bluuebunny/crossref_metadata_2025 huggingface dataset:
Synergetic Antioxidant and Vasodilatory Action of Carbon Monoxide in Angiotensin II–Induced Cardiac Hypertrophy
Authors: Kobayashi Atsushi , Ishikawa Kazunobu , Matsumoto Hayato , Kimura Satoshi , Kamiyama Yoshiyuki , Maruyama Yukio
Published: October 2007

The aim of this study was to determine the effects of carbon monoxide (CO) at a nontoxic low concentration on the cardiac and vascular hypertrophic response and reactive oxygen species generation, compared with the action of a vasodilator, hydralazine. Twelve- to 16-week–old low-density lipoprotein receptor knockout mice were subjected to angiotensin II (Ang II) infusion using osmotic minipumps (Ang II group; n=11) for 2 weeks. Controls were administered saline (n=10). Animals were exposed to CO in a chamber at 60 ppm for 2 hours per day with or without Ang II infusion (Ang II+CO group, n=10; CO group, n=9). Hydralazine was administered with Ang II infusion (n=10). Animals exhibited elevated arterial carboxyhemoglobin after CO exposure. Although the CO exposure did not affect systolic blood pressure without Ang II infusion, the hypertensive response after Ang II infusion was significantly attenuated by CO. Accordingly, the mice in the Ang II+CO group showed lesser left ventricular hypertrophy compared with those in the Ang II group. CO treatment also attenuated aortic hypertrophy. Interestingly, these changes were accompanied by the reduction of reactive oxygen species production, p47
phox
and p67
phox
subunit expressions of reduced nicotinamide-adenine dinucleotide phosphate oxidase, and Akt phosphorylation. Although hydralazine showed stronger antihypertensive action, superior inhibition on cardiac hypertrophy was obtained by CO (
P
<0.05). Furthermore, Ang II–dependent myocardial reactive oxygen species generation was more effectively suppressed by CO. Low-dose exogenous CO treatment attenuates Ang II-dependent reactive oxygen species generation, suggesting that appropriate CO administration alleviates hypertension and reduces organ hypertrophy mediated by Ang II.
Whither East Asian Regionalism? An ASEAN Perspective
Authors: Chia Siow Yue
Published: October 2007

East Asia is catching up with the rest of the world in establishing regional trade arrangements (RTAs). This region is responding to pressures from globalization, regionalism in the Americas and Europe, the rise of China and India, improved political relations in the region with the end of the Cold War, as well as market-driven trade and investment integration and the emergence of production networks. ASEAN formed the first RTA in 1992, and by the turn of the decade, ASEAN was signing or negotiating free trade agreements (FTAs) with Japan, China, South Korea, India, Australia–New Zealand, and the European Union. It also entered into bilateral FTAs with the United States and countries in Latin America, Africa, the Middle East, and South Asia. ASEAN is also considering an East Asian FTA. Can ASEAN remain in the driver's seat of regional integration and be an effective hub? The FTA proliferation also has important consequences and effects for East Asia and the world trading system.
Made in China: From World Sweatshop to a Global Manufacturing Center?
Authors: Sung Yun-Wing
Published: October 2007

This paper argues that foreign investment is a second-best instrument that helps China to succeed in export-led growth by circumventing the many distortions that discriminate against domestic private enterprises. China's dependence on foreign investment for exports should decline as China builds up its market economy, but its generous preferences for foreign investors may unduly prolong its dependence. It is found that China's exports are increasingly dominated by the low value-added processing exports of foreign affiliates. In the case of Hong Kong investment in export processing on the Chinese mainland, the value-added in the Mainland is often less than that of re-exporting the output in Hong Kong. Since 2004, China has amended its treatment of foreign investments to attract higher-quality foreign investment and upgrade processing exports in order to transform itself from a world sweatshop to a global manufacturing center. The policies appear to have the intended effects.
Modeling and Improving Emergency Department Systems using Discrete Event Simulation
Authors: Duguay Christine , Chetouane Fatah
Published: October 2007

This paper describes a discrete event simulation study of an emergency department at Dr. Georges-L. Dumont Hospital in Moncton (Canada). The objective of the study was to reduce patient waiting times and to improve overall service delivery and system throughput. As patient waiting times are linked to resource availability, a number of alternatives were designed based on adding resource scenarios. Model development was made using Arena software.
Three-dimensional Models for Cardiac Bioelectricity Simulation: Cell to Organ
Authors: Huang Heng , Shen Li , Nguyen Nha
Published: October 2007

Computer models of the heart have become useful tools in improving understanding of cardiac electrical activation at the cellular level, and in analyzing mechanisms of arrhythmias and antiarrhythmic therapies. In this paper, we propose to use spherical harmonic (SPHARM) surface reconstruction and alignment methods to generate curvilinear meshes for finite element models of ventricular anatomy which incorporate detailed structural information. The endocardial and epicardial surfaces are defined by SPHARM, and the volume between these surfaces is divided into nested shells. Consequently, the resulting mesh comprises hexahedral elements. Using this novel SPHARM-based meshing method, the transmembrane potential propagation is simulated, based on FitzHugh—Nagumo reaction—diffusion equations. The dynamic electrical activation propagations are simulated on realistic cardiac data during a heart cycle. The obtained results clearly demonstrate an accurate resolution of the cardiac potential during the excitation. Our novel curvilinear mesh models have a great potential to be used in an improved simulation of cardiovascular pathologies for testing therapy strategies and planning interventions.
Predicting the Influence of Social Resources on African American Wife and Daughter Caregivers' Depressive Symptoms
Authors: Rozario Philip A. , Chadiha Letha A. , Proctor Enola K. , Morrow-Howell Nancy
Published: October 2007

This study—on 100 African American wife and 258 daughter primary caregivers — uses a contextual approach in its examination of the relationship between social resources and caregiver depressive symptoms. At the bivariate level, significant differences in certain key characteristics of primary caregivers and care receivers underscore the generational differences between the caregiver samples. Using separate ordinary least squares regression models, the authors found that satisfaction with family functioning was a significant predictor for lower depressive symptoms for both wives' and daughters' depressive symptoms. However, social participation and availability of secondary help were negatively associated with depressive symptoms for daughters. Receipt of instrumental support was predictive of higher levels of depressive symptoms among daughters. The findings indicate the importance of accounting for the contextual differences in our understanding of depressive symptoms, specifically the differences in the relationship between social resources and depressive symptoms for wives and daughters. Practice and theoretical implications are also discussed.
Transgendering care: Practices of care within transgender communities
Authors: Hines Sally
Published: October 2007

This paper examines practices of care within transgender support and self-help groups. Its aim is to widen the focus of work into practices and meanings of care by bringing an under-researched social group to the analysis of caring practices. The paper draws on qualitative research data to substantively explore transgender practices of care in relation to support groups and self-help organizations. Findings indicate that care is identified as a key value within transgender movements and education is articulated as an `ethic of care'. Critiques are brought to bear on medical understandings and systems of care, and transgender communities develop distinct practices of care based on notions of `shared understanding' and `giving back' to communities, which fill the gaps left by professional care services. Yet involvement in transgender communities is divergently situated in relation to politics of transgender identity and visibility. In conclusion I suggest that an analysis of transgender practices of care is not only important in relation to issues of social inclusion, citizenship and welfare provision, but is key to sociological understandings of the diversity of shifting practices of identity, intimacy and care in contemporary society.
“Tomorrow Never Knows”: the end of cataloguing?
Authors: Danskin Alan
Published: October 2007

This paper reviews the perceived threats to the future of cataloguing posed by the increasing volume of publications in all media, coupled with a resource base which is declining in real terms. It argues that cataloguing is more rather than less important in such an environment and considers some of the ways in which cataloguing will have to change in order to survive.
Weapons Used by Juveniles and Adult Offenders in U.S. Parricide Cases
Authors: Heide Kathleen M. , Petee Thomas A.
Published: October 2007

In recent decades, attention has focused on juveniles who kill their parents. Research has indicated that increases in juvenile homicide have been associated with the availability of firearms, but little is known about the weapons juveniles use to kill their parents and whether their weapon usage is different from that of adult children who kill their parents. This article uses Supplementary Homicide Report data for the 24-year period 1976 to 1999 to investigate weapons selected by parricide offenders to kill biological mothers and fathers. Significant differences were found in the weapons used in matricide and patricide incidents and in the weapons selected by juvenile and adult offenders. A comparison with an earlier study by Heide revealed that weapon usage in parricide events is stable. Differences found in both studies between weapons used to kill parents and offender age are consistent with a physical strength hypothesis proposed by Heide in 1993.
Clinical Epidemiology of Urban Violence
Authors: Harpaz-Rotem Ilan , Murphy Robert A. , Berkowitz Steven , Marans Steven , Rosenheck Robert A.
Published: October 2007

This study explores the clinical epidemiology of children's exposure to violence as addressed by a program in which mental health clinicians work with law-enforcement agents in 10 U.S. cities. Data were collected on all participants contacted by the Child Development Community Policing Program ( N = 7,313 individuals involved in 2,466 community incidents). Multivariate regression was used to examine sociodemographic and clinical correlates of the role of participants (victim, offender, or witness), location, and type of incident. The majority of incidents occurred in participants' homes. Adolescents were at a higher risk than children of being: (a) victimized, (b) involved in incidents outside their home, (c) experiencing a threat to their lives, and (d) suffering physical injuries. Males were more likely to be offenders than females, and to be subjected to physical injuries or involved in incidents that imposed a threat to their life. Females were significantly more likely to be victimized.
The Truth Behind Practices: Wittgenstein, Robinson Crusoe and Ecclesiology
Authors: Insole Christopher J.
Published: October 2007

The Wittgensteinian claim that meaning is immanent to 'practices', influential in contemporary theology, is capable of two readings: the first takes `practice' to refer to the social activities of actual communities; the second implies no more than a way of going on that is in principle communicable. The first reading is palpably unattractive, both philosophically and exegetically; the second reading is much less ambitious, providing a plausible critique of empiricist theories of meaning. I suggest that it is the first implausible reading that is often at work in theological appropriations of Wittgenstein, such as we find in Stanley Hauerwas. I fill-out this claim by exploring — with an ear to Scripture — the implications for ecclesiology of adopting either of the two readings. I conclude by raising the alarm about two dangers: of being too Wittgensteinian in some respects, and not Wittgensteinian enough in others.
Genetic Manipulation and the Body of Christ
Authors: Song Robert
Published: October 2007

Efforts to distinguish therapeutic from non-therapeutic genetic interventions in the human body have floundered on the assumption that the body should be understood as a psycho-physical corpus. This article argues by contrast that the body of Christ, that is the church, should be seen as the hermeneutical key to interpreting the body, and therefore that features of the corporate life of the church can provide criteria for distinguishing acceptable from unacceptable forms of genetic intervention. Formation of the bodies of Christians in the church is contrasted with the formation of the body by the reflexive project of modern self-identity.
Transposition of EU social policy in the new member states
Authors: Toshkov Dimiter
Published: October 2007

This article analyses transposition of European Union (EU) social policy legislation in the new member states (NMS) from Central and Eastern Europe (CEE). In order to account for the varying rate of adoption of EU law at the national level the article develops several hypotheses about the impact of government preferences and administrative capacity on the pace of transposition in the social policy field. The hypotheses are tested on a new dataset comprising data on the transposition of EU social policy directives in the new member states. The results of the quantitative empirical analysis show that government support for European integration and administrative effectiveness has positive and substantial effects on the number of directives transposed in a given period of time. However, government positions on the Left—Right and libertarianism—traditionalism dimensions do not affect the adoption of EU social policy legislation in CEE.
Learning The Art of Networking: A Critical Skill for Enhancing Social Capital and Career Success
Authors: de Janasz Suzanne C. , Forret Monica L.
Published: October 2007

In this era of boundaryless careers, with individuals making frequent career moves and needing to get up-to-speed quickly, networking is seen as a critical competency. Developing and maintaining relationships with others for the purpose of mutual benefit can help individuals search for and secure employment opportunities, gain access to needed information or resources— especially on short notice—and obtain guidance, sponsorship, and social support. Such networking skills are crucial for enhancing social capital and career success; however, many individuals feel uncomfortable with, or unskilled in, networking. Given the importance of networking for business students, we discuss the benefits and challenges of networking and then share a set of exercises and experiences that have been effective in increasing students' networking abilities.
Sixteen Million Neighbors
Authors: Völker Beate , Flap Henk
Published: October 2007

This article discusses the role of neighbors in the personal networks of people living in the Netherlands. It aims to establish the conditions for the inclusion of neighbors in such a network. Three complementary theoretical perspectives for developing hypotheses are employed: meeting opportunities, sharing groups, and social capital. Arguments are tested using nationally representative data ( N = 902) and multilevel regression models. The results show that all three perspectives contribute to explain the number of neighbor relations in personal networks, although none of the theoretical perspectives is fully confirmed. Interestingly, local facilities such as primary schools and day care facilities, which draw their members not only from the neighborhood but also from a larger local area, influence the likelihood of including neighbors in personal networks: primary schools encourage these relations, while the existence of day care facilities discourages neighboring.
James the Just in History and Tradition: Perspectives of Past and Present Scholarship (Part II)
Authors: Myllykoski Matti
Published: October 2007

Part I of this article, published in CBR 5.1 (pp. 73-122), includes a general introduction to the scholarship on James the Just, discussion on James and the family of Jesus in the Gospels, Jesus' resurrection and the leadership of James, and a detailed survey on scholarly opinions concerning the so-called apostolic council and the conflict at Antioch (Acts 15 and Gal. 2). Part II of the article focuses on the study of traditions concerning James's ritual purity, his martyrdom, and succession, as well as his role in the Gnostic writings and later Christian evidence. The article concludes with reflections on the role of James the Just in present scholarship.
Cultural Consensus Theory: Applications and Frequently Asked Questions
Authors: Weller Susan C.
Published: October 2007

In the ethnographic context, where answers to questions are unknown, consensus theory estimates the culturally appropriate or correct answers to the questions and individual differences in cultural knowledge. The cultural consensus model is a formal model of the process for asking and answering questions and is limited to categorical response data. An informal version of the model is available as a set of analytic procedures and obtains similar information with fewer assumptions. This article describes the assumptions, appropriate interview materials, and analytic procedures for carrying out a consensus analysis. Finally, issues that sometimes arise during the application of a consensus analysis are discussed.
Toxicogenomic analysis incorporating operon-transcriptional coupling and toxicant concentration-expression response: analysis of MX-treated Salmonella
Authors: Ward William O , Swartz Carol D , Porwollik Steffen , Warren Sarah H , Hanley Nancy M , Knapp Geremy W , McClelland Michael , DeMarini David M
Published: October 2007

Background

Deficiencies in microarray technology cause unwanted variation in the hybridization signal, obscuring the true measurements of intracellular transcript levels. Here we describe a general method that can improve microarray analysis of toxicant-exposed cells that uses the intrinsic power of transcriptional coupling and toxicant concentration-expression response data. To illustrate this approach, we characterized changes in global gene expression induced in Salmonella typhimurium TA100 by 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), the primary mutagen in chlorinated drinking water. We used the co-expression of genes within an operon and the monotonic increases or decreases in gene expression relative to increasing toxicant concentration to augment our identification of differentially expressed genes beyond Bayesian-t analysis.

Results

Operon analysis increased the number of altered genes by 95% from the list identified by a Bayesian t-test of control to the highest concentration of MX. Monotonic analysis added 46% more genes. A functional analysis of the resulting 448 differentially expressed genes yielded functional changes beyond what would be expected from only the mutagenic properties of MX. In addition to gene-expression changes in DNA-damage response, MX induced changes in expression of genes involved in membrane transport and porphyrin metabolism, among other biological processes. The disruption of porphyrin metabolism might be attributable to the structural similarity of MX, which is a chlorinated furanone, to ligands indigenous to the porphyrin metabolism pathway. Interestingly, our results indicate that the lexA regulon in Salmonella, which partially mediates the response to DNA damage, may contain only 60% of the genes present in this regulon in E. coli. In addition, nanH was found to be highly induced by MX and contains a putative lexA regulatory motif in its regulatory region, suggesting that it may be regulated by lexA.

Conclusion

Operon and monotonic analyses improved the determination of differentially expressed genes beyond that of Bayesian-t analysis, showing that MX alters cellular metabolism involving pathways other than DNA damage. Because co-expression of similarly functioning genes also occurs in eukaryotes, this method has general applicability for improving analysis of toxicogenomic data.
Developmental expression and differentiation-related neuron-specific splicing of metastasis suppressor 1(Mtss1) in normal and transformed cerebellar cells
Authors: Glassmann Alexander , Molly Sabine , Surchev Lachezar , Nazwar Tommy A , Holst Martin , Hartmann Wolfgang , Baader Stephan L , Oberdick John , Pietsch Torsten , Schilling Karl
Published: October 2007

Background

Mtss1 encodes an actin-binding protein, dysregulated in a variety of tumors, that interacts with sonic hedgehog/Gli signaling in epidermal cells. Given the prime importance of this pathway for cerebellar development and tumorigenesis, we assessed expression of Mtss1 in the developing murine cerebellum and human medulloblastoma specimens.

Results

During development, Mtss1 is transiently expressed in granule cells, from the time point they cease to proliferate to their synaptic integration. It is also expressed by granule cell precursor-derived medulloblastomas. In the adult CNS, Mtss1 is found exclusively in cerebellar Purkinje cells. Neuronal differentiation is accompanied by a switch in Mtss1 splicing. Whereas immature granule cells express a Mtss1 variant observed also in peripheral tissues and comprising exon 12, this exon is replaced by a CNS-specific exon, 12a, in more mature granule cells and in adult Purkinje cells. Bioinformatic analysis of Mtss1 suggests that differential exon usage may affect interaction with Fyn and Src, two tyrosine kinases previously recognized as critical for cerebellar cell migration and histogenesis. Further, this approach led to the identification of two evolutionary conserved nuclear localization sequences. These overlap with the actin filament binding site of Mtss1, and one also harbors a potential PKA and PKC phosphorylation site.

Conclusion

Both the pattern of expression and splicing of Mtss1 is developmentally regulated in the murine cerebellum. These findings are discussed with a view on the potential role of Mtss1 for cytoskeletal dynamics in developing and mature cerebellar neurons.
Tripartite chimeric pseudogene from the genome of rice blast fungus Magnaporthe grisea suggests double template jumps during long interspersed nuclear element (LINE) reverse transcription
Authors: Gogvadze Elena , Barbisan Crystel , Lebrun Marc-Henri , Buzdin Anton
Published: October 2007

Background

A systematic survey of loci carrying retrotransposons in the genome of the rice blast fungus Magnaporthe grisea allowed the identification of novel non-canonical retropseudogenes. These elements are chimeric retrogenes composed of DNA copies from different cellular transcripts directly fused to each other. Their components are copies of a non protein-coding highly expressed RNA of unknown function termed WEIRD and of two fungal retrotransposons: MGL and Mg-SINE. Many of these chimeras are transcribed in various M. grisea tissues and during plant infection. Chimeric retroelements with a similar structure were recently found in three mammalian genomes. All these chimeras are likely formed by RNA template switches during the reverse transcription of diverse LINE elements.

Results

We have shown that in M. grisea template switching occurs at specific sites within the initial template RNA which contains a characteristic consensus sequence. We also provide evidence that both single and double template switches may occur during LINE retrotransposition, resulting in the fusion of three different transcript copies. In addition to the 33 bipartite elements, one tripartite chimera corresponding to the fusion of three retrotranscripts (WEIRD, Mg-SINE, MGL-LINE) was identified in the M. grisea genome. Unlike the previously reported two human tripartite elements, this fungal retroelement is flanked by identical 14 bp-long direct repeats. The presence of these short terminal direct repeats demonstrates that the LINE enzymatic machinery was involved in the formation of this chimera and its integration in the M. grisea genome.

Conclusion

A survey of mammalian genomic databases also revealed two novel tripartite chimeric retroelements, suggesting that double template switches occur during reverse transcription of LINE retrotransposons in different eukaryotic organisms.
Gene profile analysis of osteoblast genes differentially regulated by histone deacetylase inhibitors
Authors: Schroeder Tania M , Nair Aswathy K , Staggs Rodney , Lamblin Anne-Francoise , Westendorf Jennifer J
Published: October 2007

Background

Osteoblast differentiation requires the coordinated stepwise expression of multiple genes. Histone deacetylase inhibitors (HDIs) accelerate the osteoblast differentiation process by blocking the activity of histone deacetylases (HDACs), which alter gene expression by modifying chromatin structure. We previously demonstrated that HDIs and HDAC3 shRNAs accelerate matrix mineralization and the expression of osteoblast maturation genes (e.g. alkaline phosphatase, osteocalcin). Identifying other genes that are differentially regulated by HDIs might identify new pathways that contribute to osteoblast differentiation.

Results

To identify other osteoblast genes that are altered early by HDIs, we incubated MC3T3-E1 preosteoblasts with HDIs (trichostatin A, MS-275, or valproic acid) for 18 hours in osteogenic conditions. The promotion of osteoblast differentiation by HDIs in this experiment was confirmed by osteogenic assays. Gene expression profiles relative to vehicle-treated cells were assessed by microarray analysis with Affymetrix GeneChip 430 2.0 arrays. The regulation of several genes by HDIs in MC3T3-E1 cells and primary osteoblasts was verified by quantitative real-time PCR. Nine genes were differentially regulated by at least two-fold after exposure to each of the three HDIs and six were verified by PCR in osteoblasts. Four of the verified genes (solute carrier family 9 isoform 3 regulator 1 (Slc9a3r1), sorbitol dehydrogenase 1, a kinase anchor protein, and glutathione S-transferase alpha 4) were induced. Two genes (proteasome subunit, beta type 10 and adaptor-related protein complex AP-4 sigma 1) were suppressed. We also identified eight growth factors and growth factor receptor genes that are significantly altered by each of the HDIs, including Frizzled related proteins 1 and 4, which modulate the Wnt signaling pathway.

Conclusion

This study identifies osteoblast genes that are regulated early by HDIs and indicates pathways that might promote osteoblast maturation following HDI exposure. One gene whose upregulation following HDI treatment is consistent with this notion is Slc9a3r1. Also known as NHERF1, Slc9a3r1 is required for optimal bone density. Similarly, the regulation of Wnt receptor genes indicates that this crucial pathway in osteoblast development is also affected by HDIs. These data support the hypothesis that HDIs regulate the expression of genes that promote osteoblast differentiation and maturation.
Identification of genes that regulate multiple cellular processes/responses in the context of lipotoxicity to hepatoma cells
Authors: Srivastava Shireesh , Li Zheng , Yang Xuerui , Yedwabnick Matthew , Shaw Stephen , Chan Christina
Published: October 2007

Background

In order to devise efficient treatments for complex, multi-factorial diseases, it is important to identify the genes which regulate multiple cellular processes. Exposure to elevated levels of free fatty acids (FFAs) and tumor necrosis factor alpha (TNF-α) alters multiple cellular processes, causing lipotoxicity. Intracellular lipid accumulation has been shown to reduce the lipotoxicity of saturated FFA. We hypothesized that the genes which simultaneously regulate lipid accumulation as well as cytotoxicity may provide better targets to counter lipotoxicity of saturated FFA.

Results

As a model system to test this hypothesis, human hepatoblastoma cells (HepG2) were exposed to elevated physiological levels of FFAs and TNF-α. Triglyceride (TG) accumulation, toxicity and the genomic responses to the treatments were measured. Here, we present a framework to identify such genes in the context of lipotoxicity. The aim of the current study is to identify the genes that could be altered to treat or ameliorate the cellular responses affected by a complex disease rather than to identify the causal genes. Genes that regulate the TG accumulation, cytotoxicity or both were identified by a modified genetic algorithm partial least squares (GA/PLS) analysis. The analyses identified NADH dehydrogenase and mitogen activated protein kinases (MAPKs) as important regulators of both cytotoxicity and lipid accumulation in response to FFA and TNF-α exposure. In agreement with the predictions, inhibiting NADH dehydrogenase and c-Jun N-terminal kinase (JNK) reduced cytotoxicity significantly and increased intracellular TG accumulation. Inhibiting another MAPK pathway, the extracellular signal regulated kinase (ERK), on the other hand, improved the cytotoxicity without changing TG accumulation. Much greater reduction in the toxicity was observed upon inhibiting the NADH dehydrogenase and MAPK (which were identified by the dual-response analysis), than for the stearoyl-CoA desaturase (SCD) activation (which was identified for the TG-alone analysis).

Conclusion

These results demonstrate the applicability of GA/PLS in identifying the genes that regulate multiple cellular responses of interest and that genes regulating multiple cellular responses may be better candidates for countering complex diseases.
Mitochondrial respiratory chain is involved in insulin-stimulated hydrogen peroxide production and plays an integral role in insulin receptor autophosphorylation in neurons
Authors: Storozhevykh Tatiana P , Senilova Yana E , Persiyantseva Nadezhda A , Pinelis Vsevolod G , Pomytkin Igor A
Published: October 2007

Background

Accumulated evidence suggests that hydrogen peroxide (H2O2) generated in cells during insulin stimulation plays an integral role in insulin receptor signal transduction. The role of insulin-induced H2O2in neuronal insulin receptor activation and the origin of insulin-induced H2O2in neurons remain unclear. The aim of the present study is to test the following hypotheses (1) whether insulin-induced H2O2is required for insulin receptor autophosphorylation in neurons, and (2) whether mitochondrial respiratory chain is involved in insulin-stimulated H2O2production, thus playing an integral role in insulin receptor autophosphorylation in neurons.

Results

Insulin stimulation elicited rapid insulin receptor autophosphorylation accompanied by an increase in H2O2release from cultured cerebellar granule neurons (CGN). N-acetylcysteine (NAC), a H2O2scavenger, inhibited both insulin-stimulated H2O2release and insulin-stimulated autophosphorylation of insulin receptor. Inhibitors of respiratory chain-mediated H2O2production, malonate and carbonyl cyanide-4-(trifluoromethoxy)-phenylhydrazone (FCCP), inhibited both insulin-stimulated H2O2release from neurons and insulin-stimulated autophosphorylation of insulin receptor. Dicholine salt of succinic acid, a respiratory substrate, significantly enhanced the effect of suboptimal insulin concentration on the insulin receptor autophosphorylation in CGN.

Conclusion

Results of the present study suggest that insulin-induced H2O2is required for the enhancement of insulin receptor autophosphorylation in neurons. The mitochondrial respiratory chain is involved in insulin-stimulated H2O2production, thus playing an integral role in the insulin receptor autophosphorylation in neurons.
An EST database from saffron stigmas
Authors: D'Agostino Nunzio , Pizzichini Daniele , Chiusano Maria Luisa , Giuliano Giovanni
Published: October 2007

Background

Saffron (Crocus sativus L., Iridaceae) flowers have been used as a spice and medicinal plant ever since the Greek-Minoan civilization. The edible part – the stigmas – are commonly considered the most expensive spice in the world and are the site of a peculiar secondary metabolism, responsible for the characteristic color and flavor of saffron.

Results

We produced 6,603 high quality Expressed Sequence Tags (ESTs) from a saffron stigma cDNA library. This collection is accessible and searchable through the Saffron Genes database http://www.saffrongenes.org. The ESTs have been grouped into 1,893 Clusters, each corresponding to a different expressed gene, and annotated. The complete set of raw EST sequences, as well as of their electopherograms, are maintained in the database, allowing users to investigate sequence qualities and EST structural features (vector contamination, repeat regions). The saffron stigma transcriptome contains a series of interesting sequences (putative sex determination genes, lipid and carotenoid metabolism enzymes, transcription factors).

Conclusion

The Saffron Genes database represents the first reference collection for the genomics of Iridaceae, for the molecular biology of stigma biogenesis, as well as for the metabolic pathways underlying saffron secondary metabolism.
Structural disorder promotes assembly of protein complexes
Authors: Hegyi Hedi , Schad Eva , Tompa Peter
Published: October 2007

Background

The idea that the assembly of protein complexes is linked with protein disorder has been inferred from a few large complexes, such as the viral capsid or bacterial flagellar system, only. The relationship, which suggests that larger complexes have more disorder, has never been systematically tested. The recent high-throughput analyses of protein-protein interactions and protein complexes in the cell generated data that enable to address this issue by bioinformatic means.

Results

In this work we predicted structural disorder for both E. coli and S. cerevisiae, and correlated it with the size of complexes. Using IUPred to predict the disorder for each complex, we found a statistically significant correlation between disorder and the number of proteins assembled into complexes. The distribution of disorder has a median value of 10% in yeast for complexes of 2–4 components (6% in E. coli), but 18% for complexes in the size range of 11–100 proteins (12% in E. coli). The level of disorder as assessed for regions longer than 30 consecutive disordered residues shows an even stronger division between small and large complexes (median values about 4% for complexes of 2–4 components, but 12% for complexes of 11–100 components in yeast). The predicted correlation is also supported by experimental evidence, by observing the structural disorder in protein components of complexes that can be found in the Protein Data Bank (median values 1. 5% for complexes of 2–4 components, and 9.6% for complexes of 11–100 components in yeast). Further analysis shows that this correlation is not directly linked with the increased disorder in hub proteins, but reflects a genuine systemic property of the proteins that make up the complexes.

Conclusion

Overall, it is suggested and discussed that the assembly of protein-protein complexes is enabled and probably promoted by protein disorder.
Pharmacokinetics of recombinant human growth hormone administered by cool.click™ 2, a new needle-free device, compared with subcutaneous administration using a conventional syringe and needle
Authors: Brearley Chris , Priestley Anthony , Leighton-Scott James , Christen Michel
Published: October 2007

Background

Growth hormone (GH) is used to treat growth hormone deficiency (GHD, adult and paediatric), short bowel syndrome in patients on a specialized diet, HIV-associated wasting and, in children, growth failure due to a number of disorders including Turner's syndrome and chronic renal failure, and in children born small for gestational age. Different brands and generic forms of recombinant human growth hormone (r-hGH) are approved for varying indications in different countries. New ways of administering GH are required because the use of a needle and syringe or a device where a patient still has to insert the needle manually into the skin on a daily basis can lead to low adherence and sub-optimal treatment outcomes. The objective of this study was to assess the relative bioavailability of r-hGH (Saizen®, Merck Serono) administered by a new needle-free device, cool.click™ 2, and a standard needle and syringe.

Methods

The study was performed with 38 healthy volunteers who underwent pituitary somatotrope cell down-regulation using somatostatin, according to a randomized, two-period, two-sequence crossover design. Following subcutaneous administration of r-hGH using cool.click™ 2 or needle and syringe, pharmacokinetic parameters were analysed by non-compartmental methods. Bioequivalence was assessed based on log-transformed AUC and Cmax values.

Results

The 90% confidence intervals for test/reference mean ratio of the plasma pharmacokinetic variables Cmax and AUC0-inf were 103.7–118.3 and 97.1–110.0, respectively, which is within the accepted bioequivalence range of 80–125%. r-hGH administered by cool.click™ 2 is, therefore, bioequivalent to administration by needle and syringe with respect to the rate and extent of GH exposure. Treatment using cool.click™ 2 was found to be well tolerated. With cool.click™ 2 the tmax was less (3.0 hours) than for needle and syringe delivery (4.5 hours), p = 0.002 (Friedman test), although this is unlikely to have any clinical implications.

Conclusion

These results demonstrate that cool.click™ 2 delivers subcutaneous r-hGH exposure that is bioequivalent to the conventional mode of injection. The new device has the additional advantage of being needle-free, and should help to increase patient adherence and achieve good therapeutic outcomes from r-hGH treatment.
Patient-provider interaction from the perspectives of type 2 diabetes patients in Muscat, Oman: a qualitative study
Authors: Abdulhadi Nadia , Al Shafaee Mohammed , Freudenthal Solveig , Östenson Claes-Göran , Wahlström Rolf
Published: October 2007

Background

Patients' expectations and perceptions of the medical encounter and interactions are important tools in diabetes management. Some problems regarding the interaction during encounters may be related to a lack of communication skills on the part of either the physician or the patient.

This study aimed at exploring the perceptions of type 2 diabetes patients regarding the medical encounters and quality of interactions with their primary health-care providers.

Methods

Four focus group discussions (two women and two men groups) were conducted among 27 purposively selected patients (13 men and 14 women) from six primary health-care centres in Muscat, Oman. Qualitative content analysis was applied.

Results

The patients identified some weaknesses regarding the patient-provider communication like: unfriendly welcoming; interrupted consultation privacy; poor attention and eye contact; lack of encouraging the patients to ask questions on the providers' side; and inability to participate in medical dialogue or express concerns on the patients' side. Other barriers and difficulties related to issues of patient-centeredness, organization of diabetes clinics, health education and professional competency regarding diabetes care were also identified.

Conclusion

The diabetes patients' experiences with the primary health-care providers showed dissatisfaction with the services. We suggest appropriate training for health-care providers with regard to diabetes care and developing of communication skills with emphasis on a patient-centred approach. An efficient use of available resources in diabetes clinics and distributing responsibilities between team members in close collaboration with patients and their families seems necessary. Further exploration of the providers' work situation and barriers to good interaction is needed. Our findings can help the policy makers in Oman, and countries with similar health systems, to improve the quality and organizational efficiency of diabetes care services.
Sleep in Kcna2 knockout mice
Authors: Douglas Christopher L , Vyazovskiy Vladyslav , Southard Teresa , Chiu Shing-Yan , Messing Albee , Tononi Giulio , Cirelli Chiara
Published: October 2007

Background

Shaker codes for a Drosophila voltage-dependent potassium channel. Flies carrying Shaker null or hypomorphic mutations sleep 3–4 h/day instead of 8–14 h/day as their wild-type siblings do. Shaker-like channels are conserved across species but it is unknown whether they affect sleep in mammals. To address this issue, we studied sleep in Kcna2 knockout (KO) mice. Kcna2 codes for Kv1.2, the alpha subunit of a Shaker-like voltage-dependent potassium channel with high expression in the mammalian thalamocortical system.

Results

Continuous (24 h) electroencephalograph (EEG), electromyogram (EMG), and video recordings were used to measure sleep and waking in Kcna2 KO, heterozygous (HZ) and wild-type (WT) pups (P17) and HZ and WT adult mice (P67). Sleep stages were scored visually based on 4-s epochs. EEG power spectra (0–20 Hz) were calculated on consecutive 4-s epochs. KO pups die by P28 due to generalized seizures. At P17 seizures are either absent or very rare in KO pups (< 1% of the 24-h recording time), and abnormal EEG activity is only present during the seizure. KO pups have significantly less non-rapid eye movement (NREM) sleep (-23%) and significantly more waking (+21%) than HZ and WT siblings with no change in rapid eye movement (REM) sleep time. The decrease in NREM sleep is due to an increase in the number of waking episodes, with no change in number or duration of sleep episodes. Sleep patterns, daily amounts of sleep and waking, and the response to 6 h sleep deprivation are similar in HZ and WT adult mice.

Conclusion

Kv1.2, a mammalian homologue of Shaker, regulates neuronal excitability and affects NREM sleep.
Immune Restoration Syndrome with disseminated Penicillium marneffei and Cytomegalovirus co-infections in an AIDS patient
Authors: Gupta Swati , Mathur Purva , Maskey Dipesh , Wig Naveet , Singh Sarman
Published: October 2007

Background

Penicillium marneffei is a dimorphic fungus, endemic in South-east Asia. The fungus causes severe disease in immunocompromised patients such as AIDS. However, no case of immune restoration disease of Penicillium marneffei is reported in literature from a non-endemic area.

Case Presentation

We report the first case of Penicillium marneffei and Cytomegalovirus infection manifesting as a result of immune restoration one month after initiating HAART. This severely immunocompromised patient had presented with multiple lymphadenopathy, massive hepatosplenomegaly, visual impairment and mild icterus, but no skin lesions. Penicillium marneffei was isolated from lymph node fine-needle aspirates and blood cultures.

Conclusion

In order to diagnose such rare cases, the clinicians, histopathologists and microbiologists alike need to maintain a strong index of suspicion for making initial diagnosis as well as for suspecting immune reconstitution syndrome (IRS) with Penicillium marneffei.
Cloning of full genome sequence of hepatitis E virus of Shanghai swine isolate using RACE method
Authors: Shen Quan , Zhang Wen , Cao Xiangrong , Mou Jing , Cui Li , Hua Xiuguo
Published: October 2007

Genotype 4 hepatitis E virus (HEV) was reportedly transmitted freely between humans and swine in eastern China. The full-length genomic sequence of Shanghai swine isolate (SH-SW-zs1) recovered from feces sample of a pig which was infected with HEV RNA positive swine serum was determined using RT-PCR and RACE (Rapid Amplification of cDNA Ends) methods. The full genome of the SH-SW-zs1 isolate was 7265 nucleotides in length and phylogenetic analysis indicated that this isolate belonged to genotype 4. Comparison of the 3' UTR sequence with the corresponding regions of other 38 HEV strains from different region revealed that the Shanghai swine isolate is 21–49 bp longer than the other stains.
Postprandial ghrelin suppression is exaggerated following major surgery; implications for nutritional recovery
Authors: Nematy Mohsen , Brynes Audrey E , Hornick Philip I , Patterson Michael , Ghatei Mohammad A , Bloom Stephen R , Brett Stephen J , Frost Gary S
Published: October 2007

Meeting patients' nutritional requirements and preventing malnutrition is a challenge following major surgical procedures. The role of ghrelin in nutritional recovery after non-gastrointestinal major surgery is unknown. We used coronary artery bypass grafting (CABG) as an example of anticipated good recovery post major surgery.

Seventeen patients undergoing CABG (mean ± SEM: 70.1 ± 2.2 yrs, BMI 29.1 ± 1.4 kg/m2, 15 male) underwent fasting and postprandial (45 mins after standard test breakfast) blood sampling pre-operatively (day 0), post-operatively (day 6) and at follow-up (day 40). Changes in food intake, biochemical and anthropometric markers of nutritional status were recorded. A comparison was made to 17 matched healthy controls (70.6 ± 2.3 yrs, BMI 28.4 ± 1.3 kg/m2).

We observed significantly increased post-operative and follow-up fasting ghrelin concentrations compared with pre-operatively (pre-op. 402 ± 42 pmol/L vs post-op. 642 ± 97 pmol/L vs follow-up 603 ± 94 pmol/L) (ANOVA p < 0.05). Significantly exaggerated postprandial suppression of ghrelin was seen postoperatively and continued until follow-up (Δ pre-op. 10 ± 51 pmol/L vs Δ post-op. -152 ± 43 pmol/L vs Δ follow-up -159 ± 65 pmol/L, p < 0.05). This was associated with a 50% reduction in food intake {post-op. 4.5 ± 0.5 MJ/D (1076 ± 120 kcal/D) compared with estimated requirements 9.9 ± 0.5 MJ/D (2366 ± 120 kcal/D)}, leading to a 4% weight loss and a 5% reduction in muscle arm circumference loss over length of follow up.

Our data support the hypothesis that prolonged changes in fasting and postprandial plasma ghrelin concentrations are associated with impaired nutritional recovery after CABG. These findings reinforce the need to investigate ghrelin in other patients groups undergoing major surgery.
Respiratory function and bronchial responsiveness among industrial workers exposed to different classes of occupational agents: a study from Algeria
Authors: Ould-Kadi Farid , Nawrot Tim S , Hoet Peter H , Nemery Benoit
Published: October 2007

Occupational exposures play a role in the onset of several chronic airway diseases. We investigated, in a cross-sectional study, lung function parameters and bronchial hyper-responsiveness to histamine in workers exposed to different airborne compounds.

The study group totalled 546 male subjects of whom 114 were exposed to welding fumes, 106 to solvents, 107 to mineral dust, 97 to organic dust and 123 without known exposure to airway irritants. A questionnaire was administered and spirometry and bronchial responsiveness to histamine were assessed by one observer, in the morning before work to prevent effects of acute exposure.

The mean (SD) age of the participants was 39.3 (7.8) years, with a mean duration of employment of 13.8 (6.6) years. Both before and after adjustment for smoking status, forced expiratory volume in 1 second (FEV1, expressed as % predicted) was lower in welders -4.0% (95% confidence interval [CI], -6.3 to -1.8; p = 0.01) and workers exposed to solvents -5.6% (CI: -7.9 to -3.3; p = 0.0009) than in control subjects. Furthermore, solvent workers had an odds ratio of 3.43 (95% CI: 1.09–11.6; p = 0.037) for bronchial hyperresponsiveness compared with the reference group.

The higher prevalence of bronchial hyperresponsiveness in solvent workers adds to the growing body of evidence of adverse respiratory effects of occupational solvent exposure. These results point to the necessity of preventive measures in solvent workers to avoid these adverse respiratory effects.