bluuebunny/crossref_metadata_2025 huggingface dataset:
Social Connections in China: Institutions, Culture, and the Changing Nature of Guanxi. Edited by Thomas Gold, Doug Guthrie, and David Wank. [New York: Cambridge University Press. 2002. 276 pp. £16.95. ISBN 0521-53031-8.]
Authors: Hsing You-tien
Published: February 2004

This collection about guanxi in China is timely. It is timely because, as studies of social networks have reached maturity, it is important to reconsider the relevance of guanxi to social organization and change in China, especially since China has experienced such radical social and economic transformations in the last three decades. It is timely also because there is now increasing discussion about the possibilities of understanding non-Western societies with non-Western analytical categories, and about the strategies of resolving the tension between the particular and the universal. So guanxi, as the Chinese expression of the universal practice of building interpersonal relationships, may serve as a good example of understanding a social feature in specific cultural-institutional contexts and at a more universal level. The authors of this book have dealt with these issues in three broad ways.

The first is to see if the instrumental and emotional dimensions of guanxi offer a more satisfying analysis than one based on extreme rationalism. The authors who took on this issue made useful distinctions between the perception, practice, and real effects of guanxi. For these authors, guanxi is a good way to understand the ambivalence of, and shifts between, the rational and the emotional in social relations, and between behaviour and discourse in social analysis. It remains a great challenge, however, to use the concept of guanxi as an analytical category to resolve the tension between the deep ambivalence of human relations and the methodological clarity demanded by many social scientists.
Der Aufstieg Ostasiens in der Weltpolitik 1840–2000 (The Rise of East Asia in World Politics, 1840–2000). By Gottfried-Karl Kindermann. [Stuttgart: Deutsche Verlags-Anstalt, 2001. €44.99. 727 pp. ISBN 3-421-05174-7.]
Authors: Drifte Reinhard
Published: February 2004

This monumental work is in many ways the essence of Professor Kindermann's 50 years' research on East Asia, theoretically based on the Munich school of neo-realism (of which he is the pre-eminent representative) and inspired by his many personal encounters with those Asian leaders who shaped the region's rise in world politics. It also introduces interesting research by other German scholars, which is often excluded from the English-language literature that dominates the Asian studies field. The focus of the analysis is on the foreign policy of the states in the West Pacific region (including Myanmar and Indochina), their interactions and their place in world politics. It is impossible to summarize the 34 chapters within this review. The books offer a superb chronological and contextual overview of a crucial period in East Asia that is highly readable and illustrated with relevant photos. The most space is devoted to China, documenting its rise from imperial victim to major economic power. The coverage of China's interaction with foreign powers and the domestic background is very detailed, especially concerning the Kuomintang before and after 1949, and the Taiwan issue. The account of the era after the Pacific War focuses mostly on the People's Republic of China. Several pages are devoted to the Quemoy crisis of 1954–55, which revealed the complexities of the US–PRC–Taiwan triangle. Kindermann demonstrates how this crisis was the first application of Washington's “calculated ambiguity” towards the PRC concerning Taiwan. A whole chapter is devoted to the second Taiwan crisis of 1958 and its aftermath in 1962. Kindermann's interviews in Taiwan show how the US actively prevented Chiang Kai-shek's plan of occupying two mainland Chinese cities to start the “liberation” of the PRC. There are four chapters on how the Communist Party established and maintained its rule over China, but the majority deal with China's foreign interactions. On Tibet, Kindermann argues that the 17-item agreement of 1951 between Tibetan leaders and the Communist government may have served as a tolerable solution to the Tibet issue and thus have prevented a lot of hardship for the Tibetan people, even though the Tibetan representatives had been coerced into signing it.
The Tiger and the Pangolin: Nature, Culture and Conservation in China. By Chris Coggins. [Honolulu: University of Hawai‘i Press, 2003. xi +339 pp. $55.00. ISBN 0-8248-2506-3.]
Authors: Tisdell Clem
Published: February 2004

Much of this book is based on extensive fieldwork in the Meihuashan Nature Reserve (and nearby protected areas) of western Fujian as well as substantial examination of relevant historical records. Its basic purpose is to explore the interaction between people (in this case Hakka) and their surrounding ecological environments as influenced by their culture. The study is set within a long-term historical context stretching in the case of the tiger over approximately 2000 years. The chronicling of the status of the tiger illustrates how culture and ecological conditions are intertwined. While the tiger is a focal point in this book, it is not the only ecological case analysed in considering how and why ecological conditions have altered in this part of China as a result of variations in local cultural, social and economic conditions.

The basic thesis of this book is that culture dominates man-induced ecological change. Hence, little or no progress can be made in understanding ecological change without a thorough study of the way cultural factors influence attitudes to nature. It is especially important to do this at the local level, particularly in China.

There are two reasons why this is a desirable approach. First, in-depth local studies can enhance understanding of the national situation. Local or regional studies can be very valuable even when their results cannot be completely transferred to other parts of the country. Secondly, Coggins argues that local people are often the final arbiters of ecological change and that nature conservation can make little progress without local support and knowledge (for example, p. 283).
China to Chinatown: Chinese Food in the West. By J.A.G. Roberts [London: Reaktion Books, 2002. 256 pp. £19.95. ISBN 1-86189-133-4.]
Authors: Wu David Y.H.
Published: February 2004

Following his earlier publication of three volumes of China through Western Eyes (1991–96), Roberts now concentrates on the Western perception of Chinese food and eating behaviour. In the first half of the present book, Roberts quotes travellers' tales from Marco Polo and other adventurers, personal journals of European missionaries in the 16th and 17th centuries, reports of English envoys such as Lord Macartney, merchants of the 19th century, and journalists' accounts from the Second World War to the Cultural Revolution. Part one, “West to East” starts with a succinctly written introduction and a chapter that draws from anthropological works on Chinese diet, food beliefs, and table manners. Roberts then discusses Western perceptions (more often imaginations) of Chinese food, which transformed from curiosity to aversion, rejection, and eventual popular acceptance.
Kings versus Bandits: Anti-colonialism in a Bandit Narrative
Authors: Mayaram Shail
Published: February 2004

Debate and controversy have bedevilled the subject of social banditry. The early writing on social banditry saw it as primitive rebellion, as prepolitical and antithetical to class consciousness. Another approach identified it with weak state formation. The literature on South Asia saw social banditry as absent having been eroded by the institutional structure of caste. This article examines and critiques some of these theses on banditry. It argues, firstly, that social banditry can be simultaneous with a phase of intensified state formation. The specific theme investigated here is the interaction of the king, peasant and bandit in an Indian kingdom under late colonialism. A window to this universe is opened up by a folk epic from the oral tradition of a community of Muslims called the Meos. Far from being prepolitical, banditry raises crucial questions with respect to authority and legitimacy. This narrative not only interrogates the legitimacy of kingship, it also challenges the authority of the colonial state. Secondly, the article challenges the argument of South Asian exceptionalism to banditry that is perhaps easier to refute. Thirdly, as this article demonstrates, banditry need not relate to a pre-industrial capitalist world. Our bandit narrative indicates the reverberations of industrialism and attendant exchange relations and institutions in the colony even though it belongs to an area of ‘indirect’ rule.
Ôba Osamu
Authors: Loewe Michael
Published: February 2004

A leading Japanese scholar of Chinese history who was based in Kansai, Ôba Osamu (1927–2002) spent a highly productive career, holding appointments from 1953 onwards at Seishin Joshi Daigaku, Ryûkoku Daigaku and Osaka Daigaku. A Professor of Kansai Daigaku in 1965, he later served there as the head of the Faculty of Letters (Bungaku bu) and at one time as Director of the University Library. Outside Japan he held short-term appointments, or was invited to be a visiting scholar, at a number of centres of learning, including some in China (Liaoning, Shandong, Hong Kong and Beijing), the United States of America (Princeton), Belgium (Leuven) and the United Kingdom (Cambridge and London). He held the title of Guest Professor in the Archaeological Research Institute, Gansu, and at the Chinese Academy of Social Sciences, Beijing.
Parasuizide bei Kindern und Jugendlichen
Authors: Baving Lioba
Published: February 2004

Zusammenfassung. In dieser Übersichtsarbeit werden spezifische Aspekte parasuizidalen Verhaltens bei Kindern und Jugendlichen dargestellt. Bedeutsame Risikofaktoren sind psychische Störungen der Minderjährigen sowie ein niedriges Funktionsniveau ihrer Familien, aber auch diverse andere personbezogene und psychosoziale Variablen sind überzufällig häufig mit Parasuiziden assoziiert. Eine kleine Untergruppe der Kinder und Jugendlichen zeigt wiederholt auftretendes parasuizidales Verhalten. Diagnostische und therapeutische Implikationen der dargestellten wissenschaftlichen Befunde werden erörtet.
Carbon isotopic fractionation (εp) of C37 alkenones in deep‐sea sediments: Its potential as a paleonutrient proxy
Authors: Schulte Sonja , Benthien Albert , Müller Peter J. , Rühlemann Carsten
Published: February 2004

We compared ocean atlas values of surface water [PO43−] and [CO2(aq)] against the carbon isotopic fractionation (εp) of alkenones obtained from surface sediments of the South Atlantic and the central Pacific (Pacific data are from Pagani et al. [2002]). We observed a positive correlation between εp and 1/[CO2(aq)], which is opposite of what would be expected if the concentration of CO2(aq) were the major factor controlling the carbon isotopic fractionation of C37:2 alkenones. Instead, we found inverse relationships between εp and [PO43−] for the two ocean basins (for the Atlantic, εp = −4.6*[PO43−] + 15.1, R = 0.76; for the Pacific, εp = −4.1*[PO43−] + 13.7, R = 0.64), suggesting that εp is predominantly controlled by growth rate, which in turn is related to nutrient concentration. The similarity of the slopes implies that a general relationship between both parameters may exist. Using the relationship obtained from the South Atlantic, we estimated surface water nutrient concentrations for the past 200,000 years from a deep‐sea sediment core recovered off Angola. Low εp values, indicating high nutrient concentrations, coincide with high contents of total organic carbon and C37 alkenones, low surface water temperatures, and decreased bulk δ15N values, suggesting an increased upwelling of nutrient‐rich cool subsurface waters as the main cause for the observed εp decrease.
Response of the water balance to climate change in the United States over the 20th and 21st centuries: Results from the VEMAP Phase 2 model intercomparisons
Authors: Gordon W. S. , Famiglietti J. S.
Published: February 2004

Using the VEMAP Phase 2 data set, we tested the hypothesis that changes in climate would result in changes in the water balance as projected by four terrestrial ecosystem models: BIOME‐BGC, Century, LPJ, and MC1. We examined trends in runoff and actual evapotranspiration (AET), changes in runoff in relation to changes in precipitation, and differences in runoff ratios as produced by these models for 13 United States watersheds. Observed climate data were used as inputs for simulations covering 1895–1993. From 1994 to 2100, the Canadian Centre for Climate Modeling and Analysis (CGCM1) and the Hadley Centre for Climate Prediction and Research (HADCM2) general circulation models provided climate forcing. Runoff and AET trends were significantly positive in the majority of 13 watersheds examined. Percentage changes in runoff exceeded the underlying changes in precipitation and this amplification increased over time. Calculated runoff ratios showed model variability and differences based on the two GCM scenarios.
Estimates of anthropogenic carbon in the Indian Ocean with allowance for mixing and time‐varying air‐sea CO2 disequilibrium
Authors: Hall Timothy M. , Waugh Darryn W. , Haine Thomas W. N. , Robbins Paul E. , Khatiwala Samar
Published: February 2004

We apply to the Indian Ocean a novel technique to estimate the distribution, total mass, and net air‐sea flux of anthropogenic carbon. Chlorofluorocarbon data are used to constrain distributions of transit times from the surface to the interior that are constructed to accommodate a range of mixing scenarios, from no mixing (pure bulk advection) to strong mixing. The transit time distributions are then used to propagate to the interior the surface water history of anthropogenic carbon estimated in a way that includes temporal variation in CO2 air‐sea disequilibrium. By allowing for mixing in transport and for variable air‐sea disequilibrium, we remove two sources of positive bias common in other studies. We estimate that the anthropogenic carbon mass in the Indian Ocean was 14.3–20.5 Gt in 2000, and the net air‐sea flux was 0.26–0.36 Gt/yr. The upper bound of this range, the no‐mixing limit, generally coincides with previous studies, while the lower bound, the strong‐mixing limit, is significantly below previous studies.
Spatial statistics of marine boundary layer clouds
Authors: Lewis Gregory M. , Austin Philip H. , Szczodrak Malgorzata
Published: February 2004

An analysis is presented of the structure functions and scalar spectra for 25 satellite‐derived marine stratocumulus cloud optical depth fields. The scenes, which cover a horizontal domain of 58 × 58 km at a resolution of 28.5 m, are partitioned into two ensembles on the basis of cloud fraction. For the fully cloudy scenes, although there is wide scene‐to‐scene variability, both the average isotropic scalar spectrum and the average isotropic second‐order structure function exhibit power law behavior over approximately two decades, with scale‐invariant exponents equal to those expected for inertial‐subrange passive tracer fluctuations. Higher‐order structure functions show anomalous scaling that closely matches that observed for wind tunnel temperature fluctuations and for other fully cloudy observations. The partly cloudy scenes, while scaling, show different behavior. The average isotropic second‐order structure function and average isotropic scalar spectrum have scale‐invariant exponents that are significantly smaller than those of the fully cloudy scenes, and the analysis of the higher‐order structure functions indicates that the field has much more intermittent fluctuations than the fully cloudy scenes. Fits to random cascade models for the fully cloudy scenes show that the increment statistics are consistent with an underlying log normal distribution. For the partly cloudy scenes a divergence of higher‐order moments is predicted, indicating that the field fluctuations are necessarily derived from fat‐tailed distributions and that there will be significant realization dependence of the measured statistics. In addition, the presence of long‐range correlations in all the data predicts that single‐point histograms of the field values will have significant scene‐to‐scene variability, or equivalently, the use of spatial averages in the approximation of the parameters of the single‐point probability density function of the field will result in random fluctuations of the estimated parameters.
An analysis of satellite, radiosonde, and lidar observations of upper tropospheric water vapor from the Atmospheric Radiation Measurement Program
Authors: Soden Brian J. , Turner David D. , Lesht Barry M. , Miloshevich Larry M.
Published: February 2004

To improve our understanding of the distribution and radiative effects of water vapor, the U.S. Department of Energy Atmospheric Radiation Measurement (ARM) Program has conducted a series of coordinated water vapor Intensive Observation Periods (IOPs). This study uses observations collected from four ARM IOPs to accomplish two goals: First we compare radiosonde and Raman lidar observations of upper tropospheric water vapor with colocated geostationary satellite radiances at 6.7 μm. During all four IOPs we find excellent agreement between the satellite and Raman lidar observations of upper tropospheric humidity with systematic differences of ∼10%. In contrast, radiosondes equipped with Vaisala sensors are shown to be systematically drier in the upper troposphere by ∼40% relative to both the lidar and satellite measurements. Second, we assess the performance of various “correction” strategies designed to rectify known deficiencies in the radiosonde measurements. It is shown that existing methods for correcting the radiosonde dry bias, while effective in the lower troposphere, offer little improvement in the upper troposphere. An alternative method based on variational assimilation of satellite radiances is presented and, when applied to the radiosonde measurements, is shown to significantly improve their agreement with coincident Raman lidar observations. It is suggested that a similar strategy could be used to improve the quality of the global historical record of radiosonde water vapor observations during the satellite era.
Organic aerosol formation via sulphate cluster activation
Authors: Kulmala Markku , Kerminen Veli‐Matti , Anttila Tatu , Laaksonen Ari , O'Dowd Colin D.
Published: February 2004

The formation of aerosols, and subsequent cloud condensation nuclei, remains one of the least understood atmospheric processes upon which global climate change critically depends. Under atmospheric conditions, the process of homogeneous nucleation (formation of stable clusters ∼ 1 nm in size), and their subsequent growth into new particles (>3 nm), determines the aerosol and cloud nuclei population, yet, hitherto, no theory has elucidated the new particle formation phenomenon in detail. In this study, we present a new theory which provides a mechanistic explanation for new particle formation via activation of stable inorganic clusters by organic vapors. The new nano‐particle activation theory is analogous to Köhler theory which describes cloud formation in a supersaturated water vapor field but differs in that it describes the activation of inorganic stable nano‐clusters into aerosol particles in a supersaturated organic vapor which initiates spontaneous and rapid growth of clusters. Inclusion of the new theory into aerosol formation models predicts that increases in organic vapor densities lead to even greater increases in particle production, which, in turn, will influence the global radiative cooling effect of atmospheric aerosols.
Effects of cloud overlap in photochemical models
Authors: Feng Yan , Penner Joyce E. , Sillman Sanford , Liu Xiaohong
Published: February 2004

Different schemes have been used to represent the vertical coherence of clouds for radiation and cloud microphysics in general circulation models and for photolysis in photochemical transport models. Here, we examine the maximum‐random overlap scheme, the random overlap scheme, and a linear scheme (linear scaling of the cloud optical depth in a grid box with cloud fraction) and evaluate their effects on averaged photolysis frequencies and OH concentrations in a global photochemical model. Photolysis frequencies are increased in the upper tropical troposphere and decreased in the lower troposphere if clouds are assumed to be randomly overlapped or if a linear assumption is followed rather than the maximum‐random overlap assumption. The underestimate is of order 50% and 20–30% at the surface in the tropics and over some continental midlatitude regions for the linear and the random assumptions, respectively, relative to the maximum‐random assumption. The global average CH4 + OH reaction rate‐weighted OH concentration calculated with the random overlap assumption is within a few percent of that calculated with the maximum‐random overlap assumption but is underestimated with the nonphysically based linear assumption, by 4 to 6% relative to the maximum‐random overlap assumption and by 6 to 7% relative to the random overlap assumption. An underestimate of rate‐weighted OH concentration implies that the tropospheric lifetime for CH4 and other greenhouse gases that react with OH is too long in models that use this scheme.
Permeation of atmospheric gases through polymer O‐rings used in flasks for air sampling
Authors: Sturm P. , Leuenberger M. , Sirignano C. , Neubert R. E. M. , Meijer H. A. J. , Langenfelds R. , Brand W. A. , Tohjima Y.
Published: February 2004

Permeation of various gases through elastomeric O‐ring seals can have important effects on the integrity of atmospheric air samples collected in flasks and measured some time later. Depending on the materials and geometry of flasks and valves and on partial pressure differences between sample and surrounding air, the concentrations of different components of air can be significantly altered during storage. The influence of permeation is discussed for O2/N2, Ar/N2, CO2, δ13C in CO2, and water vapor. Results of sample storage tests for various flask and valve types and different storage conditions are presented and are compared with theoretical calculations. Effects of permeation can be reduced by maintaining short storage times and small partial pressure differences and by using a new valve design that buffers exchange of gases with surrounding air or by using less permeable materials (such as Kel‐F) as sealing material. General awareness of possible permeation effects helps to achieve more reliable measurements of atmospheric composition with flask sampling techniques.
The role of the inhibitors of interleukin-6 signal transduction SHP2 and SOCS3 for desensitization of interleukin-6 signalling
Authors: FISCHER Patrick , LEHMANN Ute , SOBOTA Radoslaw M. , SCHMITZ Jochen , NIEMAND Claudia , LINNEMANN Sonja , HAAN Serge , BEHRMANN Iris , YOSHIMURA Akihiko , JOHNSTON James A. , MÜLLER-NEWEN Gerhard , HEINRICH Peter C. , SCHAPER Fred
Published: February 2004

The immediate early response of cells treated with IL-6 (interleukin-6) is the activation of the signal transducer and activator of transcription (STAT)3. The Src homology domain 2 (SH2)-containing protein tyrosine phosphatase SHP2 and the feedback inhibitor SOCS3 (suppressor of cytokine signalling) are potent inhibitors of IL-6 signal transduction. Impaired function of SOCS3 or SHP2 leads to enhanced and prolonged IL-6 signalling. The inhibitory function of both proteins depends on their recruitment to the tyrosine motif 759 within glycoprotein gp130. In contrast to inactivation, desensitization of signal transduction is regarded as impaired responsiveness due to prestimulation. Usually, after activation the sensing receptor becomes inactivated by modifications such as phosphorylation, internalization or degradation. We designed an experimental approach which allows discrimination between desensitization and inactivation of IL-6 signal transduction. We observed that pre-stimulation with IL-6 renders cells less sensitive to further stimulation with IL-6. After several hours, the cells become sensitive again. We show that not only signal transduction through previously activated receptors is affected by desensitization but signalling through receptors which were not targeted by the first stimulation was also attenuated (trans-desensitization). Interestingly, in contrast to inhibition, desensitization does not depend on the presence of functional SHP2. Furthermore, cells lacking SOCS3 show constitutive STAT3 activation which is not affected by pre-stimulation with IL-6. All these observations suggest that desensitization and inhibition of signalling are mechanistically distinct.
Cytosolic phospholipase A2-p11 interaction controls arachidonic acid release as a function of epithelial cell confluence
Authors: BAILLEUX Anne , WENDUM Dominique , AUDUBERT François , JOUNIAUX Anne-Marie , KOUMANOV Kamen , TRUGNAN Germain , MASLIAH Joëlle
Published: February 2004

Madin–Darby canine kidney type II cells were shown to release low amounts of AA (arachidonic acid) and prostaglandin E2 in response to various stimuli when analysed after cell confluence. In contrast, non-confluent Madin–Darby canine kidney type II cells released much higher amounts of AA and prostaglandin E2. In both stationary and non-confluent cells, AA was released by type IV cPLA2 (cytosolic phospholipase A2), as shown by the use of specific inhibitors and by analysis of the profile of fatty acids released. This confluence-dependent cPLA2 activation was not due to a difference in expression, or in phosphorylation of the enzyme, or in the amount of its substrate. To find out the mechanism by which cPLA2 activation may be regulated as a function of cell confluence, immunofluorescence and co-immunoprecipitation experiments were performed using cPLA2, p11, a natural inhibitor of the enzyme, and annexin II, the natural ligand of p11. These three proteins were expressed at a constant level, regardless of the cell confluence. In contrast, whereas annexin II and cPLA2 interacted at a constant rate, p11 and cPLA2 interacted more strongly in stationary cells, thus indicating that cPLA2 activation is regulated by its accessibility to p11, independent of their expression level. Our results indicate that, in epithelial cells, the cell confluence, i.e. the establishment of cell–cell contacts, rather than cell proliferation directly controls cPLA2 activation by changing the stoichiometry of p11/cPLA2 interaction.
Influence of zinc deficiency on cell-membrane fluidity in Jurkat, 3T3 and IMR-32 cells
Authors: VERSTRAETEN Sandra V. , ZAGO M. Paola , MACKENZIE Gerardo G. , KEEN Carl L. , OTEIZA Patricia I.
Published: February 2004

We investigated whether zinc deficiency can affect plasma membrane rheology. Three cell lines, human leukaemia T-cells (Jurkat), rat fibroblasts (3T3) and human neuroblastoma cells (IMR-32), were cultured for 48 h in control medium, in zinc-deficient medium (1.5 µM zinc; 1.5 Zn), or in the zinc-deficient medium supplemented with 15 µM zinc (15 Zn). The number of viable cells was lower in the 1.5 Zn group than in the control and 15 Zn groups. The frequency of apoptosis was higher in the 1.5 Zn group than in the control and 15 Zn groups. Membrane fluidity was evaluated using the 6-(9-anthroyloxy)stearic acid and 16-(9-anthroyloxy)palmitic acid probes. Membrane fluidity was higher in 1.5 Zn cells than in the control cells; no differences were observed between control cells and 15 Zn cells. The effect of zinc deficiency on membrane fluidity at the water/lipid interface was associated with a higher phosphatidylserine externalization. The higher membrane fluidity in the hydrophobic region of the bilayer was correlated with a lower content of arachidonic acid. We suggest that the increased fluidity of the membrane secondary to zinc deficiency is in part due to a decrease in arachidonic acid content and the apoptosis-related changes in phosphatidylserine distribution.
Complexity of glutamine metabolism in kidney tubules from fed and fasted rats
Authors: VERCOUTÈRE Barbara , DUROZARD Daniel , BAVEREL Gabriel , MARTIN Guy
Published: February 2004

Glutamine is an important renal glucose precursor and energy provider. In order to advance our understanding of the underlying metabolic processes, we studied the metabolism of variously labelled [13C]glutamine and [14C]glutamine molecules and the effects of fasting in isolated rat renal proximal tubules. Absolute fluxes through the enzymes involved, including enzymes of four different cycles operating concomitantly, were assessed by combining mainly the 13C NMR data with an appropriate model of glutamine metabolism. In both nutritional states, unidirectional glutamine removal by glutaminase was partially masked by the concomitant operation of glutamine synthetase; fasting accelerated glutamine removal by increasing flux solely through glutaminase, without changing that through glutamine synthetase. Fasting stimulated net glutamate degradation only by decreasing flux through glutamate dehydrogenase in the reductive amination direction, but surprisingly did not significantly alter complete oxidation of the glutamine carbon skeleton. Finally, gluconeogenesis from glutamine involved not only substantial recycling through the tricarboxylic acid cycle, but also an important anaplerotic flux through pyruvate carboxylase that was accelerated dramatically by fasting. Thus renal glutamine metabolism follows an unexpectedly complex route that is precisely regulated during fasting.
Membrane and raft association of reggie-1/flotillin-2: role of myristoylation, palmitoylation and oligomerization and induction of filopodia by overexpression
Authors: NEUMANN-GIESEN Carolin , FALKENBACH Bianca , BEICHT Peter , CLAASEN Stephanie , LÜERS Georg , STUERMER Claudia A. O. , HERZOG Volker , TIKKANEN Ritva
Published: February 2004

The reggie protein family consists of two proteins, reggie-1 and -2, also called flotillins, which are highly ubiquitous and evolutionarily conserved. Both reggies have been shown to be associated with membrane rafts and are involved in various cellular processes such as T-cell activation, phagocytosis and insulin signalling. However, the exact molecular function of these proteins remains to be determined. In addition, the mechanism of membrane association of reggie-1, which does not contain any transmembrane domain, is not known. In this study, we have produced a fusion protein of reggie-1 with enhanced green fluorescent protein and generated targeted substitutions for the inactivation of putative palmitoylation and myristoylation sites. We were able to show that reggie-1 is myristoylated and multiply palmitoylated and that lipid modifications are necessary for membrane association of reggie-1. Overexpression of reggie-1 resulted in the induction of numerous filopodia-like protrusions in various cell lines, suggesting a role for reggie-1 as a signalling protein in actin-dependent processes.
B-Myb acts as a repressor of human COL1A1 collagen gene expression by interacting with Sp1 and CBF factors in scleroderma fibroblasts
Authors: CICCHILLITTI Lucia , JIMENEZ Sergio A. , SALA Arturo , SAITTA Biagio
Published: February 2004

We investigated the role of B-Myb, a cell-cycle-regulated transcription factor, in the expression of the α1 (I) pro-collagen gene (COL1A1) in scleroderma fibroblasts. Scleroderma or SSc (systemic sclerosis) is a fibrotic disease characterized by excessive production of extracellular matrix components, especially type I collagen. Northern-blot analysis showed an inverse relationship between COL1A1 mRNA expression and that of B-Myb during exponential cell growth and during quiescence in human SSc fibroblasts. Overexpression of B-Myb in SSc fibroblasts was correlated with decreased COL1A1 mRNA expression. Transient transfections localized the down-regulatory effect of B-Myb to a region containing the proximal 174 bp of the COL1A1 promoter that does not contain B-Myb consensus binding sites. Gel-shift analysis, using nuclear extracts from normal and SSc fibroblasts transfected with B-Myb, showed no differences in DNA–protein complex formation when compared with the nuclear extracts from mock-transfected cells. However, we found that B-Myb decreases Sp1 (specificity protein 1) and CBF (CCAAT-binding factor) binding for their specific sites localized in the 174 bp COL1A1 proximal promoter. These results were also confirmed using B-Myb-immunodepleted nuclear extracts. Furthermore, immunoprecipitation assays using SSc nuclear extracts demonstrated a physical interaction of B-Myb with Sp1 and CBF transcription factors, and also an interaction between Sp1 and CBF. In addition, by employing full-length or deleted B-Myb cDNA construct, we found that B-Myb down-regulates the COL1A1 proximal promoter through its C-terminal domain. Thus these results suggest that B-Myb may be an important factor in the pathway(s) regulating collagen production in SSc fibroblasts.
Genomic organization and linkage via a bidirectional promoter of the AP-3 (adaptor protein-3) mu3A and AK (adenosine kinase) genes: deletion mutants of AK in Chinese hamster cells extend into the AP-3 mu3A gene
Authors: SINGH Bhag , GUPTA Radhey S.
Published: February 2004

The cDNA and genomic DNA for the µ3A subunit of the AP-3 (adaptor protein-3) complex were cloned from Chinese hamster cells. The AP-3 µ3A genes in Chinese hamster, human and mouse each comprise nine exons and eight introns, with all introns located in identical positions in the species studied. The AP-3 µ3A genes in these species are linked in a head-to-head fashion with the gene for the purine salvage pathway enzyme AK (adenosine kinase). These genes share the first exon, and a 512 bp fragment covering the intervening untranslated sequence has the characteristic of a CpG island promoter, and it effectively carried out transcription in both directions. Deletion studies indicate that this region contains both positive and negative regulatory elements affecting transcription of these genes. In comparison with the AP-3 µ3A gene (27 kb), the AK gene in human is very large (558 kb), with average exon and intron lengths of approx. 100 bp and 55.7 kb respectively. The ratio of non-coding to coding sequence in the human AK gene is >550, which is the highest reported for any gene. We also present evidence that a number of AK− mutants of Chinese hamster ovary cells contain large deletions that affect both of these genes. In addition to lacking part of the AK gene, two of these mutants also lacked all of the exons and introns corresponding to the AP-3 µ3A gene. These mutants should prove useful in elucidating the role of AP-3 µ3A in vesicle-mediated protein sorting – a process that is altered in Hermansky–Pudlak syndrome. Detailed phylogenetic analysis of the µ family of proteins presented here also provides insight into how different AP complexes are related and may have evolved.
Effect of glycosylphosphatidylinositol (GPI)-phospholipase D overexpression on GPI metabolism
Authors: MANN Karl J. , HEPWORTH Matthew R. , RAIKWAR Nandita S. , DEEG Mark A. , SEVLEVER Daniel
Published: February 2004

GPI-PLD [glycosylphosphatidylinositol (GPI)-specific phospholipase D (PLD)] is a secreted mammalian enzyme that specifically cleaves GPI-anchored proteins. In addition, the enzyme has been shown to cleave GPI anchor intermediates in cell lysates. The biosynthesis of the GPI anchor is well characterized; however, the mechanisms by which the levels of GPI anchor intermediates are regulated are still unknown. To investigate whether GPI-PLD plays a role in this regulation, we isolated stable HeLa cells overexpressing the enzyme. GPI-PLD-HeLa (GPI-PLD-transfected HeLa) cells showed a 3-fold increase in intracellular GPI-PLD activity and drastically decreased the levels of GPI-anchored proteins when compared with untransfected HeLa controls. Intracellular cleavage of GPI-anchored proteins has been suggested to occur early in the secretory pathway and, in agreement with this proposal, GPI-PLD activity in GPI-PLD-HeLa cells was detected not only in the endoplasmic reticulum and Golgi apparatus, but also in the plasma membrane. The enzyme was also active in lipid rafts, membrane microdomains in which GPI-anchored proteins and GPI anchor intermediates are concentrated, indicating that intracellular GPI-PLD cleavage may also occur in this compartment. Pulse–chase paradigms revealed the turnover rate of the last intermediate of the GPI anchor pathway in GPI-PLD-HeLa cells to be accelerated compared with the controls. Furthermore, 1,10-phenanthroline, a GPI-PLD inhibitor, reversed this effect. Our studies demonstrated that GPI-PLD can cleave not only GPI-anchored proteins, but also GPI anchor intermediates intracellularly. This observation opens the possibility that GPI-PLD can influence the steady-state levels of GPI-anchored proteins by hydrolysing the anchor before and after its attachment to proteins.
Comparative analysis of tandem C2 domains from the mammalian synaptotagmin family
Authors: RICKMAN Colin , CRAXTON Molly , OSBORNE Shona , DAVLETOV Bazbek
Published: February 2004

Intracellular membrane traffic is governed by a conserved set of proteins, including Syts (synaptotagmins). The mammalian Syt family includes 15 isoforms. Syts are membrane proteins that possess tandem C2 domains (C2AB) implicated in calcium-dependent phospholipid binding. We performed a pair-wise amino acid sequence comparison, together with functional studies of rat Syt C2ABs, to examine common and divergent properties within the mammalian family. Sequence analysis indicates three different C2AB classes, the members of which share a high degree of sequence similarity. All the other C2ABs are highly divergent in sequence. Nearly half of the Syt family does not exhibit calcium/phospholipid binding in comparison to Syt I, the major brain isoform. Syts do, however, possess a more conserved function, namely calcium-independent binding to target SNARE (soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor) heterodimers. All tested isoforms, except Syt XII and Syt XIII, bound the target SNARE heterodimer comprising syntaxin 1 and SNAP-25 (25 kDa synaptosome-associated protein). Our present study suggests that many Syt isoforms can function in membrane trafficking to interact with the target SNARE heterodimer on the pathway to calcium-triggered membrane fusion.
Differences in regulatory properties between human and rat glucokinase regulatory protein
Authors: BROCKLEHURST Katy J. , DAVIES Rick A. , AGIUS Loranne
Published: February 2004

The inhibition of glucokinase by rat and Xenopus GKRPs (glucokinase regulatory protein) is well documented. We report a comparison of the effects of human and rat GKRPs on glucokinase activity. Human GKRP is a more potent inhibitor of glucokinase than rat GKRP in the absence of fructose 6-phosphate or sorbitol 6-phosphate, and has a higher affinity for these ligands. However, human and rat GKRPs have similar affinities for fructose 1-phosphate and chloride. Residues that are not conserved between the rodent and human proteins affect both the affinity for fructose 6-phosphate and sorbitol 6-phosphate and the inhibitory potency of GKRP on glucokinase in the absence of these ligands.
Thyroid-hormone-dependent negative regulation of thyrotropin beta gene by thyroid hormone receptors: study with a new experimental system using CV1 cells
Authors: NAKANO Keiko , MATSUSHITA Akio , SASAKI Shigekazu , MISAWA Hiroko , NISHIYAMA Kozo , KASHIWABARA Yumiko , NAKAMURA Hirotoshi
Published: February 2004

The molecular mechanism involved in the liganded thyroid hormone receptor suppression of the TSHβ (thyroid-stimulating hormone β, or thyrotropin β) gene transcription is undetermined. One of the main reasons is the limitation of useful cell lines for the experiments. We have developed an assay system using non-pituitary CV1 cells and studied the negative regulation of the TSHβ gene. In CV1 cells, the TSHβ–CAT (chloramphenicol acetyltransferase) reporter was stimulated by Pit1 and GATA2 and suppressed by T3 (3,3´,5-tri-iodothyronine)-bound thyroid hormone receptor. The suppression was dependent on the amounts of T3 and the receptor. Unliganded receptor did not stimulate TSHβ activity, suggesting that the receptor itself is not an activator. Analyses using various receptor mutants revealed that the intact DNA-binding domain is crucial to the TSHβ gene suppression. Co-activators and co-repressors are not necessarily essential, but are required for the full suppression of the TSHβ gene. Among the three receptor isoforms, β2 exhibited the strongest inhibition and its protein level was the most predominant in a thyrotroph cell line, TαT1, in Western blotting. The dominant-negative effects of various receptor mutants measured on the TSHβ–CAT reporter were not simple mirror images of those in the positive regulation under physiological T3 concentration.
A novel partner for D-type cyclins: protein kinase A-anchoring protein AKAP95
Authors: ARSENIJEVIC Tatjana , DEGRAEF Chantal , DUMONT Jacques E. , ROGER Pierre P. , PIRSON Isabelle
Published: February 2004

Using a yeast interaction screen to search for proteins that interact with cyclin D3 in thyroid gland, we identified the cAMP-dependent AKAP95 (protein kinase A-anchoring protein 95). AKAP95 is a scaffolding protein that primarily co-fractionates with the nuclear matrix, whereas a minor fraction associates with chromatin in interphase cells. In co-transfected Chinese-hamster ovary cells, AKAP95 strongly interacted with the three D-type cyclins, but not with CDK4 (cyclin-dependent kinase 4) or with p27kip1. CDK4 displaced the interaction between cyclin D3 and AKAP95, suggesting that AKAP95 could not be the elusive bridging adaptor between D-type cyclins and CDK4 or play a role in the regulation of cyclin D3–CDK4 activity. Interaction between endogenous AKAP95 and cyclin D3 or cyclin D1 was detected in canine thyrocytes, human fibroblasts and NIH-3T3 cells. As both AKAP95 and cyclins D were recently reported to associate with minichromosome maintenance proteins [Eide, Tasken, Carlson, Williams, Jahnsen, Tasken and Collas (2003) J. Biol. Chem. 278, 26750–26756; Gladden and Diehl (2003) J. Biol. Chem. 278, 9754–9760], we hypothesize that the interaction between AKAP95 and D-type cyclins might serve to facilitate the emerging regulatory role of cyclin D–CDK4 in the formation of the prereplication complex at the DNA replication origins.
Intermittent altitude exposures reduce acute mountain sickness at 4300 m
Authors: BEIDLEMAN Beth A. , MUZA Stephen R. , FULCO Charles S. , CYMERMAN Allen , DITZLER Dan , STULZ Dean , STAAB Janet E. , SKRINAR Gary S. , LEWIS Steven F. , SAWKA Michael N.
Published: February 2004

Acute mountain sickness (AMS) commonly occurs at altitudes exceeding 2000–2500 m and usually resolves after acclimatization induced by a few days of chronic residence at the same altitude. Increased ventilation and diuresis may contribute to the reduction in AMS with altitude acclimatization. The aim of the present study was to examine the effects of intermittent altitude exposures (IAE), in combination with rest and exercise training, on the incidence and severity of AMS, resting ventilation and 24-h urine volume at 4300 m. Six lowlanders (age, 23±2 years; body weight, 77±6 kg; values are means±S.E.M.) completed an Environmental Symptoms Questionnaire (ESQ) and Lake Louise AMS Scoring System (LLS), a resting end-tidal partial pressure of CO2 (PETCO2) test and a 24-h urine volume collection at sea level (SL) and during a 30 h exposure to 4300 m altitude-equivalent (barometric pressure=446 mmHg) once before (PreIAE) and once after (PostIAE) a 3-week period of IAE (4 h·day-1, 5 days·week-1, 4300 m). The previously validated factor score, AMS cerebral score, was calculated from the ESQ and the self-report score was calculated from the LLS at 24 h of altitude exposure to assess the incidence and severity of AMS. During each IAE, three subjects cycled for 45–60 min·day-1 at 60–70% of maximal O2 uptake (VO2 max) and three subjects rested. Cycle training during each IAE did not affect any of the measured variables, so data from all six subjects were combined. The results showed that the incidence of AMS (%), determined from both the ESQ and LLS, increased (P<0.05) from SL (0±0) to PreIAE (50±22) at 24 h of altitude exposure and decreased (P<0.05) from PreIAE to PostIAE (0±0). The severity of AMS (i.e. AMS cerebral symptom and LLS self-report scores) increased (P<0.05) from SL (0.02±0.02 and 0.17±0.17 respectively) to PreIAE (0.49±0.18 and 4.17±0.94 respectively) at 24 h of altitude exposure, and decreased (P<0.05) from PreIAE to PostIAE (0.03±0.02 and 0.83±0.31 respectively). Resting PETCO2 (mmHg) decreased (i.e. increase in ventilation; P<0.05) from SL (38±1) to PreIAE (32±1) at 24 h of altitude exposure and decreased further (P<0.05) from PreIAE to PostIAE (28±1). In addition, 24-h urine volumes were similar at SL, PreIAE and PostIAE. In conclusion, our findings suggest that 3 weeks of IAE provide an effective alternative to chronic altitude residence for increasing resting ventilation and reducing the incidence and severity of AMS.
Effect of magnesium, high altitude and acute mountain sickness on blood flow velocity in the middle cerebral artery
Authors: LYSAKOWSKI Christopher , ELM Erik VON , DUMONT Lionel , JUNOD Jean-Daniel , TASSONYI Edömer , KAYSER Bengt , TRAMÈR Martin R.
Published: February 2004

Cerebral blood flow is thought to increase at high altitude and in subjects suffering from acute mountain sickness (AMS); however, data from the literature are contentious. Blood flow velocity in the middle cerebral artery (MCAv) may be used as a proxy measure of cerebral blood flow. Using transcranial Doppler sonography, MCAv was measured during normo- and hyper-ventilation in subjects who participated in a trial that tested the effect of magnesium supplementation on the prevention of AMS. First, MCAv was recorded at 353 m (baseline). Subjects were then randomized to receive oral magnesium citrate and matching placebo. A second measurement was taken after a 24±2 h ascent from 1130 m to 4559 m (altitude I), and a third after a 20–24 h stay at 4559 m (altitude II). Using multivariate linear regression, an association was sought between MCAv and magnesium supplementation, subjects′ age and gender, altitude itself, a temporary stay at altitude, and the presence of AMS (Lake Louise Score >6 with ataxia, nausea and/or headache). Subjects with AMS had additional Doppler recordings immediately before and after rescue medication (oxygen, dexamethasone and acetazolamide). Forty-seven subjects had measurements at baseline, 39 (21 receiving magnesium and 18 placebo) at altitude I and 26 (13 receiving magnesium and 13 placebo) at altitude II. During hyperventilation, MCAv decreased consistently (for each measurement, P<0.001). Magnesium significantly increased MCAv by 8.4 cm·s-1 (95% confidence interval, 1.8–15), but did not prevent AMS. No other factors were associated with MCAv. Eleven subjects had severe AMS [median score (range), 11 (8–16)] and, after rescue medication, the median score decreased to 3 (range, 0–5; P=0.001), but MCAv remained unchanged (65±18 cm·s-1 before compared with 67±16 cm·s-1 after rescue medication; P=0.79). MCAv was increased in subjects who received magnesium, but was not affected by exposure to high altitude or by severe AMS.