bluuebunny/crossref_metadata_2025 huggingface dataset:
Cerebral Endothelial Cell Apoptosis after Ischemia—Reperfusion: Role of PARP Activation and AIF Translocation
Authors: Zhang Yunhong , Zhang Xiaochun , Park Tae S , Gidday Jeffrey M
Published: February 2005

Cerebral ischemia-reperfusion leads to vascular dysfunction characterized by endothelial cell injury or death. In the present study, we used an in vitro model to elucidate mechanisms of human brain microvascular endothelial cell (HBMEC) injury after episodic ischemia-reperfusion. Near-confluent HBMEC cultures were exposed to intermittent hypoxia-reoxygenation (HX/RO) and, at different recovery time points, cell viability was assessed by the MTT assay, apoptotic death by fluorescence microscopy of terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate-biotin nick end labeling (TUNEL)-positive cells, and nuclear translocation of apoptosis-inducing factor (AIF) and cleavage of poly(ADP-ribose) polymerase-1 (PARP-1) by immunoblotting of subcellular fractions. Reductions in HBMEC viability were proportional to the number of HX/RO cycles, and not the total duration of hypoxia. Using four cycles of 1-h HX with 1 h of intervening normoxic RO, cell viability was reduced 30% to 40% between 12 and 48 h. Treatment with the PARP-1 inhibitors 3-aminobenzamide or 4-amino-1,8-naphthalimide during the insult improved HBMEC viability at 24 h after insult, and resulted in dose-dependent reductions in TUNEL-positivity at 16 h after insult, but not if these treatments were delayed by 4 h. HX/RO-induced increases in nuclear AIF translocation, as well as PARP-1 cleavage, were also reduced dose-dependently at 4 h after insult by the inhibitors. The caspase inhibitor z-VAD-fmk blocked PARP-1 cleavage, but did not affect AIF translocation and was only modestly cytoprotective. These findings indicate that PARP-1 activation and a PARP-1-dependent, caspase-independent, nuclear translocation of AIF contribute to apoptotic cerebral endothelial cell death after ischemia-reperfusion, underscoring the potential for ischemic microvascular protection by inhibiting PARP activation or preventing AIF translocation.
Tumor Necrosis Factor-α Neutralization Reduced Cerebral Edema Through Inhibition of Matrix Metalloproteinase Production After Transient Focal Cerebral Ischemia
Authors: Hosomi Naohisa , Ban Camelia R , Naya Takayuki , Takahashi Tsutomu , Guo Peng , Song Xiao-yu R , Kohno Masakazu
Published: February 2005

After focal cerebral ischemia, tumor necrosis factor-α deteriorates cerebral edema and survival rate. Therefore, tumor necrosis factor-α neutralization could reduce cerebral microvascular permeability in acute cerebral ischemia. Left middle cerebral artery occlusion for 120 mins followed by reperfusion was performed with the thread method under halothane anesthesia in Sprague-Dawley rats. Antirat tumor necrosis factor-α neutralizing monoclonal antibody with a rat IgG Fc portion (15 mg/kg) was infused intravenously right after reperfusion. Stroke index score, infarct volume, cerebral specific gravity, and the endogenous expression of tumor necrosis factor-α, matrix metalloproteinase (MMP)-2, MMP-9, and membrane type 1-MMP in the brain tissue were quantified in the ischemic and matched contralateral nonischemic hemisphere. In the antitumor necrosis factor-α neutralizing antibody-treated rats, infarct volume was significantly reduced ( P = 0.014, n = 7; respectively), and cerebral specific gravity was dramatically increased in the cortex and caudate putamen ( P<0.001, n = 7; respectively) in association with a reduction in MMP-9 and membrane type 1-MMP upregulation. Tumor necrosis factor-α in the brain tissue was significantly elevated in the ischemic hemisphere 6 h after reperfusion in the nonspecific IgG-treated rats ( P = 0.021, n = 7) and was decreased in the antitumor necrosis factor-α neutralizing antibody-treated rats ( P = 0.001, n = 7). Postreperfusion treatment with antirat tumor necrosis factor-α neutralizing antibody reduced brain infarct volume and cerebral edema, which is likely mediated by a reduction in MMP upregulation.
Microsatellite instability regulates transcription factor binding and gene expression
Authors: Martin Patricia , Makepeace Katherine , Hill Stuart A. , Hood Derek W. , Moxon E. Richard
Published: February 2005

Microsatellites are tandemly repeated simple sequence DNA motifs widely prevalent in eukaryotic and prokaryotic genomes. In pathogenic bacteria, instability of these hypermutable loci through slipped-strand mispairing mediates the high-frequency reversible switching of phenotype expression, i.e., phase variation. Phase-variable expression of NadA, an outer membrane protein and adhesin of the pathogenNeisseria meningitidis, is mediated by changes in the number of TAAA repeats located upstream of the core promoter ofnadA. Here we report that loss or gain of TAAA repeats affects the binding of the transcriptional regulatory protein IHF to thenadApromoter. Thus, phase-variable transcription ofnadApotentially incorporates interplay between stochastic (mutational) and prescriptive (classical) mechanisms of gene regulation.
Circulating transcriptome reveals markers of atherosclerosis
Authors: Patino Willmar D. , Mian Omar Y. , Kang Ju-Gyeong , Matoba Satoaki , Bartlett Linda D. , Holbrook Brenda , Trout Hugh H. , Kozloff Louis , Hwang Paul M.
Published: February 2005

Circulating monocytes mediate inflammation in atherosclerosis and may serve as easily accessible reporters of disease. To search for markers of atherosclerosis, we compared the
in vivo
transcriptomes of monocytes purified from patients undergoing carotid endarterectomy and normal subjects by using the serial analysis of gene expression technique. We selected a subset of differentially expressed monocyte-specific genes and confirmed their expression levels. The Finkel–Biskis–Jinkins osteosarcoma (FOS) gene was significantly increased in patients, and the highest levels of FOS associated with patients who had previously undergone coronary revascularization. The correlation between coronary revascularization and FOS was higher than that compared with the cardiac risk marker high sensitivity C-reactive protein.
In vitro
inhibition of FOS using small interfering RNA and 3-hydroxy-3-methyl-glutaryl CoA reductase inhibitor simvastatin (statin) affected monocyte activation and suggested an important role in pathogenesis. Given the prominent role of FOS in inflammation and calcification, its association with atherosclerosis severity has clear pathophysiologic bases as well as clinical implications as a marker. Our results suggest that analysis of gene expression in circulating cells may provide biological and clinical insights into human atherosclerosis, and that this type of approach may be applicable for studying other types of diseases.
Barrier-to-autointegration factor is required to segregate and enclose chromosomes within the nuclear envelope and assemble the nuclear lamina
Authors: Margalit Ayelet , Segura-Totten Miriam , Gruenbaum Yosef , Wilson Katherine L.
Published: February 2005

Barrier-to-autointegration factor (BAF) binds dsDNA, LEM-domain proteins, and lamins.
Caenorhabditis elegans
BAF requires Ce-lamin and two LEM-domain proteins (Ce-emerin and Ce-MAN1) to localize during nuclear assembly. It was unknown whether Ce-lamin and LEM proteins, in turn, depend on Ce-BAF (mutually dependent structural roles). RNA interference-mediated down-regulation of Ce-BAF caused gross defects in chromosome segregation, chromatin decondensation, and mitotic progression as early as the two-cell stage, and embryos died at the ≈100-cell stage. Nuclear pores reassembled, whereas Ce-lamin, Ce-emerin, and Ce-MAN1 bound chromatin but remained patchy and disorganized. The nuclear membranes formed but failed to enclose anaphase-bridged chromatin. Time-lapse imaging showed two phenotypes: anaphase-bridged chromatin that eventually resolved, and segregated chromatin that returned to the midzone. Thus, the assembly of BAF, lamins, and LEM-domain proteins is mutually dependent, and is required to capture segregated chromosomes within the nascent nuclear envelope. Embryos that escaped lethality by down-regulation of Ce-BAF grew into sterile adults with misplaced distal tip cells and gonads, further suggesting that mild postembryonic reductions in BAF disrupt tissue-specific functions.
Association of tissue-specific differentially methylated regions (TDMs) with differential gene expression
Authors: Song Fei , Smith Joseph F. , Kimura Makoto T. , Morrow Arlene D. , Matsuyama Tomoki , Nagase Hiroki , Held William A.
Published: February 2005

Early studies proposed that DNA methylation could have a role in regulating gene expression during development [Riggs, A.D. (1975)
Cytogenet. Cell Genet.
14, 9–25]. However, some studies of DNA methylation in known tissue-specific genes during development do not support a major role for DNA methylation. In the results presented here, tissue-specific differentially methylated regions (TDMs) were first identified, and then expression of genes associated with these regions correlated with methylation status. Restriction landmark genomic scanning (RLGS) was used in conjunction with virtual RLGS to identify 150 TDMs [Matsuyama, T., Kimura, M.T., Koike, K., Abe, T., Nakao, T., Asami, T., Ebisuzaki, T., Held, W.A., Yoshida, S. & Nagase, H. (2003)
Nucleic Acids Res.
31, 4490–4496]. Analysis of 14 TDMs by methylation-specific PCR and by bisulfite genomic sequencing confirms that the regions identified by RLGS are differentially methylated in a tissue-specific manner. The results indicate that 5% or more of the CpG islands are TDMs, disputing the general notion that all CpG islands are unmethylated. Some of the TDMs are within 5′ promoter CpG islands of genes, which exhibit a tissue-specific expression pattern that is consistent with methylation status and a role in tissue differentiation.
Platelet-derived growth factor C induces liver fibrosis, steatosis, and hepatocellular carcinoma
Authors: Campbell Jean S. , Hughes Steven D. , Gilbertson Debra G. , Palmer Thomas E. , Holdren Matthew S. , Haran Aaron C. , Odell Melissa M. , Bauer Renay L. , Ren Hong-Ping , Haugen Harald S. , Yeh Matthew M. , Fausto Nelson
Published: February 2005

Members of the platelet-derived growth factor (PDGF) ligand family are known to play important roles in wound healing and fibrotic disease. We show that both transient and stable expression of PDGF-C results in the development of liver fibrosis consisting of the deposition of collagen in a pericellular and perivenular pattern that resembles human alcoholic and nonalcoholic fatty liver disease. Fibrosis in PDGF-C transgenic mice, as demonstrated by staining and hydroxyproline content, is preceded by activation and proliferation of hepatic stellate cells, as shown by collagen, α-smooth muscle actin and glial fibrillary acidic protein staining and between 8 and 12 months of age is followed by the development of liver adenomas and hepatocellular carcinomas. The hepatic expression of a number of known profibrotic genes, including type β1 TGF, PDGF receptors α and β, and tissue inhibitors of matrix metalloproteinases-1 and -2, increased by 4 weeks of age. Increased PDGF receptor α and β protein levels were associated with activation of extracellular regulated kinase-1 and -2 and protein kinase B. At 9 months of age, PDGF-C transgenic mice had enlarged livers associated with increased fibrosis, steatosis, cell dysplasia, and hepatocellular carcinomas. These studies indicate that hepatic expression of PDGF-C induces a number of profibrotic pathways, suggesting that this growth factor may act as an initiator of fibrosis. Moreover, PDGF-C transgenic mice represent a unique model for the study of hepatic fibrosis progressing to tumorigenesis.
Phosphorylation of spinophilin by ERK and cyclin-dependent PK 5 (Cdk5)
Authors: Futter Marie , Uematsu Ken , Bullock Stewart A. , Kim Yong , Hemmings Hugh C. , Nishi Akinori , Greengard Paul , Nairn Angus C.
Published: February 2005

Spinophilin is a protein that binds to protein phosphatase-1 and actin and modulates excitatory synaptic transmission and dendritic spine morphology. We have identified three sites phosphorylated by ERK2 (Ser-15 and Ser-205) and cyclin-dependent PK 5 (Cdk5) (Ser-17), within the actin-binding domain of spinophilin. Cdk5 and ERK2 both phosphorylated spinophilin in intact cells. However,
in vitro
, phosphorylation by ERK2, but not by Cdk5, was able to modulate the ability of spinophilin to bind to and bundle actin filaments. In neurons and HEK293 cells expressing GFP-tagged variants of spinophilin, imaging studies demonstrated that introduction of a phospho-site mimic (Ser-15 to glutamate) was associated with increased filopodial density. These results support a role for spinophilin phosphorylation by ERK2 in the regulation of spine morphogenesis.
Rhodopsin C terminus, the site of mutations causing retinal disease, regulates trafficking by binding to ADP-ribosylation factor 4 (ARF4)
Authors: Deretic Dusanka , Williams Andrew H. , Ransom Nancy , Morel Valerie , Hargrave Paul A. , Arendt Anatol
Published: February 2005

The maintenance of photoreceptor cell polarity is compromised by the rhodopsin mutations causing the human disease autosomal dominant retinitis pigmentosa. The severe form mutations occur in the C-terminal sorting signal of rhodopsin, VXPX-COOH. Here, we report that this sorting motif binds specifically to the small GTPase ARF4, a member of the ARF family of membrane budding and protein sorting regulators. The effects of blocking ARF4 action were functionally equivalent to the effects of blocking the rhodopsin C-terminal sorting signal. ARF4 was essential for the generation of post-Golgi carriers targeted to the rod outer segments of retinal photoreceptors. Thus, the severe retinitis pigmentosa alleles that affect the rhodopsin sorting signal interfere with interactions between ARF4 and rhodopsin, leading to aberrant trafficking and initiation of retinal degeneration.
Enforced Bcl-2 expression overrides serum and feeder cell requirements for mouse embryonic stem cell self-renewal
Authors: Yamane Toshiyuki , Dylla Scott J. , Muijtjens Manja , Weissman Irving L.
Published: February 2005

Leukemia inhibitory factor (LIF) is required, but not sufficient, for pluripotent mouse embryonic stem (ES) cell expansion
in vitro
in the absence of serum or a feeder cell layer, suggesting that additional signals are provided by serum or feeders that are necessary to support self-renewal. Here we show that transgenic ES cell lines expressing Bcl-2, an antiapoptotic protein, continue to self-renew in serum- and feeder-free conditions when supplemented with LIF; even in the absence of bone morphogenic proteins. Bcl-2-expressing clones sustain the characteristics of undifferentiated, pluripotent ES cells during long-term culture, and maintain their potential to differentiate into mature cell types. These results suggest that LIF and Bcl-2 overexpression are sufficient to expand these mouse pluripotent stem cells
in vitro
.
Hard superconducting nitrides
Authors: Chen Xiao-Jia , Struzhkin Viktor V. , Wu Zhigang , Somayazulu Maddury , Qian Jiang , Kung Simon , Christensen Axel Nørlund , Zhao Yusheng , Cohen Ronald E. , Mao Ho-kwang , Hemley Russell J.
Published: February 2005

Detailed study of the equation of state, elasticity, and hardness of selected superconducting transition-metal nitrides reveals interesting correlations among their physical properties. Both the bulk modulus and Vickers hardness are found to decrease with increasing zero-pressure volume in NbN, HfN, and ZrN. The computed elastic constants from first principles satisfy
c
11
>
c
12
>
c
44
for NbN, but
c
11
>
c
44
>
c
12
for HfN and ZrN, which are in good agreement with the neutron scattering data. The cubic δ-NbN superconducting phase possesses a bulk modulus of 348 GPa, comparable to that of cubic boron nitride, and a Vickers hardness of 20 GPa, which is close to sapphire. Theoretical calculations for NbN show that all elastic moduli increase monotonically with increasing pressure. These results suggest technological applications of such materials in extreme environments.
Intramembrane aspartic acid in SCAP protein governs cholesterol-induced conformational change
Authors: Feramisco Jamison D. , Radhakrishnan Arun , Ikeda Yukio , Reitz Julian , Brown Michael S. , Goldstein Joseph L.
Published: February 2005

The polytopic membrane protein SCAP transports sterol regulatory element-binding proteins (SREBPs) from the endoplasmic reticulum (ER) to the Golgi, thereby activating cholesterol synthesis. Cholesterol accumulation in the ER membranes changes SCAP to an alternate conformation in which it binds ER retention proteins called Insigs, thereby terminating cholesterol synthesis. Here, we show that the conserved Asp-428 in the sixth transmembrane helix of SCAP is essential for SCAP's dissociation from Insigs. In transfected hamster cells, mutant SCAP in which Asp-428 is replaced by alanine (D428A) remained in an Insig-binding conformation when cells were depleted of sterols. As a result, mutant SCAP failed to dissociate from Insigs, and it failed to carry SREBPs to the Golgi. These data identify an important functional residue in SCAP, and they provide genetic evidence that the conformation of SCAP dictates the rate of cholesterol synthesis in animal cells.
Quantitative kinetic analysis of the bacteriophage λ genetic network
Authors: Kobiler Oren , Rokney Assaf , Friedman Nir , Court Donald L. , Stavans Joel , Oppenheim Amos B.
Published: February 2005

The lysis–lysogeny decision of bacteriophage λ has been a paradigm for a developmental genetic network, which is composed of interlocked positive and negative feedback loops. This genetic network is capable of responding to environmental signals and to the number of infecting phages. An interplay between CI and Cro functions suggested a bistable switch model for the lysis–lysogeny decision. Here, we present a real-time picture of the execution of lytic and lysogenic pathways with unprecedented temporal resolution. We monitor,
in vivo
, both the level and function of the CII and Q gene regulators. These activators are cotranscribed yet control opposite developmental pathways. Conditions that favor the lysogenic response show severe delay and down-regulation of Q activity, in both CII-dependent and CII-independent ways. Whereas CII activity correlates with its protein level, Q shows a pronounced threshold before its function is observed. Our quantitative analyses suggest that by regulating CII and CIII, Cro plays a key role in the ability of the λ genetic network to sense the difference between one and more than one phage particles infecting a cell. Thus, our results provide an improved framework to explain the longstanding puzzle of the decision process.
Role of cytoplasmic dynein in the axonal transport of microtubules and neurofilaments
Authors: He Yan , Francis Franto , Myers Kenneth A. , Yu Wenqian , Black Mark M. , Baas Peter W.
Published: February 2005

Recent studies have shown that the transport of microtubules (MTs) and neurofilaments (NFs) within the axon is rapid, infrequent, asynchronous, and bidirectional. Here, we used RNA interference to investigate the role of cytoplasmic dynein in powering these transport events. To reveal transport of MTs and NFs, we expressed EGFP-tagged tubulin or NF proteins in cultured rat sympathetic neurons and performed live-cell imaging of the fluorescent cytoskeletal elements in photobleached regions of the axon. The occurrence of anterograde MT and retrograde NF movements was significantly diminished in neurons that had been depleted of dynein heavy chain, whereas the occurrence of retrograde MT and anterograde NF movements was unaffected. These results support a cargo model for NF transport and a sliding filament model for MT transport.
Bcl-XL specifically activates Bak to induce swelling and restructuring of the endoplasmic reticulum
Authors: Klee Martina , Pimentel-Muiños Felipe X.
Published: February 2005

Bcl-2 family members Bak and Bax constitute a mitochondrial gateway for multiple death pathways. Both proteins are also present in the endoplasmic reticulum where they control apoptosis through the regulation of calcium levels. We show here that reticular Bak has the additional capacity of modulating the structure of this organelle. Coexpression of Bak and Bcl-XL provokes extensive swelling and vacuolization of reticular cisternae. A Bak version lacking the BH3 domain suffices to induce this phenotype, and reticular targeting of this mutant retains the activity. Expression of upstream BH3-only activators in similar conditions recapitulates ER swelling and vacuolization if ryanodine receptor calcium channel activity is inhibited. Experiments with Bak and Bax-deficient mouse embryonic fibroblasts show that endogenous Bak mediates the effect, whereas Bax is mainly irrelevant. These results reveal a previously unidentified role of Bak in regulating reticular conformation. Because this activity is absent in Bax, it constitutes one of the first examples of functional divergence between the two multidomain homologues.
Ethylene-Induced Differential Growth of Petioles in Arabidopsis. Analyzing Natural Variation, Response Kinetics, and Regulation
Authors: Millenaar Frank F. , Cox Marjolein C.H. , van Berkel Yvonne E.M. de Jong , Welschen Rob A.M. , Pierik Ronald , Voesenek Laurentius A.J.C. , Peeters Anton J.M.
Published: February 2005

Plants can reorient their organs in response to changes in environmental conditions. In some species, ethylene can induce resource-directed growth by stimulating a more vertical orientation of the petioles (hyponasty) and enhanced elongation. In this study on Arabidopsis (Arabidopsis thaliana), we show significant natural variation in ethylene-induced petiole elongation and hyponastic growth. This hyponastic growth was rapidly induced and also reversible because the petioles returned to normal after ethylene withdrawal. To unravel the mechanisms behind the natural variation, two contrasting accessions in ethylene-induced hyponasty were studied in detail. Columbia-0 showed a strong hyponastic response to ethylene, whereas this response was almost absent in Landsberg erecta (Ler). To test whether Ler is capable of showing hyponastic growth at all, several signals were applied. From all the signals applied, only spectrally neutral shade (20 μmol m−2 s−1) could induce a strong hyponastic response in Ler. Therefore, Ler has the capacity for hyponastic growth. Furthermore, the lack of ethylene-induced hyponastic growth in Ler is not the result of already-saturating ethylene production rates or insensitivity to ethylene, as an ethylene-responsive gene was up-regulated upon ethylene treatment in the petioles. Therefore, we conclude that Ler is missing an essential component between the primary ethylene signal transduction chain and a downstream part of the hyponastic growth signal transduction pathway.
Impact of Reduced O-Acetylserine(thiol)lyase Isoform Contents on Potato Plant Metabolism
Authors: Riemenschneider Anja , Riedel Kerstin , Hoefgen Rainer , Papenbrock Jutta , Hesse Holger
Published: February 2005

Plant cysteine (Cys) synthesis can occur in three cellular compartments: the chloroplast, cytoplasm, and mitochondrion. Cys formation is catalyzed by the enzyme O-acetylserine(thiol)lyase (OASTL) using O-acetylserine (OAS) and sulfide as substrates. To unravel the function of different isoforms of OASTL in cellular metabolism, a transgenic approach was used to down-regulate specifically the plastidial and cytosolic isoforms in potato (Solanum tuberosum). This approach resulted in decreased RNA, protein, and enzymatic activity levels. Intriguingly, H2S-releasing capacity was also reduced in these lines. Unexpectedly, the thiol levels in the transgenic lines were, regardless of the selected OASTL isoform, significantly elevated. Furthermore, levels of metabolites such as serine, OAS, methionine, threonine, isoleucine, and lysine also increased in the investigated transgenic lines. This indicates that higher Cys levels might influence methionine synthesis and subsequently pathway-related amino acids. The increase of serine and OAS points to suboptimal Cys synthesis in transgenic plants. Taking these findings together, it can be assumed that excess OASTL activity regulates not only Cys de novo synthesis but also its homeostasis. A model for the regulation of Cys levels in plants is proposed.
Low Temperature Induction of Arabidopsis CBF1, 2, and 3 Is Gated by the Circadian Clock
Authors: Fowler Sarah G. , Cook Daniel , Thomashow Michael F.
Published: February 2005

Exposing Arabidopsis (Arabidopsis thaliana) plants to low temperature results in rapid induction of CBF1, 2, and 3 (CBF1-3; also known as DREB1B, C, and A, respectively), which encode transcriptional activators that induce expression of a battery of genes that increase plant freezing and chilling tolerance. Recently, it has been shown that basal levels of CBF3 transcripts and those of certain CBF-regulated genes exhibit circadian cycling. Here, we further explored the regulation of CBF1-3 by the circadian clock. The results indicated that the extent to which CBF1-3 transcripts accumulated in response to low temperature was dependent on the time of day that the plants were exposed to low temperature and that this was regulated by the circadian clock. The highest and lowest levels of cold-induced CBF1-3 transcript accumulation occurred at 4 and 16 h after subjective dawn, respectively. An analysis of CBF2 promoter-reporter gene fusions indicated that this control included transcriptional regulation. In addition, the cold responsiveness of RAV1 and ZAT12, genes that are cold induced in parallel with CBF1-3, was also subject to circadian regulation. However, whereas the maximum level of cold-induced RAV1 transcript accumulation occurred at the same time of day as did CBF1-3 transcripts, that of ZAT12 was in reverse phase, i.e. the highest level of cold-induced ZAT12 transcript accumulation occurred 16 h after subjective dawn. These results indicate that cold-induced expression of CBF1-3, RAV1, and ZAT12 is gated by the circadian clock and suggest that this regulation likely occurs through at least two nonidentical (though potentially overlapping) signaling pathways.
Impaired pH Homeostasis in Arabidopsis Lacking the Vacuolar Dicarboxylate Transporter and Analysis of Carboxylic Acid Transport across the Tonoplast
Authors: Hurth Marco Alois , Suh Su Jeoung , Kretzschmar Tobias , Geis Tina , Bregante Monica , Gambale Franco , Martinoia Enrico , Neuhaus H. Ekkehard
Published: February 2005

Arabidopsis (Arabidopsis thaliana) mutants lacking the tonoplastic malate transporter AttDT (A. thaliana tonoplast dicarboxylate transporter) and wild-type plants showed no phenotypic differences when grown under standard conditions. To identify putative metabolic changes in AttDT knock-out plants, we provoked a metabolic scenario connected to an increased consumption of dicarboxylates. Acidification of leaf discs stimulated dicarboxylate consumption and led to extremely low levels of dicarboxylates in mutants. To investigate whether reduced dicarboxylate concentrations in mutant leaf cells and, hence, reduced capacity to produce OH− to overcome acidification might affect metabolism, we measured photosynthetic oxygen evolution under conditions where the cytosol is acidified. AttDT::tDNA protoplasts showed a much stronger inhibition of oxygen evolution at low pH values when compared to wild-type protoplasts. Apparently citrate, which is present in higher amounts in knock-out plants, is not able to replace dicarboxylates to overcome acidification. To raise more information on the cellular level, we performed localization studies of carboxylates. Although the total pool of carboxylates in mutant vacuoles was nearly unaltered, these organelles contained a lower proportion of malate and fumarate and a higher proportion of citrate when compared to wild-type vacuoles. These alterations concur with the observation that radioactively labeled malate and citrate are transported into Arabidopsis vacuoles by different carriers. In addition, wild-type vacuoles and corresponding organelles from AttDT::tDNA mutants exhibited similar malate channel activities. In conclusion, these results show that Arabidopsis vacuoles contain at least two transporters and a channel for dicarboxylates and citrate and that the activity of AttDT is critical for regulation of pH homeostasis.
A model for HRM strategic integration
Authors: Sheehan Cathy
Published: February 2005

Purpose

The broad aims of this research are to analyse the status of, and processes underlying, strategic human resource management (HRM) integration within organisations and to contribute to theory development in the area. A great deal of attention is given in the literature to the facilitative role that HRM can take in organisational change but as yet little attention has been given to modelling the change processes within HRM itself. This paper addresses that gap by providing a model of the proposed influences on the move towards strategic HRM integration.

Design/methodology/approach

In‐depth interviews with senior HR, finance and line managers in 13 Australian Best Practice companies are used to explore the supports and barriers underlying strategic HRM integration.

Findings

The model that is developed uses ideas from the change literature to explain that the engagement of strategic HRM integration requires a certain set of symbolic and ritualistic gestures. These symbolic changes, however, do not always result in desired strategic HRM outcomes: symbolic adjustments must be accompanied by deeper levels of change both from within the HR profession and from other stakeholders in the organisation.

Practical implications

The research holds a number of practical implications for the career design of HR professionals: a case is made, for example, for a broader business career background requirement that may provide the level of business acumen necessary to be a credible participant at the senior management strategic decision‐making level. Intended future research will draw from a larger sample to test the proposed model.

Originality/value

This research model's specific responses and outcomes require an ideological shift both from the HR profession and from stakeholders within the organisation.
Organizationally‐induced work stress
Authors: Conner Deondra S. , Douglas Scott C.
Published: February 2005

Purpose

This paper offers a model that illustrates the relationship between organizational structure, work stress and perceived strain based on the concept of bureaucratic orientation.

Design/methodology/approach

After a brief review of the stress and structure literatures, a number of propositions are developed concerning organizationally‐induced stressors that are fostered by mechanistic or organic structures. Next, a model is presented illustrating the impact of members' bureaucratic orientation on the organizationally induced stressor‐strain relationship.

Findings

It is argued that highly‐mechanized structures manifest different stressors for employees from highly organic structures. The model also demonstrates how organizationally‐induced stressors such as role conflict and ambiguity mediate the relation between structure and strain. However, the extent to which these stressors result in perceived strain is also dependent on employees' predisposition toward dominance, autonomy, achievement, ambiguity and control. Based on the model and propositions presented, conclusions and suggestions for future research are provided.

Practical implications

Noted implications include more flexible workplace rules for female executives to eliminate stress associated with work‐family conflict as well as improved effectiveness of social support and person‐organization fit based on individual bureaucratic orientation.

Originality/value

This paper uniquely advocates consideration of employee bureaucratic orientation and organizational structure in relation to person‐organization fit and work stress. The propositions offered are of value to practitioners and researchers due to their implications for fostering person‐organization fit and reducing work stress.
FDRx (Federated Drug Reference) project as change agent
Authors: Jankowski Terry Ann , Ketchell Debra S.
Published: February 2005

Purpose

At the foundation of FDRx was the drug formulary for UW Medicine published by the Drug Information Center. The DIC pharmacist had contracted with USPDI to receive the full text of its drug information electronically and reformat it into a print, pocket‐sized guide for distribution to clinicians. The goal of the FDRx project was to add to this core and distribute an expanded drug reference as part of a clinical resource.

Design/methodology/approach

Librarians at the University of Washington Health Sciences Libraries collaborated with clinicians to create an electronic federated drug knowledge resource, FDRx, to be used at the point of care.

Findings

Skills and experiences gained in previous projects, e.g. negotiating the licensure of campus‐wide access to bibliographic databases, project leadership, developing interfaces, instruction in the use of information resources, and IAIMS planning, easily transferred to the development of the FDRx project. The most immediate outcome, FDRx itself, had a short but successful lifespan, meeting the drug information needs of its users.

Originality/value

This partnership set the stage for future developments in the knowledge management arena at the University of Washington and changes in the roles of librarians.
Consumer health librarian
Authors: Hammond Patricia A.
Published: February 2005

Purpose

Aims to confirm that societal changes and access to the internet have heightened interest in health information by the general public. Patients/consumers are more involved in their health care. Patients’ rights to make informed health‐care decisions are more recognised by the medical community. Approximately 27 percent of the entire US adult population has visited a web site for health‐care purposes. Increasingly, hospitals in the USA and other countries are providing consumer health information centers for patients and their families.

Design/methodology/approach

In February 2002, a patient/consumer health information service opened at Virginia Commonwealth University (VCU) in Richmond, Virginia. This article will discuss the partnership that was forged to create the Community Health Education Center (CHEC) and the role VCU Libraries has in the partnership.

Findings

Apart from the obvious value of having The Community Health Education Center, its existence has opened new doors to the three partners for networking, community outreach and obtaining extramural funding.

Originality/value

The health system's visibility in the community has increased because of CHEC's involvement in community events. The strategy and marketing department has come to rely on CHEC staff to represent the health system at exhibits as a result, whilst other VCUHS departments have learned about CHEC's mission and see CHEC staff as part of the patient care team.
Micromachined sensor design for optical‐fiber flow measurement
Authors: Mireles José
Published: February 2005

Purpose

Owing to the technology growth, especially in Microsystems technology and Nanotechnology, new products will provide new ways to sense variables that are crucial for product improvement and system reliability. A big concern of the scientific community is the measurement of low level flow measurements, especially for the biomedical and/or systems on a chip approaches.Design/methodology/approach– A new flow meter concept design consists of a surface micromachined sensor having an optical high reflective mirror made of gold, which is attached to unique cantilever designs that bend due to the drag force of mass flow. The bending of the cantilevers produces the mirror to approach/depart from an optical fiber end‐tip. The reflective light to fiber is modulated using a Fabry‐Perot interferometry technique to determine the mirror separation to the fiber, which corresponds to the mass flow.Findings– The new concept design shows a big potential approach to measure low flow measurements for air, gas and liquids of low viscosity. The results of this concept, through finite element analysis, show that the material used to build the sensor, makes them excellent candidates for fabrication. The stresses of the materials and allowable (readable) bending are among the tolerances of such materials/construction‐design. The sensor is not affected by electromagnetic interference and does not require electrical currents to sense, i.e. it is perfectly suited for biomedical and low mass‐flow sensing such as lab‐on‐chip applications.Originality/value– Among all approaches to sense low flow measurements, most of them need either “big” turbine approaches (dimensions over 1 cm diameter), or the need of an electrical approach needed in the end measurement sensor. This work proposes a non‐electrical approach.
A primary standard piston prover for measurement of very small gas flows: an update
Authors: Cignolo Giorgio , Alasia Franco , Capelli Andrea , Goria Roberto , La Piana Gaetano
Published: February 2005

Purpose

A prototype gas prover was constructed to serve as the Italian primary standard for gas flow rates in the range 0.1 ml/min to 2 l/min. The new prover is used to calibrate high‐quality industrial standards, as well as the MFCs used in microelectronic fabrications and preparation of reference gas mixtures.Design/methodology/approach – The prover measures gas volume transfers caused by displacements of a 120 mm dia. motor‐operated piston, which is introduced into a temperature‐controlled chamber containing up to 3 l of the required working gas at near ambient conditions. Gas delivery is made at constant rate, whereas possibly variable incoming flows are measured at constant pressure. Displacements of the piston are measured by an optical interferometer.Findings – The analysis shows that standard uncertainty ranges between 0.013 and 0.03 percent. Owing to the very accurate control and measurement of both pressures and temperatures, these figures refer equally to volume and mass flowrate. Experimental comparisons with similar national standards at LNE‐France and NIST‐USA confirmed the consistency of measurement results in the three Nations.Research limitations/implications – The gas prover should be used with inert gases only.Practical implications – The national industrial gas standards and the best flow transducers can now be calibrated accurately down to unprecedented flowrate values.Originality/value – The need for measurement of extremely low gas flows is quite recent, therefore possibly less than ten primary national standards are available today worldwide. Several completely different principles and designs have been developed; description of design and performance of each instrument is important to assess their respective merits. The described apparatus is innovative as regards measurement range, accuracy and control techniques.
Efficiency outcomes from space charging in UK higher education estates
Authors: Lou Downie Mary
Published: February 2005

Purpose

Higher education (HE) in the UK has recently suffered financial pressure due to reduced central funding, and the requirement to widen student access. The estate is typically the second highest revenue expense and is an obvious target for efficiency gains. Sector‐wide statistics show there are opportunities for improving efficiency and many influential bodies have advocated space charging as a way of achieving them. This paper aims to investigate space performance indicators for evidence that space charging improves space use efficiency.

Design/methodology/approach

The approach used is a statistical analysis of space performance indicators for space charging and other higher education institution (HEIs).

Findings

Approximately one‐quarter of HEIs in the UK operated space charging in 2000‐2001 but only ten out of 31 space‐related performance indicators for the period 1998‐2001 suggest that increased efficiency results. Scrutiny of the background data shows they predominantly reflect differences in institutional wealth and activities, rather than space use management. Efficiency measures relating space to use provide no evidence of efficiency gains, suggesting that the application of charging as a space management tool is ineffective.

Research limitations/implications

The methodology does not reveal the reasons for the disparity between theory and results of space charging. Qualitative research into the application of charging systems is required to provide an explanation.

Practical implications

The conclusions are important for HE managers who are considering implementing expensive systems to improve space efficiency. The results also shed light on the usefulness of space performance indicators for HE estates.

Originality/value

Although there have been many assertions that space charging will improve space use efficiency in the HE sector, this research provides evidence to the contrary.
An evaluation of the property tax in Tanzania
Authors: McCluskey William James , Franzsen Riel
Published: February 2005

Purpose

This paper aims to investigate the potential role of property taxes as a revenue source for local government in Tanzania. Often this tax is beset with political and administrative problems that affect its operational efficiencies.

Design/methodology/approach

The research is the result of extensive fieldwork undertaken in Tanzania during 2002 to investigate and evaluate the valuations done for purposes of the property tax in Dar es Salaam and eight regional towns.

Findings

Urban local government revenues, and in particular those classified as own revenues in Tanzania and other East African countries, are generally not sufficient enough to develop and supply adequate urban services to the region's fast growing urban population. The main findings of the paper highlight the difficulties faced by municipalities in developing and maintaining a property tax system.

Research limitations/implications

The key problems were lack of experienced staff, limited equipment and significant political interference.

Practical implications

This research clearly identified the need for developing countries to recognize the importance of creating sustainable tax sources that are easily managed at low costs. The work found that the property tax system as designed for Tanzania was not sustainable and suggests a range of possible improvements.

Originality/value

The research did indicate that significant results could be achieved through implementing improvements in developing a simplified valuation basis and through greater collection efficiency. The research should be of particular interest to policy and decision makers within other developing countries who are embarked on a process of property tax reform.
The “advantage of latecomer” in abating air‐pollution: the East Asian experience
Authors: Iwami Toru
Published: February 2005

Purpose

Aims to focus on air pollution as one of the environmental problems that tends to improve at higher income levels.Design/methodology/approach– The paper provides a combination of narrative with argument and analysis.Findings– Between the early 1970s and the mid‐1980s, air pollution in Japan, in particular that caused by sulfur dioxide (SO2), was reduced to a remarkable degree. This reduction resulted from responses to mounting civil protest: governmental regulation policy on the one hand, and innovation of abatement technology and energy efficiency on the other. In large Southeast Asian cities, despite rapid economic growth, air pollution is less severe than it was in Japan in the early 1970s. This is because both government and industry in Southeast Asia took early initiatives to prevent environmental degradation, learning from the experiences of developed countries.Originality/value– The conclusions drawn help in understanding the prerequisites for reducing CO2emissions. If developed countries actually succeed in creating abatement technology for CO2, this will surely affect the development policy in developing countries.
Microstructural features contributing to enhanced behaviour of Sn‐Ag based solder joints
Authors: Lee J.G. , Subramanian K.N.
Published: February 2005

Purpose

To determine the role of microstructure in the creep and thermomechanical fatigue (TMF) properties of solder joints made with eutectic Sn‐Ag solder, and Sn‐Ag solder with Cu and/or Ni additions.

Design/methodology/approach

Quaternary alloys containing small amounts of Cu and Ni exhibit better high temperature creep resistance and also better resistance to damage under TMF cycles with a longer dwell time at the high temperature extreme, than eutectic Sn‐Ag, and Sn‐Ag‐Cu ternary alloy solder joints. Microstructural evaluation was conducted to investigate the effects of Ni additions to Sn‐Ag‐based solder joints.

Findings

Microstructural studies of the quaternary solder alloys revealed the presence of small ternary Cu‐Ni‐Sn intermetallic compound particles at Sn‐Sn grain boundaries. These precipitates can retard the grain boundary sliding that will occur during TMF with longer dwell times at the high temperature extreme, and during high temperature creep.

Originality/value

The findings of this paper will help to provide an understanding of the effects of alloying elements on Sn‐Ag based solder joints.
Marketing education
Authors: Russell Marilyn
Published: February 2005

Purpose

To discuss the requirement for a university to adopt a clearly defined marketing strategy to increase its international student population and generate additional revenue.

Design/methodology/approach

Primary research was undertaken to investigate the notion that customer satisfaction influences perceived quality and in turn affects profitability. The research methodology carried out among hospitality and tourism management students at Bournemouth University combined qualitative and quantitative methods. A student focus group and staff members with specialised knowledge were interviewed using a semi‐structured approach to allow a pre‐determined core of open‐ended questions to be addressed, while enabling other related issues to be pursued.

Findings

Within Bournemouth University, the reputation of the hospitality and tourism programmes and educational links are the most important considerations in student decision making, regarding their choice of programme and place of study.

Research limitations/implications

It could be argued that the courses selected attract more outgoing individuals and those more prepared to adapt to change and adopt a different culture. However, the students were from a range of countries and were representative of the mix at the University.

Practical implications

In an increasingly competitive market for international students, institutions need to provide an optimum service. International education marketing to international students should be managed to enhance consumer satisfaction, and raise perceived quality.

Originality/value

The findings should be taken into account when programmes are revalidated to ensure that these disciplines continue to provide students with the knowledge required by a global industry.