bluuebunny/crossref_metadata_2025 huggingface dataset:
Cellular response to oxidative stress: Signaling for suicide and survival*
Authors: Martindale Jennifer L. , Holbrook Nikki J.
Published: October 2002

Reactive oxygen species (ROS), whether produced endogenously as a consequence of normal cell functions or derived from external sources, pose a constant threat to cells living in an aerobic environment as they can result in severe damage to DNA, protein, and lipids. The importance of oxidative damage to the pathogenesis of many diseases as well as to degenerative processes of aging has becoming increasingly apparent over the past few years. Cells contain a number of antioxidant defenses to minimize fluctuations in ROS, but ROS generation often exceeds the cell's antioxidant capacity, resulting in a condition termed oxidative stress. Host survival depends upon the ability of cells and tissues to adapt to or resist the stress, and repair or remove damaged molecules or cells. Numerous stress response mechanisms have evolved for these purposes, and they are rapidly activated in response to oxidative insults. Some of the pathways are preferentially linked to enhanced survival, while others are more frequently associated with cell death. Still others have been implicated in both extremes depending on the particular circumstances. In this review, we discuss the various signaling pathways known to be activated in response to oxidative stress in mammalian cells, the mechanisms leading to their activation, and their roles in influencing cell survival. These pathways constitute important avenues for therapeutic interventions aimed at limiting oxidative damage or attenuating its sequelae. Published 2002 Wiley‐Liss, Inc.
GADD45b and GADD45g are cdc2/cyclinB1 kinase inhibitors with a role in S and G2/M cell cycle checkpoints induced by genotoxic stress
Authors: Vairapandi Mariappan , Balliet Arthur G. , Hoffman Barbara , Liebermann Dan A.
Published: October 2002

Gadd45a (Gadd45), Gadd45b (MyD118), and Gadd45g (CR6) constitute a family of evolutionarily conserved, small, acidic, nuclear proteins, which have been implicated in terminal differentiation, growth suppression, and apoptosis. How Gadd45 proteins function in negative growth control is not fully understood. Recent evidence has implicated Gadd45a in inhibition of cdc2/cyclinB1 kinase and in G2/M cell cycle arrest. Yet, whether Gadd45b and/or Gadd45g function as inhibitors of cdc2/cyclinB1 kinase and/or play a role in G2/M cell cycle arrest has not been fully established. In this work, we show that Gadd45b and Gadd45g specifically interact with the Cdk1/CyclinB1 complex, but not with other Cdk/Cyclin complexes, in vitro and in vivo. Data also has been obtained that Gadd45b and Gadd45g, as well as GADD45a, interact with both Cdk1 and cyclinB1, resulting in inhibition of the kinase activity of the Cdk1/cyclinB1 complex. Inhibition of Cdk1/cyclinB1 kinase activity by Gadd45b and Gadd45a was found to involve disruption of the complex, whereas Gadd45g did not disrupt the complex. Moreover, using RKO lung carcinoma cell lines, which express antisense Gadd45 RNA, data has been obtained, which indicates that all three Gadd45 proteins are likely to cooperate in activation of S and G2/M checkpoints following exposure of cells to UV irradiation. © 2002 Wiley‐Liss, Inc.
Studies on glycogen autophagy: Effects of phorbol myristate acetate, ionophore A23187, or phentolamine
Authors: Kalamidas S.A. , Kotoulas O.B. , Hann A.C.
Published: October 2002

The effects of agents that could manipulate the lysosomal calcium such as phorbol myristate acetate, ionophore A23187, and phentolamine on the lysosomal glycogen degradation were studied by electron microscopy, morphometric analysis, and biochemical assays in newborn rat hepatocytes. Phorbol myristate acetate, which promotes the input of calcium to lysosomes, increased the total volume of autophagic vacuoles and the activity of lysosomal glycogen‐hydrolyzing acid alpha 1,4 glucosidase and decreased the fractional volume of undigested glycogen inside the autophagic vacuoles and also decreased the activity of acid mannose 6‐phosphatase. Ionophore A23187, which releases lysosomal calcium, produced opposite results in these enzyme activities. Phentolamine, an alpha‐adrenergic blocking agent which interferes with the generation of phosphoinositides and may activate the lysosomal calcium uptake pump, increased the total volume of autophagic vacuoles and the activity of lysosomal glycogen‐hydrolyzing acid glucosidase and decreased the fractional volume of undigested glycogen inside the autophagic vacuoles. The results of this study constitute evidence that changes in lysosomal calcium may influence certain aspects of autophagy, including the degradation of glycogen inside the autophagic vacuoles. They also support our previous postulate [Kalamidas and Kotoulas (2000a,b) Histol Histopathol 15:29–35, 1011–1018] that stimulation of autophagic mechanisms in newborn rat hepatocytes may be associated with acid mannose 6‐phosphatase activity‐deficient lysosomes. Microsc. Res. Tech. 57:507–511, 2002. © 2002 Wiley‐Liss, Inc.
Evolution of median fin modules in the axial skeleton of fishes
Authors: Mabee Paula M. , Crotwell Patricia L. , Bird Nathan C. , Burke Ann C.
Published: October 2002

Detailed examples of how hierarchical assemblages of modules change over time are few. We found broadly conserved phylogenetic patterns in the directions of development within the median fins of fishes. From these, we identify four modules involved in their positioning and patterning. The evolutionary sequence of their hierarchical assembly and secondary dissociation is described. The changes in these modules during the evolution of fishes appear to be produced through dissociation, duplication and divergence, and co‐option. Although the relationship between identified median fin modules and underlying mechanisms is unclear, Hox addresses may be correlated. Comparing homologous gene expression and function in various fishes may test these predictions.

The earliest actinopterygians likely had dorsal and anal fins that were symmetrically positioned via a positioning module. The common patterning (differentiation) of skeletal elements within the dorsal and anal fins may have been set into motion by linkage to this positioning module. Frequent evolutionary changes in dorsal and anal fin position indicate a high level of dissociability of the positioning module from the patterning module. In contrast, the patterning of the dorsal and anal fins remains linked: In nearly all fishes, the endo‐ and exoskeletal elements of the two fins co‐differentiate. In all fishes, the exoskeletal fin rays differentiate in the same directions as the endoskeletal supports, indicating complete developmental integration. In acanthopterygians, a new first dorsal fin module evolved via duplication and divergence. The median fins provide an example of how basic modularity is maintained over 400 million years of evolution. J. Exp. Zool. (Mol. Dev. Evol.) 294:77–90, 2002. © 2002 Wiley‐Liss, Inc.
The tet‐off system is more effective than the tet‐on system for regulating transgene expression in a single adenovirus vector
Authors: Mizuguchi Hiroyuki , Hayakawa Takao
Published: October 2002

Background

Control of transgene expression in mammalian cells is desirable for gene therapy and the study of gene function in basic research. This study evaluates the functionality of single adenovirus (Ad) vectors containing a tetracycline‐controllable expression system (tet‐off or tet‐on system).

Methods

An Ad‐mediated binary transgene expression system was generated containing a tet‐off or a tet‐on system, which introduced the gene of interest with a tetracycline‐regulatable promoter and the tetracycline‐responsive transcriptional activator gene into the E1 and E3 deletion regions, respectively. The functionality of the Ad‐mediated tet‐off and tet‐on systems was compared under various conditions in vitro and in vivo.

Results

The Ad vector containing the tet‐off system provided negative control of gene expression ranging from 20‐ to 500‐fold, depending on the cell type and condition. In contrast, the Ad vector containing the tet‐on system increased gene expression by only 2‐ to 28‐fold and required about two‐log orders higher concentration of an inducer (doxycycline) to switch on the gene expression, compared with the Ad vector containing the tet‐off system.

Conclusion

Ad vectors containing the tet‐off system are a better choice for regulated gene expression than Ad vectors containing the tet‐on system. Single Ad vectors containing the tetracycline‐controllable expression system will greatly facilitate in vitro and in vivo analyses of gene function and may be useful for gene therapy. Copyright © 2002 John Wiley & Sons, Ltd.
Syngeneic fibroblasts transfected with a plasmid encoding interleukin‐4 as non‐viral vectors for anti‐inflammatory gene therapy in collagen‐induced arthritis
Authors: Bessis Natacha , Cottard Virginie , Saidenberg‐Kermanach Nathalie , Lemeiter Delphine , Fournier Catherine , Boissier Marie‐Christophe
Published: October 2002

Background

No effective long‐term treatment is available for rheumatoid arthritis. Recent advances in gene therapy and cell therapy have demonstrated efficiency in collagen‐induced arthritis (CIA). Interleukin‐4 (IL‐4) is already known to be efficient in CIA in systemic injection or administered by gene therapy. This study was designed to evaluate the effect of a non‐viral gene therapy of CIA, involving injection of syngeneic fibroblasts transfected with a plasmid encoding for IL‐4.

Methods

Immortalised fibroblasts from DBA/1 mice (DBA/1/0 cells) were transfected with a plasmid expressing IL‐4 cDNA (DBA/1/IL‐4 cells). Xenogeneic fibroblasts from Chinese hamster ovary (CHO) transfected with a plasmid expressing IL‐4 cDNA (CHO/IL‐4) were studied also. The cells were engrafted in mice developing CIA by subcutaneous injection of 3 × 106 DBA/1/0 or DBA/1/IL‐4 or CHO/IL‐4 cells.

Results

Injection of DBA/1/IL‐4 cells, on days 10 and 25 after immunisation, was associated with a significant and lasting improvement in the clinical and histological evidence of joint inflammation and destruction as compared with DBA/1/0 and CHO/IL‐4 cells. DBA/1/IL‐4 cell treatment decreased also the production of IgG2a antibody to CII and the proliferation of CIIB‐specific nodal T cells. Later treatments (engraftments on days 23 and 35 after immunisation) exerted also an anti‐inflammatory effect, as evaluated on clinical and histological signs of CIA.

Conclusions

Taken together, these findings indicate that systemic administration of syngeneic cells transfected with an anti‐inflammatory cytokine gene, namely IL‐4, with a non‐viral method is effective in CIA and may attenuate the cytokine imbalance seen in this disease. Copyright © 2002 John Wiley & Sons, Ltd.
Social funds: evidence on targeting, impacts and sustainability
Authors: van Domelen Julie
Published: October 2002

Impact evaluations show that social fund resources are pro‐poor, and that targeting has improved over time. Despite the leakage which occurs to better‐off areas and households, social fund performance compares favorably with other public programmes. Investments largely reflect community needs and priorities and have increased access to, quality and utilization of basic social infrastructure. These benefits have generally translated into improvements in the health and education status of households, though specific impacts vary by country, region, and sector. The vast majority of facilities are operating several years after completion, but long‐term sustainability of water systems is particularly problematic given insufficient cost recovery. Copyright © 2002 John Wiley & Sons, Ltd.
A post Keynesian critique of privatization policies in transition economies
Authors: Marangos John
Published: October 2002

The privatization policies implemented in transition economies were based on the neoclassical principles of economic thought. The neoclassical privatization policies contributed to the well‐known results of a large reduction in output, high unemployment and inflation and a breakdown of institutional norms resulting in corruption and illegal activities. For the post Keynesians, there could have been a transition to a market economy without a substantial change in property ownership. This was because ownership, as such, was less important than competition, the incentive structure and the nature of regulatory policies. Consequently, post Keynesian policies of privatization would had resulted in a substantially smaller social cost of transition. Copyright © 2002 John Wiley & Sons, Ltd.
Synthesis of 5‐[4,5‐13C2]‐ and 5‐[1,5‐13C2]aminolevulinic acid
Authors: Iida Katsumi , Tokiwa Shinji , Ishii Toshihiro , Kajiwara Masahiro
Published: October 2002

5‐[4,5‐13C2]‐ and 5‐[1,5‐13C2]Aminolevulinic acid (ALA) have been synthesized by the Gabriel condensation of potassium phthalimide with ethyl bromo[1,2‐13C2]acetate (derived from [1,2‐13C2]acetic acid) or ethyl bromo[2‐13C]‐acetate (derived from sodium [2‐13C]acetate), followed by conversion to the chloride, coupling reaction with 2‐ethoxycarbonylethylzinc iodide derived from ethyl 3‐iodopropionate or 2‐methoxy[13C]carbonylethylzinc iodide derived from methyl 3‐iodo[1‐13C]propionate (generated from potassium [13C]cyanide), and hydrolysis. Copyright © 2002 John Wiley & Sons, Ltd.
Synthesis of (±)‐6,6‐[2H6]dimethyl‐11‐nor‐Δ9‐tetrahydrocannabivarin‐9‐carboxylic acid
Authors: Feng Shixia , ElSohly Mahmoud A.
Published: October 2002

Starting from divarinol (4) using previously published procedures, (±)‐6,6‐[2H6]Dimethyl‐11‐nor‐Δ9THCV‐9‐carboxylic acid (3) was synthesized for use as an internal standard in GC/MS analysis of 11‐nor‐Δ9THCV‐9‐carboxylic acid (2). The detection of 2 distinguishes the use of marijuana from the ingestion of Marinol®. Copyright © 2002 John Wiley & Sons, Ltd.
Synthesis of covalent [14C]‐labeled diarylsulfonylurea (DASU) inhibitors of the processing and release of IL‐1
Authors: Eggler J. F. , Gabel C. A. , Zandi K. , Weaver J. D. , McKechney H. , Dombroski M. A. , Peurano H. , Hawryluk N.
Published: October 2002

CP‐452,759 and CP‐470,947, two covalent [14C]‐labeled diarylsulfonylurea (DASU) inhibitors of the processing and release of IL‐1 from human monocytes, have been synthesized. The radiosyntheses utilize [14C]‐labeled phosgene to prepare labeled isocyanates which are coupled with an epoxide sulfonamide to give the [14C]‐DASUs. These tools should allow future studies aimed at purifying and identifying the DASU binding protein involved in the inhibition of the processing and release of IL‐1 from human monocytes. Copyright © 2002 John Wiley & Sons, Ltd.
Identification of phenylbutyrylglutamine, a new metabolite of phenylbutyrate metabolism in humans
Authors: Comte Blandine , Kasumov Takhar , Pierce Bradley A. , Puchowicz Michelle A. , Scott Mary‐Ellen , Dahms Williams , Kerr Douglas , Nissim Itzhak , Brunengraber Henri
Published: October 2002

Phenylbutyrate is used in humans for treating inborn errors of ureagenesis, certain forms of cancer, cystic fibrosis and thalassemia. The known metabolism of phenylbutyrate leads to phenylacetylglutamine, which is excreted in urine. We have identified phenylbutyrylglutamine as a new metabolite of phenylbutyrate in human plasma and urine. We describe the synthesis of phenylbutyrylglutamine and its assay by gas chromatography/mass spectrometry as a tert‐butyldimethylsilyl or methyl derivative, using standards of [2H5]phenylbutyrylglutamine and phenylpropionylglutamine. After administration of phenylbutyrate to normal humans, the cumulative urinary excretion of phenylacetate, phenylbutyrate, phenylacetylglutamine and phenylbutyrylglutamine amounts to about half of the dose of phenylbutyrate. Thus, additional metabolites of phenylbutyrate are yet to be identified. Copyright © 2002 John Wiley & Sons, Ltd.
Gas‐phase ion chemistry in germane–propane and germane–propene mixtures
Authors: Benzi Paola , Operti Lorenza , Rabezzana Roberto , Vaglio Gian Angelo
Published: October 2002

Germane–propane and germane–propene gaseous mixtures were studied by ion trap mass spectrometry. Variations of ion abundances observed under different partial pressure ratios and mechanisms of ion–molecule reactions elucidated by multiple isolation steps are reported. In addition, the rate constants for the main reactions were experimentally determined and compared with the collisional rate constants to obtain the reaction efficiencies. The yield of ions containing both Ge and C atoms is higher in the germane–propene than in the germane–propane system. In the former mixture, chain propagation takes place starting from germane ions reacting with propene and proceeds with the formation of clusters such as Ge2C4Hn+ and Ge3CHn+. Copyright © 2002 John Wiley & Sons, Ltd.
Study of non‐covalent complexation between catechin derivatives and peptides by electrospray ionization mass spectrometry
Authors: Sarni‐Manchado Pascale , Cheynier Véronique
Published: October 2002

The recent development of electrospray ionization mass spectrometry (ESI‐MS) has allowed its use to study molecular interactions driven by non‐covalent forces. ESI‐MS has been used to detect non‐covalent complexes between proteins and metals, ligands and peptides and interactions involving DNA, RNA, oligonucleotides and drugs. Surprisingly, the study of the interaction between polyphenolic molecules and peptides/proteins is still an area where ESI‐MS has not benefited. With regard to the important influence of these interactions in the biological and food domains, ESI‐MS was applied to the detection and the characterization of soluble polyphenol–peptide complexes formed in model solution. The ability to observe and monitor the weak interactions involved in such macromolecular complexation phenomena was demonstrated for monomeric and dimeric flavonoid molecules (catechin‐derived compounds) largely encountered in plants and plant derived products. Intact non‐covalent polyphenol–peptide complexes were observed by ESI‐MS using different experimental conditions. Utilizing mild ESI interface conditions allowed the detection of 1 : 1 polyphenol–peptide complexes in all tested solutions and 2 : 1 complexes for the dimers and galloylated polyphenols (flavanols). These results show that there is a preferential interaction between polymerized and/or galloylated polyphenols and peptide compared with that between monomeric polyphenols and peptides. Thus, ESI‐MS shows potential for the study of small polyphenolic molecule–peptide interactions and determination of stoichiometry. Copyright © 2002 John Wiley & Sons, Ltd.
Endemic hepatitis C virus infection in a Sicilian town: Further evidence for iatrogenic transmission
Authors: Di Stefano Rosa , Stroffolini Tommaso , Ferraro Donatella , Usticano Antonella , Valenza Lilli Mario , Montalbano Luigi , Pomara Giuseppina , Craxì Antonio
Published: October 2002

The prevalence of and risk factors for HCV and HBV infections in the general population and the predictive value of ALT screening in identifying anti‐HCV positive subjects have been evaluated in a small Sicilian town. A random 1:4 sampling from the census of the general population was performed. Anti‐HCV, HCV‐RNA, HCV genotype, HBsAg, and anti‐HBc were tested. The linkage between HCV infection and potential risk factors was evaluated by multiple logistic regression analysis. Among 721 subjects studied, 75 (10.4%) were anti‐HCV positive. The HCV infection rate increased from 0.4% in subjects 10–29 years of age to 34% in those > 60 years of age. Among the 75 anti‐HCV positive subjects, 66.7% were HCV‐RNA positive and 36% had abnormal ALT, in contrast abnormal ALT levels were found in 4.3% of the 646 anti‐HCV negative subjects (P < 0.01). HCV genotype 1b infected the majority (88.0%) of viremic subjects. Exposure to HBV infection (anti‐HBc positivity) was found in 11.2% of subjects; HBsAg positivity was 0.7%. At multivariate analysis, two variables were associated with HCV infection: age ≥ 45 years (OR 27.8; CI 95% = 11.0–70.2) and previous hospitalization (OR 2.5; CI 95% = 1.3–4.7). ALT testing had low positive predictive value (PPV = 49.1%) for HCV infection. The positive predictive value was good (88%) in people ≥ 60 years of age, but minimal (16.7%) in those below 60. These findings indicate that HCV infection is common in the elderly, perhaps as a result of past iatrogenic transmission. The present low rate of HCV infection among the younger generations coupled with the low progression of the viral related liver damage does not support the projection of a future increasing incidence in the next decades of the burden of HCV‐related chronic disease. HBV infection, formerly common in this area, is already in sharp decline. In an area of high HCV endemicity, screening of the general population by ALT cannot be used a surrogate marker to detect HCV infection in those susceptible to treatment. J. Med Virol. 67:339–344, 2002. © 2002 Wiley‐Liss, Inc.
Hepatitis B immunization and hepatocellular carcinoma: The Gambia hepatitis Intervention Study
Authors: Montesano Ruggero
Published: October 2002

The Gambia Hepatitis Intervention Study (GHIS) was initiated by the International Agency for Research on Cancer (IARC) in 1986. It consisted of a randomized trial in the Gambian population, aiming to evaluate the protection provided by HBV vaccination administered during the first year of life against primary infection, the development of chronic carriage, and primary liver cancer. The results, reported at 9 years from the introduction of the vaccine as conferring a high degree of protection (83% against primary infection and 95% against chronic carriage), are briefly discussed. It is expected that HBV vaccination will result in a reduction of mortality from hepatocellular carcinoma, the most frequent cancer in males in sub‐Sahara Africa. J. Med. Virol. 67:444–446, 2002. © 2002 Wiley‐Liss, Inc.
Core promoter mutations (A1762T and G1764A) and viral genotype in chronic hepatitis B and hepatocellular carcinoma in Guangxi, China
Authors: Fang Zhong‐Liao , Yang Jinye , Ge Xianmin , Zhuang Hui , Gong Jian , Li Rongcheng , Ling Roger , Harrison Tim J.
Published: October 2002

Hepatitis B viruses (HBV) with core promoter mutations (A1762T, G1764A) were found in a previous study to be highly prevalent in patients from Guangxi, China with hepatocellular carcinoma (HCC). The aim of this study was to determine whether the mutations are prevalent in areas of Guangxi with high and lower incidences of HCC and whether they are associated with other severe sequelae of chronic hepatitis B, including the development of cirrhosis. In addition, the genotypes of the various HBV sequences were determined. Core promoter mutations were significantly more common in HCC patients than asymptomatic carriers from both regions of Guangxi and also were common in patients with cirrhosis and chronic hepatitis. The data also support the hypothesis that genotype C HBV causes more severe liver disease than does genotype B. J. Med. Virol. 68:33–40, 2002. © 2002 Wiley‐Liss, Inc.
Electromagnetic field representations and computations in complex structures I: complexity architecture and generalized network formulation
Authors: Felsen Leopold B. , Mongiardo Mauro , Russer Peter
Published: October 2002

In this three‐part sequence of papers, we outline an architecture for systematically dealing in an efficient and rigorous manner with electromagnetic field representations and computations in complex structures. The approach is based on the topological partitioning of the complex structure into several subdomains joined together by interfaces. In analogy with network theory, individual subdomains are characterized via subdomain relations, obtained either analytically or numerically, and described in a unified format by using a generalized network formulation; the various subdomains are linked together via connection relations provided by the complex structure topology. Together these two relations yield the Tableau equations which combine all of the necessary information. The suggested framework accommodates the use of different analytic/numerical methods (hybridization), the choice of problem‐matched alternative Green's function representations, as well as different types of field representations. In the present paper, we focus on the general architecture, various options and their implications, in Part II [1] we furnish formal expressions for the subdomain relationships via alternative Green's functions representations; and in part III [2], we discuss the connection network properties. Copyright © 2002 John Wiley & Sons, Ltd.
A difficulty in numerically solving the telegraph and the diffusion equations by means of the transmission line matrix modelling method (TLM)
Authors: Enders Peter , Vanneste Christian
Published: October 2002

A stub leakage resistor at the nodes of an otherwise lossless TLM chain (i.e. without series resistors) introduces losses, although the corresponding absorption term in the Telegraphers' equation vanishes due to the absence of series resistors. This contradiction is outlined, an explanation is proposed and the practical implications are discussed. Copyright © 2002 John Wiley & Sons, Ltd.
Distribution in TLM models for diffusion (Part I: one‐dimensional treatment)
Authors: Chardaire P. , de Cogan D.
Published: October 2002

The signal obtained at each time step of a TLM simulation for one‐dimensional diffusion is analysed for single shot injections. A combinatorial formula is provided to predict the signal value at any given spatial positions. Formulas for expectation and variance are obtained using a technique based on generating functions. We briefly compare the resulting variance and that of the underlying diffusion process. Copyright © 2002 John Wiley & Sons, Ltd.
Oligodendrocytes as providers of growth factors
Authors: Du Yangzhou , Dreyfus Cheryl F.
Published: October 2002

Glial cells recently are being appreciated as supporters of brain neurons. This review addresses their role as growth factor providers. While the function of astrocytes in this capacity is known, new data indicate that oligodendrocytes, the myelinating cells of the brain, exhibit similar abilities. Oligodendrocytes provide trophic signals to nearby neurons and synthesize defined growth factors. Expression of growth factors is influenced by neural signals. The review summarizes these roles and their implications in brain function. © 2002 Wiley‐Liss, Inc.
Studies on neuronal death in the mouse model of Niemann‐Pick C disease
Authors: Erickson Robert P. , Bernard Ora
Published: October 2002

A mouse model of Niemann‐Pick disease type C (NPC) carries a genetic defect that causes biochemical changes in lipid levels and a progressive neuropathology that parallels the effects of NPC disease in humans. It is a moot point whether or not the loss of Purkinje and other neuronal cells proceeds by apoptotic death. Therefore, we have introduced into these mice a transgene expressing human Bcl‐2 protein which has previously been demonstrated to prevent developmental neuronal death and death induced by a variety of stimuli. The human Bcl‐2 transgene was driven by the neuron‐specific enolase promoter and was abundantly expressed in Purkinje and other neuronal cells. npc1−/−/bcl‐2 transgenic mice did not show a significant delay in the onset of neurological disorders. Neuropathological examination of the npc1−/−/bcl‐2 transgenic mice did not disclose significant differences in numbers of surviving Purkinje cells between the npc1−/−, tg+ and npc1−/−, tg− mice. When the npc1−/− mice were treated with minocycline, a drug which was shown to inhibit apparent apoptotic death in other mouse models of neurological disease, no delay in onset of neurological disorders were observed in either npc1−/−, or npc1−/− /mdrla−/− mice (mdr1a deficiency was used to enhance brain availability of minocycline). Caspase‐1 levels were not altered in npc1−/− mice, with or without minocycline treatment. These results suggest that Purkinje cell loss in npc1−/− mice does not proceed by an apoptotic pathway that can be inhibited by Bcl‐2 or minocycline. © 2002 Wiley‐Liss, Inc.
SHP‐1 expression in avian mixed neural/glial cultures
Authors: Sorbel Jeffrey D. , Brooks Diane M. , Lurie Diana I.
Published: October 2002

The central nervous system response to injury includes astrocyte proliferation and hypertrophy as well as microglial activation and proliferation. However, not all glial cells enter the cell cycle following damage, and the mechanism that determines which glial cells will proliferate and which will remain quiescent has yet to be elucidated. Protein tyrosine phosphorylation has been shown to play an important role in the regulation of the cell cycle in a number of different systems and has been implicated in both astrocyte proliferation and differentation. Of particular interest is the protein tyrosine phosphatase SHP‐1 (Src homology 2‐containing protein tyrosine phosphatase 1), which: (1) modulates cellular proliferation in the hematopoietic system, (2) is involved in various growth factor second messenger signaling cascades, and (3) has been demonstrated by our laboratory to increase in immunoreactivity within a subpopulation of astrocytes following deafferentation of the chicken auditory brainstem. These SHP‐1+ cells appear to be those which fail to enter the cell cycle following deafferentation. The present study examines whether manipulation of cellular proliferation in vitro modifies the expression of SHP‐1 immunoreactivity in mixed neural/glial cultures of the avian auditory brainstem. In addition, the effect of the protein tyrosine phosphatase inhibitor sodium orthovanadate on cellular proliferation was assessed in these cultures. Our results demonstrate that SHP‐1 expression can be modulated by changes in proliferation and that inhibiting tyrosine phosphatase activity results in increased proliferation. Taken together, these results indicate that SHP‐1 may play central role in negatively regulating glial proliferation following injury. © 2002 Wiley‐Liss, Inc.
A secreted Delta1‐Fc fusion protein functions both as an activator and inhibitor of Notch1 signaling
Authors: Hicks Carol , Ladi Ena , Lindsell Claire , Hsieh James J.‐D. , Hayward S. Diane , Collazo Andres , Weinmaster Gerry
Published: October 2002

Signaling induced through interactions between DSL (Delta, serrate, LAG‐2) ligand‐signaling cells and Notch‐responding cells influences the developmental fate of a wide variety of invertebrate and vertebrate cell types. Consistently with a requirement for direct cell–cell interactions, secreted DSL ligands expressed in flies do not appear to activate Notch signaling but rather produce phenotypes reminiscent of losses in Notch signaling. In contrast, secreted DSL ligands expressed in Caenorhabditis elegans or supplied to mammalian cells in culture produce effects indicative of Notch activation. In fact, engineered secreted DSL ligands have been used to study Notch signaling in neurogenesis, gliogenesis, hematopoeisis, neurite morphogenesis and ligand‐induced nuclear translocation of the Notch intracellular domain. Using a recombinant, secreted form of the DSL ligand Delta1, we found that antibody‐induced oligomerization (termed “clustering”) was required for this soluble ligand to bind specifically to Notch1‐expressing cells, undergo internalization, and activate downstream signaling. Interestingly, clustering with either limiting or excess antibody led to ligand binding in the absence of Notch signaling, indicating that ligand binding is necessary but not sufficient for activation of Notch signaling. Moreover, such antibody clustering conditions blocked Notch1 signaling induced by membrane‐bound DSL ligands. We propose that multimerization influences whether ligand binding to Notch results in activation or inhibition of downstream signaling and suggest that differences in ligand presentation might account for why secreted forms of DSL ligands have been reported to function as agonists and antagonists of Notch signal transduction. © 2002 Wiley‐Liss, Inc.
Atypical neuroleptics stimulate neurogenesis in adult rat brain
Authors: Wakade Chandramohan G. , Mahadik Sahebarao P. , Waller Jennifer L. , Chiu Fung‐Chow
Published: October 2002

Schizophrenia has been treated effectively with atypical neuroleptics without serious side effects. We have shown previously that long‐term treatment with atypical neuroleptics is correlated with an improvement of cognition in adult rats. We report here that atypical neuroleptics stimulate a 2‐ to 3‐fold increase in newly divided cells in the subventricular zone in the rat and that some of these new cells in the subventricular zone and hippocampus also express a neuronal marker. We used bromodeoxyuridine (BrdU) to identify newly divided cells and confirmed the observation with antibody to a cell‐cycle‐specific, endogenous proliferating cell nuclear antigen (PCNA). Identification of BrdU‐positive cells in the anterior subventricular zone (SVZa) particularly in rats treated with the atypical neuroleptics but not in those in the haloperidol‐treated and control rats, suggests increased rostral migratory stream (RMS) cell traffic to replenish neurons in the olfactory bulb. Expression of a neuronal marker, NeuN, in BrdU‐positive cells in rats treated with atypical neuroleptics, also suggests that these compounds may modulate in vivo differentiation of neuronal progenitor cells even within a day of BrdU injection. Our results indicate that atypical neuroleptics have a mechanism of action other than the previously proposed mechanisms, which might explain their role in improved cognition in animal and in schizophrenic patients. If substantiated by future studies, our findings may lead to an expanded use of atypical neuroleptics in other neurodegenerative diseases to stimulate neuronal replacement and repair. © 2002 Wiley‐Liss, Inc.
CNS myelinogenesis in vitro: Myelin basic protein deficient shiverer oligodendrocytes
Authors: Seiwa Chika , Kojima‐Aikawa Kyoko , Matsumoto Isamu , Asou Hiroaki
Published: October 2002

The shiverer mutant mouse is an autosomal recessive mutant characterized by incomplete myelin sheath formation in the central nervous system (CNS). Such mice contain a deletion in the MBP gene, do not produce MBP proteins, and have little or no compact myelin in the CNS. To investigate the myelin sheath formation in shiverer mutant mice resulting from the absence of compact myelin, firstly we developed new methods for generating oligodendrocyte precursor cells (OPCs) from an E17 mouse brain, and examined homozygous shiverer (shi/shi) OPCs with respect to myelinogenesis in vitro. After treatment of shi/shi OPCs in vitro with PDGF or bFGF, proliferation of shi/shi OPCs was enhanced similar to that observed in wild‐type OPCs. The majority of cells from the shiverer mutant mouse, however, remained as A2B5‐immunoreactive early OPCs. To determine which molecular events affect the differentiation of shi/shi OPCs, we determined the signaling pathway that could be responsible for activating myelin sheath‐specific proteins. We found that the developmental schedule of shi/shi OPCs in vitro was accelerated by the addition of cyclic AMP analogs, dibutyryl cAMP (dbcAMP). Treatment of shi/shi OPCs with dbcAMP had significant effect on the differentiation of OPCs that became MAG‐expressing oligodendrocytes. To further determine the possible mechanism involved in the activation of MAG by dbcAMP, we examined the cAMP‐dependent signaling cascades. The activation of JNK was markedly stimulated by treatment with dbcAMP, and the phosphorylation of transcription factor ATF‐2 was also stimulated by dbcAMP. We demonstrated that the MAG‐positive shi/shi oligodendrocytes extend processes around axons and finally covered the axon, this was clearly observed by immunocytochemistry of shi/shi oligodendrocyte‐DRG cocultures. These results suggest that ATF‐2 coupled to specific signal transduction cascades plays an important regulatory role in MAG expression at a specific stage of shi/shi oligodendrocyte differentiation, and OPCs grow to become myelin‐forming cells with numerous cell processes that wraps around an axon to form a thin myelin sheath. © 2002 Wiley‐Liss, Inc.
Developmentally regulated changes in cellular compartmentation and synaptic distribution of actin in hippocampal neurons
Authors: Zhang Wandong , Benson Deanna L.
Published: October 2002

Actin dynamics and actin‐based motility are important for neurite outgrowth and synapse plasticity. Recent work implicates actin in synapse assembly, but the morphological relationship between actin and synapses during development is unclear. Here we used developing hippocampal neurons grown in culture to examine the relationship between F‐ and G‐actin and clusters of synaptic proteins. Both F‐ and G‐actin are most enriched in dendritic and axonal growth cones, but only G‐actin is present within the distal tips of filopodia. Outside of growth cones, F‐actin levels are greater in dendrites than in axons, whereas G‐actin levels are slightly greater in axons than in dendrites. The distribution of both F‐ and G‐actin is consistent with their presence at synapses, but only F‐actin levels become detectably enhanced at synaptic sites. Quantitative analyses suggest that first‐forming synapses are associated with enhanced levels of pre‐ and postsynaptic F‐actin that do not necessarily remain elevated during synapse maturation. However, nearly all mature excitatory synapses become associated with high, mostly postsynaptic concentrations of F‐actin contained principally within dendritic spines. Mature shaft and GABAergic synapses are also associated with enhanced levels of F‐actin, but to a lesser degree. Thus, although F‐actin is essential for function and maintenance of young synapses, it need not be highly concentrated at every site. The large increase in postsynaptic F‐actin concentration observed in mature neurons is likely to reflect actin's role in dendritic spine morphology and in synapse plasticity. © 2002 Wiley‐Liss, Inc.
Are our referencing errors undermining our scholarship and credibility? The case of expatriate failure rates
Authors: Harzing Anne‐Wil
Published: October 2002

Using a citation network of 60 references on expatriate failure rates, I demonstrate how commonplace is the violation of the principles for good academic referencing. Inappropriate references undermine scholarship and its credibility. In the case of expatriate failure rates, miscitation has promoted a firmly entrenched myth unsubstantiated by any empirical evidence. I discuss the implications of referencing errors for academics and practitioners and demonstrate how these errors can be avoided. Copyright © 2002 John Wiley & Sons, Ltd.
The effects of leadership dimensions, safety climate, and assigned priorities on minor injuries in work groups
Authors: Zohar Dov
Published: October 2002

This study is based on three premises: (a) Leadership style affects the level of concern for subordinate safety; (b) Concern for safety, operationalized with supervisory practices, provides the source for safety climate perceptions; and (c) Safety priority as assigned by higher superiors influences supervisory safety practice independently of leadership style. Assigned safety priority was expected to moderate the relationship between leadership style and injury rate in organizational subunits, with safety climate mediating this leadership–injury relationship due to its demonstrable effect on safety behavior. A within‐group split‐sample analysis of 42 work groups, coupled with prospective design, indicated that transformational and constructive leadership predicted injury rate, while corrective leadership provided indirect, conditional prediction. Leadership effects were moderated by assigned safety priorities and mediated by commensurate safety‐climate variables. The results suggest that transformational and transactional leadership provide complementary modes of (mediated and moderated) influence on safety behavior of group members. Copyright © 2002 John Wiley & Sons, Ltd.
Promise breaking during radical organizational change: do justice interventions make a difference?
Authors: Kickul Jill , Lester Scott W. , Finkl Jonathon
Published: October 2002

Previous research examining the relationship between organizational justice perceptions and reactions to psychological contract breach has not considered how the type of outcome being breached may influence the effects that procedural and interactional justice have in determining employee responses. By delineating between intrinsic (e.g., autonomy) and extrinsic (e.g., pay) contract breaches, this study attempts to clarify the differential roles of procedural and interactional justice. As expected, results revealed that procedural justice has a significant effect on responses to breaches of extrinsic outcomes while interactional justice significantly affects employee responses to breaches of intrinsic outcomes. Specifically, significant two‐way interactions between extrinsic contract breach and procedural justice showed that job satisfaction, in‐role job performance, and organizational citizenship behavior were lower and intentions to leave were higher when procedural justice was perceived to be low following an extrinsic contract breach. Furthermore, significant two‐way interactions between intrinsic contract breach and interactional justice revealed that job satisfaction, in‐role job performance, and organizational citizenship behavior directed toward other individuals were lower and intentions to leave were higher when interactional justice was perceived to be low following an intrinsic contract breach. Implications of the differential roles of procedural and interactional justice are discussed. Copyright © 2002 John Wiley & Sons, Ltd.
The IT way of loafing on the job: cyberloafing, neutralizing and organizational justice
Authors: Lim Vivien K. G.
Published: October 2002

Much attention has been devoted to how technological advancements have created a brave new workplace, revolutionzing the ways in which work is being carried out, and how employees can improve their productivity and efficiency. However, the advent of technology has also opened up new avenues and opportunities for individuals to misbehave. This study focused on cyberloafing—the act of employees using their companies' internet access for personal purposes during work hours. Cyberloafing, thus, represents a form of production deviance. Using the theoretical frameworks offered by social exchange, organizational justice and neutralization, we examined the often‐neglected dark side of the internet and the role that neutralization techniques play in facilitating this misbehavior at the workplace. Specifically, we developed a model which suggested that when individuals perceived their organizations to be distributively, procedurally and interactionally unjust, they were likely to invoke the metaphor of the ledger as a neutralization technique to legitimize their subsequent engagement in the act of cyberloafing.

Data were collected with the use of an electronic questionnaire and focus group interviews from 188 working adults with access to the internet at the workplace. Results of structural equation modelling provided empirical support for all of our hypotheses. Implications of our findings for organizational internet policies are discussed. Copyright © 2002 John Wiley & Sons, Ltd.
The influence of the winter Arctic oscillation on the northern Russia spring temperature
Authors: Kryjov Vladimir N.
Published: October 2002

Correlation and trend analyses are applied to examine relationships between the northern Russia snow/ice season surface air temperature (SAT) and winter circulation, represented by the January–March Arctic oscillation (AO) index. The 1935–99 series of winter and spring monthly SAT from five stations are used, with the winter season being defined as January–March and the spring season being defined specifically for each station in accordance with local snow/ice season duration from April–May through April–July.

It is shown that the influence of the winter circulation on SAT is evident at least until the end of snow/ice season, which suggests that this influence is implemented via feedbacks provided by snow and sea ice. The winter AO accounts for some 25–50% (15–20%) of the winter (spring) SAT variance. More than 50% of the 30 year (1968–97) trends in both winter and spring SAT for northwestern Russia and more than 40% for northwestern Siberia are linearly correlated with the winter AO. It is proposed that in the Arctic Ocean regions, where snow and ice do not melt completely, the winter AO influence on SAT is likely to be evident at least until the next year's winter. Copyright © 2002 Royal Meteorological Society
Raman spectroscopic study of lichen‐assisted weathering of sandstone outcrops in the High Atlas Mountains, Morocco
Authors: Edwards Howell G. M. , Holder Jacci M. , Seaward Mark R. D. , Robinson David A.
Published: October 2002

The lichen Aspicilia caesiocinerea agg. colonizing Triassic sandstone rock outcrops between 1600 and 2800 m elevation in the High Atlas Mountains of Morocco has been observed to have some unusual growth strategies, including a probably unique undercutting of escarpments, which produce severe bioweathering of the substrata. Fourier transform Raman spectroscopy was applied to studies of lichen–substratal surface transects in order to identify key wavenumber spectral markers of the biogeological changes. The Raman data were combined with previously determined energy‐dispersive x‐ray spectral information on similar specimens to build up a picture of the survival strategy of the lichen in this seasonally arid environment, where temperature extremes on rock surfaces range between −20 and +60 °C and precipitation varies from rain and surface snow cover in winter to long periods of drought in summer. Copyright © 2002 John Wiley & Sons, Ltd.
Investigation of resonantly selected Raman spectra of intermediates in organic pyrolysis reactions
Authors: Matsui Hiroshi , Kobko Nadya , Dannenberg J. J. , Jonas Seth H. , Viswanathan Raji
Published: October 2002

The usefulness of UV resonance Raman (UVRR) spectroscopy in determining intermediate configurations in pyrolysis reactions was examined. We investigated the conformations of the nitrosoketene, E‐ and Z‐isomers, generated via the pyrolysis of isonitroso Meldrum's acid by their characteristic vibrational wavenumbers. In this system, UVRR with 355 nm excitation worked exceptionally well to enhance selectively the nitrosoketene peaks. The signal was virtually free from other intermediates interferences, which was a major problem in IR spectroscopy. While both E‐ and Z‐nitrosoketene were found as the intermediates of the isonitroso Meldrum's acid pyrolysis by UVRR, we consider that the observation of two isomers is due to their interconversions at 150 °C, based upon computational analysis. Therefore, spectroscopic information on a shorter time‐scale is necessary to determine the intermediate configuration in pyrolysis reactions. This method will still be useful for monitoring reactions at low temperatures, which may not involve significant interconversions of isomers. Copyright © 2002 John Wiley & Sons, Ltd.