bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of protein kinase C ζ isoform in Fas resistance of immature myeloid KG1a leukemic cells
Authors: de Thonel Aurélie , Bettaı̈eb Ali , Jean Christine , Laurent Guy , Quillet-Mary Anne
Published: October 2002

Leukemic CD34+ immature acute myeloid leukemia (AML) cells express Fas receptor but are frequently resistant to Fas agonistic reagents. Fas plays an important role in T-cell–mediated cytotoxicity, and recently it has been suggested that altered Fas signaling may contribute to drug resistance. Therefore, Fas resistance could be one of the mechanisms by which AML progenitors escape chemotherapy or T-cell–based immune intervention. However, the molecular mechanism of Fas resistance in AML cells has not been identified. Fas signaling can be interrupted at 3 mains levels: Fas clustering, alteration of death-inducing-signaling-complex (DISC) formation, and effector caspase inhibition of downstream caspase-8. This study shows that in the Fas-resistant CD34+CD38− KG1a cells, Fas agonists resulted in Fas aggregation but not in caspase-8 activation, related to a defect in DISC formation. However, pretreatment with chelerythrin, but not with calphostin C, resulted in the restoration of Fas-induced caspase-8 activation and cytotoxicity, suggesting that some atypical protein kinase C (PKC) isoforms contributed to the lack of DISC formation. Indeed, treatment with antisense oligonucleotides directed against PKCζ and enforced expression of Par-4, a negative regulator of PKCζ activity, restored Fas-induced caspase-8 activity and apoptosis. Moreover, it was found that PKCζ interacts with FADD and that PKCζ immunoextracts prepared from KG1a cells are able to phosphorylate FADD in vitro, whereas this phosphorylation is dramatically reduced in Par-4 transfectant cells. In conclusion, it is suggested that in AML cells, PKCζ plays an important role in Fas resistance by inhibiting DISC formation, possibly by phosphorylating FADD.
A novel Notch ligand, Dll4, induces T-cell leukemia/lymphoma when overexpressed in mice by retroviral-mediated gene transfer
Authors: Yan Xiao-Qiang , Sarmiento Ulla , Sun Yu , Huang Guo , Guo Jane , Juan Todd , Van Gwyneth , Qi Mei-Ying , Scully Sheila , Senaldi Giorgio , Fletcher Frederick A.
Published: October 2002

Notch receptors mediate cell-fate decisions through interaction with specific ligands during development. The biological role of a novel Notch ligand, Dll4, in mice was explored by reconstituting lethally irradiated mice with bone marrow (BM) cells transduced with Dll4 retroviral vector. White blood cell and lymphocyte counts in Dll4-overexpressing mice were reduced at the early stage of reconstitution but increased significantly at approximately 10 weeks after BM transplantation. BM, spleen, lymph nodes, and peripheral blood ofDll4-overexpressing mice contained predominantly CD4+CD8+ T cells and virtually lacked B cells. The Dll4-overexpressing mice eventually developed a lethal phenotype that was characterized by the progression of a T-cell lymphoproliferative disease (restricted to BM and lymphoid tissues) to transplantable monoclonal T-cell leukemia/lymphoma scattered to multiple organs. Results suggest that the interaction of Dll4with Notch1 may provide key signals for T-cell development.
Multiple cis elements regulate an alternative splicing event at 4.1R pre-mRNA during erythroid differentiation
Authors: Deguillien Mireille , Huang Shu-Ching , Morinière Madeleine , Dreumont Natacha , Benz Edward J. , Baklouti Faouzi
Published: October 2002

The inclusion of exon 16 in the mature protein 4.1R messenger RNA (mRNA) is a critical event in red blood cell membrane biogenesis. It occurs during late erythroid development and results in inclusion of the 10-kd domain needed for stabilization of the spectrin/actin lattice. In this study, an experimental model was established in murine erythroleukemia cells that reproduces the endogenous exon 16 splicing patterns from a transfected minigene. Exon 16 was excluded in predifferentiated and predominantly included after induction. This suggests that the minigene contained exon and abutting intronic sequences sufficient for splicing regulation. A systematic analysis of the cis-acting regulatory sequences that reside within the exon and flanking introns was performed. Results showed that (1) the upstream intron of 4.1R pre-mRNA is required for exon recognition and it displays 2 enhancer elements, a distal element acting in differentiating cells and a proximal constitutive enhancer that resides within the 25 nucleotides preceding the acceptor site; (2) the exon itself contains a strong constitutive splicing silencer; (3) the exon has a weak 5′ splice site; and (4) the downstream intron contains at least 2 splicing enhancer elements acting in differentiating cells, a proximal element at the vicinity of the 5′ splice site, and a distal element containing 3 copies of the UGCAUG motif. These results suggest that the interplay between negative and positive elements may determine the inclusion or exclusion of exon 16. The activation of the enhancer elements in late erythroid differentiation may play an important role in the retention of exon 16.
Correction of cross-linker sensitivity of Fanconi anemia group F cells by CD33-mediated protein transfer
Authors: Holmes Rebecca K. , Harutyunyan Karine , Shah Maulik , Joenje Hans , Youssoufian Hagop
Published: October 2002

Studies have previously described the feasibility of receptor-mediated protein transfer in a cell culture model of Fanconi anemia (FA) group C. This study explores the versatility of this approach by using an antibody single-chain fusion protein to correct the phenotypic defect in FA group F cells. A 68.5-kd chimeric protein (His-M195FANCF) was expressed, consisting of a His tag, a single-chain antibody to the myeloid antigen CD33, and the FANCF protein, as well as a 43-kd His-FANCF fusion protein lacking the antibody motif, inEscherichia coli. The nickel-agarose–purified His-M195FANCF protein bound specifically to the surface of HeLa cells transfected with CD33 and internalized through vesicular structures. The fusion protein, but not CD33, sorted to the nucleus, consistent with the known nuclear localization of FANCF. No similar binding or internalization was observed with His-FANCF. Pretreatment of the transfected cells with chloroquine abolished nuclear accumulation, but there was little change with brefeldin A, indicating a minimal if any role for the Golgi apparatus in mediating transport from endosomes to the cytosol and the nucleus. The intracellular half-life of His-M195FANCF was approximately 160 minutes. Treatment of CD33-transfected FA group F lymphoblastoid cells with 0.1 mg/mL His-M195FANCF conferred resistance to mitomycin C. No similar protection was noted in CD33− parental cells or CD33+ FA cells belonging to groups A and C. These results demonstrate that antibody-directed, receptor-mediated protein transfer is a versatile method for the delivery of biologically active proteins into hematopoietic cells.
Molecular basis of the adult i phenotype and the gene responsible for the expression of the human blood group I antigen
Authors: Yu Lung-Chih , Twu Yuh-Ching , Chang Ching-Yi , Lin Marie
Published: October 2002

The human blood group i and I antigens are characterized as linear and branched repeats of N-acetyllactosamine, respectively. Conversion of the i to the I structure requires the activity of I-branching β-1,6-N-acetylglucosaminyltransferase (IGnT). Thus the blood group I gene is assigned to encode a β-1,6-N-acetylglucosaminyltransferase; however, its identity has not been confirmed. The null phenotype of I, the adult i phenotype, provides a means to identify the I gene. Interestingly, the adult i phenotype has been noted to be associated with congenital cataracts in Asians. Molecular genetic studies of 3 adult i pedigrees are reported here. The results obtained on mutation detection within the 2 I-branching enzyme encoding genes, segregation analyses, and enzyme function assays identify molecular changes associated with the adult i phenotype. The adult i phenotype in 2 of the pedigrees studied resulted from 1043G→A and 1148G→A mutations, which predict Gly348Glu and Arg383His alterations, respectively, in theIGnT gene. These amino acid changes abolished the original GlcNAc-transferase activity. Deletion of the IGnT gene was observed in the person with adult i phenotype in the third pedigree. These findings suggest that the IGnT gene, first reported in 1993, is the candidate for the blood group I gene. Confirmation of the blood group I gene will further assist in the investigations of the molecular genetics that control I antigen expression in secretions and the molecular basis for the association of the adult i phenotype with congenital cataracts in Asians.
Salvage therapy for multiple myeloma with thalidomide and CED chemotherapy
Authors: Moehler Thomas M. , Neben Kai , Benner Axel , Egerer Gerlinde , Krasniqi Fatime , Ho Anthony D. , Goldschmidt Hartmut
Published: October 2002

The feasibility and efficacy of a combination of thalidomide, cyclophosphamide, etoposide, and dexamethasone were studied in 56 patients with poor-prognosis multiple myeloma. Of 50 patients evaluable for response, 4% achieved complete response (CR), 64% partial response (PR), 18% minimal response (MR), 6% stable disease (SD), and 8% progressive disease (PD), resulting in an objective response rate (≥ MR) of 86.0% (76.7% overall objective response rate in intent-to-treat analysis; n = 56). Subsequent to successful remission induction, 18 patients received autologous or allogeneic stem cell transplantation. The median progression-free survival in all patients was 16 months. The median overall survival time could not be calculated, since the last observed death occurred after 16 months of follow-up (median follow-up of 14 months) with a corresponding estimated survival probability of 55%. Severe adverse effects (World Health Organization III/IV) included infectious complications (35.7%) and cardiovascular events (7.1%). The data suggest that Thal improves antitumor activity of salvage chemotherapy regimens in poor-prognosis multiple myeloma.
Identification and characterization of cis elements in the STAT3 gene regulating STAT3α and STAT3β messenger RNA splicing
Authors: Shao Huang , Quintero Andres J. , Tweardy David J.
Published: October 2002

Signal transducer and activator of transcription 3 (STAT3) is an oncogene and a critical regulator of multiple cell-fate decisions, including myeloid cell differentiation. Two isoforms of STAT3 have been identified: α (p92) and β (p83). These differ structurally in their C-terminal transactivation domains, resulting in distinct functional activities. The cis genetic elements that regulate the ratio of α to β messenger RNA (mRNA) are unknown. In this study, cloning, sequencing, and splicing analysis of the human and murine STAT3 genes revealed a highly conserved 5′ donor site for generation of both α and β mRNA and distinct branch-point sequences, polypyrimidine tracts, and 3′ acceptor sites (ASs) for each. The β 3′ AS was found to be located 50 nucleotides downstream of the α 3′ AS in exon 23. Two additional cryptic 3′ ASs (δ and ε) were also identified. Thus, we identified for the first time the cisregulatory sequences responsible for generation of STAT3α and STAT3β mRNA.
Autologous stem cell transplantation for HIV-associated lymphoma
Authors: Krishnan Amrita , Molina Arturo , Zaia John , Nademanee Auayporn , Kogut Neil , Rosenthal Joseph , Woo Doni , Forman Stephen J.
Published: October 2002

Is peripheral stem cell mobilization followed by autologous stem cell transplantation (ASCT) feasible in patients with human immunodeficiency virus (HIV)– associated lymphoma (HIV-L)? Studies have demonstrated that, in the HIV- negative (HIV−) setting, ASCT may improve lymphoma-free survival in high-risk non-Hodgkin lymphoma (NHL) or relapsed Hodgkin disease (HD) and NHL. Given the poor prognosis of HIV-L with conventional chemotherapy, this dose-intensive approach was explored. Nine patients with HIV-HD or NHL mobilized a median of 10.6 × 106 CD34+ cells/kg and engrafted after ASCT. CD4 counts recovered to pretransplantation levels and HIV viral loads were controlled in patients compliant with antiretroviral therapy. Seven of 9 patients remain in remission from their lymphoma at a median of 19 months after transplantation. Thus, patients with HIV-L on antiretroviral therapy can engraft following ASCT. Prolonged lymphoma remissions, without significant compromise of immune function, can be seen, suggesting that ASCT can be used in selected patients with HIV-L.
Administration of cyclosporine for 24 months compared with 6 months for prevention of chronic graft-versus-host disease: a prospective randomized clinical trial
Authors: Kansu Emin , Gooley Ted , Flowers Mary E. D. , Anasetti Claudio , Deeg H. Joachim , Nash Richard A. , Sanders Jean E. , Witherspoon Robert P. , Appelbaum Frederick R. , Storb Rainer , Martin Paul J.
Published: October 2002

This study compared the incidence of clinical extensive chronic graft-versus-host disease (GVHD), transplantation-related mortality, survival, and relapse-free survival among recipients randomly assigned to receive a 24-month or a 6-month course of cyclosporine prophylaxis after transplantation of allogeneic marrow from an HLA-identical sibling or alternative donor. Patients who did not have clinical manifestations of chronic GVHD on day 80 after transplantation were eligible for the study if they previously had acute GVHD or if a skin biopsy showed histologic evidence of chronic GVHD. Clinical extensive chronic GVHD developed in 35 of the 89 patients (39%) in the 24-month group and 37 of the 73 patients (51%) in the 6-month group. The hazard of developing chronic GVHD was not significantly different in the 2 groups (hazard ratio = 0.76; 95% confidence interval, 0.48-1.21; P = .25). In addition, there were no significant differences between the 2 groups in transplantation-related mortality, survival, or disease-free survival.
Relationships between circulation strength and the variability of growing-season and cold-season climate in northern and central Europe
Authors: Jones Philip D. , Briffa Keith R. , Osborn Timothy J. , Moberg Anders , Bergström Hans
Published: October 2002

This paper examines variability in surface climate and the relationship with two circulation indices using recently produced 200–250 year long European daily and monthly climatic series. Assessments are made of the influence of circulation indices (zonal over western Europe and average pressure over central Europe) on regional temperature, precipitation and drought series for northern and central Europe. Changes in the circulation are shown to be very important during the winter in northern Europe, but only over western and central Europe in summer. Circulation indices in winter, however, only explain up to 25% of surface-climate variability and, except for the British Isles, do not explain any decadal and longer timescale variability in summer. Extreme temperatures and growing-season and frost-season durations and degree-day series are calcu lated for four sites (Central England, Stockholm, Uppsala and St. Petersburg). Degree-day counts are shown to be very strongly correlated (r > 0.9) to average extended summer (‘growing’ season, May to September) and extended winter (‘frost’ season, October to April) temperatures. Durations of the growing and frost seasons are only weakly correlated (r ~ 0.2–0.4) with the appropriate extended seasonal temperatures or degree-day counts. Warmer growing/frost seasons, therefore, need not necessarily be longer/shorter. Counts of extremely warm days in each year are more highly correlated with the growing-season mean temperature than with coldseason temperature. Similarly, counts of extremely cold days in each year are more highly correlated with cold-season temperature than with growing-season temperature. Both the growing-season temperature and the corresponding degree-day counts clearly show warmer temperatures over all series in Fennoscandia before 1860. Over central Europe, and for the Central England temperature series, growing seasons now are of similar warmth to those before 1860. Annually averaged temperatures across the three regions indicate long-term warming which is, however, almost entirely the result of warming during the October to April period.
Low-frequency summer temperature variation in central Sweden since the tenth century inferred from tree rings
Authors: Gunnarson Bjön E. , Linderholm Hans W.
Published: October 2002

Living and subfossil Scots pine ( Pinus sylvestris L.) sampled close to the present tree-line in the central Scandinavian Mountains were used to build a continuous 1091-year long tree-ring-width chronology, spanning from ad 909 to 1998. Summer temperatures of the growth year had the highest influence on annual growth. The Håckren chronology represent a record of summer temperatures, where periods of low growth and poor regeneration of pine represent unfavourable climate conditions. Low growth was encountered in the mid-twelfth, thirteenth, late sixteenth, early seventeenth and late eighteenth centuries. Periods of high growth (high regeneration rate and above-average growth), indicating high summer temperatures, were recognized in the mid-tenth to late eleventh, mid-fourteenth, mid-seventeenth and twentieth centuries. As the chronology is well correlated with other high-latitude proxy data from Fennoscandia, as well as the Northern Hemisphere, we argue that the Håckren chronology is a valid proxy-data record of regional summer temperatures.
The supra-long Scots pine tree-ring record for Finnish Lapland: Part 1, chronology construction and initial inferences
Authors: Eronen Matti , Zetterberg Pentti , Briffa Keith R. , Lindholm Markus , Meriläinen Jouko , Timonen Mauri
Published: October 2002

This paper reviews the development of the current ‘supra-long’ pine chronology for northern Finnish Lapland. In the forest-tundra ecotone region of northern Finnish Lapland over 250 samples from living Scots pines (Pinus sylvestris L.) and over 1700 samples of subfossil pines have been collected for dendrochronological studies. In addition, over 1400 subfossils have been sampled from the forested area of Finnish Lapland. The goal of the research was to build a more than 7000-year long continuous pine ring-width chronology. The construction of the chronology is now completed. The intensive phase of the data collection and chronology building lasted about 10 years, 1989 to 1999. The major part of the Finnish Lapland master curve was con structed several years ago, but it was extremely difficult to bridge the c. 300-year gap, prior to 165 bc between the ‘absolute’ younger part of the chronology and the “‘ oating’ older part. The crucial samples were identified and assembled in the chronology in early 1999, and there is now an unbroken pine chronology about 7500 years long constructed from the subfossil forest-limit pines of northern Finnish Lapland. The severe growth depression centred on 330 bc is likely to have been caused by increased wetness. A brief summary is presented of inferred tree-line changes from the location of the samples.
The supra-long Scots pine tree-ring record for Finnish Lapland: Part 2, interannual to centennial variability in summer temperatures for 7500 years
Authors: Helama Samuli , Lindholm Markus , Timonen Mauri , Meriläinen Jouko , Eronen Matti
Published: October 2002

Midsummer (July) temperatures are reconstructed for the last 7500 years using the long ring-width chronology of Scots pine (Pinus sylvestris L.) from northern Finland. The chronology was built using regional curve standardization (RCS), which allows for long-term (low-frequency) variability to be extracted from this annually resolved record of 1087 samples from living trees and subfossil timber. Short-and long-term changes in reconstructed July temperatures are presented. The regression model accounts for 37% of the dependent instrumental temperature variance between ad 1879 and 1992. The warmest 30-year periods were ad 560–531, ad 560–531, 1190–1161 bc and ad 1541–1570, and the coldest 5240–5211, 5150–5121 and 3710–3681 bc. The warmest 100-year periods were ad 1501–1600, 600–501 bc and 300–201 bc, and the coldest 5200–5101, 2500–2401 and 1500–1401 bc. Broad comparisons are made with dendrochronological, lacustrine and glacial proxy evidence.
Depositional frequency of German subfossil oaks: climatically and non-climatically induced fluctuations in the Holocene
Authors: Spurk Marco , Leuschner Hanns Hubert , Baillie Michael G.L. , Briffa Keith R. , Friedrich Michael
Published: October 2002

A highly resolved record of the depositional frequency of subfossil trees since 8263 bc in the valley of the River Main is presented. Different aspects of forest dynamics are explored including depositional anomal ies (phases of low or zero departures), changes in forest density based on tree growth trend classes (GTCs), and regeneration using mean lifespan (ML) data. This reveals a number of climatically induced environmental changes that are synchronous with events in the North Atlantic region and therefore may reflect a facet of the North Atlantic climate system. Three periods are recognized: (1) pre-3500 bc, when depositional frequency was dominated by climatic events with notable anomalies at 6200 and 4100 bc; (2) between 3500 and 1200 bc, when climatically triggered events were enhanced by forest clearances, especially marked anomalies occurring around 2700, 2300 and 1700 bc; and (3) post-1200 bc, when the climatic information is obscured by human activities.
Subfossil European bog oaks: population dynamics and long-term growth depressions as indicators of changes in the Holocene hydro-regime and climate
Authors: Leuschner Hanns Hubert , Sass-Klaassen Ute , Jansma Esther , Baillie Michael G.L. , Spurk Marco
Published: October 2002

Some 2600 bog oaks have been dated from German, Dutch and Irish bogs covering the period 6000 bc to ad 1000. The ring patterns of these ‘bog oaks’ are characterized by recurrent, long-term growth depressions. In addition, obvious changes in the temporal distribution of the bog-oak trunks throughout the Holocene are found. Both features were probably caused by unfavourable growth conditions, which are most likely linked to changes in site hydrology. We use a new variable, ‘annual mean age’, as a tool to analyse the population dynamics of bog oaks in more detail, enabling the detection of synchronous intersite and interregional changes. It is calculated as the arithmetic mean of the age of all trees in each calendar year. We performed the calculation on regional (Germany, The Netherlands, Ireland) subsets of the bog-oak series. Abrupt changes in annual mean age are taken to indicate periods of generation change. We find good agreement for the interval from 5000 bc to 2000 bc between the continental (combined German and Dutch) and the Irish mean-age chronologies. Most changes in population dynamics correspond with contemporary changes in the associated regional tree-ring chronologies. It is concluded that the observed changes in population dynamics and growth activity are responses to common environmental forcing, most likely related to climate.
A continuous multimillennial ring-width chronology in Yamal, northwestern Siberia
Authors: Hantemirov Rashit M. , Shiyatov Stepan G.
Published: October 2002

Remains of subfossil Siberian larch trees in the Holocene deposits of the Yamal Peninsula (Western Siberia) have been collected in order to develop a continuous, multimillennium tree-ring-width chronology. This work has produced a calendar-age dated 4000-year (2000 bc to ad 1996) series. From these data, summer-temperature variability in this region has been estimated on annual to multidecadal timescales. Radiocarbon dating of selected older material shows that the oldest subfossil wood is 9400 years old and the dates of the sampled material are generally distributed evenly through time. It will, therefore, be possible to develop a tree-ring chronology for more than nine millennia. An initial assessment of long-term ‘ uctuations in Yamal summer warmth has been realized through the reconstruction of tree-line dynamics using a combination of dendrochronological (absolute) dated material and less precisely (radiocarbon) dated older subfossils.
Tree-ring width and density data around the Northern Hemisphere: Part 2, spatio-temporal variability and associated climate patterns
Authors: Briffa Keith R. , Osborn Timothy J. , Schweingruber Fritz H. , Jones Philip D. , Shiyatov Stepan G. , Vaganov Eugene A.
Published: October 2002

Patterns of summer temperature over the Northern Hemisphere, obtained from a calibration of a treering network, are presented for every year from 1600 to 1877. The network of tree-ring density chronologies is shown to exhibit spatially coherent modes of variability. These modes closely match summer half-year tempera ture variations, in terms of similar spatial patterns and similar temporal evolution during the instrumental period. They can, therefore, be considered to be proxies for the temperature patterns, and time series for the eight most dominant patterns are presented back to the late seventeenth century. The first pattern represents spatially coherent warming or cooling and it appears to respond to climate forcings, especially volcanic erup tions. Most other patterns appear to be related to atmospheric pressure anomalies and they can be partially explained by heat advection associated with anomalous atmospheric circulation. This provides the potential for reconstructing past variations in atmospheric circulation for the summer half-year. To investigate this poten tial, modes of summer-pressure variability are defined, and an attempt is made to reconstruct them using principal components regression. Poor verification statistics and high sensitivity to the design of the regression procedure provide little confidence in the reconstructions presented, which are regarded as being preliminary only. A repeat study using instrumental temperature predictors shows that the poor performance is attributable mainly to the weakness of the relationship between air temperature over land and atmospheric circulation during summer: though a relationship exists, it is not strong enough to yield reliable regression models when only a relatively short overlap period (55 years in this study) exists for calibration and verification. Further attempts to reconstruct large-scale atmospheric circulation patterns that include precipitation-sensitive networks of tree-ring data are likely to produce improved results.
Children’s Participation in the Decision-Making Process During Hospitalization: an observational study
Authors: Runeson Ingrid , Hallström Inger , Elander Gunnel , Hermerén Göran
Published: October 2002

Twenty-four children (aged 5 months to 18 years) who were admitted to a university hospital were observed for a total of 135 hours with the aim of describing their degree of participation in decisions concerning their own care. Grading of their participation was made by using a 5-point scale. An assessment was also made of what was considered as optimal participation in each situation. The results indicate that children are not always allowed to participate in decision making to the extent that is considered optimal. In no case was it judged that a child participated in or was forced to make a decision that was too difficult for the child. The interactions between children, parents and staff were also described in connection with discussions and decision-making processes. This showed that parents do not always support their children in difficult situations and that health care staff often inform children about what is going to happen without presenting alternatives or asking for their views. Staff may, however, find themselves facing an ethical conflict in deciding between supporting a child’s view or following hospital routine. It is of great importance that children are looked upon as potentially autonomous individuals and that staff members realize that one of their core duties is to facilitate children’s participation in decision making concerning their health care.
Rewriting the village: geographies of food and belonging in Clovelly, Australia
Authors: Duruz Jean
Published: October 2002

This essay focuses on intersecting meanings of food and femininity, place and time, as an excavation of their ‘secret geographies’. Drawing on women’s narratives of mundane rituals and practices associated with food shopping, cooking, eating and ‘eating out’, the article traces moments of looking backwards and of looking forwards towards remembered and imagined landscapes of consumption. In the process, the ‘village’ of Burnie Street, Clovelly (a beachside suburb in Sydney, Australia) becomes a spatial metaphor for examples of ‘local’ changes in domestic food cultures and their material structures since the mid-1940s. This image of the village also allows the argument to chart some intriguing shifts in social relations (particularly of gender, class and ethnicity). The article concludes that useful public narratives for tracing geographies of the urban are not necessarily to be found in attempts to rework the past or the present in mythic terms, as either bad times or good. Instead, subtle rewritings of the village vested in everyday belongings hint at more productive analytical directions.
Producing space(s), representing landscapes: maps and resource conflicts in Trinidad
Authors: Sletto Bjørn
Published: October 2002

In the mid-1990s Trinidadians witnessed a hotly contested resource conflict in the Nariva Swamp, a wetland located on the east coast of the island. This conflict resulted in a stricter regime of environmental protection and greater influence of conservation-oriented government agencies, and demonstrates the role of representations in influencing spatial practice. Drawing on the critical landscape literature, post-structural political ecology and the work of Henri Lefebvre, this article views landscapes as visualized dimensions of space, produced in accordance with specific ideologies and material priorities. In this case, linkages between hegemonic discourses on nature and conceptualizations of local practices lent the power of ‘representation of space’ to conservationiosts fighting to evict commercial rice growers from the wetlands. These hegemonic representations were refracted and reformulated by swamp dwellers, who conceptualized their everyday practices through verbal and cartographic counter-representations.
Distillations of something larger: the local scale and American national identity
Authors: Appleton Louise
Published: October 2002

This paper examines the role of the local scale in popular cultural constructions of American nationhood between 1942 and 1969. By local scale, I refer to a geographical, sociological and psychological space that is limited to face-to-face experiences, but is the manifestation of constantly changing relations of interdependence between social, political, economic and cultural processes operating at scales smaller and larger than the local. Drawing upon empirical material from the Saturday Evening Post, it illustrates how the local scale operates as a medium through which shifting notions of American identities are articulated. It argues that throughout this period the Post promoted the image of a united America, and the local scale provided tangible links with the nation that attempted to integrate readers into a sense of national community. The local scale was used to define the United States as a nation that was united by subsuming internal differences, but, in time, the local came to articulate a nation where unity was expressed through a shared political creed of democracy in which difference and diversity were celebrated. The paper also traces the changing meaning and significance of the local scale for mediating the nation. The paper shows that the meaning of the local scale shifted between notions of community, locality, neighbourhood and territory. The metonymic value of the local scale also changed and the paper argues that while the local scale was useful for defining an integrated nation during and after World War II that relied on an inward-looking perspective, by the late 1950s that perspective had become less introspective and more outward looking. By the 1960s, the paper shows how the significance of the local scale as a metonym of the nation had diminished, but instead was used as a means of attracting readers in a rapidly changing social and economic climate. The result is a deeper understanding of the way the media articulate the nation through imagined places to render it accessible for readers, and how this is inherently tied to the economic climate of the magazine.
Creating regional identity, moral orders and spatial contiguity: imagined landscapes of Mormon Americanization
Authors: Yorgason Ethan
Published: October 2002

I explore how moral orders, regional identity, and regional space were simultaneously reconstructed in the Mormon culture region during a period of great social change. Careful attention to the concept of moral orders helps us understand how regions are culturally constructed. In addition, I urge more attention to the spatial form of such regional cultural constructions. In recent years, scholars have been prone to disregard contiguity as deserving of spatial theorizing. I argue, to the contrary, that we need to understand how, where and why contiguities arise. I use the example of the Mormon culture region’s reworked moral orders that utilize cultural visions of particular natural environments to demonstrate this point.
Anatomical and Functional Evidence for a Neural Hypothalamic-Testicular Pathway that Is Independent of the Pituitary
Authors: Lee Soon , Miselis Richard , Rivier Catherine
Published: October 2002

Testosterone (T) secretion is classically considered to be under the primary control of pituitary LH, itself regulated by the hypothalamic peptide LH-releasing hormone. Secretagogues present in the general circulation and/or manufactured in the testis can also alter Leydig cell activity independently of the pituitary. Finally, spanchnic innervation regulates testicular LH receptors and blood flow. In the present work, we provide evidence that, in addition, there may be a neural brain-testicular circuit that regulates T release function independently of LH release. We had recently reported that the intracerebroventricular injection of IL-1β, corticotropin-releasing factor, or β-adrenergic agonists significantly interfered with the T response to human chorionic gonadotropin through mechanisms that did not involve LH. Here, we show that the injection of the transganglionic retrograde tracer pseudorabies virus into the testes caused viral staining in the spinal cord, the brain stem, and the hypothalamus. This observation indicates the presence of a neural pathway between the central nervous system and the testis. We then demonstrated that spinal cord injury significantly interfered with this staining, thus supporting the hypothesis that the proposed circuit travels through the cord. Finally, we showed that spinal cord injury completely abolished the ability of intracerebroventricularly injected IL-1β or corticotropin-releasing factor to blunt the T response to human chorionic gonadotropin, which suggests that these two secretagogues act within the brain to stimulate a neural pathway that interferes with Leydig cell function independently of the pituitary. The hitherto unsuspected brain-testicular circuit that these experiments have uncovered may play a role in pathologies, so far unexplained, that are characterized by decreased T levels despite normal LH production.
Externalization of Annexin I from A Folliculo-Stellate-Like Cell Line
Authors: Chapman Lee , Nishimura Aya , Buckingham Julia C. , Morris John F. , Christian Helen C.
Published: October 2002

Our recent studies on rat pituitary tissue suggest that the annexin I-dependent inhibitory actions of glucocorticoids may not be exerted directly on endocrine cells but indirectly via folliculo-stellate (FS) cells. FS cells contain glucocorticoid receptors and abundant annexin I. We have studied the localization of annexin I in FS cells and the ability of dexamethasone to induce annexin I secretion by an FS (TtT/GF) cell line, using Western blotting and immunofluorescence microscopy. Exposure of TtT/GF cells to dexamethasone (0.1 μm, 3 h) caused an increase in the amount of annexin I protein in the intracellular compartment and attached to the surface of the cells. In nonpermeabilized cells, immunofluorescence labeling revealed that annexin I immunoreactivity was associated with the cell surface and concentrated in focal patches on the ends of cytoplasmic processes; dexamethasone (0.1 μm, 3 h) increased both the number and intensity of these foci. Immunogold electron microscopy confirmed in anterior pituitary tissue the presence of immunoreactive-annexin at the surface of FS cell processes contacting endocrine cells. These data support our hypothesis that annexin I is released by FS cells in response to glucocorticoids to mediate glucocorticoid inhibitory actions on pituitary hormone release via a juxtacrine mechanism.
Prolonged Retention after Aggregation into Secretory Granules of Human R183H-Growth Hormone (GH), a Mutant that Causes Autosomal Dominant GH Deficiency Type II
Authors: Zhu Yong Lian , Conway-Campbell Becky , Waters Michael J. , Dannies Priscilla S.
Published: October 2002

Human R183H-GH causes autosomal dominant GH deficiency type II. Because we show here that the mutant hormone is fully bioactive, we have sought to locate an impairment in its progress through the secretory pathway as assessed by pulse chase experiments. Newly synthesized wild-type and R183H-GH were stable when expressed transiently in AtT20 cells, and both formed equivalent amounts of Lubrol-insoluble aggregates within 40 min after synthesis. There was no evidence for intermolecular disulfide bond formation in aggregates of wild-type hormone or the R183H mutant. Both wild-type and R183H-GH were packaged into secretory granules, assessed by the ability of 1 mm BaCl2 to stimulate release and by immunocytochemistry. The mutant differed from wild-type hormone in its retention in the cells after packaging into secretory granules; 50% more R183H-GH than wild-type aggregates were retained in AtT20 cells 120 min after synthesis, and stimulated release of R183H-GH or a mixture of R183H-GH and wild-type that had been retained in the cell was reduced. The longer retention of R183H-GH aggregates indicates that a single point mutation in a protein contained in secretory granules affects the rate of secretory granule release.
Immunocytochemical Localization of Vasopressin V1a Receptors in the Rat Pituitary Gonadotropes
Authors: Orcel Hélène , Tobin Vicky A. , Alonso Gérard , Rabié Alain
Published: October 2002

Immunocytochemical labeling using a specific antibody against vasopressin V1a receptor allowed the localization of this receptor within a subset of cells from male rat anterior pituitary. The presence of transcripts of the corresponding gene in the anterior pituitary was confirmed by RT-PCR. Multiple immunocytochemical labeling combined with confocal microscopy allowed the identification of the V1a-labeled cells as gonadotropes. At the subcellular level, the vasopressin V1a receptor was mainly associated with cytoplasmic vesicles dispersed throughout the cell, which were not the secretory granules storing LH or FSH. In addition to effects exerted by vasopressin via central targets involved in the reproductive pathways, the presence of vasopressin V1a receptors on gonadotropes supports the controversial hypothesis of a local direct action of the neuropeptide on this cell type.
Unexpected Deposition of Brown Fat in Mammary Gland During Postnatal Development
Authors: Gouon-Evans Valérie , Pollard Jeffrey W.
Published: October 2002

Mammary fat tissue is crucial for mammary ductal morphogenesis in both fetal and adult mice. There are two kinds of adipocytes, the energy-storing white and the energy-dissipating brown adipocyte. The precise identity of the types of adipocyte in the mammary gland has never been investigated but was always assumed to be only white fat. In this study, we show that both white and brown adipocytes are present in the postnatal mammary gland. The amount of brown adipose tissue (BAT) examined by histology and electron microscopy correlates with the transcript levels of uncoupling protein 1, which is a mitochondrial carrier expressed exclusively in BAT. Uncoupling protein 1 mRNAs are the highest during prepuberty, decrease upon puberty, and are finally undetectable in the adult mammary gland. The analysis of a BAT-depleted mouse model showed that depletion of mammary BAT in early postnatal development induces epithelial differentiation. Alveolar structures were formed along all ducts and were functional since they produced β-casein. However, mammary transplantation experiments indicated that a systemic effect was responsible for epithelium differentiation. Our data suggest that BAT negatively regulates the differentiation of mammary epithelial cells in a systemic manner during prepubertal ductal outgrowth.
Synaptosome-Associated Protein of 25 Kilodaltons Modulates Kv2.1 Voltage-Dependent K+ Channels in Neuroendocrine Islet β-Cells through an Interaction with the Channel N Terminus
Authors: MacDonald Patrick E. , Wang Guotang , Tsuk Sharon , Dodo Chikvashvili , Kang Youhou , Tang Lan , Wheeler Michael B. , Cattral Mark S. , Lakey Jonathan R. T. , Salapatek Anne Marie F. , Lotan Ilana , Gaisano Herbert Y.
Published: October 2002

Insulin secretion is initiated by ionic events involving membrane depolarization and Ca2+ entry, whereas exocytic SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins mediate exocytosis itself. In the present study, we characterize the interaction of the SNARE protein SNAP-25 (synaptosome-associated protein of 25 kDa) with the β-cell voltage-dependent K+ channel Kv2.1. Expression of Kv2.1, SNAP-25, and syntaxin 1A was detected in human islet lysates by Western blot, and coimmunoprecipitation studies showed that heterologously expressed SNAP-25 and syntaxin 1A associate with Kv2.1. SNAP-25 reduced currents from recombinant Kv2.1 channels by approximately 70% without affecting channel localization. This inhibitory effect could be partially alleviated by codialysis of a Kv2.1N-terminal peptide that can bind in vitro SNAP-25, but not the Kv2.1C-terminal peptide. Similarly, SNAP-25 blocked voltage-dependent outward K+ currents from rat β-cells by approximately 40%, an effect that was completely reversed by codialysis of the Kv2.1N fragment. Finally, SNAP-25 had no effect on outward K+ currents in β-cells where Kv2.1 channels had been functionally knocked out using a dominant-negative approach, indicating that the interaction is specific to Kv2.1 channels as compared with other β-cell Kv channels. This study demonstrates that SNAP-25 can regulate Kv2.1 through an interaction at the channel N terminus and supports the hypothesis that SNARE proteins modulate secretion through their involvement in regulation of membrane ion channels in addition to exocytic membrane fusion.
A Novel Mutation in Helix 12 of the Vitamin D Receptor Impairs Coactivator Interaction and Causes Hereditary 1,25-Dihydroxyvitamin D-Resistant Rickets without Alopecia
Authors: Malloy Peter J. , Xu Rong , Peng Lihong , Clark Pamela A. , Feldman David
Published: October 2002

Hereditary vitamin D-resistant rickets (HVDRR) is a genetic disorder most often caused by mutations in the vitamin D receptor (VDR). The patient in this study exhibited the typical clinical features of HVDRR with early onset rickets, hypocalcemia, secondary hyperparathyroidism, and elevated serum concentrations of alkaline phosphatase and 1,25-dihydroxyvitamin D [1,25-(OH)2D3]. The patient did not have alopecia. Assays of the VDR showed a normal high affinity low capacity binding site for [3H]1,25-(OH)2D3 in extracts from the patient’s fibroblasts. However, the cells were resistant to 1,25-dihydroxyvitamin D action as demonstrated by the failure of the patient’s cultured fibroblasts to induce the 24-hydroxylase gene when treated with either high doses of 1,25-(OH)2D3 or vitamin D analogs. A novel point mutation was identified in helix H12 in the ligand-binding domain of the VDR that changed a highly conserved glutamic acid at amino acid 420 to lysine (E420K). The patient was homozygous for the mutation. The E420K mutant receptor recreated by site-directed mutagenesis exhibited many normal properties including ligand binding, heterodimerization with the retinoid X receptor, and binding to vitamin D response elements. However, the mutant VDR was unable to elicit 1,25-(OH)2D3-dependent transactivation. Subsequent studies demonstrated that the mutant VDR had a marked impairment in binding steroid receptor coactivator 1 (SRC-1) and DRIP205, a subunit of the vitamin D receptor-interacting protein (DRIP) coactivator complex. Taken together, our data indicate that the mutation in helix H12 alters the coactivator binding site preventing coactivator binding and transactivation. In conclusion, we have identified the first case of a naturally occurring mutation in the VDR (E420K) that disrupts coactivator binding to the VDR and causes HVDRR.
Homologous and Heterologous Regulation of Somatostatin Receptor 2
Authors: Elberg Gerard , Hipkin R. William , Schonbrunn Agnes
Published: October 2002

We previously demonstrated that phosphorylation of somatostatin receptor 2A (sst2A) is rapidly increased in transfected cells both by agonist and by the protein kinase C (PKC) activator phorbol myristate acetate (PMA). Here, we investigate whether PKC-mediated receptor phosphorylation is involved in the homologous or heterologous regulation of endogenous sst2 receptors in AR42J pancreatic acinar cells upon stimulation by agonist or by cholecystokinin (CCK) or bombesin (BBS). Somatostatin, PMA, CCK, and BBS all increased sst2A receptor phosphorylation 5- to 10-fold within minutes. Somatostatin binding also caused rapid internalization of the ligand-receptor complex, and PMA, CCK, and BBS all stimulated this internalization further. Additionally, sst2 receptor-mediated inhibition of adenylyl cyclase was desensitized by all treatments. Somatostatin, as well as peptidic (SMS201–995) and nonpeptidic (L-779,976) sst2 receptor agonists increased the EC50 for somatostatin inhibition 20-fold. In contrast, pretreatment with BBS, CCK, or PMA caused a modest 2-fold increase in the EC50 for cyclase inhibition. Whereas the PKC inhibitor GF109203X abolished sst2A receptor phosphorylation by CCK, BBS, and PMA, it did not alter the effect of somatostatin, demonstrating that these reactions were catalyzed by different kinases. Consistent with a functional role for PKC-mediated receptor phosphorylation, GF109203X prevented PMA stimulation of sst2 receptor internalization. Surprisingly, however, GF109203X did not inhibit BBS and CCK stimulation of sst2A receptor endocytosis. These results demonstrate that homologous and heterologous hormones induce sst2A receptor phosphorylation by PKC-independent and -dependent mechanisms, respectively, and produce distinct effects on receptor signaling and internalization. In addition, the heterologous hormones also modulate sst2 receptor internalization by a novel mechanism that is independent of receptor phosphorylation.
Distraction Effects of Background Television on Homework Performance
Authors: Pool Marina M.
Published: October 2002

Students regularly combine their homework with listening to the radio or watching television. A survey study demonstrated that about 80% of the high school students regularly do homework with a radio and 50% more or less frequently do homework with a television in the background (Beentjes, Koolstra, & van der Voort, 1996). With so many students combining homework with background media, the question arises whether students' cognitive system is capable of processing the information given in an assignment as accurately with background media as in a single-task situation without background media.