bluuebunny/crossref_metadata_2025 huggingface dataset:
Does emotion predict the course of major depressive disorder? A review of prospective studies
Authors: Morris Bethany H. , Bylsma Lauren M. , Rottenberg Jonathan
Published: February 2009

Purpose.Emotional dysfunction is a hallmark of major depressive disorder (MDD). There has been wide interest in identifying the nature and significance of emotional deficits in MDD. Given the paramount goal of identifying etiological markers of MDD that can sharpen prevention and treatment efforts, researchers have pursued emotion as a functionally significant factor and predictor of clinical course in MDD. This review is the first to summarize the literature examining emotion as a predictor of the clinical course of MDD.

Method.We conducted a systematic review of all published studies reporting on the prospective relationship between positive and negative emotionality (PE and NE) – measured at the state or trait level – and the longitudinal course of MDD in diagnosed adults. Physiological, behavioural, and subjective indices of emotion were considered. The primary analyses encompassed 28 research reports that included data from 3,798 participants and tested a total of 60 hypotheses.

Results.Lower levels of PE predicted poorer MDD course with some consistency. Paradoxically, both lower levels of state NE and higher levels of trait NE predicted poorer MDD course. The relationships between emotionality and MDD course generally held even after initial depression symptom severity was taken into account.

Conclusion.Emotion shows promise as a predictor of MDD course. Implications of these data for current theories of emotion and MDD, the apparently divergent relation between state and trait NE and course, and future directions to further clarify the functional significance of emotion in the context of MDD are discussed.
The effects of subjective norms on behaviour in the theory of planned behaviour: A meta‐analysis
Authors: Manning Mark
Published: February 2009

A meta‐analysis investigated the effects of perceived injunctive (IN) and descriptive (DN) norms on behaviour (BEH) within the theory of planned behaviour (TPB) in a sample of 196 studies. Two related correlation matrices (pairwise and listwise) were synthesized from the data and used to model the TPB relations with path analyses. Convergent evidence indicated that the relation between DN and BEH was stronger than the relation between IN and BEH. Evidence also suggested a significant direct relation between DN and BEH in the context of TPB. A suppressor effect of IN on DN in its relation with BEH was also noted. Moderator analyses indicated that the DN–BEH relation was stronger when there was more time between measures of cognition and behaviour, when behaviours were not socially approved, more socially motive and more pleasant; results were mixed in the case of the IN–BEH relation. Results imply that IN and DN are conceptually different constructs.
Measuring the combined risk to young children's cognitive development: An alternative to cumulative indices
Authors: Hall James E. , Sammons Pam , Sylva Kathy , Melhuish Edward , Taggart Brenda , Siraj‐Blatchford Iram , Smees Rebecca
Published: February 2009

In studies of child development, the combined effect of multiple risks acting in unison has been represented in a variety of ways. This investigation builds upon this preceding work and presents a new procedure for capturing the combined effect of multiple risks. A representative sample of 2,899 British children had their cognitive development measured at 36 and 58 months of age along with 10 potential risks during this period of development. Comparing a cumulative index of these risks against the previously undocumented alternative of confirmatory factor analysis using formative measurement, this study found differences favouring the factor analysis. The factor analysis procedure demonstrated greater predictive power of children's cognitive development while it systematically tested two of the assumptions implicit in cumulative risk indices.
Assessing the impact of healthy work organization intervention
Authors: DeJoy David M. , Wilson Mark G. , Vandenberg Robert J. , McGrath‐Higgins Allison L. , Griffin‐Blake C. Shannon
Published: February 2009

This research evaluates a healthy work organization intervention implemented in a retail setting. Using a participatory process, employee teams in 11 intervention stores developed customized plans for improving work organization at their sites. Ten comparable stores served as controls. Employee surveys were administered prior to the intervention and twice again at 12‐month intervals. Business results were compiled monthly for each store. The baseline data were used by the teams to identify needs and establish action priorities for their stores. Most study outcomes declined across time for all stores, due primarily to internal corporate events and a generally adverse economic environment. However, the intervention process appeared to buffer some of these declines; intervention stores fared better in terms of selected aspects of organizational climate and psychological work adjustment. Intervention stores also performed better than controls on general indices of perceived health and safety and two of the four business outcomes: employee turnover and sales per labour hour. These results are discussed in terms of the challenges involved in evaluating organizational‐level interventions in work settings.
Weekly work engagement and performance: A study among starting teachers
Authors: Bakker Arnold B. , Bal Matthijs P.
Published: February 2009

This study among 54 Dutch teachers tested a model of weekly work engagement. On the basis of theories about the motivational potential of job resources, we predicted that teachers' weekly job resources are positively related to their week‐levels of work engagement, and that week‐level work engagement is predictive of week‐level performance. In addition, we hypothesized that momentary work engagement has a positive, lagged effect on next week's job resources. Teachers were asked to fill in a weekly questionnaire every Friday during 5 consecutive weeks. Results of multi‐level analyses largely confirmed our hypotheses, by showing that week‐levels of autonomy, exchange with the supervisor, and opportunities for development (but not social support) were positively related to weekly engagement, which, in turn, was positively related to weekly job performance. Moreover, momentary work engagement was positively related to job resources in the subsequent week. These findings show how intra‐individual variability in employees' experiences at work can explain weekly job performance.
An interpretative phenomenological analysis of living with chronic low back pain
Authors: Snelgrove Sherrill , Liossi Christina
Published: February 2009

Objectives A predominantly quantitative approach to the psychological study of chronic low back pain (CLBP) has shown that enduring negative emotional responses and passive coping strategies contribute towards disability. The main objective of this study was to extend existing knowledge by providing a detailed and contextualized understanding of the meaning of CLBP for participants with long‐standing experiences of chronic pain.

Design This is a qualitative, semi‐structured interview study. The data were analysed using interpretative phenomenological analysis (IPA). This is the first of three sets of individual interviews comprising a longitudinal study of the same participants over 3 years.

Methods Ten patients with CLBP were interviewed prior to their attendance at a medically staffed chronic pain clinic. The sample comprised seven females and three males. Ages ranged between 39 and 66 years. All had experienced CLBP for at least 4 years.

Conclusions The participants' experiences are represented by three main themes: ‘maintaining integrity’, ‘the crucial nature of the pain’ and ‘managing the pain’ that highlight participants' understanding of their pain within a biomedical framework. The findings are discussed with reference to the role of illness beliefs in the management of CLBP.
Nanocrystal assembly for bottom-up plasmonic materials and surface-enhanced Raman spectroscopy (SERS) sensing
Authors: Tao Andrea R.
Published: February 2009

Plasmonic materials are emerging as key platforms for applications that rely on the manipulation of light at small length scales. Sub-wavelength metallic features support surface plasmons that can induce huge local electromagnetic fields at the metal surface, facilitating a host of extraordinary optical phenomena. Ag nanocrystals (NCs) and nanowires (NWs) are ideal building blocks for the bottom-up fabrication of plasmonic materials for photonics, spectroscopy, and chemical sensing. Faceted Ag nanostructures are synthesized using a colloidal approach to regulate nucleation and crystallographic growth direction. Next, new methods of nanoscale organization using Langmuir-Blodgett (LB) compression are presented where one- and two-dimensional assemblies can be constructed with impressive alignment over large areas. Using this method, plasmon coupling between Ag nanostructures can be controlled by varying spacing and density, achieving for the first time a completely tunable plasmon response in the visible wavelengths. Lastly, these assemblies are demonstrated as exceptional substrates for surface-enhanced Raman spectroscopy (SERS) by achieving high chemical sensitivity and specificity, exhibiting their utility as portable field sensors, and integrating them into multiplexed "lab-on-a-chip" devices.
In Situ Zymography and Immunolabeling in Fixed and Decalcified Craniofacial Tissues
Authors: Porto Isabel M. , Rocha Lenaldo B. , Rossi Marcos A. , Gerlach Raquel F.
Published: February 2009

In situ zymography is a very important technique that shows the proteolytic activity in sections and allows researchers to observe the specific sites of proteolysis in tissues or cells. It is normally performed in non-fixed frozen sections and is not routinely performed in calcified tissues. In this study, we describe a technique that maintains proteolytic activity in fixed and decalcified sections obtained after routine paraffin sectioning in conventional microtome and cryostat sections. We used adult rat hemimandibles, which presented bone, enamel, and dentine matrices; the substrate used was dye-quenched-gelatin. Gelatinolytic activity was colocalized with MMP-2 using fluorescent antibodies. Specific proteolytic activity was observed in all sections, compatible with metalloproteinase activity, particularly in dentine and bone. Furthermore, matrix metalloproteinase-2 was colocalized to the sites of green fluorescence in dentine. In conclusion, the technique presented here will allow in situ zymography reactions in fixed, decalcified, and paraffin-embedded tissues, and we showed that paraformaldehyde-lysine-periodate–fixed cryostat sections are suitable for colocalization of gelatinolytic activity and protein labeling with antibodies. (J Histochem Cytochem 57:615–622, 2009)
Enzyme Activity and Immunohistochemical Localization of Dipeptidyl Peptidase 8 and 9 in Male Reproductive Tissues
Authors: Dubois Véronique , Ginneken Chris Van , Cock Hilde De , Lambeir Anne-Marie , Veken Pieter Van der , Augustyns Koen , Chen Xin , Scharpé Simon , Meester Ingrid De
Published: February 2009

The mRNA expression pattern of dipeptidyl peptidase (DPP) 8 and DPP9, two DPP4 homologs, was studied previously and showed a broad tissue distribution. In this study, protein expression and activity of DPP8 and DPP9 were investigated in male reproductive tissues of different mammals. Based on specific DPP activities and inhibition profiles, the proline-selective DPP activity in the bovine and rat testis could predominantly be attributed to DPP8/9 and not to DPP4. This is in contrast to the epididymis, where most of the activity was caused by DPP4. Bovine sperm preparations had very low or undetectable DPP8/9 activity. After characterization of polyclonal antibodies specific for DPP8 or DPP9, we could localize both enzymes in seminiferous tubules of the testis. A specific staining for DPP9 was found associated with spermatozoids embedded in the epithelium, just before their release into the lumen, and in spermatids. DPP8 was localized in spermatozoids in an earlier stage of maturation. These findings help to provide insight into the physiological role of DPP4-like enzymes in the male reproductive system. This manuscript contains online supplemental material at http://www.jhc.org . Please visit this article online to view these materials.
Measurement of the shear properties of clear wood by the Arcan test
Authors: Xavier José , Oliveira Marcelo , Morais José , Pinto Tiago
Published: February 2009

In this work, the identification of the shear properties of maritime pine (Pinus pinasterAit.) wood was investigated by applying the Arcan test method. For this purpose, an ad hoc Arcan fixture was designed for which clear wood samples could be tested along all the material planes of symmetry –LR,LTandRTplanes. For the accurate evaluation of the shear moduli, correction factors taking into account the non-uniformity of the shear stress and the shear strain distributions at the gauge section were determined with finite element analyses. Experimentally, two 0/90 rosettes were glued on both frontal and back surfaces of the specimens in order to take into account any through-to-thickness shear strain variation. It was found that the Arcan test is suitable for the identification of the shear moduli of wood in all its natural planes. The failure of the Arcan specimens systematically occurred under a concentrated stress state nearby the V-notches. Nevertheless, it was shown that an accurate estimation of the shear strengths of wood can be achieved by the Arcan test.
Editorial
Authors: Jeronimidis George
Published: February 2009

No abstract available
Fission Yeast Rgf2p Is a Rho1p Guanine Nucleotide Exchange Factor Required for Spore Wall Maturation and for the Maintenance of Cell Integrity in the Absence of Rgf1p
Authors: García Patricia , García Ignacio , Marcos Félix , de Garibay Gorka Ruiz , Sánchez Yolanda
Published: February 2009

Schizosaccharomyces pombe Rho1p is essential, directly activates β-1,3-glucan synthase, and participates in the regulation of morphogenesis. In S. pombe, Rho1p is activated by at least three guanine nucleotide exchange factors (GEFs): Rgf1p, Rgf2p, and Rgf3p. In this study we show that Rgf2p is a Rho1p GEF required for sporulation. The rgf2+ deletion did not affect forespore membrane formation and the nuclei were encapsulated properly. However, the mutant ascospores appeared dark and immature. The rgf2Δ zygotes were not able to release the ascospores spontaneously, and the germination efficiency was greatly reduced compared to wild-type (wt) spores. This phenotype resembles that of the mutants in bgs2+, which encodes a sporulation-specific glucan synthase subunit. In fact, glucan synthase activity was diminished in sporulating rgf2Δ diploids. Rgf2p also plays a role in β-glucan biosynthesis during vegetative growth. Overexpression of rgf2+ specifically increased GTP-bound Rho1p, caused changes in cell morphology, and elicited an increase in β-1,3-glucan synthase activity. Moreover, the simultaneous disruption of rgf1+ and rgf2+ was lethal and both Rgf1p and Rgf2p were able to partially substitute for each other. Our results suggest that Rgf1p and Rgf2p are alternative GEFs with an essential overlapping function in Rho1p activation during vegetative growth.
Genetics ofSex-linked yellowin the Syrian Hamster
Authors: Alizadeh Azita , Hong Lewis Z , Kaelin Christopher B , Raudsepp Terje , Manuel Hermogenes , Barsh Gregory S
Published: February 2009

Alternating patches of black and yellow pigment are a ubiquitous feature of mammalian color variation that contributes to camouflage, species recognition, and morphologic diversity. X-linked determinants of this pattern—recognized by variegation in females but not in males—have been described in the domestic cat as Orange, and in the Syrian hamster as Sex-linked yellow (Sly), but are curiously absent from other vertebrate species. Using a comparative genomic approach, we develop molecular markers and a linkage map for the euchromatic region of the Syrian hamster X chromosome that places Sly in a region homologous to the centromere-proximal region of human Xp. Comparison to analogous work carried out for Orange in domestic cats indicates, surprisingly, that the cat and hamster mutations lie in nonhomologous regions of the X chromosome. We also identify the molecular cause of recessively inherited black coat color in hamsters (historically referred to as nonagouti) as a Cys115Tyr mutation in the Agouti gene. Animals doubly mutant for Sly and nonagouti exhibit a Sly phenotype. Our results indicate that Sly represents a melanocortin pathway component that acts similarly to, but is genetically distinct from, Mc1r and that has implications for understanding both the evolutionary history and the mutational mechanisms of pigment-type switching.
The Decay of the Chromosomally Encoded ccdO157 Toxin–Antitoxin System in the Escherichia coli Species
Authors: Mine Natacha , Guglielmini Julien , Wilbaux Myriam , Van Melderen Laurence
Published: February 2009

The origin and the evolution of toxin–antitoxin (TA) systems remain to be uncovered. TA systems are abundant in bacterial chromosomes and are thought to be part of the flexible genome that originates from horizontal gene transfer. To gain insight into TA system evolution, we analyzed the distribution of the chromosomally encoded ccdO157 system in 395 natural isolates of Escherichia coli. It was discovered in the E. coli O157:H7 strain in which it constitutes a genomic islet between two core genes (folA and apaH). Our study revealed that the folA–apaH intergenic region is plastic and subject to insertion of foreign DNA. It could be composed (i) of a repetitive extragenic palindromic (REP) sequence, (ii) of the ccdO157 system or subtle variants of it, (iii) of a large DNA piece that contained a ccdAO157 antitoxin remnant in association with ORFs of unknown function, or (iv) of a variant of it containing an insertion sequence in the ccdAO157 remnant. Sequence analysis and functional tests of the ccdO157 variants revealed that 69% of the variants were composed of an active toxin and antitoxin, 29% were composed of an active antitoxin and an inactive toxin, and in 2% of the cases both ORFs were inactive. Molecular evolution analysis showed that ccdBO157 is under neutral evolution, suggesting that this system is devoid of any biological role in the E. coli species.
Cis-regulatory Mutations in the Caenorhabditis elegans Homeobox Gene Locus cog-1 Affect Neuronal Development
Authors: O'Meara M Maggie , Bigelow Henry , Flibotte Stephane , Etchberger John F , Moerman Donald G , Hobert Oliver
Published: February 2009

We apply here comparative genome hybridization as a novel tool to identify the molecular lesion in two Caenorhabditis elegans mutant strains that affect a neuronal cell fate decision. The phenotype of the mutant strains resembles those of the loss-of-function alleles of the cog-1 homeobox gene, an inducer of the fate of the gustatory neuron ASER. We find that both lesions map to the cis-regulatory control region of cog-1 and affect a phylogenetically conserved binding site for the C2H2 zinc-finger transcription factor CHE-1, a previously known regulator of cog-1 expression in ASER. Identification of this CHE-1-binding site as a critical regulator of cog-1 expression in the ASER in vivo represents one of the rare demonstrations of the in vivo relevance of an experimentally determined or predicted transcription-factor-binding site. Aside from the mutationally defined CHE-1-binding site, cog-1 contains a second, functional CHE-1-binding site, which in isolation is sufficient to drive reporter gene expression in the ASER but in an in vivo context is apparently insufficient for promoting appropriate ASER expression. The cis-regulatory control regions of other ASE-expressed genes also contain ASE motifs that can promote ASE neuron expression when isolated from their genomic context, but appear to depend on multiple ASE motifs in their normal genomic context. The multiplicity of cis-regulatory elements may ensure the robustness of gene expression.
Linkage Disequilibrium and Demographic History of Wild and Domestic Canids
Authors: Gray Melissa M , Granka Julie M , Bustamante Carlos D , Sutter Nathan B , Boyko Adam R , Zhu Lan , Ostrander Elaine A , Wayne Robert K
Published: February 2009

Assessing the extent of linkage disequilibrium (LD) in natural populations of a nonmodel species has been difficult due to the lack of available genomic markers. However, with advances in genotyping and genome sequencing, genomic characterization of natural populations has become feasible. Using sequence data and SNP genotypes, we measured LD and modeled the demographic history of wild canid populations and domestic dog breeds. In 11 gray wolf populations and one coyote population, we find that the extent of LD as measured by the distance at which r2 = 0.2 extends <10 kb in outbred populations to >1.7 Mb in populations that have experienced significant founder events and bottlenecks. This large range in the extent of LD parallels that observed in 18 dog breeds where the r2 value varies from ∼20 kb to >5 Mb. Furthermore, in modeling demographic history under a composite-likelihood framework, we find that two of five wild canid populations exhibit evidence of a historical population contraction. Five domestic dog breeds display evidence for a minor population contraction during domestication and a more severe contraction during breed formation. Only a 5% reduction in nucleotide diversity was observed as a result of domestication, whereas the loss of nucleotide diversity with breed formation averaged 35%.
GPC-1, a G Protein γ-Subunit, Regulates Olfactory Adaptation inCaenorhabditis elegans
Authors: Yamada Koji , Hirotsu Takaaki , Matsuki Masahiro , Kunitomo Hirofumi , Iino Yuichi
Published: February 2009

Caenorhabditis elegans genome carries two Gγ genes, gpc-1 and gpc-2, and two Gβ genes, gpb-1 and gpb-2. Of these, gpc-2 and gpb-1 are expressed ubiquitously and are essential for viability. Through a genetic screen, we identified gpc-1 as essential for olfactory adaptation. While wild-type animals show decreased chemotaxis to the odorant benzaldehyde after a short preexposure to the odorant, gpc-1 mutants are still attracted to the odorant after the same preexposure. Cell-specific rescue experiments show that gpc-1 acts in the AWC olfactory neurons. Coexpression of GPC-1 and GPB-1, but not GPB-2, caused enhanced adaptation, indicating that GPC-1 may act with GPB-1. On the other hand, knock down of gpc-2 by cell-targeted RNAi caused reduced chemotaxis to the odorant in unadapted animals, indicating that GPC-2 mainly act for olfactory sensation and the two Gγ's have differential functions. Nonetheless, overexpression of gpc-2 in AWC neurons rescued the adaptation defects of gpc-1 mutants, suggesting partially overlapping functions of the two Gγ's. We further tested genetic interaction of gpc-1 with several other genes involved in olfactory adaptation. Our analyses place goa-1 Goα and let-60 Ras in parallel to gpc-1. In contrast, a gain-of-function mutation in egl-30 Gqα was epistatic to gpc-1, suggesting the possibility that gpc-1 Gγ may act upstream of egl-30 Gqα.
Episodic Selection and the Maintenance of Competence and Natural Transformation inBacillus subtilis
Authors: Johnsen P J , Dubnau D , Levin B R
Published: February 2009

We present a new hypothesis for the selective pressures responsible for maintaining natural competence and transformation. Our hypothesis is based in part on the observation that in Bacillus subtilis, where transformation is widespread, competence is associated with periods of nongrowth in otherwise growing populations. As postulated for the phenomenon of persistence, the short-term fitness cost associated with the production of transiently nongrowing bacteria can be compensated for and the capacity to produce these competent cells can be favored due to episodes where the population encounters conditions that kill dividing bacteria. With the aid of a mathematical model, we demonstrate that under realistic conditions this “episodic selection” for transiently nongrowing (persisting) bacteria can maintain competence for the uptake and expression of exogenous DNA transformation. We also show that these conditions for maintaining competence are dramatically augmented even by rare episodes where selection favors transformants. Using experimental populations of B. subtilis and antibiotic-mediated episodic selection, we test and provide support for the validity of the assumptions behind this model and the predictions generated from our analysis of its properties. We discuss the potential generality of episodic selection for the maintenance of competence in other naturally transforming species of bacteria and critically evaluate other hypotheses for the maintenance (and evolution) of competence and their relationship to this hypothesis.
Degradation and sorption of 2-propenyl and benzyl isothiocyanate in soil
Authors: Gimsing Anne L. , Strobel Bjarne W. , Hansen Hans C. B.
Published: February 2009

Isothiocyanates of natural origin produced by the hydrolysis of plant-produced glucosinolates have the potential to control soil pests, but getting sufficiently high isothiocyanate concentrations in soil is difficult. Furthermore, the isothiocyanates have proven toxic to a wide range of organisms and hence may also harm nontarget organisms. Knowledge of the sorption and degradation of the isothiocyanates is essential to optimize the use of natural isothiocyanates for pest control while minimizing the environmental impact. We have conducted studies on the sorption and degradation of two isothiocyanates of natural origin, 2-propenyl isothiocyanate and benzyl isothiocyanate. The experiments show the isothiocyanates degrade very quickly (t1/2 = 0.93–4.25 h) in a 1:1 soil water slurry at 25°C and they are sorbed by the organic matter in soil. From an environmental point of view, a fast degradation is desirable, but if the natural isothiocyanates are to be utilized for pest control, a fast degradation may imply they are not present long enough to have the desired effect on pests.
Specific Local Cardiovascular Changes of Nɛ-(Carboxymethyl)lysine, Vascular Endothelial Growth Factor, and Smad2 in the Developing Embryos Coincide With Maternal Diabetes–Induced Congenital Heart Defects
Authors: Roest Pauline A.M. , Molin Daniël G.M. , Schalkwijk Casper G. , van Iperen Liesbeth , Wentzel Parri , Eriksson Ulf J. , Gittenberger-de Groot Adriana C.
Published: February 2009

OBJECTIVE

Embryos exposed to a diabetic environment in utero have an increased risk to develop congenital heart malformations. The mechanism behind the teratogenicity of diabetes still remains enigmatic. Detrimental effects of glycation products in diabetic patients have been well documented. We therefore studied a possible link between glycation products and the development of congenital cardiovascular malformations. Furthermore, we investigated other possible mechanisms involved in this pathogenesis: alterations in the levels of vascular endothelial growth factor (VEGF) or phosphorylated Smad2 (the latter can be induced by both glycation products and VEGF).

RESEARCH DESIGN AND METHODS

We examined the temporal spatial patterning of the glycation products Nε(carboxymethyl)lysine (CML) and methylglyoxal (MG) adducts, VEGF expression, and phosphorylated Smad2 during cardiovascular development in embryos from normal and diabetic rats.

RESULTS

Maternal diabetes increased the CML accumulation in the areas susceptible to diabetes-induced congenital heart disease, including the outflow tract of the heart and the aortic arch. No MG adducts could be detected, suggesting that CML is more likely to be indicative for increased oxidative stress than for glycation. An increase of CML in the outflow tract of the heart was accompanied by an increase in phosphorylated Smad2, unrelated to VEGF. VEGF showed a time-specific decrease in the outflow tract of embryos from diabetic dams.

CONCLUSIONS

From our results, we can conclude that maternal diabetes results in transient and localized alterations in CML, VEGF expression, and Smad2 phosphorylation overlapping with those regions of the developing heart that are most sensitive to diabetes-induced congenital heart disease.
Interleukin-6 Attenuates Insulin-Mediated Increases in Endothelial Cell Signaling but Augments Skeletal Muscle Insulin Action via Differential Effects on Tumor Necrosis Factor-α Expression
Authors: Yuen Derek Y.C. , Dwyer Renee M. , Matthews Vance B. , Zhang Lei , Drew Brian G. , Neill Bronwyn , Kingwell Bronwyn A. , Clark Michael G. , Rattigan Stephen , Febbraio Mark A.
Published: February 2009

OBJECTIVE

The cytokine interleukin-6 (IL-6) stimulates AMP-activated protein kinase (AMPK) and insulin signaling in skeletal muscle, both of which result in the activation of endothelial nitric oxide synthase (eNOS). We hypothesized that IL-6 promotes endothelial cell signaling and capillary recruitment in vivo, contributing to increased glucose uptake.

RESEARCH DESIGN AND METHODS

The effect of IL-6 with and without insulin on AMPK, insulin, and eNOS signaling in and nitric oxide (NO) release from human aortic endothelial cells (HAECs) was examined. The physiological significance of these in vitro signaling events was assessed by measuring capillary recruitment in rats during control and euglycemic-hyperinsulinemic clamps with or without IL-6 infusion.

RESULTS

IL-6 blunted increases in insulin signaling, eNOS phosphorylation (Ser1177), and NO production and reduced phosphorylation of AMPK in HAEC in vitro and capillary recruitment in vivo. In contrast, IL-6 increased Akt phosphorylation (Ser473) in hindlimb skeletal muscle and enhanced whole-body glucose disappearance and glucose uptake during the clamp. The differences in endothelial cell and skeletal muscle signaling were mediated by the cell-specific, additive effects of IL-6 and insulin because this treatment markedly increased tumor necrosis factor (TNF)-α protein expression in HAECs without any effect on TNF-α in skeletal muscle. When HAECs were incubated with a TNF-α–neutralizing antibody, the negative effects of IL-6 on eNOS signaling were abolished.

CONCLUSIONS

In the presence of insulin, IL-6 contributes to aberrant endothelial cell signaling because of increased TNF-α expression.
Do Non-HLA Genes Influence Development of Persistent Islet Autoimmunity and Type 1 Diabetes in Children With High-Risk HLA-DR,DQ Genotypes?
Authors: Steck Andrea K. , Zhang Weiming , Bugawan Teodorica L. , Barriga Katherine J. , Blair Alan , Erlich Henry A. , Eisenbarth George S. , Norris Jill M. , Rewers Marian J.
Published: February 2009

OBJECTIVE

Specific alleles of non-HLA genes INS, CTLA-4, and PTPN22 have been associated with type 1 diabetes. We examined whether some of these alleles influence development of islet autoimmunity or progression from persistent islet autoimmunity to type 1 diabetes in children with high-risk HLA-DR,DQ genotypes.

RESEARCH DESIGN AND METHODS

Since 1993, the Diabetes Autoimmunity Study in the Young (DAISY) has followed 2,449 young children carrying HLA-DR,DQ genotypes associated with type 1 diabetes. Of those, 112 have developed islet autoimmunity (persistent autoantibodies to insulin, GAD65, and/or IA-2), and 47 of these have progressed to type 1 diabetes. The influence of polymorphisms of INS(−23Hph1), CTLA-4(T17A), and PTPN22(R620W) on development of persistent islet autoimmunity and progression to type 1 diabetes was evaluated by parametric models and by survival analyses.

RESULTS

PTPN22(R620W) allele T was associated with development of persistent islet autoimmunity (hazard ratio 1.83 [95% CI 1.27–2.63]) controlling for ethnicity, presence of HLA-DR3/4,DQB1*0302, and having a first-degree relative with type 1 diabetes. Survival analyses showed a significantly (P = 0.002) higher risk of persistent islet autoimmunity by age 10 years for the TT genotype (27.3%) than for the CT or CC genotype (7.9 and 5.3%, respectively). Cumulative risk of persistent islet autoimmunity was slightly higher (P = 0.02) for the INS(−23Hph1) AA genotype (7.8%) than for the AT or TT genotype (4.2 and 6.4% risk by age 10 years, respectively).

CONCLUSIONS

Whereas the HLA-DR3/4,DQB1*0302 genotype had a dramatic influence on both development of islet autoimmunity and progression to type 1 diabetes, the PTPN22(R620W) T allele significantly influences progression to persistent islet autoimmunity in the DAISY cohort.
Liver-Specific Loss of Lipolysis-Stimulated Lipoprotein Receptor Triggers Systemic Hyperlipidemia in Mice
Authors: Narvekar Prachiti , Berriel Diaz Mauricio , Krones-Herzig Anja , Hardeland Ulrike , Strzoda Daniela , Stöhr Sigrid , Frohme Marcus , Herzig Stephan
Published: February 2009

OBJECTIVE

In mammals, proper storage and distribution of lipids in and between tissues is essential for the maintenance of energy homeostasis. In contrast, aberrantly high levels of triglycerides in the blood (“hypertriglyceridemia”) represent a hallmark of the metabolic syndrome and type 2 diabetes. As hypertriglyceridemia has been identified as an important risk factor for cardiovascular complications, in this study we aimed to identify molecular mechanisms in aberrant triglyceride elevation under these conditions.

RESEARCH DESIGN AND METHODS

To determine the importance of hepatic lipid handling for systemic dyslipidemia, we profiled the expression patterns of various hepatic lipid transporters and receptors under healthy and type 2 diabetic conditions. A differentially expressed lipoprotein receptor was functionally characterized by generating acute, liver-specific loss- and gain-of-function animal models.

RESULTS

We show that the hepatic expression of lipid transporter lipolysis-stimulated lipoprotein receptor (LSR) is specifically impaired in mouse models of obesity and type 2 diabetes and can be restored by leptin replacement. Experimental imitation of this pathophysiological situation by liver-specific knockdown of LSR promotes hypertriglyceridemia and elevated apolipoprotein (Apo)B and E serum levels in lean wild-type and ApoE knockout mice. In contrast, genetic restoration of LSR expression in obese animals to wild-type levels improves serum triglyceride levels and serum profiles in these mice.

CONCLUSIONS

The dysregulation of hepatic LSR under obese and diabetic conditions may provide a molecular rationale for systemic dyslipidemia in type 2 diabetes and the metabolic syndrome and represent a novel target for alternative treatment strategies in these patients.
Kinetics of GLUT4 Trafficking in Rat and Human Skeletal Muscle
Authors: Karlsson Håkan K.R. , Chibalin Alexander V. , Koistinen Heikki A. , Yang Jing , Koumanov Francoise , Wallberg-Henriksson Harriet , Zierath Juleen R. , Holman Geoffrey D.
Published: February 2009

OBJECTIVE

In skeletal muscle, insulin stimulates glucose transport activity three- to fourfold, and a large part of this stimulation is associated with a net translocation of GLUT4 from an intracellular compartment to the cell surface. We examined the extent to which insulin or the AMP-activated protein kinase activator AICAR can lead to a stimulation of the exocytosis limb of the GLUT4 translocation pathway and thereby account for the net increase in glucose transport activity.

RESEARCH DESIGN AND METHODS

Using a biotinylated photoaffinity label, we tagged endogenous GLUT4 and studied the kinetics of exocytosis of the tagged protein in rat and human skeletal muscle in response to insulin or AICAR. Isolated epitrochlearis muscles were obtained from male Wistar rats. Vastus lateralis skeletal muscle strips were prepared from open muscle biopsies obtained from six healthy men (age 39 ± 11 years and BMI 25.8 ± 0.8 kg/m2).

RESULTS

In rat epitrochlearis muscle, insulin exposure leads to a sixfold stimulation of the GLUT4 exocytosis rate (with basal and insulin-stimulated rate constants of 0.010 and 0.067 min−1, respectively). In human vastus lateralis muscle, insulin stimulates GLUT4 translocation by a similar sixfold increase in the exocytosis rate constant (with basal and insulin-stimulated rate constants of 0.011 and 0.075 min−1, respectively). In contrast, AICAR treatment does not markedly increase exocytosis in either rat or human muscle.

CONCLUSIONS

Insulin stimulation of the GLUT4 exocytosis rate constant is sufficient to account for most of the observed increase in glucose transport activity in rat and human muscle.
Religiosity as a public good
Authors: Sherlock Richard
Published: February 2009

Public Goods can be seen as one important way in which societies sustain themselves over time. These are part of the puzzle of the development of political order. Public goods like the rule of law are non-substractable and non-excludable. For economists the classic textbook examples are national defense and police protection. In this paper I argue that religiosity can function like police protection, a means of sustaining order through fear of punishment from a transcendent source. As a means of reducing defection from social norms it has a role to play as a public good. But religion cannot at the same time be seen as the source of such norms or dissention will undermine the very order that punishment seems to reinforce.
Socialists, Populists, Resources, and the Divergent Development of Alberta and Saskatchewan
Authors: Herbert Emery J.C. , Kneebone Ronald D.
Published: February 2009

Canada's federal government established the provinces of Saskatchewan and Alberta in 1905, making them approximately equal in area, population, and economy. Roughly one hundred years later, Alberta has three times the population of Saskatchewan and a gross domestic product (GDP) that is more than four times greater. The creation of the border represents a “natural experiment” that allows us to assess the relative importance of institutions versus geography to explain the divergent development of the twin provinces. While the perception persists that Saskatchewan's political climate hindered that province's development relative to Alberta's, it is Alberta's early lead in manufacturing, and vast mineral endowments, that present a more convincing explanation for the divergence.
Overeducated Immigrants in the Canadian Labour Market: Evidence from the Workplace and Employee Survey
Authors: Wald Steven , Fang Tony
Published: February 2009

This paper addresses the overeducation of recent immigrants in the Canadian labour market. Data from the 1999 Workplace and Employee Survey are used to explore the determinants and earnings consequences of overeducation. Although a well-developed body of literature examines the earnings consequences of overeducation, this paper presents the first Canadian estimates of returns to years of schooling that are contingent upon perceived job requirements. Compared with Canadian-born workers, recent immigrants are found to have a relatively high incidence of overeducation and to earn relatively low returns for surplus schooling. These are shown to be major contributors to the earnings gap between recent immigrants and workers born in Canada.
Microsimulation Calibration Using Speed-Flow Relationships
Authors: Menneni Sandeep , Sun Carlos , Vortisch Peter
Published: February 2009

A microsimulation calibration methodology based on matching speed-flow graphs from field and simulation is presented. Evaluation and automation of matching speed-flow graphs are based on methods from pattern recognition. The methodology was applied to the US-101 freeway network in San Francisco, California, by using an evolutionary algorithm. The methodology is compared to traditional methods of calibration based on capacity and is shown to perform better. In addition, a small-scale test-network simulation model was developed to assist in calibration of large-scale simulation models. The performance of the test-network-based calibration is comparable to the US-101 simulation model.
Comparison of Simulation-Based and Model-Based Calibrations of Traffic-Flow Microsimulation Models
Authors: Ciuffo Biagio , Punzo Vincenzo , Torrieri Vincenzo
Published: February 2009

Parameter calibration of traffic microsimulation models usually takes the form of a simulation-based optimization problem, that is, an optimization in which every objective function evaluation calls for a simulation. It is recognized that such a problem is computationally intractable. Running time grows exponentially both in the number of parameters and in the digits accuracy. In addition, considerable computing time is required by each objective function evaluation. This means that only heuristic techniques can be applied. Accordingly, results of the application of the OptQuest/Multistart algorithm to the calibration of AIMSUN microsimulation model parameters on a freeway network are presented. Furthermore, it is claimed that the search for an effective solution to the calibration problem cannot be exhausted by the choice of the most efficient optimization algorithm. The use of available information concerning the phenomenon could allow calibration performance to be enhanced, for example, by reducing dimensions of the domain of feasible solutions. It is argued that this goal could be achieved by using information from the stationary counterpart of microscopic traffic-flow models that depict the aggregate variables of traffic flows as a function of drivers’ microscopic parameters. Because they have a closed analytical formulation, they are well suited for faster calibrations. Results show that values of parameters from stationary model-based calibrations are not far from the optimal ones. Thus the integration of the two approaches cannot be excluded but is worth investigating.
Oversaturated Freeway Flow Algorithm for Use in Next Generation Simulation
Authors: Yeo Hwasoo , Skabardonis Alexander , Halkias John , Colyar James , Alexiadis Vassili
Published: February 2009

Existing simulation models have difficulty in accurately modeling oversaturated traffic conditions on freeways. A new behavioral algorithm for oversaturated freeway flow can be used in microscopic simulation models; it was developed as part of the Next Generation Simulation (NGSIM) project, sponsored by FHWA. The proposed algorithm is an integrated car-following and lane-changing modeling framework that is consistent with the kinematic wave theory. The algorithm can explicitly model mandatory and discretionary lane changing, including cooperation during lane changing. As an extension of the algorithm, a new on-ramp merging model was developed and incorporated into the model. The proposed algorithm also accounts for the relaxation process following lane changing. The proposed model includes a small number of parameters that can be readily measured in the field. The proposed model was implemented into a microscopic simulator, and it was validated with both vehicle trajectory data and macroscopic detector data from an NGSIM test site. The results show good agreement with real-world traffic behavior. The study products, including an algorithm description, analysis results, and computer code, are documented and made available to developers and users of traffic simulation tools.
Empirical Study of Behavioral Theory of Traffic Flow
Authors: Şahin Ismail , Altun Ibrahim
Published: February 2009

An empirical study was conducted of driver behavioral theory of multi-lane freeway traffic flow and capacity drop. The study focused on a freeway segment with a horizontal curve located in a stretch of the O-1 highway approaching the European side of the Bosporus Bridge in Istanbul, Turkey. The stretch behaves as a recurrent bottleneck in the afternoon peak. Flow data were extracted manually from video recordings taken from stations along the highway stretch and then converted into cumulative vehicle count curves constructed for each lane at the count stations. Radar detector data taken from a point within the horizontal curve were used to construct an occupancy-flow diagram. The empirical results show that drivers behave in some respects as outlined in the theory. For example, drivers in the median lane do not redistribute themselves across lanes although their speeds are below those in the shoulder lane, as opposed to the theory, but redistribution occurs later. This implies that more than speed differential across lanes affects driver behavior in the median lane. Flow differences and then equalization were observed in the median and shoulder lanes in free-flow and congested-flow states, respectively. There was a fast-moving queue in the median lane in a semicongested state while free-flow conditions in the shoulder lane were prevailing, in harmony with the theory. A relation between capacity drop due to bottleneck activation and bottleneck segment density is also presented.
Comparisons of Speed-Spacing Relations under General Car following versus Lane Changing
Authors: Ma Tingting , Ahn Soyoung
Published: February 2009

Data from two freeway locations show that absent lane changing, the relationships between congested speed and spacing are linear in most ranges of congested speed. The relationships are also found to be statistically indifferent across lanes, indicating that a single general model would suffice for all lanes. Moreover, speed-spacing relationships for different types of lane changers (discretionary versus mandatory due to merging and diverging) are also found to be statistically indifferent. Anticipation and relaxation periods, defined as durations of perturbed car-following behavior before and after a lane-change maneuver, were measured for lane changers and the vehicles immediately behind the followers. Lane changers exhibited anticipation and relaxation periods of 8 and 14 s, respectively. The followers in the initial lanes exhibited anticipation and relaxation periods of 4 and 8 s, which are smaller than the periods for the followers in the target lanes (12 and 16 s) as well as the periods for the lane changers. The findings suggest that car-following behavior on a freeway can be predicted according to Newell's simplified car-following theory, and a single model can be used without much loss of accuracy for different lanes. The findings also suggest that the anticipation and relaxation processes are independent of lane-changing types but are different for lane changers and followers.
Calibrating Car-Following Models by Using Trajectory Data
Authors: Kesting Arne , Treiber Martin
Published: February 2009

The car-following behavior of individual drivers in real city traffic is studied on the basis of (publicly available) trajectory data sets recorded by a vehicle equipped with a radar sensor. By means of a nonlinear optimization procedure based on a genetic algorithm, the intelligent driver model and the velocity difference model are calibrated by minimizing the deviations between the observed driving dynamics and the simulated trajectory in following the same leading vehicle. The reliability and robustness of the nonlinear fits are assessed by applying different optimization criteria, that is, different measures for the deviations between two trajectories. The obtained errors are between 11% and 29%, which is consistent with typical error ranges obtained in previous studies. It is also found that the calibrated parameter values of the velocity difference model depend strongly on the optimization criterion, whereas the intelligent driver model is more robust. The influence of a reaction time is investigated by applying an explicit delay to the model input. A negligible influence of the reaction time is found and indicates that drivers compensate for their reaction time by anticipation. Furthermore, the parameter sets calibrated to a certain trajectory are applied to the other trajectories; this step allows for model validation. The results indicate that intradriver variability rather than interdriver variability accounts for a large part of the calibration errors. The results are used to suggest some criteria toward a benchmarking of car-following models.