methods. Cationic or anionic lipids can potentially destabilize the cell membrane and could consequently enhance gene delivery by a physical method such as electrotransfer. A plasmid model encoding luciferase was used, either free or associated with differently‐charged lipoplexes before electrotransfer.ResultsElectrotransfer alone strongly enhanced gene expression after intramuscular and intradermal injection of naked DNA. On the other hand, cationic and anionic lipoplex formulations decreased gene expression after electrotransfer, whereas poorly‐charged thiourea‐based complexes, brought no benefit. Pre‐injection of the lipids, followed by administration of naked DNA, did not modified gene expression induced by electroporation in the skin.ConclusionsThe results obtained in the present study suggest that packing of DNA plasmid in lipoplexes strongly decreases the efficiency of gene electrotransfer, independently of the lipoplex charge. Non‐aggregating complexes, such as poorly‐charged thiourea‐based complexes, should be preferred to increase DNA release. Copyright © 2010 John Wiley & Sons, Ltd.
Long‐term human growth hormone expression and partial phenotypic correction by plasmid‐based gene therapy in an animal model of isolated growth hormone deficiency
Authors: Oliveira Nélio A. J. , Cecchi Cláudia R. , Higuti Eliza , Oliveira João E. , Jensen Thomas G. , Bartolini Paolo , Peroni Cibele N. 
Published: June 2010

AbstractBackgroundA model for in vivo gene therapy based on electroporation of human growth hormone (hGH)‐coding naked DNA in the muscle of dwarf (lit/lit) and immunodeficient dwarf (lit/scid) mice is described.MethodsA plasmid containing the ubiquitin C promoter and the genomic hGH sequence was administered to the exposed quadriceps muscle, followed by electrotransfer using eight 50‐V pulses of 20 ms at a 0.5‐s interval. Serum hGH levels were determined after various days of DNA administration and a long‐term body weight gain experiment was carried out.ResultsSerum hGH, determined 3 days after DNA administration, revealed a significant dose‐response curve (p < 0.01) in the 0–50 µg range. Because 50 µg of plasmid DNA produced circulating hGH levels of 2–3 ng/ml for at least 12 days, a long‐term body weight gain assay was carried out. After 60 days, the weight of treated lit/scid mice increased 33.1% compared to a 4.2% weight decrease for the control group. hGH circulating levels were of the order of 1.5–3 ng/ml throughout the experiment and the average weight increase during the first 10 days was comparable to that obtained upon regular daily injection of 10 µg of recombinant hGH per mouse, producing comparable circulating levels of the hormone. A lower, but still significant increase in body weight was obtained upon repeating the experiment in immunocompetent dwarf mice (lit/lit).ConclusionsWe report for the first time sustained levels of circulating hGH after intramuscular naked DNA administration and, consequently, a highly significant weight increase of dwarf ‘little’ mice. Copyright © 2010 John Wiley & Sons, Ltd.
Tumor suppression by apoptotic and anti‐angiogenic effects of mortalin‐targeting adeno‐oncolytic virus
Authors: Yoo Ji Young , Ryu Jihoon , Gao Ran , Yaguchi Tomoko , Kaul Sunil C. , Wadhwa Renu , Yun Chae‐Ok 
Published: June 2010

AbstractBackgroundAdeno‐oncolytic (Adon) viruses offer an effective cancer therapeutic tool with several advantages, including wide host cell permeability, high transduction efficiency, safety, tumor selectivity, non‐invasiveness, high genetic modifiability and high level of expression of the integrated transgenes. Armed Adon viruses in which the therapeutic efficacy of virus is enhanced by their coupling with cytotoxic, anti‐angiogenic or anti‐vascular gene products have gained importance because they engage additional mechanisms for tumor cell killing. In the present study, we selected mortalin, a stress chaperone that is tightly involved in human carcinogenesis, constructed a mortalin‐targeting Adon (mot‐Adon) virus and examined its therapeutic potential both in vitro and in vivo.MethodsMortalin‐targeting plasmid and viral vectors that harbored mortalin‐specific small interfering RNA sequences were constructed. The therapeutic value of these vectors was investigated in vitro and in vivo by cell culture and nude mice tumor models.ResultsWe demonstrate that the mot‐Adon virus has selective cytotoxicity for human cancer cells in vitro. Retrovirus‐mediated overexpression of mortalin protected the cells against mot‐Adon virus, confirming that mortalin silencing was the real cause of cancer cell death. Although mortalin overexpression enhanced malignant properties of cancer cells in breast xenograft models, mot‐Adon virus elicited an enhanced anti‐tumor effect. Immunohistochemical examination of the tumors showed that the mot‐Adon virus caused enhanced apoptosis (mediated by reactivation of p53) and suppression of microvessel formation.ConclusionsMortalin is up‐regulated in a large variety of tumors and hence mot‐Adon virus is proposed as a candidate cancer therapeutic agent. Copyright © 2010 John Wiley & Sons, Ltd.