bluuebunny/crossref_metadata_2025_split huggingface dataset:
Membrane actions of vitamin D metabolites 1α,25(OH)2D3 and 24R,25(OH)2D3 are retained in growth plate cartilage cells from vitamin D receptor knockout mice
Authors: Boyan Barbara D. , Sylvia V.L. , McKinney N. , Schwartz Z. 
Published: November 2003

Abstract1α,25(OH)2D3 regulates rat growth plate chondrocytes via nuclear vitamin D receptor (1,25‐nVDR) and membrane VDR (1,25‐mVDR) mechanisms. To assess the relationship between the receptors, we examined the membrane response to 1α,25(OH)2D3 in costochondral cartilage cells from wild type VDR(+/+) and VDR(−/−) mice, the latter lacking the 1,25‐nVDR and exhibiting type II rickets and alopecia. Methods were developed for isolation and culture of cells from the resting zone (RC) and growth zone (GC, prehypertrophic and upper hypertrophic zones) of the costochondral cartilages from wild type and homozygous knockout mice. 1α,25(OH)2D3 had no effect on [3H]‐thymidine incorporation in VDR(−/−) GC cells, but it increased [3H]‐thymidine incorporation in VDR(+/+) cells. Proteoglycan production was increased in cultures of both VDR(−/−) and VDR(+/+) cells, based on [35S]‐sulfate incorporation. These effects were partially blocked by chelerythrine, which is a specific inhibitor of protein kinase C (PKC), indicating that PKC‐signaling was involved. 1α,25(OH)2D3 caused a 10‐fold increase in PKC specific activity in VDR(−/−), and VDR(+/+) GC cells as early as 1 min, supporting this hypothesis. In contrast, 1α,25(OH)2D3 had no effect on PKC activity in RC cells isolated from VDR(−/−) or VDR(+/+) mice and neither 1β,25(OH)2D3 nor 24R,25(OH)2D3 affected PKC in GC cells from these mice. Phospholipase C (PLC) activity was also increased within 1 min in GC chondrocyte cultures treated with 1α,25(OH)2D3. As noted previously for rat growth plate chondrocytes, 1α,25(OH)2D3 mediated its increases in PKC and PLC activities in the VDR(−/−) GC cells through activation of phospholipase A2 (PLA2). These responses to 1α,25(OH)2D3 were blocked by antibodies to 1,25‐MARRS, which is a [3H]‐1,25(OH)2D3 binding protein identified in chick enterocytes. 24R,25(OH)2D3 regulated PKC in VDR(−/−) and VDR(+/+) RC cells. Wild type RC cells responded to 24R,25(OH)2D3 with an increase in PKC, whereas treatment of RC cells from mice lacking a functional 1,25‐nVDR caused a time‐dependent decrease in PKC between 6 and 9 min. 24R,25(OH)2D3 dependent PKC was mediated by phospholipase D, but not by PLC, as noted previously for rat RC cells treated with 24R,25(OH)2D3. These results provide definitive evidence that there are two distinct receptors to 1α,25(OH)2D3. 1α,25(OH)2D3‐dependent regulation of DNA synthesis in GC cells requires the 1,25‐nVDR, although other physiological responses to the vitamin D metabolite, such as proteoglycan sulfation, involve regulation via the 1,25‐mVDR. © 2003 Wiley‐Liss, Inc.
Biochemical and functional changes of rat liver spheroids during spheroid formation and maintenance in culture: I. morphological maturation and kinetic changes of energy metabolism, albumin synthesis, and activities of some enzymes
Authors: Ma Mingwen , Xu Jinsheng , Purcell Wendy M. 
Published: November 2003

AbstractIn the process of isolated single liver cells coming together to form three‐dimensional spheroids, cells undergo dramatic environmental changes. How liver cells respond to these changes has not been well studied before. This study characterized the functional and biochemical changes during liver spheroid formation and maintenance. Spheroids were prepared in 6‐well plates from freshly isolated liver cells from male Sprague rats by a gyrotatory‐mediated method. Morphological formation, and functional and biochemical parameters of liver spheroids were evaluated over a period of 21 days in culture. Liver spheroid formation was divided into two stages, immature (1–5 days) and mature (>5 days), according to their size and shape, and changes in their functionality. Galactose and pyruvate consumption was maintained at a relatively stable level throughout the period of observation. However, glucose secretion and cellular GPT and GOT activities were higher in immature spheroids, decreased upto day 5 and remained stable thereafter. Cellular γ‐glutamyltransferase (γ‐GT) and lactate dehydrogenase (LDH) activities were initially undetectable or low and increased as spheroids matured. Albumin secretion decreased rapidly within the first 2 days and increased as spheroids matured. It is concluded that cells undergo functional and biochemical changes during spheroid formation following isolation of liver cells from intact tissue. Functionality and biochemical properties recovered and were maintained in mature spheroids. A relatively stable period (6–15 days) of functionality in mature spheroids was identified and is recommended for applications of the model. © 2003 Wiley‐Liss, Inc.
Transcriptional characterization of bone morphogenetic proteins (BMPs)‐mediated osteogenic signaling
Authors: Peng Ying , Kang Quan , Cheng Hongwei , Li Xinmin , Sun Michael H. , Jiang Wei , Luu Hue H. , Park Jae Yoon , Haydon Rex C. , He Tong‐Chuan 
Published: November 2003

AbstractBone formation is presumably a complex and well‐orchestrated process of osteoblast lineage‐specific differentiation. As members of the TGFβ superfamily, bone morphogenetic proteins (BMPs) play an important role in regulating osteoblast differentiation and subsequent bone formation. Several BMPs are able to induce de novo bone formation. Although significant progress has recently been made about the transcriptional control of osteoblast differentiation, detailed molecular events underlying the osteogenic process remain to be elucidated. In order to identify potentially important signaling mediators activated by osteogenic BMPs but not by non‐osteogenic BMPs, we sought to determine the transcriptional differences between three osteogenic BMPs (i.e., BMP‐2, BMP‐6, and BMP‐9) and two inhibitory/non‐osteogenic BMPs (i.e., BMP‐3 and BMP‐12). Through the microarray analysis of approximately 12,000 genes in pre‐osteoblast progenitor cells, we found that expression level of 203 genes (105 up‐regulated and 98 down‐regulated) was altered >2‐fold upon osteogenic BMP stimulation. Gene ontology analysis revealed that osteogenic BMPs, but not inhibitory/non‐osteogenic BMPs, activate genes involved in the proliferation of pre‐osteoblast progenitor cells towards osteoblastic differentiation, and simultaneously inhibit myoblast‐specific gene expression. BMP‐regulated expression of the selected target genes was confirmed by RT‐PCR, as well as by the CodeLink Bioarray analysis. Our findings are consistent with the notion that osteogenesis and myogenesis are two divergent processes. Further functional characterization of these downstream target genes should provide important insights into the molecular mechanisms behind BMP‐mediated bone formation. © 2003 Wiley‐Liss, Inc.
Evolution of the thymus size in response to physiological and random events throughout life
Authors: Domínguez‐Gerpe Lourdes , Rey‐Méndez Manuel 
Published: November 2003

AbstractDuring embryogenesis and in the early stages of life, the thymus is a crucial organ for the generation of the T cell repertoire. T cells are generated from hematopoietic stem cells already differentiated to precursor T cells in the bone marrow. These cells enter the thymus guided by chemotactic factors secreted by this organ. The complex maturation process takes place that ensures self‐tolerance and homeostasis. Thymocytes that show autoreactivity do not leave the thymus, but rather die by apoptosis. The final percentage of mature T cells that survive to migrate from the thymus to the periphery is very low: at most 5%, under optimal conditions. The highest migration occurs in childhood and adulthood, at least in mice and humans; however, it declines throughout life and is minimal in the elderly. Under normal circumstances, the thymus commences involution soon after birth, and this involution correlates with the capacity to export mature T cells to the periphery. Hormones, cytokines, and neurotransmitters all play a role in this age‐associated process, but the reasons for and mechanisms of this involution remain unknown. Apart from physiological conditions that change throughout life and govern age‐related thymus evolution, random states and events provoked by intrinsic or extrinsic factors can induce either thymus involution, as in reversible transient thymic hypoplasias, or thymic hyperplasias. The age‐associated involution, unlike transient involutions, follows a regular pattern for all individuals, though there are clear differences between the sexes. Nevertheless, even the age‐associated involution seems to be reversible, raising the possibility of therapeutic strategies aimed at enhancing thymus function in the elderly. Microsc. Res. Tech. 62:464–476, 2003. © 2003 Wiley‐Liss, Inc.
Aging of the vertebrate immune system
Authors: Torroba Marta , Zapata Agustín G. 
Published: November 2003

AbstractWe have summarized current knowledge on the aging of the immune system in three vertebrate groups: fish, amphibians and birds. Available data are few due to difficulties in studying ageing in natural populations and in accurately determining age. In all vertebrates, the most obvious evidence of the senescence of lymphoid tissue is the involution of thymus, which courses with decreased numbers of thymocytes, and loss of the histological organization of gland. On the other hand, there is little information on aged secondary lymphoid organs. Possible influence of the endocrine system in the changes observed in aged lymphoid organs is also discussed. Microsc. Res. Tech. 62:477–481, 2003. © 2003 Wiley‐Liss, Inc.
Age‐related changes in the avian primary lymphoid organs (thymus and bursa of Fabricius)
Authors: Ciriaco Emilia , Píñera Pablo P. , Díaz‐Esnal Belén , Laurà Rosaria 
Published: November 2003

AbstractThe avian primary lymphoid organs, the thymus and the bursa of Fabricius, undergo age‐dependent changes leading in some cases to the complete atrophy of the organ. Nevertheless, the timetable of the involutive process as well as the consequences in the structure and functionality of the organs vary largely in the time frame and structural changes among species. On the other hand, and in contrast with the large body of literature reporting the structural and functional changes in mammalian primary lymphoid organs, the age‐dependent changes in avian thymus and bursa of Fabricius are scarce, fragmentary, and heterogeneous. This article reviews the current literature on this topic, and focuses primarily on the involution of the bursa of Fabricius. Microsc. Res. Tech. 62:482–487, 2003. © 2003 Wiley‐Liss, Inc.
Hepatitis C virus core protein upregulates transforming growth factor‐β1 transcription
Authors: Taniguchi Hiroyoshi , Kato Naoya , Otsuka Motoyuki , Goto Tadashi , Yoshida Hideo , Shiratori Yasushi , Omata Masao 
Published: November 2003

AbstractThe majority of persons with chronic hepatitis C virus (HCV) infection develop liver fibrosis. Transforming growth factor (TGF)‐β1 plays a pivotal role in the pathogenesis of post‐inflammatory liver scarring. To clarify the influence of HCV infection on liver fibrosis, a reporter assay was used to investigate the effect of viral proteins on TGF‐β1 expression in human hepatoma cells. Of all HCV proteins investigated (core, E1/E2/p7, NS2, NS3, NS4A, NS4B, NS5A, and NS5B), only the core protein activated the TGF‐β1 promoter and upregulated TGF‐β1 expression measured by an RNase protection assay. Bases −376 to −331 bp in the promoter region of TGF‐β1 are responsible for upregulation by HCV core protein, and the nuclear protein that binds to this region increased with the stimulation of HCV core protein. Blocking the mitogen‐activated protein kinase pathway prevented upregulation of TGF‐β1 by HCV core protein. The immunological response is supposed to be a major factor to cause the secretion of TGF‐β1 from non‐parenchymal cells, but the results suggest that the HCV core protein expression may upregulate directly TGF‐β1 transcription in parenchymal cells and suggest a new paradigm for exacerbation of liver fibrosis by HCV infection. J. Med. Virol. 72:52–59, 2004. © 2004 Wiley‐Liss, Inc.
Intracellular localization of the Epstein‐Barr virus BFRF1 gene product in lymphoid cell lines and oral hairy leukoplakia lesions
Authors: Farina Antonella , Cardinali Giorgia , Santarelli Roberta , Gonnella Roberta , Webster‐Cyriaque Jennifer , Bei Roberto , Muraro Raffaella , Frati Luigi , Angeloni Antonio , Torrisi Maria Rosaria , Faggioni Alberto 
Published: November 2003

AbstractA novel protein encoded by the BFRF1 gene of the Epstein‐Barr virus was identified recently [Farina et al. (2000) J Virol 74:3235–3244], which is antigenic “in vivo” and expressed early in the viral replicative cycle. In the present study, its subcellular localization was examined in greater detail comparing Epstein‐Barr virus (EBV) induced producing and nonproducing cell lines by immunofluorescence: in 12‐0‐tetradecanoyl phorbol‐13‐acetate (TPA)‐induced Raji and B95‐8 cells, as well as in anti‐IgG‐stimulated Akata cells, the protein appeared to be localized over the cell nuclear membrane. A similar nuclear membrane localization was observed in epithelial cells of oral hairy leukoplakia, a pathological manifestation of permissive EBV infection. In contrast, upon transfection of BFRF1 in the EBV‐negative Burkitt's lymphoma cell line DG75, the protein was localized predominantly over the plasma membrane. The membrane localization was abolished when DG75 cells were transfected with a C‐terminal deletion mutant of BFRF1 lacking the transmembrane domain. Because induced Raji cells do not produce virus, the above observations indicate that the nuclear membrane localization is not associated with viral production, but requires the expression of EBV genes, and suggest that additional proteins, expressed early during viral lytic infection, might be necessary to target the protein to the nuclear membrane. Immunogold electron microscopy on ultrathin cryosections of induced B95‐8 cells showed that BFRF1 on the nuclear membranes was concentrated over multilayered domains representing areas of active viral replication or at the sites of viral budding, suggesting that BFRF1 is involved in the process of viral assembly. J. Med. Virol. 72:102–111, 2004. © 2004 Wiley‐Liss, Inc.
Role of phosphatidylinositol 3‐kinase in neuronal survival and axonal outgrowth of adult mouse dorsal root ganglia explants
Authors: Edström Anders , Ekström Per A.R. 
Published: November 2003

AbstractAdult ganglionic peripheral neurons have lost dependence on target‐derived neurotrophin signaling for survival and regeneration after injury. To understand the mechanisms required to sustain such processes at maturity, we are studying neuronal survival and axonal outgrowth of adult mouse dorsal root ganglia (DRG) explants. We have here examined the role of phosphatidylinositol 3‐kinase (PI3‐K) activity. Both neuronal survival and axonal outgrowth of spontaneously growing preparations were decreased significantly by the PI3‐K inhibitor LY294002 as was the increased outgrowth caused by nerve growth factor or glial cell line‐derived factor. Inhibition of PI3‐K activity promoted neuronal cell death to the same extent in the presence as in the absence of a growth factor, whereas inhibition of mitogen‐activated protein kinase, MAPK, lacked effect. Using a compartmentalized system, it could be shown that only axonal outgrowth was decreased when the outgrowth region only was exposed to LY294002. Already‐formed growth cones showed morphological changes within 5–10 min after exposure to LY294002. Akt (PKB) is one downstream effector of PI3‐K. Immunofluorescence revealed the presence of activated Akt in DRG cell bodies and in axonal growth cones. Immunoreactivity was decreased by PI3‐K inhibition. The results suggest that Akt is constitutively active in adult DRG neurons, and that PI3‐K mediated processes are involved in neuronal survival of one or more DRG neuronal subpopulations and also in axonal elongation. The possible significance of Akt signaling for these effects is discussed. © 2003 Wiley‐Liss, Inc.
Protective effects of extracellular glutathione against Zn2+‐induced cell death in vitro and in vivo
Authors: Cho Ik Hyun , Im Joo‐Young , Kim Doyeun , Kim Kyoung‐Shim , Lee Ja‐Kyeong , Han Pyung‐Lim 
Published: November 2003

AbstractThe central nervous system reserves high concentrations of free Zn2+ in certain excitatory synaptic vesicles. In pathological conditions such as transient cerebral ischemia, traumatic brain injury, and kainic acid (KA)‐induced seizure, free Zn2+ is released in excess at synapses, which causes neuronal and glial death. We report here that glutathione (GSH) can be used as an effective means for protection of neural cells from Zn2+‐induced cell death in vitro and in vivo. Chronic treatment with 35 μM Zn2+ led to death of primary cortical neurons and primary astrocytes. The Zn2+ toxicity of cortical neurons was partially protected by 1 mM of GSH, whereas the Zn2+ toxicity of primary astrocyte cultures was blocked completely by 100 μM of GSH. To evaluate the beneficial effects of GSH in vivo, an excitotoxin‐induced neural cell death model was established by intracerebroventricular (i.c.v.) injection of 0.94 nmol (0.2 μg) KA, which produced selective neuronal death, especially in CA1 and CA3 hippocampal regions. The i.c.v. co‐injection of 200 pmol of GSH significantly attenuated KA‐induced neuronal cell death and reactive gliosis in hippocampus. The results of this study suggest the contribution of Zn2+ in the excitotoxin‐induced neural cell death model and a potential value of GSH as a therapeutic means against Zn2+‐induced pathogenesis in brain. © 2003 Wiley‐Liss, Inc.
Inhibition of NMDA receptors induces delayed neuronal maturation and sustained proliferation of progenitor cells during neocortical development
Authors: Hirasawa Takae , Wada Hidenori , Kohsaka Shinichi , Uchino Shigeo 
Published: November 2003

AbstractTo elucidate the role of N‐methyl‐D‐aspartate (NMDA) receptors during the early stage of cerebral neocortical development, we investigated the effect of an NMDA receptor antagonist, D(−)‐2‐amino‐5‐phosphonopentanoic acid (D‐APV), on cell migration and proliferation in slice cultures and dissociated primary cultures prepared from rat cerebral neocortex at embryonic Day 17. Pulse‐labeling experiments with 5‐bromo‐2′‐deoxyuridine (BrdU) showed that chronic exposure to D‐APV in slices delayed neuronal migration. Calcium imaging experiments revealed that functional NMDA receptors were expressed in neurons and the treatment with D‐APV delayed neuronal maturation judging from the subunit composition of NMDA receptor subtypes. The results using pulse‐labeling with BrdU indicated that exposure to D‐APV for 3 days induced a clear increase in the number of proliferating progenitor cells in the ventricular zone in neocortical slices. Exposure to D‐APV in primary cultures also increased the proliferation of progenitor cells. The effect of D‐APV on progenitor cell proliferation was possibly mediated through neuronal cells. To elucidate the mechanism of enhanced progenitor cell proliferation induced by D‐APV, we investigated expression of Hes1 and Hes5 mRNA in the ventricular zone of neocortical slices by reverse transcription‐polymerase chain reaction. Tissue exposed to D‐APV for 3 days showed higher expression of Hes1 and Hes5 mRNA than did unexposed control tissue. These results suggest that NMDA receptors expressed in neurons function in neuronal migration and maturation and in the proliferation of progenitor cells. © 2003 Wiley‐Liss, Inc.
Learning more by crossing levels: evidence from airplanes, hospitals, and orchestras
Authors: Hackman J. Richard 
Published: November 2003

AbstractScholars generally conduct research at a single level of analysis (such as the individual, the group, or the organization level), although they often turn to the next‐lower level for explanatory mechanisms. I suggest that robust understanding of social and organizational dynamics requires attention to higher as well as lower levels of analysis. The benefits of research and theory that ‘brackets’ one's focal phenomenon by attending to constructs at both higher and lower levels of analyses are illustrated with findings from research on aircraft cockpit crews, hospital patient care teams, and professional musical ensembles. Copyright © 2003 John Wiley & Sons, Ltd.
The effects of job complexity and autonomy on cohesiveness in collectivistic and individualistic work groups: a cross‐cultural analysis
Authors: Man Derek C. , Lam Simon S. K. 
Published: November 2003

AbstractIncreased job complexity and autonomy have often been associated with improved performance in work groups. This study examines the mediating effect of group cohesiveness. The moderating effects of individualism/collectivism on the relationship between job characteristics (both complexity and autonomy) and cohesiveness are also tested. The sample consists of 381 teams drawn from the Hong Kong and U.S. branches of an international bank. The findings indicate that an increase in job complexity and/or task autonomy will increase group cohesiveness, which subsequently translates to better performance. The positive effects of job complexity and autonomy on group cohesiveness are also found to be more prominent for individualistic rather than collectivistic work groups. The theoretical implications of the results and the limitations of the study are also discussed. Copyright © 2003 John Wiley & Sons, Ltd.
Understanding the emotional labor process: a control theory perspective
Authors: Diefendorff James M. , Gosserand Robin H. 
Published: November 2003

AbstractA dynamic, process‐oriented approach to understanding emotional labor is presented, utilizing concepts from control theory models of behavioral self‐regulation. Emotional labor is characterized as involving a discrepancy monitoring and reduction process, whereby perceptions of emotional displays and emotional display rules are continuously compared. If a discrepancy between emotional displays and display rules is detected, individuals are proposed to use emotion regulation strategies to reduce the discrepancy. The goal hierarchy aspect of control theory is used to describe emotional labor in the broader context of job performance and explain how positive and negative outcomes can result from the emotional labor process. Propositions are developed throughout the paper. Copyright © 2003 John Wiley & Sons, Ltd.
Situational and dispositional predictors of displays of positive emotions
Authors: Tan Hwee H. , Foo Maw D. , Chong Chee L. , Ng Renee 
Published: November 2003

AbstractThe study examined the effects of situational (store busyness and customer demand) and dispositional (extraversion, neuroticism, and psychoticism) factors on the display of positive emotions. We found that for situational factors, customer demand was positively related to displayed positive emotions. For personality factors, extraversion was positively related to displayed positive emotions and neuroticism was negatively related to displayed positive emotions. Usefulness analysis showed that both situational and personality factors contributed significantly to explain the level of positive displayed emotion. Copyright © 2003 John Wiley & Sons, Ltd.
Practice makes perfect: Putting learning to use in today's organizations
Authors: Holland Deryn , Firsht Linda , Wickes Stuart 
Published: November 2003

AbstractDespite the enormous investments of time and money that organizations put into learning initiatives, little
attention is paid to putting what is learned into practice. This results in waste, lost opportunities, and
frustration. A study done at the BBC, which suspected that learning wasn't being leveraged as much as it
could be, examined the reasons why learning is often not put to use.