bluuebunny/crossref_metadata_2025 huggingface dataset:
Surfing in the air: a grounded theory of the dynamics of street life and its policy implications
Authors: Conticini Alessandro
Published: April 2008

Nearly 20 years after the emergence of a specialised literature dealing with homeless children and youth, best practices are still rare and a divide remains between our understanding of street life, and the policy and programmes that are promoted to reach out to street‐living children: a persisting dichotomy between theory and practice.

While much of the literature available is still entrapped in a sort of ‘pathology of case studies’ unable to provide systematic information to policy makers and practitioners, this paper claims originality in presenting an inter‐disciplinary understanding of the processes of street adaptation followed by children. In doing so, the paper presents a grounded theory to predict the consequences of street life and to plan interventions accordingly. Copyright © 2008 John Wiley & Sons, Ltd.
Pacific islands' bilateral trade: the role of remoteness and of transport costs
Authors: Borgatti Lisa
Published: April 2008

Bilateral trade of geographically distant countries is likely to be negatively affected by the distance separating them from their trading partners and positively affected by their remoteness, defined as the average weighted distance between two countries with weights reflecting the absorptive capacity of the partner country. In presence of competitive transport costs, the effect of remoteness and distance is diluted. An augmented gravity model applied to the Pacific islands' bilateral trade from 1980 to 2004 shows that a doubling of the elasticity of distance would decrease their average bilateral trade by 80 per cent. Remoteness positively affects the Pacific islands' bilateral trade, but does not compensate for the negative effect of distance. The opposite is found for the Caribbean islands, where the elasticity of trade with respect to remoteness is six times bigger than that for the Pacific islands. By lowering transport costs, improved infrastructure fosters trade. A cluster analysis for 30 small island developing states shows that the Pacific islands belong to the clusters with the weaker infrastructure stocks, leaving them with a large scope for improvement. Copyright © 2008 John Wiley & Sons, Ltd.
Public sector efficiency, foreign aid and small island developing states
Authors: Feeny Simon , Rogers Mark
Published: April 2008

This paper examines the efficiency of public sector expenditures and foreign aid at achieving social sector outcomes in Small Island Developing States (SIDS). Efficiency is estimated using a Stochastic Production Function (SPF) approach and panel data since 1990. A second stage of the analysis examines the determinants of efficiency. Results indicate that the efficiency of aid and public sectors at improving life expectancy has deteriorated during the 1990s but efficiency at improving school enrolments has increased. Higher levels of governance are associated with higher efficiency. There is also evidence to suggest that efficiency is lower in SIDS, as well as in Sub‐Saharan Africa. Copyright © 2008 John Wiley & Sons, Ltd.
Brain‐derived neurotrophic factor stimulates the neural differentiation of human umbilical cord blood‐derived mesenchymal stem cells and survival of differentiated cells through MAPK/ERK and PI3K/Akt‐dependent signaling pathways
Authors: Lim Jung Yeon , Park Sang In , Oh Ji Hyeon , Kim Seong Muk , Jeong Chang Hyun , Jun Jin Ae , Lee Kwan‐Sung , Oh Wonil , Lee Jae‐Kwon , Jeun Sin‐Soo
Published: April 2008

Brain‐derived neurotrophic factor (BDNF) plays an important role in the differentiation, development, and survival of neural stem cells. In this study, we analyzed its effects on the stimulation of human umbilical cord blood‐derived mesenchymal stem cells in terms of their potential to differentiate into neuron‐like cells, their survival characteristics, and the molecular mechanisms involved. The treatment of cells with neural induction medium (NIM) and BDNF generated more cells that were neuron‐like and produced stronger expression of neural‐lineage markers than cells treated with NIM and without BDNF. Raf‐1 and ERK phosphorylation and p35 expression levels increased significantly in cells treated with both NIM and BDNF. This treatment also effectively blocked cell death following neural induction and increased Akt phosphorylation and Bcl2 expression compared with cells treated with NIM without BDNF. Inhibition of ERKs inhibited the BDNF‐stimulated up‐regulation of p35 and Bcl2. In addition, the inhibition of PI3K abrogated Akt phosphorylation and Bcl2 expression, but not p35 expression. Thus, MAPK/ERK‐dependent p35 up‐regulation and MAPK/ERK‐dependent and PI3K/Akt‐dependent Bcl2 up‐regulation contribute to BDNF‐stimulated neural differentiation and to the survival of differentiated cells. © 2008 Wiley‐Liss, Inc.
Role of Rho kinase pathway in chondroitin sulfate proteoglycan‐mediated inhibition of neurite outgrowth in PC12 cells
Authors: Gopalakrishnan Sujatha M. , Teusch Nicole , Imhof Christiane , Bakker Margot H. M. , Schurdak Mark , Burns David J. , Warrior Usha
Published: April 2008

Activation of the Rho kinase (ROCK) pathway has been associated with inhibition of neurite regeneration and outgrowth in spinal cord injury. Growth‐inhibitory substances present in the glial scar such as chondroitin sulfate proteoglycans (CSPGs) have been shown to create a nonpermissive environment for axon regeneration that results in growth cone collapse. In this study, an in vitro model was developed in nerve growth factor‐differentiated PC12 cells where the Rho/ROCK pathway was modulated by CSPG. CSPG elicited concentration‐dependent inhibition of neurite outgrowth in PC12 cells, which was reversed by ROCK inhibitors such as fasudil, dimethylfasudil, and Y27632. Further studies on the interactions of CSPG with ROCK inhibitors revealed that the modulation of ROCK by CSPG is noncompetitive in nature. It was also observed that ROCK inhibitors increased neurite outgrowth in undifferentiated PC12 cells, indicating constitutive ROCK activity in the cells. Analysis of signaling pathways demonstrated that the effect of CSPG increases the phosphorylation of myosin phosphatase, a substrate immediately downstream of ROCK activation. Fasudil, dimethylfasudil, and Y27632 inhibited the phosphorylation of myosin phosphatase induced by CSPG with rank order potencies comparable to those observed in the neurite outgrowth assay. In addition, ROCK inhibitors reversed cofilin phosphorylation induced by CSPG with similar rank order potencies. Taken together, our data demonstrate that the interaction of CSPG with the ROCK pathway involves downstream effectors of ROCK such as myosin phosphatase and cofilin. © 2008 Wiley‐Liss, Inc.
Maternal immune activation in mice delays myelination and axonal development in the hippocampus of the offspring
Authors: Makinodan Manabu , Tatsumi Kouko , Manabe Takayuki , Yamauchi Takahira , Makinodan Eri , Matsuyoshi Hiroko , Shimoda Shigero , Noriyama Yoshinobu , Kishimoto Toshifumi , Wanaka Akio
Published: April 2008

Epidemiological data suggest a relationship between maternal infection and a high incidence of schizophrenia in offspring. An animal model based on this hypothesis was made by injecting double‐stranded RNA, polyinosinic‐polycytidylic acid (poly‐I:C), into early pregnant mice, and their offspring were examined for biochemical and histological abnormalities. Mouse brains were examined with special reference to oligodendrocytes, which have been implicated in several neurodevelopmental disorders. We detected a significant decrease of myelin basic protein (MBP) mRNA and protein at early postnatal periods in poly‐I:C mice. MBP immunocytochemistry and electron microscopy revealed that the hippocampus of juvenile poly‐I:C mice was less myelinated than in PBS mice, with no significant loss of oligodendrocytes. In addition, axonal diameters were significantly smaller in juvenile poly‐I:C mice than in control mice. These abnormalities reverted to normal levels when the animals reached the adult stage. These findings suggest that retarded myelination and axonal abnormalities in early postnatal stages caused by maternal immune activation could be related to schizophrenia‐related behaviors in adulthood. © 2008 Wiley‐Liss, Inc.
Histone deacetylase‐related protein inhibits AES‐mediated neuronal cell death by direct interaction
Authors: Zhang Xiaoguang , Chen Hsin‐Mei , Jaramillo Eduardo , Wang Lulu , D'Mello Santosh R.
Published: April 2008

Histone deacetylase‐related protein (HDRP), an alternatively spliced and truncated form of histone deacetylase‐9 that lacks a C‐terminal catalytic domain, protects neurons from death. In an effort to understand the mechanism by which HDRP mediates its neuroprotective effect, we screened for proteins in the brain that interact with HDRP by using a yeast two‐hybrid assay. One of the HDRP‐interacting proteins identified in this screen was amino enhancer of split (AES), a 197–amino acid protein belonging to the Groucho family. Interaction between HDRP and AES was verified by in vitro binding assays, coimmunoprecipitation, and colocalization studies. To investigate the significance of the HDRP‐AES association to the regulation of neuronal survival, we used cultured cerebellar granule neurons, which undergo apoptosis when treated with low potassium (LK) medium. We found that in contrast to HDRP, whose expression is markedly reduced by LK treatment, AES expression was not appreciably altered. Forced expression of AES in healthy neurons results in cell death, an action that is blocked by the coexpression of HDRP. AES is a truncated version of larger Groucho‐related proteins, one of which is transducin‐like enhancer of split (TLE)‐1. We found that the expression of TLE1 is reduced in LK‐treated neurons and the forced expression of TLE1 blocks LK‐induced neuronal death as well as death induced by AES. Our results show that AES has apoptotic activity in neurons and suggest that neuroprotection by HDRP is mediated by the inhibition of this activity through direct interaction. © 2008 Wiley‐Liss, Inc.
Triptolide modulates T‐cell inflammatory responses and ameliorates experimental autoimmune encephalomyelitis
Authors: Wang Ying , Mei Yunhua , Feng Dechun , Xu Lingyun
Published: April 2008

Triptolide (TPT), a diterpenoid triepoxide, is the major component isolated from the Chinese herb Tripterygium wilfordii Hook. f. Previous studies have shown that TPT has immunosuppressive properties and is effective in prolonging graft survival and suppressing autoimmune responses. The aim of this study was to investigate theprotective effect of TPT in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. Treatment of C57BL/6 mice with TPT from the date of EAE induction significantly delayed EAE onset and suppressed disease severity, accompanied with reduced inflammation and demyelination in the central nervous system. TPT treatment lead to a significant inhibition of the mRNA expression of both Th1/ThIL‐17 and Th2 cytokines in spleen mononuclear cells (MNC) as well as in spinal cord tissues. In addition, the expression of Forkhead box p3 (Foxp3) was up‐regulated in spleen MNC after TPT treatment. Furthermore, we detected apparent inhibition of nuclear factor–kappa B (NF‐κB)‐DNA binding activity, increased expression of the inhibitor of nuclear factor–kappa Bα (IκBα) and decreased expression of pIκBα in spleen MNC in TPT‐treated EAE mice. Taken together, these findings indicate that TPT has profound immunoregulatory functions and potential protective values for the treatment of autoimmune inflammatory disorders. © 2008 Wiley‐Liss, Inc.
Increase in dopaminergic neurons from mouse embryonic stem cell‐derived neural progenitor/stem cells is mediated by hypoxia inducible factor‐1α
Authors: Kim Tae‐Sun , Misumi Sachiyo , Jung Cha‐Gyun , Masuda Tadashi , Isobe Yoshiaki , Furuyama Fujiya , Nishino Hitoo , Hida Hideki
Published: April 2008

A reliable method to induce neural progenitor/stem cells (NPCs) into dopaminergic (DAergic) neurons has not yet been established. As well, the mechanism involved remains to be elucidated. To induce DAergic differentiation from NPCs, a cytokine mixture (C‐Mix) of interleukin (IL)‐1β, IL‐11, leukemia‐inhibitory factor (LIF), and glial‐derived neurotrophic factor or low oxygen (3.5% O2: L‐Oxy) was used to treat embryonic stem (ES) cell‐derived NPCs. Treatment with C‐Mix increased the number of tyrosine hydroxylase (TH)‐positive cells compared with controls (2.20‐fold of control). The C‐Mix effect was induced by mainly LIF or IL‐1β treatment. Although L‐Oxy caused an increase in TH‐positive cells (1.34‐fold), the combination of L‐Oxy with C‐Mix did not show an additive effect. Increases in DA in the medium were shown in the presence of C‐Mix, LIF, and L‐Oxy by high‐performance liquid chromatography. Gene expression patterns of neural markers [tryptophan hydroxylase (TPH), GAD67, GluT1, β‐tubulin III, glial fibrillary acidc protein, and TH] were different in C‐Mix and L‐Oxy treatments. Because increases in hypoxia‐inducible factor (HIF)‐1α protein were found in both treatments, we investigated the effect of HIF‐1α on differentiation of NPCs to DAergic neurons. Inhibition of HIF‐1α by the application of antisense oligodeoxynucleotides (ODNs) to NPCs caused a decrease in TH‐positive cells induced by LIF treatment. Gene expressions of TH, GAD67, and GluT1 were decreased, and those of TPH, β‐tubulin III, and S‐100β were increased by treatment with just ODNs, indicating the importance of the endogenous effect of HIF‐1α on neuronal differentiation. These data suggest that enhanced differentiation into DAergic neurons from ES cell‐derived NPCs was induced by C‐Mix or L‐Oxy mediated by HIF‐1α. © 2008 Wiley‐Liss, Inc.
Effect of cortistatin on tau phosphorylation at Ser262 site
Authors: Rubio Alicia , Pérez Mar , de Lecea Luis , Ávila Jesús
Published: April 2008

The development of intraneuronal lesions as a result of the progressive deposition of hyperphosphorylated tau at specific brain regions (such as hippocampus and cortex) plays a key role in the pathological process of Alzheimer's disease. However, the mechanisms by which tau phosphorylation is regulated, mainly in the pathology found in the cortex, are still poorly understood. Here, we analyzed the effect of cortistatin, a cortical neuropeptide related to somatostatin, on tau phosphorylation at Ser262 in cultures of murine cortical neurons. Both somatostatin and cortistatin induce tau phosphorylation at Ser262, a site modified in Alzheimer's disease, although with different kinetics in cortex. The effect of cortistatin likely is mediated by heterodimeric receptors composed of somatostatin receptor subtypes 2 and 4 and also by protein kinase C signaling. Cortistatin‐deficient mice show decreased tau phosphorylation at Ser262 in the cortex but not in other brain regions tested. Our results suggest an important role for cortistatin in the regulation of tau phosphorylation that may be associated with the pathophysiology of Alzheimer's disease in regions such as the cerebral cortex. © 2008 Wiley‐Liss, Inc.
Localization of N‐methyl‐norsalsolinol within rodent and human brain
Authors: DeCuypere Michael , Kalabokis Vassilios N. , Hao Ruyi , Schroeder Dorothy , Miller Duane D. , LeDoux Mark S.
Published: April 2008

The isoquinoline derivative N‐methyl‐6,7‐dihydroxytetrahydroisoquinoline (N‐methyl‐norsalsolinol) is present in normal human brain and has been identified in the cerebrospinal fluid of patients with Parkinson's disease (PD). Endogenously, N‐methyl‐norsalsolinol may be derived from dopamine by condensation with aldehydes or α‐ketoacids. In vitro experiments suggest that N‐methyl‐norsalsolinol is neurotoxic. In this study, high‐performance liquid chromatography with electrochemical detection (HPLC‐EC) was used to determine N‐methyl‐norsalsolinol concentrations in mouse, rat, normal human, and PD brain. In addition, a monoclonal antibody was generated against N‐methyl‐norsalsolinol and used to determine the cellular localization of N‐methyl‐norsalsolinol in brain. With HPLC‐EC, N‐methyl‐norsalsolinol was detected in all regions of rodent and human brain subjected to analysis. In rodent brains, N‐methyl‐norsalsolinol tissue concentrations were similar among frontal cortex, ventral midbrain, striatum, hippocampus, and cerebellum. Conversely, in normal human control brains, N‐methyl‐norsalsolinol was concentrated in the substantia nigra and striatum. In comparison to normal human controls, N‐methyl‐norsalsolinol levels were significantly lower in the substantia nigra and caudate nuclei from PD patients, a finding possibly related to the death of nigrostriatal dopaminergic neurons. N‐methyl‐norsalsolinol immunoreactivity colocalized with a general neuronal marker (neuron‐specific enolase) and a monoaminergic marker (tyrosine hydroxylase) but not with a glial marker (glial fibrillary acidic protein). The widespread neuronal localization of N‐methyl‐norsalsolinol in several mammalian species suggests that, in isolation, this compound is a “weak” neurotoxin. However, endogeneously derived N‐methyl‐norsalsolinol could contribute to the pathobiology of PD in genetically predisposed individuals after years of accumulation in dopaminergic neurons. © 2008 Wiley‐Liss, Inc.
Expression of the receptor for advanced glycation end products in oligodendrocytes in response to oxidative stress
Authors: Qin Jingdong , Goswami Rajendra , Dawson Sylvia , Dawson Glyn
Published: April 2008

Demyelination is a common result of oxidative stress in the nervous system, and we report here that the response of oligodendrocytes to oxidative stress involves the receptor for advanced glycation end products (RAGE). RAGE has not previously been reported in neonatal rat oligodendrocytes (NRO), but, by using primers specific for rat RAGE, we were able to show expression of messenger RNA (mRNA) for RAGE in NRO, and a 55‐kDa protein was detected by Western blotting with antibodies to RAGE. Neonatal rat oligodendrocytes stained strongly for RAGE, suggesting membrane localization of RAGE. Addition of low concentrations of hydrogen peroxide (100 μM) initiated 55‐kDa RAGE shedding from the cell membrane and the appearance of “soluble” 45‐kDa RAGE in the culture medium, followed by restoration of RAGE expression to normal levels. Increasing hydrogen peroxide concentration (>200 μM) resulted in no restoration of RAGE, and the cells underwent apoptosis and necrosis. We further confirmed the observation in a human oligodendroglioma‐derived (HOG) cell line. Both the antioxidant N‐acetyl‐L‐cysteine and the broad‐spectrum metalloproteases inhibitor TAPI0 were able partially to inhibit shedding of RAGE, suggesting involvement of metalloproteases in cleavage to produce soluble RAGE. The level of 55‐kDa RAGE in autopsy brain of patients undergoing neurodegeneration with accompanying inflammation [multiple sclerosis and neuronal ceroid‐lipofuscinosis (Batten's disease)] was much lower than that in age‐matched controls, suggesting that shedding of RAGE might occur as reactive oxygen species accumulate in brain cells and be part of the process of neurodegeneration. © 2008 Wiley‐Liss, Inc.
Blockade of chloride intracellular ion channel 1 stimulates Aβ phagocytosis
Authors: Paradisi Silvia , Matteucci Andrea , Fabrizi Cinzia , Denti Michela A. , Abeti Rosella , Breit Samuel N. , Malchiodi‐Albedi Fiorella , Mazzanti Michele
Published: April 2008

In amyloid‐β (Aβ)‐stimulated microglial cells, blockade of chloride intracellular ion channel 1 (CLIC1) reverts the increase in tumor necrosis factor‐α and nitric oxide (NO) production and results in neuroprotection of cocultured neurons. This effect could be of therapeutic efficacy in Alzheimer's disease (AD), where microglial activation may contribute to neurodegeneration, but it could reduce Aβ phagocytosis, which could facilitate amyloid plaque removal. Here, we analyzed the CLIC1 blockade effect on Aβ‐stimulated mononuclear phagocytosis. In the microglial cell line BV‐2, Aβ25–35 treatment enhanced fluorescent bead phagocytosis, which persisted also in the presence of IAA‐94, a CLIC1 channel blocker. The same result was obtained in rat primary microglia and in BV2 cells, where CLIC1 expression had been knocked down with a plasmid producing small interfering RNAs. To address specifically the issue of Aβ phagocytosis, we treated BV‐2 cells with biotinylated Aβ1–42 and measured intracellular amyloid by morphometric analysis. IAA‐94‐treated cells showed an increased Aβ phagocytosis after 24 hr and efficient degradation of ingested material after 72 hr. In addition, we tested Aβ1–42 phagocytosis in adult rat peritoneal macrophages. Also, these cells actively phagocytosed Aβ1–42 in the presence of IAA‐94. However, the increased expression of inducible NO synthase (iNOS), stimulated by Aβ, was reverted by IAA‐94. In parallel, a decrease in NO release was detected. These results suggest that blockade of CLIC1 stimulates Aβ phagocytosis in mononuclear phagocytes while inhibiting the induction of iNOS and further point to CLIC1 as a possible therapeutic target in AD. © 2008 Wiley‐Liss, Inc.
Tinnitus and inferior colliculus activity in chinchillas related to three distinct patterns of cochlear trauma
Authors: Bauer Carol A. , Turner Jeremy G. , Caspary Donald M. , Myers Kristin S. , Brozoski Thomas J.
Published: April 2008

A longstanding hypothesis is that tinnitus, the perception of sound without an external acoustic source, is triggered by a distinctive pattern of cochlear hair cell (HC) damage and that this subsequently leads to altered neural activity in the central auditory pathway. This hypothesis was tested by assessing behavioral evidence of tinnitus and spontaneous neural activity in the inferior colliculus (IC) after unilateral cochlear trauma. Chinchillas were assigned to four cochlear treatment groups. Each treatment produced a distinctive pattern of HC damage, as follows: acoustic exposure (AEx): sparse low‐frequency inner hair cell (IHC) and outer hair cell (OHC) loss; round window cisplatin (CisEx): pronounced OHC loss mixed with some IHC loss; round window carboplatin (CarbEx): pronounced IHC loss without OHC loss; control: no loss. Compared with controls, all experimental groups displayed significant and similar psychophysical evidence of tinnitus with features resembling a 1‐kHz tone. Contralateral IC spontaneous activity was elevated in the AEx and CisEx groups, which showed increased spiking and increased cross‐fiber synchrony. A multidimensional analysis identified a subpopulation of neurons more prevalent in animals with tinnitus. These units were characterized by high bursting, low ISI variance, and within‐burst peak spiking of approximately 1,000/sec. It was concluded that cochlear trauma in general, rather than its specific features, leads to multiple changes in central activity that underpin tinnitus. Particularly affected was a subpopulation ensemble of IC neurons with the described unique triad of features. © 2008 Wiley‐Liss, Inc.
Accumulation of chondroitin sulfate proteoglycans in the microenvironment of spinal motor neurons in amyotrophic lateral sclerosis transgenic rats
Authors: Mizuno Hideki , Warita Hitoshi , Aoki Masashi , Itoyama Yasuto
Published: April 2008

Chondroitin sulfate proteoglycans (CSPGs) are the major components of extracellular matrix in the central nervous system. In the spinal cord under various types of injury, reactive gliosis emerges in the lesion accompanied by CSPG up‐regulation. Several types of CSPG core proteins and their side chains have been shown to inhibit axonal regeneration in vitro and in vivo. In the present study, we examined spatiotemporal expression of CSPGs in the spinal cord of transgenic (Tg) rats with His46Arg mutation in the Cu/Zn superoxide dismutase gene, a model of amyotrophic lateral sclerosis (ALS). Immunofluorescence disclosed a significant up‐regulation of neurocan, versican, and phosphacan in the ventral spinal cord of Tg rats compared with age‐matched controls. Notably, Tg rats showed progressive and prominent accumulation of neurocan even at the presymptomatic stage. Immunoblotting confirmed the distinct increase in the levels of both the full‐length neurocan and their fragment isoforms. On the other hand, the up‐regulation of versican and phosphacan peaked at the early symptomatic stage, followed by diminishment at the late symptomatic stage. In addition, double immunofluorescence revealed a colocalization between reactive astrocytes and immunoreactivities for neurocan and phosphacan, especially around residual large ventral horn neurons. Thus, reactive astrocytes are suggested to be participants in the CSPG accumulation. Although the possible neuroprotective involvement of CSPG remains to be investigated, the present results suggest that both the reactive astrocytes and the differential accumulation of CSPGs may create a nonpermissive microenvironment for neural regeneration in neurodegenerative diseases such as ALS. © 2008 Wiley‐Liss, Inc.
To prosper, organizational psychology should … overcome methodological barriers to progress
Authors: Edwards Jeffrey R.
Published: April 2008

Progress in organizational psychology (OP) research depends on the rigor and quality of the methods we use. This paper identifies ten methodological barriers to progress and offers suggestions for overcoming the barriers, in part or whole. The barriers address how we derive hypotheses from theories, the nature and scope of the questions we pursue in our studies, the ways we address causality, the manner in which we draw samples and measure constructs, and how we conduct statistical tests and draw inferences from our research. The paper concludes with recommendations for integrating research methods into our ongoing development goals as scholars and framing methods as tools that help us achieve shared objectives in our field. Copyright © 2008 John Wiley & Sons, Ltd.
To prosper, organizational psychology should… adopt a global perspective
Authors: Gelfand Michele J. , Leslie Lisa M. , Fehr Ryan
Published: April 2008

We argue that for the field of organizational psychology to prosper, it must adopt a global perspective. In this article, we discuss three specific ideals for a more global organizational psychology, our progress toward these ideals (or lack thereof), and potential solutions to move toward a truly global science. First, we argue that a truly global organizational psychology must incorporate global voices. Yet cross‐cultural research in organizational psychology still remains largely a U.S. export business wherein the very questions we ask are colored by Western assumptions and values which are then explored to other cultures. To be a global science, we must acknowledge that the questions we ask are value‐laden, and we must ensure that the questions we ask to have global relevance. Second, a truly global organizational psychology must articulate with precision the level at which culture operates. Yet the level at which culture is defined varies widely across studies and levels of analysis confusion abounds in the literature. We discuss a number of conceptualizations and measures of culture and suggest the conditions under which each may be warranted. Third, a truly global organizational psychology must advance an understanding of when culture matters. Despite abundant evidence that behavior in organizations is influenced by multiple contextual factors (e.g., the work team, organization, industry), we have little understanding of how national culture and non‐cultural factors jointly influence behavior in organizations. We discuss several promising models to guide such efforts. Copyright © 2008 John Wiley & Sons, Ltd.
Repeatability of monolithic HPLC columns while using a flow program
Authors: Kaminski Lukas , El Deeb Sami , Wätzig Hermann
Published: April 2008

Fast HPLC methods are becoming more and more important. Using monolithic HPLC columns for fast separations, a flow program can be applied for further decrease in the total run time. An interesting issue was whether the flow program affects repeatability. The investigated method was a generic assay for the oral antidiabetic drugs glibenclamide and glimepiride in the presence of two of their degradation products. A flow program ranging from 5.0 to 9.9 mL/min had been set up to decrease the run time to approximately 1.7 min. Within‐day RSD% (n = 40) for both retention times and peak areas were less than 1%. At flow rates higher than 7 mL/min, repeatability was impaired to some extent. It became mainly noticeable through the day‐to‐day precision (n = 60) which showed RSD% up to 2%. However, further investigations indicated that this was rather related to pump inefficiency at high flow rates than to the flow program as such. Presuming the use of appropriate equipment, qualified for high flow rates, the application of a flow program for shortening the run time is absolutely reasonable and does not affect repeatability.
Monodisperse Gelatin Microspheres as a Drug Delivery Vehicle: Release Profile and Effect of Crosslinking Density
Authors: Choy Young Bin , Cheng Felice , Choi Hyungsoo , Kim Kyekyoon (Kevin)
Published: April 2008

Uniform gelatin microspheres (GMS) of a wet size of 100 µm in diameter were fabricated by the electric field assisted precision particle fabrication (E‐PPF) method and crosslinked with different glutaraldehyde (GA) concentrations to study the effect of the crosslinking density on drug release. The drug release profiles of the crosslinked GMS were studied along with the intraparticle drug distribution and the particle degradation characteristics. Due to the concentration gradient of GA along the diffusion path into the GMS, the crosslinking density is higher on the GMS surface, making it less susceptible to degradation. As a result, the GMS with higher GA concentrations (0.375–0.875%) exhibited a highly resistant surface toward enzymatic degradation. On the other hand, the amount of drug complexation at the surface decreases as the GA concentration increases, which can be attributed to the lowered basicity of gelatin caused by the increased crosslinking density. These factors collectively affect the drug release kinetics and give rise to similar release profiles for GMS above a GA concentration of 0.375%.

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Profiling of apoptosis genes identifies distinct types of primary cutaneous large B cell lymphoma
Authors: van Galen JC , Hoefnagel JJ , Vermeer MH , Willemze R , Dijkman R , Tensen CP , de Boer WPH , Meijer CJ , Oudejans JJ
Published: April 2008

Two distinct primary cutaneous large B cell lymphomas are recognized: primary cutaneous follicle centre lymphoma (PCFCL), characterized by an excellent prognosis, and primary cutaneous large B cell lymphoma, leg‐type (PCLBCL leg‐type), with an unfavourable prognosis. To determine whether inhibition of the apoptosis pathways may underlie the difference in clinical outcome between PCFCL and PCLBCL leg‐type, we investigated the expression of only apoptosis‐related genes by microarray expression profiling. Unsupervised cluster analysis was carried out using 169 genes involved in apoptosis on a group of 21 previously untreated patients diagnosed with primary cutaneous large B cell lymphoma. Cluster analysis resulted in two separate groups which showed large overlap with the PCFCL and PCLBCL leg‐type. One group was characterized by high expression levels of pro‐ and anti‐apoptotic genes. The other group was characterized by high expression levels of apoptosis‐inducing cytotoxic effector genes, possibly reflecting a cellular cytotoxic immune response. Our results suggest that the clinically favourable PCFCLs are characterized by a relatively intense cellular cytotoxic immune response and that PCLBCL leg‐types are characterized by constitutive activation of the intrinsic mediated apoptosis pathway, with concomitant downstream inhibition of this apoptosis pathway. Thus, strategies neutralizing the function of apoptosis‐inhibiting proteins might be effective in PCLBCL leg‐type. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
A role for VICKZ proteins in the progression of colorectal carcinomas: regulating lamellipodia formation
Authors: Vainer G , Vainer‐Mosse E , Pikarsky A , Shenoy SM , Oberman F , Yeffet A , Singer RH , Pikarsky E , Yisraeli JK
Published: April 2008

VICKZ proteins are a highly conserved family of RNA binding proteins, implicated in RNA regulatory processes such as intracellular RNA localization, RNA stability, and translational control. During embryogenesis, VICKZ proteins are required for neural crest migration and in adults, the proteins are overexpressed primarily in different cancers. We hypothesized that VICKZ proteins may play a role in cancer cell migration. In patients, VICKZ expression varies with tumour type, with over 60% of colon, lung, and ovarian tumours showing strong expression. In colorectal carcinomas (CRCs), expression is detected at early stages, and the frequency and intensity of staining increase with progression of the disease to lymph node metastases, of which 97% express the protein at high levels. Indeed, in stage II CRC, the level of VICKZ expression in the primary lesion correlates with the degree of lymph node metastasis. In culture, VICKZ proteins rapidly accumulate in processes at the leading edge of PMA‐stimulated SW480 CRC cells, where they co‐localize with β‐actin mRNA. Two distinct cocktails of shRNAs, each targeting all three VICKZ paralogues, cause a dramatic drop in lamellipodia and ruffle formation in stimulated cells. Thus, VICKZ proteins help to facilitate the dynamic cell surface morphology required for cell motility. We propose that these proteins play an important role in CRC metastasis by shuttling requisite RNAs to the lamellipodia of migrating cells. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Validity and comparison of two measures of days supply in medicaid claims data
Authors: Gross Robert , Bilker Warren B. , Strom Brian L. , Hennessy Sean
Published: April 2008

Background

In claims‐based pharmacoepidemiologic and health services research studies of chronic medications, days supply can be determined using either an observed measure or a measure calculated from quantity dispensed and dosing directions. The two measures should yield the same duration, but if not, the preferred method is unknown.

Objectives

We aimed to determine whether the observed or calculated measure of days supply more closely approximated the actual refill interval.

Methods

Using California Medicaid data from 1998to 2001, we identified all prescriptions followed by ≥ 1 refill for nevirapine and abacavir tablets. For each record, we calculated the difference between the days supply and the refill interval for each method. In a subgroup analysis, we compared the measures only in records where the methods were discordant.

Results

Of 29 646 records, in 27 230 (92.5%) the measures were identical. The difference between the days supply and the refill interval was identical for each measure with a median difference of 4 days (range 0–1142 days), p = 0.5 for the difference between them. In the discordant subset, the median difference for the observed measure was 10 days (range 0–1053 days) and for the calculated measure it was 12 days (range 0–1023 days), p = 0.003 for the difference between them.

Conclusions

In California Medicaid, observed and calculated measures of days supply generally provided identical data which closely approximated the refill interval. In the few discordant records, the observed measure was slightly more accurate. These findings suggest that both variables provide valid data for temporal relations between anti‐retroviral prescriptions and events. Copyright © 2008 John Wiley & Sons, Ltd.
Schwingende Puppen und Wolkenkratzer. Spielwiese
Authors: Ucke Christian , Schlichting Hans‐Joachim
Published: April 2008

Bei einem mit Federn verbundenen System von schwingenden Massen kann unter gewissen Randbedingungen eine Masse ganz in Ruhe bleiben, während andere Teile starke Ausschläge vollführen. Derartige Systeme werden unter dem Begriff Schwingungstilgung behandelt und haben eine enorme Bedeutung in der Technik. Schwingende Maschinenteile bis hin zu schwingenden Brücken und Wolkenkratzern werden auf diese Weise gedämpft und damit erst handhabbar und verträglich. Am Beispiel einer Spielzeugpuppe, der Millenniumsbrücke in London sowie des Taipei‐Wolkenkratzers in Taiwan und des Berliner Fernsehturms werden einige Aspekte der Schwingungstilgung beleuchtet.
Vulkaneruptionen – Ursachen und Vorhersagen. Geophysik
Authors: Keppler Hans , Audétat Andreas
Published: April 2008

Die treibende Kraft explosiver Vulkaneruptionen ist das Freisetzen von Wasser, das im Magma gelöst ist. Blasen von Wasserdampf im Magma können einen Innendruck von mehreren tausend bar aufbauen und damit einen Schlot von der Magmenkammer zur Erdoberfläche freisprengen. Die Expansion der Blasen erhöht die Aufstiegsgeschwindigkeit und führt letztlich zur Fragmentierung des Magmas. Hauptgefahrenquellen bei explosiven Eruptionen sind pyroklastische Ströme oder Glutwolken (Suspensionen von Schmelztropfen und festen Partikeln in heißen Gasen) und Schlammströme (Lahare), nicht jedoch ausfließende Lava. Eruptionen lassen sich heute in vielen Fällen gut vorhersagen. Hauptwerkzeuge für die Vorhersage sind die Beobachtung von Erdbeben, Bodendeformation und vulkanischen Gasen. Langperiodische Beben entstehen durch Eigenschwingungen von blasenhaltigem Magma, das durch Spalten im Gestein strömt. Die Abkühlung des Klimas nach großen explosiven Eruptionen beruht auf der Bildung von Schwefelsäure‐Aerosolen in der Stratosphäre.
Auf der Suche nach dem Heiligen Gral. Schleifen‐Quantengravitation
Authors: Thiemann Thomas
Published: April 2008

Die Theorie einer Quantengravitation soll die Quantentheorie und die Allgemeine Relativitätstheorie in Einklang bringen. Doch die Suche nach ihr ist seit fast siebzig Jahren ein ungelöstes Problem, sozusagen der “heilige Gral” der Grundlagenphysik. Ein guter Kandidat ist die Schleifen‐Quantengravitation (Loop Quantum Gravity, LQG), die sich in den letzten zwanzig Jahren vielversprechend entwickelt hat. Sie baut aus sogenannten Spin‐Netzwerken eine quantisierte Raumzeit auf. Daher kommt sie ohne Hintergrundmetrik als “Bühne” aus, auf der die Materie wie ein Schauspieler agieren muss. Sie ist also wie die Allgemeine Relativitätstheorie hintergrundunabhängig. Das unterscheidet sie von den Quantenfeldtheorien und Stringtheorien, deren Hintergrundabhängigkeit eine fundamentale, konzeptionelle Schwäche darstellt. Ob die Schleifen‐Quantengravitation der richtige Weg ist, müssen allerdings erst noch experimentelle Beobachtungen erweisen. Die Hoffnung ruht zum Beispiel auf der Beobachtung von kosmischen Gammastrahlungsblitzen (Gamma‐Ray Bursts).
Am Rande des Messbaren. Quantengravitation im Experiment
Authors: Lämmerzahl Claus
Published: April 2008

Die Relativitätstheorie und das Standardmodell der Elementarteilchen sind experimentell mit höchster Genauigkeit bestätigt. Dennoch sind Relativitätstheorie und Quantentheorie inkompatibel. Das kann eine zukünftige Theorie der Quantengravitation nur auflösen, indem sie mindestens eine dieser beiden Standardtheorien verletzt. Das grundlegende Problem besteht darin, dass die wichtigsten Effekte der Quantengravitation auf der Planck‐Skala zu erwarten sind. Diese ist jedoch auf absehbare Zeit experimentell nicht zugänglich. Verletzungen der Standardtheorien durch die Quantengravitation könnten jedoch Effekte verursachen, die in Laborexperimenten oder an kosmischen Objekten beobachtbar sind. Dieser Beitrag stellt einige der denkbaren Effekte vor und diskutiert Strategien, sie experimentell aufzuspüren.
Schwarzwaldidylle mit 13 PS
Authors: Müller Andreas
Published: April 2008

In der vierten Generation steht die 1825 erbaute Hexenlochmühle in einem entlegenen Ort zwischen Furtwangen und St. Märgen. Die Eigentümerfamilie Trenkle konnte die idyllische Schwarzwaldmühle, die heute ein uriges Ausflugsziel ist, originalgetreu erhalten. Die alten Holzsägen, die die Mühle einst in Gang setzte, sind heute nicht mehr in Betrieb. Die Mühle versorgt aber das gesamte Anwesen mit Strom.
Protein‐protein interactions between two‐component system transmitter and receiver domains of Myxococcus xanthus
Authors: Whitworth David E. , Millard Andrew , Hodgson David A. , Hawkins Peter F.
Published: April 2008

We present a novel dataset assessing the specificity of protein‐protein interactions between 69 transmitter and receiver domains from two‐component system (TCS)‐signalling pathways. TCS require a conserved protein‐protein interaction between partner transmitter and receiver domains for signal transduction. The complex prokaryote Myxococcus xanthus possesses an unusually large number of TCS genes, many of which have no obvious interaction partners. Interactions between TCS domains of M. xanthus were assessed using a yeast two‐hybrid assay, in which domains were expressed as both bait and prey translational fusions. LacZ production was monitored as an indicator of protein‐protein interaction, and the strength of interactions classified as weak, medium or strong. Two‐hundred and fifty‐five transmitter‐receiver domain interactions were observed (46 strong), allowing identification of potential signalling partners for individual M. xanthus TCS proteins. In addition, the dataset provides interesting ‘meta’ information. For instance, many strong interactions were identified between different transmitter domain pairs (34) and receiver domain pairs (23), suggesting a surprisingly large degree of heterodimerisation of these domains. Proteins in our dataset that exhibited similar ‘profiles’ of interactions, often shared a similar biological function, suggesting that interaction profiles can provide information on biological function, even considering sets of homologous domains.
Proteomic changes in rat thyroarytenoid muscle induced by botulinum neurotoxin injection
Authors: Welham Nathan V. , Marriott Gerard , Tateya Ichiro , Bless Diane M.
Published: April 2008

Botulinum neurotoxin (BoNT) injection into the thyroarytenoid (TA) muscle is a commonly performed medical intervention for adductor spasmodic dysphonia. The mechanism of action of BoNT at the neuromuscular junction is well understood, however, aside from reports focused on myosin heavy chain isoform abundance, there is a paucity of data addressing the effects of therapeutic BoNT injection on the TA muscle proteome. In this study, 12 adult Sprague Dawley rats underwent unilateral TA muscle BoNT serotype A injection followed by tissue harvest at 72 h, 7 days, 14 days, and 56 days postinjection. Three additional rats were reserved as controls. Proteomic analysis was performed using 2‐D SDS‐PAGE followed by MALDI‐MS. Vocal fold movement was significantly reduced by 72 h, with complete return of function by 56 days. Twenty‐five protein spots demonstrated significant protein abundance changes following BoNT injection, and were associated with alterations in energy metabolism, muscle contractile function, cellular stress response, transcription, translation, and cell proliferation. A number of protein abundance changes persisted beyond the return of gross physiologic TA function. These findings represent the first report of BoNT‐induced changes in any skeletal muscle proteome, and reinforce the utility of applying proteomic tools to the study of system‐wide biological processes in normal and perturbed TA muscle function.
Parallel post‐source decay for increasing protein identification confidence levels from 2‐D gels
Authors: Wahlander Asa , Arrigoni Giorgio , Snel Marten , Hellman Ulf , James Peter
Published: April 2008

Peptide mass fingerprinting (PMF) has over the years become one of the most commonly used tools for high‐throughput analysis and identification of proteins. This method is applicable when relatively simple samples have to be analysed and it is commonly used for analysing proteins previously separated by 2‐DE. The most common type of instrument used for this approach is the MALDI‐TOF that has proved to be particularly suitable for the PMF analysis because of its characteristics of speed, robustness, sensitivity and automation. We have used a MALDI‐TOF equipped with a novel parallel PSD capability (MALDI micro MX), to perform the analysis of two sets of different biological samples isolated by 2‐DE. By using a method that integrates the data obtained by PMF analysis with the PSD data obtained in the same experiment, we show that the new multiplexed PSD solution increases the protein identification rate compared to the normal PMF approach. We also investigated the use of a charge‐directed fragmentation modification reagent to improve the identification rate and confidence levels.
Trypsin‐immobilized fiber core in syringe needle for highly efficient proteolysis
Authors: Wang Sheng , Chen Zhi , Yang Pengyuan , Chen Gang
Published: April 2008

In this report, a core‐changeable needle enzymatic reactor was developed for highly efficient proteolysis. A piece of enzyme‐immobilized fiber core was inserted into the needle of a syringe pump to form a flow‐through bioreactor. The novel in‐needle bioreactor could be regenerated by changing its fiber core. The feasibility and performance of the unique bioreactor were demonstrated by the tryptic digestion of BSA and lysozyme and the digestion time was significantly reduced to less than 5 s. The digests were identified by MALDI‐TOF MS with sequence coverages comparable to those obtained by the conventional in‐solution tryptic digestion. The present in‐needle bioreactor provides a promising platform for the high‐throughput protein identification.
Mechanism of 4‐methyl‐1,2,4‐triazol‐3‐thione reaction with formaldehyde
Authors: Wujec Monika , Paneth Piotr
Published: April 2008

We have recently described theoretically the mechanism of the reaction between 4‐methyl‐1,2,4‐triazol‐3‐thiol and formaldehyde that leads to the N‐substituted product, N1‐hydroxymethyl‐4‐methyl‐1,2,4‐triazol‐3‐thione. New experimental findings indicate that the thione tautomeric form in reaction with formaldehyde also yields this product. This observation could not be explained on the basis of previous calculations, which predicted that the thione tautomer undergoes nucleophilic substitution at the sulfur atom, leading to the S‐substituted product. We present theoretical explanation of the observed reactivity. We show that under experimental conditions this reaction proceeds with the intervention of the anionic form of the triazole with the Gibbs free energy of activation of only 1.8 kcal/mol. Copyright © 2008 John Wiley & Sons, Ltd.
Solid phase synthesis of novel α/β‐tetrapeptides, electrospray ionization mass spectrometric evaluation of their metal cation complexation behavior, and conformational analysis using density functional theory (DFT)
Authors: Bandala Yamir , Aviña Judit , González Tania , Rivero Ignacio A. , Juaristi Eusebio
Published: April 2008

Thirty‐four novel α/β‐tetrapeptides (1–34) have been prepared employing solid‐phase and in‐parallel synthetic protocols. α/β‐Tetrapeptides 1–34 were prepared by a combination of three α‐amino acid residues (alanine (Ala), phenylalanine (Phe), and isoleucine (Ile)) with one β‐amino acid residue (β3‐homophenylglycine). The corresponding complexes of several selected α/β‐tetrapeptides with alkali, alkaline earth, and transition metals, [tP + M+], were evaluated using ion electrospray‐ionization mass spectrometry (ESI‐MS). According to the results from analysis of mixtures, we can conclude that the position of the β‐amino acid is determinant in the affinity toward different metal cations. Computational modeling (DFT, B3LYP 6‐311++G) provided useful information regarding the most likely coordination sites of the metal ions on the receptor α/β‐tetrapeptide 12, HO2C‐α‐Phe‐α‐Phe‐α‐Ile‐β3‐hPhg‐NH2, as well as the conformational changes induced by the metal upon [tP + M+] complex formation. Copyright © 2008 John Wiley & Sons, Ltd.