bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

AbstractAssessing 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 &lt;10 kb in outbred populations to &gt;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 &gt;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

AbstractCaenorhabditis 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

AbstractWe 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

Abstract
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

OBJECTIVEThe 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 METHODSThe 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.RESULTSIL-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.CONCLUSIONSIn 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.
Continuity of aggression from childhood to early adulthood as a predictor of life outcomes: implications for the adolescent‐limited and life‐course‐persistent models
Authors: Huesmann L. Rowell , Dubow Eric F. , Boxer Paul 
Published: February 2009

AbstractUsing data from the Columbia County Longitudinal Study, a 40‐year longitudinal study following an entire county's population of third‐grade students from age 8 to 48, we examine questions about the long‐term consequences of aggressive and antisocial behavior in childhood, adolescence, and young adulthood. We found moderate levels of continuity of aggression from age 8 to 48 both for males and for females. Contrary to what some have proposed, we found that continuity of aggressiveness is owing to not only the high‐aggressive participants staying high but also owing to the low‐aggressive participants staying low. Compared with life‐course‐persistent low aggressives, we found that life‐course‐persistent high aggressives had consistently poorer outcomes across domains of life success, criminal behavior, and psychosocial functioning at age 48 (e.g., arrests, traffic violations, aggression toward spouse and divorces, depression, health, occupational and educational attainment). In contrast, adolescent‐limited and child‐limited aggressives did not differ from life‐course‐persistent low aggressives on the age 48 outcomes. Finally, the outcomes for late‐onset (early adulthood) aggressives were also problematic in some domains though not as problematic as those for life‐course‐persistent aggressives. Aggr. Behav. 35:136–149, 2009. © 2009 Wiley‐Liss, Inc.
Interfacial Strain‐Induced Oxygen Disorder as the Cause of Enhanced Critical Current Density in Superconducting Thin Films
Authors: Wimbush Stuart C. , Li Meicheng , Vickers Mary E. , Maiorov Boris , Feldmann D. Matt , Jia Quanxi , MacManus‐Driscoll Judith L. 
Published: February 2009

AbstractTo understand the origin of the increase in critical current density of rare earth barium cuprate superconductor thin films with decreasing thickness, a series of sub‐300‐nm EuBa2Cu3O7−δ thin films deposited on SrTiO3 substrates are studied by X‐ray diffraction and electrical transport measurements. The out‐of‐plane crystallographic mosaic tilt and the out‐of‐plane microstrain both increase with decreasing film thickness. The calculated density of c‐axis threading dislocations matches the extent of the observed low‐field enhancement in critical current density for fields applied parallel to c. The in‐plane mosaic twist and in‐plane microstrain are both around twice the magnitude of the out‐of‐plane values, and both increase with decreasing film thickness. The results are consistent with the observed stronger field enhancement in critical current density for fields applied parallel to ab. The lattice parameter variation with thickness is not as expected from consideration of the biaxial strain with the substrate, indicative of in‐plane microstrain accommodation by oxygen disorder. Collectively, the results point to an enhancement of critical current by interfacial strain induced oxygen disorder which is greatest closest to the film‐substrate interface. The findings of this study have important implications for other thin functional oxide perovskite films and nanostructures where surface and interfacial strains dominate the properties.