bluuebunny/crossref_metadata_2025 huggingface dataset:
The Goldilocks Genes
Authors: Leslie Mitch
Published: December 2004

From cancer biologists to geneticists, scientists are tackling the question of how raising or lowering the number of gene copies from the standard two affects how we live and how soon we die. New genomic studies show that large-scale DNA duplications and deletions are more common than scientists imagined, even in healthy people. Other work demonstrates that our supply of gene copies matters in Parkinson's disease and cancer. The results raise the possibility that how fast we age depends in part on how many duplicates of certain genes we carry.
Gut Instinct
Authors: Leslie Mitch
Published: December 2004

Unsuccessful dieters complain that their stomachs rule their lives. That might be an exaggeration, but the denizens of the digestive system could dictate how much fat an individual stockpiles, according to new research on mice. Bacteria in the intestine signal rodents to amass fat, the work shows, and the results might help researchers understand why some people gain weight and others don't.
Culture Clash
Authors: Davenport R. John
Published: December 2004

Some dying yeast display signs of apoptosis, a cell-suicide process. The idea has sparked controversy partly because single-celled organisms wouldn't seem to benefit from this inclination. Work over the past year has bolstered the notion that yeast kill themselves and provided experimental evidence for how the capacity might aid yeast populations.
Nuclear Hormone Receptors, Metabolism, and Aging: What Goes Around Comes Around
Authors: Pardee Keith , Reinking Jeff , Krause Henry
Published: December 2004

Previous studies have linked the mysterious and inevitable process of aging to essential processes such as metabolism, maturation, and fecundity. Each of these processes is controlled to a large extent by nuclear hormone receptors (NHRs). NHRs also play important roles in the control of periodical processes, the most recently implicated being circadian rhythm. This Review stresses the mounting evidence for tight relationships between each of these NHR-regulated processes and the processes of aging.
Partners in Death
Authors: Leslie Mitch
Published: December 2004

Like a mob boss ordering a hit, a protein that mars the brains of Alzheimer's disease (AD) patients gets others to do its dirty work. The protein slays brain cells by activating a molecule that goads cells to kill themselves, according to new work. The findings add to evidence that the problem in AD arises within cells rather than outside of them.
Poly(ADP-Ribosyl)ation, PARP, and Aging
Authors: Beneke Sascha , Bürkle Alexander
Published: December 2004

Poly(ADP-ribose) polymerases (PARPs) catalyze the poly(ADP-ribosyl)ation of proteins. This posttranslational modification, as generated by the DNA damage-activated enzymes PARP-1 and -2, has long been known to be involved in DNA repair. Correlative data have suggested an association between DNA damage-induced poly(ADP-ribosyl)ation and mammalian longevity, and this link has recently been strengthened by the discovery of interactions between PARP-1 and the Werner syndrome protein. Emerging additional members of the PARP family display different cellular localizations and are involved in diverse processes such as the regulation of telomere or centrosome function, thereby providing further, independent links between poly(ADP-ribosyl)ation and the aging process.
Switching On Longevity
Authors: Leslie Mitch
Published: December 2004

Growing older is exhausting, even for nematodes, but a particular protein serves as a worm tonic, according to new research. The molecule senses energy shortages and fortifies the animals, extending their lives. The work also uncovers the molecule's interplay with the much-studied insulin-like signaling pathway.
Buddy System
Authors: Beckman Mary
Published: December 2004

WASHINGTON, D.C.
--According to at least one legend, 1000-year-old vampires assure themselves long, healthy lives by drinking the blood of young victims. Similarly, old mice that share the blood of young mice repair injuries with youthful prowess, according to research presented here 8 December 2004 at the American Society for Cell Biology Annual Meeting. The results suggest that youthful rodents pump a compound into the blood that keeps tissue-replenishing cells active.
Natural Foods
Authors: Davenport R. John
Published: December 2004

Even the most ascetic dieter occasionally succumbs to cravings for a bacon double cheeseburger or a pint of Ben & Jerry's Cherry Garcia ice cream. But according to a new study, frequent bingeing helps enhance the life-span-extending effects of a reduced-calorie diet--for Medflies, at least. The findings might help researchers craft a nuanced view of connections between diet and longevity.
Trashing Vision
Authors: Leslie Mitch
Published: December 2004

Put your garbage out when it's not trash day, and the waste will sit at the curb. A similar problem with rubbish collection in the eye might underlie some age-related types of blindness, according to new work. Shackling a receptor that controls cells' stickiness disrupts the normal junk-pickup schedule, the study shows. The results might help researchers better understand diseases in which cellular refuse blemishes the retina.
Mechanisms of Hair Graying: Incomplete Melanocyte Stem Cell Maintenance in the Niche
Authors: Nishimura Emi K. , Granter Scott R. , Fisher David E.
Published: December 2004

Hair graying is the most obvious sign of aging in humans, yet its mechanism is largely unknown. Here, we used melanocyte-tagged transgenic mice and aging human hair follicles to demonstrate that hair graying is caused by defective self-maintenance of melanocyte stem cells. This process is accelerated dramatically with
Bcl2
deficiency, which causes selective apoptosis of melanocyte stem cells, but not of differentiated melanocytes, within the niche at their entry into the dormant state. Furthermore, physiologic aging of melanocyte stem cells was associated with ectopic pigmentation or differentiation within the niche, a process accelerated by mutation of the melanocyte master transcriptional regulator
Mitf
.
The VGL-Chanome: A Protein Superfamily Specialized for Electrical Signaling and Ionic Homeostasis
Authors: Yu Frank H. , Catterall William A.
Published: December 2004

Complex multicellular organisms require rapid and accurate transmission of information among cells and tissues and tight coordination of distant functions. Electrical signals and resulting intracellular calcium transients, in vertebrates, control contraction of muscle, secretion of hormones, sensation of the environment, processing of information in the brain, and output from the brain to peripheral tissues. In nonexcitable cells, calcium transients signal many key cellular events, including secretion, gene expression, and cell division. In epithelial cells, huge ion fluxes are conducted across tissue boundaries. All of these physiological processes are mediated in part by members of the voltage-gated ion channel protein superfamily. This protein superfamily of 143 members is one of the largest groups of signal transduction proteins, ranking third after the G protein–coupled receptors and the protein kinases in number. Each member of this superfamily contains a similar pore structure, usually covalently attached to regulatory domains that respond to changes in membrane voltage, intracellular signaling molecules, or both. Eight families are included in this protein superfamily—voltage-gated sodium, calcium, and potassium channels; calcium-activated potassium channels; cyclic nucleotide–modulated ion channels; transient receptor potential (TRP) channels; inwardly rectifying potassium channels; and two-pore potassium channels. This article identifies all of the members of this protein superfamily in the human genome, reviews the molecular and evolutionary relations among these ion channels, and describes their functional roles in cell physiology.
Focus Issue—Signals Along a Road to the Mind?
Authors: Adler Elizabeth M. , Gough Nancy R.
Published: December 2004

Science
and
Science's STKE
tackle the intriguing questions of how the brain gives rise to thoughts, emotions, and behavior--questions so challenging and so complex that they must be addressed on many different levels before a coherent image of the whole can begin to emerge. Studies at the subcellular, cellular, neuronal network, and behavioral levels all add critical elements to our emerging vision of brain function.
Science's STKE
highlights the cellular and molecular processes that may underlie synaptic plasticity and signaling pathways that contribute to higher neural function, such as learning, memory, and behavior.
Role of Distinct NMDA Receptor Subtypes at Central Synapses
Authors: Cull-Candy Stuart G. , Leszkiewicz Daniel N.
Published: December 2004

Most excitatory synapses in the brain use the neurotransmitter glutamate to carry impulses between neurons. During fast transmission, glutamate usually activates a mixture of
N
-methyl-
d
-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in the postsynaptic cell. Experimental scrutiny of NMDARs provides insight into their involvement in excitatory synaptic transmission and related processes such as as synaptic plasticity, neural development, and pain perception. There is increasing awareness that subtle variation in NMDAR properties is imparted by specific receptor subunits, and recent studies have started to provide perspective into some of the discrete tasks carried out by individual receptor subtypes.
Focus Issue—The Dynamics of Gene Expression
Authors: Gough Nancy R.
Published: December 2004

It is gene expression that defines a cell's identity.
Science
, Science's
Science of Aging Knowledge Environment
(SAGE KE), and
Science's STKE
focus attention on the highly dynamic nature of gene expression. Mechanisms governing selective gene expression in multigene families, as well as those by which cis- and trans-acting factors contribute to regulation of gene expression, are topics under discussion. In addition, new methodologies allow researchers to gain insight into gene expression at the level of single cells and provide a glimpse at the real-time interactions among proteins and DNA.
Selective Gene Expression in Multigene Families from Yeast to Mammals
Authors: Dalgaard Jacob Z. , Vengrova Sonya
Published: December 2004

Exclusive gene expression, where only one member of a gene or gene cassette family is selected for expression, plays an important role in the establishment of cell identity in several biological systems. Here, we compare four such systems: mating-type switching in fission and budding yeast, where cells choose between expressing one of the two different mating-type cassettes, and immunoglobulin and odorant receptor gene expression in mammals, where the number of gene choices is substantially higher. The underlying mechanisms that establish this selective expression pattern in each system differ in almost every detail. In all four systems, once a successful gene activation event has taken place, a feedback mechanism affects the fate of the cell. In the mammalian systems, feedback is mediated by the expressed cell surface receptor to ensure monoallelic gene expression, whereas in the yeasts, the expressed gene cassette at the mating-type locus affects donor choice during the subsequent switching event.
The Jak-STAT Pathway Stimulated by Interferon α or Interferon β
Authors: Horvath Curt M.
Published: December 2004

Type I interferons, such as interferon α and interferon β (IFN-α and β), signal through a Janus kinase (Jak) to signal transduction and activator of transcription (STAT) pathway to stimulate gene expression. In response to ligand binding, the receptors dimerize, Jaks phosphorylate STAT1 and STAT2, which then dimerize and interact with a third transcriptional regulator IFN regulatory factor 9 (IRF9) to stimulate gene expression. IFN-α is the main innate antiviral cytokine and is essential for effective immune response to viral infection. The animation shows activation of STAT-responsive gene expression in response to type I IFNs.
Nuclear Receptor and Transcriptional Complex Cycles
Authors: Fowler Amy M. , Alarid Elaine T.
Published: December 2004

Transcriptional regulation by ligand-activated nuclear receptors, also known as steroid receptors, is a highly dynamic process. Nuclear receptors are intracellular proteins that reside in either the cytoplasm or nucleus in the inactive state. The interaction of this family of receptors with the promoters of target genes and with various proteins involved in stimulating gene expression is governed by binding to lipid soluble ligands. The animation, based on experiments following the dynamic interactions of the glucocorticoid receptor or the estrogen receptor with DNA, shows nuclear estrogen receptor and its interaction with a short two-nucleosome fragment of chromatin in the absence and presence of estrogen. The events that occur on the DNA are represented by the ordered recruitment of protein components to a larger macromolecular complex. The associated table describes the proteins and multimolecular complexes that participate in the nuclear receptor-chromatin cycles.
Ryk: Another Heretical Wnt Receptor Defies the Canon
Authors: Cheyette Benjamin N. R.
Published: December 2004

The number of proteins that serve as Wnt receptors is growing, and Ryk is one of the newest members of this group. Understanding how extracellular Wnt ligands interact with transmembrane receptors to activate intracellular signaling cascades is of broad importance to biology and to human disease because of the roles for Wnt in embryogenesis, cancer, and neural development and plasticity. The functions and properties of Ryk, a receptor tyrosine kinase–like protein, in canonical and noncanonical Wnt signaling are beginning to be uncovered. Biochemical and genetic studies reveal that the extracellular regions of Ryk and Fz can form a mutual ligand-binding domain. It remains to be seen whether Ryk can form similar complexes with other Wnt-binding proteins. If divergent transmembrane proteins can combine interchangeably to form heteromeric Wnt receptor complexes, then a stunning diversity of signaling responses might be mediated through differential expression and localization of these proteins in target cells.
Cycling of Synaptic Vesicles: How Far? How Fast!
Authors: Galli Thierry , Haucke Volker
Published: December 2004

Synaptic transmission is based on the regulated exocytotic fusion of synaptic vesicles filled with neurotransmitter. In order to sustain neurotransmitter release, these vesicles need to be recycled locally. Recent data suggest that two tracks for the cycling of synaptic vesicles coexist: a slow track in which vesicles fuse completely with the presynaptic plasma membrane, followed by clathrin-mediated recycling of the vesicular components, and a fast track that may correspond to the transient opening and closing of a fusion pore. In this review, we attempt to provide an overview of the components involved in both tracks of vesicle cycling, as well as to identify possible mechanistic links between these two pathways.
Activation of PI3K-Akt pathway mediates antiapoptotic effects of β-adrenergic agonist in airway eosinophils
Authors: Machida Kentaro , Inoue Hiromasa , Matsumoto Koichiro , Tsuda Miyuki , Fukuyama Satoru , Koto Hiroshi , Aizawa Hisamichi , Kureishi Yasuko , Hara Nobuyuki , Nakanishi Yoichi
Published: December 2004

β-Adrenoceptor agonists reportedly decrease spontaneous apoptosis of peripheral blood eosinophils; however, its signaling pathway is unknown. Survival signals can be elicited by the activation of phosphatidylinositol 3-kinase (PI3K) and Akt, both of which are known to be potent regulators of apoptosis, and Akt in turn inactivates Forkhead transcription factors, including FKHR (Forkhead in rhabdomyosarcoma). We have investigated the effect of β-agonists on apoptosis of local eosinophils isolated from the airways and the involvement of PI3K, Akt, and FKHR in its survival signal. Eosinophils obtained from immunized mice by bronchoalveolar lavage after allergen provocation underwent apoptosis in a time-dependent manner. Incubation of eosinophils with isoproterenol or formoterol dose-dependently inhibited both spontaneous eosinophil apoptosis and apoptosis induced by Fas receptor activation. Incubation with cAMP or forskolin also inhibited eosinophil apoptosis. The PI3K inhibitors wortmannin and LY-294002 and an Akt inhibitor, 1-l-6-hydroxymethyl- chiro-inositol 2-( R)-2- O-methyl-3- O-octadecylcarbonate, but not a mitogen-activated protein kinase kinase inhibitor PD-98059, blocked isoproterenol-mediated eosinophil survival. Wortmannin also inhibited cAMP-mediated eosinophil survival. Isoproterenol rapidly induced phosphorylation of Akt and FKHR in eosinophils in a PI3K-dependent manner. These findings indicate that the PI3K-Akt-FKHR pathway conveys a critical survival signal induced by β-agonists in airway eosinophils.
Enhanced nitric oxide production associated with airway hyporesponsiveness in the absence of IL-10
Authors: Ameredes Bill T. , Sethi Jigme M. , Liu He-Liang , Choi Augustine M. K. , Calhoun William J.
Published: December 2004

Interleukin (IL)-10 is an anti-inflammatory cytokine implicated in the regulation of airway inflammation in asthma. Among other activities, IL-10 suppresses production of nitric oxide (NO); consequently, its absence may permit increased NO production, which can affect airway smooth muscle contractility. Therefore, we investigated airway reactivity (AR) in response to methacholine (MCh) in IL-10 knockout (−/−) mice compared with wild-type C57BL/6 (C57) mice, in which airway NO production was measured as exhaled NO (ENO), and NO production was altered with administration of either NO synthase (NOS)-specific inhibitors or recombinant murine (rm)IL-10. AR, measured as enhanced pause in vivo, and tracheal ring tension in vitro were lower in IL-10−/−mice by 25–50%, which was associated with elevated ENOlevels (13 vs. 7 ppb). Administration of NOS inhibitors NG-nitro-l-arginine methyl ester (8 mg/kg ip) or l- N6-(1-iminoethyl)-lysine (3 mg/kg ip) to IL-10−/−mice decreased ENOby an average of 50%, which was associated with increased AR, to levels similar to C57 mice. ENOin IL-10−/−mice decreased in a dose-dependent fashion in response to administered rmIL-10, to levels similar to C57 mice (7 ppb), which was associated with a 30% increment in AR. Thus increased NO production in the absence of IL-10, decreased AR, which was reversed with inhibition of NO, either by inhibition of NOS, or with reconstitution of IL-10. These findings suggest that airway NO production can modulate airway smooth muscle contractility, resulting in airway hyporesponsiveness when IL-10 is absent.
Pharmacokinetics of pulmonary manganese absorption: evidence for increased susceptibility to manganese loading in iron-deficient rats
Authors: Heilig Elizabeth , Molina Ramon , Donaghey Thomas , Brain Joseph D. , Wessling-Resnick Marianne
Published: December 2004

High levels of airborne manganese can be neurotoxic, yet little is known about absorption of this metal via the lungs. Intestinal manganese uptake is upregulated by iron deficiency and is thought to be mediated by divalent metal transporter 1 (DMT1), an iron-regulated factor known to play a role in dietary iron absorption. To better characterize metal absorption from the lungs to the blood and test whether iron deficiency may modify this process, the pharmacokinetics of pulmonary manganese and iron absorption by control and iron-deficient rats were compared. Levels of DMT1 expression in the lungs were determined to explore potential changes induced by iron deficiency that might alter metal absorption. The pharmacokinetic curves for intratracheally instilled54Mn and59Fe were significantly different, suggesting that pulmonary uptake of the two metals involves different mechanisms. Intratracheally instilled iron-deficient rats had significantly higher blood54Mn levels, whereas blood59Fe levels were significantly reduced compared with controls. The same trend was observed when radioisotopes were delivered by intravenous injection, indicating that iron-deficient rats have altered blood clearance of manganese. In situ analysis revealed the presence of DMT1 transcripts in airway epithelium; however, mRNA levels did not change in iron deficiency. Although lung DMT1 levels and metal absorption did not appear to be influenced by iron deficiency, the differences in blood clearance of instilled manganese identified by this study support the idea that iron status can influence the potential toxicity of this metal.
Long-term hypoxia enhances proopiomelanocortin processing in the near-term ovine fetus
Authors: Myers Dean A. , Bell Paige A. , Hyatt Kimberly , Mlynarczyk Malgorzata , Ducsay Charles A.
Published: December 2004

Secondary stressors in long-term hypoxic (LTH) fetal sheep lead to altered function of the hypothalamic-pituitary-adrenal axis. Although ACTH is considered the primary mediator of glucocorticoid production in fetal sheep, proopiomelanocortin (POMC) and 22-kDa pro-ACTH (22-kDa ACTH) have been implicated in the regulation of cortisol production in the ovine fetus. This study was designed to determine whether POMC expression and processing are altered after LTH. Pregnant ewes were maintained at high altitude (3,820 m) from day 30 of gestation to near term, when the animals were transported to the laboratory. Reduced Po2 was maintained by nitrogen infusion through a maternal tracheal catheter. On days 139–141, fetal anterior pituitaries were collected from normoxic control and LTH fetuses. We measured POMC and corticotrophin-releasing factor type 1 receptor (CRF1-R) mRNA using quantitative real-time PCR, and we used Western blot analysis for quantitation of ACTH, ACTH precursor, and CRF1-R proteins. We measured plasma ACTH1–39 using a two-site immunoradiometric assay specific for ACTH1–39. Plasma ACTH precursors were measured by ELISA. Anterior pituitary POMC mRNA levels were not different between groups, whereas CRF1-R levels were significantly higher in the LTH anterior pituitaries compared with control ( P < 0.05). In contrast, protein levels of POMC, CRF1-R, 22-kDa ACTH, and ACTH1–39 were significantly lower in the LTH group. Plasma concentrations of both ACTH precursors and ACTH1–39 were significantly elevated in LTH fetuses, whereas the ratio of plasma precursors to ACTH was significantly lower. We conclude that LTH results in enhanced POMC processing and/or release to ACTH and increased hypothalamic drive.
Extracellular matrix (ECM) microstructural composition regulates local cell-ECM biomechanics and fundamental fibroblast behavior: a multidimensional perspective
Authors: Pizzo A. M. , Kokini K. , Vaughn L. C. , Waisner B. Z. , Voytik-Harbin S. L.
Published: December 2004

The extracellular matrix (ECM) provides the principal means by which mechanical information is communicated between tissue and cellular levels of function. These mechanical signals play a central role in controlling cell fate and establishing tissue structure and function. However, little is known regarding the mechanisms by which specific structural and mechanical properties of the ECM influence its interaction with cells, especially within a tissuelike context. This lack of knowledge precludes formulation of biomimetic microenvironments for effective tissue repair and replacement. The present study determined the role of collagen fibril density in regulating local cell-ECM biomechanics and fundamental fibroblast behavior. The model system consisted of fibroblasts seeded within collagen ECMs with controlled microstructure. Confocal microscopy was used to collect multidimensional images of both ECM microstructure and specific cellular characteristics. From these images temporal changes in three-dimensional cell morphology, time- and space-dependent changes in the three-dimensional local strain state of a cell and its ECM, and spatial distribution of β1-integrin were quantified. Results showed that fibroblasts grown within high-fibril-density ECMs had decreased length-to-height ratios, increased surface areas, and a greater number of projections. Furthermore, fibroblasts within low-fibril-density ECMs reorganized their ECM to a greater extent, and it appeared that β1-integrin localization was related to local strain and ECM remodeling events. Finally, fibroblast proliferation was enhanced in low-fibril-density ECMs. Collectively, these results are significant because they provide new insight into how specific physical properties of a cell’s ECM microenvironment contribute to tissue remodeling events in vivo and to the design and engineering of functional tissue replacements.
Chronic intermittent hypoxia increases infarction in the isolated rat heart
Authors: Joyeux-Faure M. , Stanke-Labesque F. , Lefebvre B. , Béguin P. , Godin-Ribuot D. , Ribuot C. , Launois S. H. , Bessard G. , Lévy P.
Published: December 2004

Coronary heart disease is frequently associated with obstructive sleep apnea syndrome and treating obstructive sleep apnea appears to significantly improve the outcome in coronary heart disease. Thus we have developed a rat model of chronic intermittent hypoxia (IH) to study the influence of this condition on myocardial ischemia-reperfusion tolerance and on functional vascular reactivity. Wistar male rats were divided in three experimental groups ( n = 12 each) subjected to chronic IH (IH group), normoxia (N group), or control conditions (control group). IH consisted of repetitive cycles of 1 min (40 s with inspired O2fraction 5% followed by 20 s normoxia) and was applied for 8 h during daytime, for 35 days. Normoxic cycles were applied in the same conditions, inspired O2fraction remaining constant at 21%. On day 36, mean arterial blood pressure (MABP) was measured before isolated hearts were submitted to an ischemia-reperfusion protocol. The thoracic aorta and left carotid artery were also excised for functional reactivity studies. MABP was not significantly different between the three experimental groups. Infarct sizes (in percent of ventricles) were significantly higher in IH group (46.9 ± 3.6%) compared with N (26.1 ± 2.8%) and control (21.7 ± 2.1%) groups. Vascular smooth muscle function was similar in aorta and carotid arteries from all groups. The endothelium-dependent relaxation in response to acetylcholine was also similar in aorta and carotid arteries from all groups. Chronic IH increased heart sensitivity to infarction, independently of a significant increase in MABP, and did not affect vascular reactivity of aorta and carotid arteries.
Time course of myogenic and metabolic gene expression in response to acute exercise in human skeletal muscle
Authors: Yang Yifan , Creer Andrew , Jemiolo Bozena , Trappe Scott
Published: December 2004

The aim of this study was to examine the time course activation of select myogenic (MRF4, Myf5, MyoD, myogenin) and metabolic (CD36, CPT1, HKII, and PDK4) genes after an acute bout of resistance (RE) or run (Run) exercise. Six RE subjects [25 ± 4 yr (mean ± SD), 74 ± 14 kg, 1.71 ± 0.11 m] and six Run subjects (25 ± 4 yr, 72 ± 5 kg, 1.81 ± 0.07 m, 63 ± 8 ml·kg−1·min−1) were studied. Eight muscle biopsies were taken from the vastus lateralis (RE) and gastrocnemius (Run) before, immediately after, and 1, 2, 4, 8, 12 and 24 h after exercise. RE increased mRNA of MRF4 (3.7- to 4.5-fold 2–4 h post), MyoD (5.8-fold 8 h post), myogenin (2.6- and 3.5-fold 8–12 h post), HKII (3.6- to 10.5-fold 2–12 h post), and PDK4 (14- to 26-fold 2–8 h post). There were no differences in Myf5, CD36, and CPT1 mRNA levels 0–24 h post-RE. Run increased mRNA of MyoD (5.0- to 8.0-fold), HKII (12- to 16-fold), and PDK4 (32- to 52-fold) at 8–12 h postexercise. There were no differences in MRF4, Myf5, myogenin, CD36 and CPT1 mRNA levels 0–24 h post-Run. These data indicate a myogenic and metabolic gene induction with RE and Run exercise. The timing of the gene induction is variable and generally peaks 4–8 h postexercise with all gene expression not significantly different from the preexercise levels by 24 h postexercise. These data provide basic information for the timing of human muscle biopsy samples for gene-expression studies involving exercise.
Low-Density Lipoprotein Subfractions and the Long-Term Risk of Ischemic Heart Disease in Men
Authors: St-Pierre Annie C. , Cantin Bernard , Dagenais Gilles R. , Mauriège Pascale , Bernard Paul-Marie , Després Jean-Pierre , Lamarche Benoît
Published: December 2004

Objective—

The objective of the present study was to investigate the association between large and small low-density lipoprotein (LDL) and long-term ischemic heart disease (IHD) risk in men of the Québec Cardiovascular Study.

Methods and Results—

Cholesterol levels in the large and small LDL subfractions (termed LDL-C
≥260Å
and LDL-C
<255Å
, respectively) were estimated from polyacrylamide gradient gel electrophoresis of whole plasma in the cohort of 2072 men of the population-based Québec Cardiovascular Study. All men were free of IHD at the baseline examination and followed-up for a period of 13 years, during which 262 first IHD events (coronary death, nonfatal myocardial infarction, and unstable angina pectoris) were recorded. Our study confirmed the strong and independent association between LDL-C
<255Å
levels as a proxy of the small dense LDL phenotype and the risk of IHD in men, particularly over the first 7 years of follow-up. However, elevated LDL-C
≥260Å
levels (third versus first tertile) were not associated with an increased risk of IHD over the 13-year follow-up (RR=0.76;
P
=0.07).

Conclusions—

These results indicated that estimated cholesterol levels in the large LDL subfraction were not associated with an increased risk of IHD in men and that the cardiovascular risk attributable to variations in the LDL size phenotype was largely related to markers of a preferential accumulation of small dense LDL particles.
Two Distinct Calcium-Dependent Mitochondrial Pathways Are Involved in Oxidized LDL-Induced Apoptosis
Authors: Vindis Cécile , Elbaz Meyer , Escargueil-Blanc Isabelle , Augé Nathalie , Heniquez Aurelia , Thiers Jean-Claude , Nègre-Salvayre Anne , Salvayre Robert
Published: December 2004

Objective—

Oxidized low-density lipoprotein (oxLDL)-induced apoptosis of vascular endothelial cells may contribute to plaque erosion and rupture. We aimed to clarify the relationship between the oxLDL-induced calcium signal and induction of apoptotic pathways.

Methods and Results—

Apoptosis was evaluated by biochemical methods, including studies of enzyme activities, protein processing, release of proapoptotic factors, chromatin cleavage, and especially by morphological methods that evaluate apoptosis/necrosis by SYTO-13/propidium iodide fluorescent labeling. The oxLDL-induced sustained calcium rise activated 2 distinct calcium-dependent mitochondrial apoptotic pathways in human microvascular endothelial cells. OxLDLs induced calpain activation and subsequent Bid cleavage and cytochrome C release, which were blocked by calpeptin. Cyclosporin-A inhibited cytochrome C release, possibly by inhibiting the opening of the mitochondrial permeability transition pore (mPTP). Calcineurin, another cyclosporin-sensitive step, was not implicated, because oxLDLs inhibited calcineurin and FK-506 treatment was ineffective. Cytochrome C release in turn induced caspase-3 activation. In addition, oxLDLs triggered release and nuclear translocation of mitochondrial apoptosis-inducing factor through a mechanism dependent on calcium but independent of calpains, mPTP, and caspases.

Conclusions—

OxLDL-induced apoptosis involves 2 distinct calcium-dependent pathways, the first mediated by calpain/mPTP/cytochrome C/caspase-3 and the second mediated by apoptosis-inducing factor, which is cyclosporin-insensitive and caspase-independent.
Heteromultimeric Kv1 Channels Contribute to Myogenic Control of Arterial Diameter
Authors: Plane Frances , Johnson Rosalyn , Kerr Paul , Wiehler William , Thorneloe Kevin , Ishii Kuniaki , Chen Tim , Cole William
Published: December 2004

Inhibition of vascular smooth muscle (VSM) delayed rectifier K
+
channels (K
DR
) by 4-aminopyridine (4-AP; 200 μmol/L) or correolide (1 μmol/L), a selective inhibitor of Kv1 channels, enhanced myogenic contraction of rat mesenteric arteries (RMAs) in response to increases in intraluminal pressure. The molecular identity of K
DR
of RMA myocytes was characterized using RT-PCR, real-time PCR, and immunocytochemistry. Transcripts encoding the pore-forming Kvα subunits, Kv1.2, Kv1.4, Kv1.5, and Kv1.6, were identified and confirmed at the protein level with subunit-specific antibodies. Kvβ transcript (β1.1, β1.2, β1.3, and β2.1) expression was also identified. Kv1.5 message was ≈2-fold more abundant than that for Kv1.2 and Kv1.6. Transcripts encoding these three Kv1α subunits were ≈2-fold more abundant in 1st/2nd order conduit compared with 4th order resistance RMAs, and Kvβ1 was 8-fold higher than Kvβ2 message. RMA K
DR
activated positive to −50 mV, exhibited incomplete inactivation, and were inhibited by 4-AP and correolide. However, neither α-dendrotoxin or κ-dendrotoxin affected RMA K
DR
, implicating the presence of Kv1.5 in all channels and the absence of Kv1.1, respectively. Currents mediated by channels because of coexpression of Kv1.2, Kv1.5, Kv1.6, and Kvβ1.2 in human embryonic kidney 293 cells had biophysical and pharmacological properties similar to those of RMA K
DR
. It is concluded that K
DR
channels composed of heteromultimers of Kv1 subunits play a critical role in myogenic control of arterial diameter.
A Randomized Controlled Trial of Early Supported Discharge and Continued Rehabilitation at Home After Stroke
Authors: Thorsén Ann-Mari , Widés Holmqvist Lotta , de Pedro-Cuesta Jesús , von Koch Lena
Published: December 2004

Background and Purpose—The optimal organization of rehabilitation services after discharge from a stroke unit has not been determined. This study sought to evaluate the effect of early supported discharge and continued rehabilitation at home (ESD), in terms of patient outcome 5 years after stroke and changes in selected data over time.

Methods—Eighty-three patients from Southwest Stockholm, mildly or moderately impaired 5 to 7 days after acute stroke, were enrolled in a randomized controlled trial. The core components of the ESD service were initial treatment in a stroke unit and the involvement of an outreach team to deliver and coordinate home-based rehabilitation in partnership with the patient. At the 5-year follow-up, measures used to assess patient outcome included survival, motor capacity, dysphasia, activities of daily living (ADL), social activities, subjective dysfunction, and self-reported falls.

Results—Fifty-four patients (30 in the intervention group and 24 in the control group) were evaluated 5 years after stroke, at which time a significantly larger proportion of patients in the intervention group were independent in extended ADL and active in household activities.

Conclusions—This ESD service has a beneficial effect on extended ADL 5 years after stroke for mildly to moderately impaired patients.
Understanding and Using the Implicit Association Test: II. Method Variables and Construct Validity
Authors: Nosek Brian A. , Greenwald Anthony G. , Banaji Mahzarin R.
Published: December 2004

The Implicit Association Test (IAT) assesses relative strengths of four associations involving two pairs of contrasted concepts (e.g., male-female and family-career). In four studies, analyses of data from 11 Web IATs, averaging 12,000 respondents per data set, supported the following conclusions: (a) sorting IAT trials into subsets does not yield conceptually distinct measures; (b) valid IAT measures can be produced using as few as two items to represent each concept; (c) there are conditions for which the administration order of IAT and self-report measures does not alter psychometric properties of either measure; and (d) a known extraneous effect of IAT task block order was sharply reduced by using extra practice trials. Together, these analyses provide additional construct validation for the IAT and suggest practical guidelines to users of the IAT.
The Shame of Failure: Examining the Link Between Fear of Failure and Shame
Authors: McGregor Holly A. , Elliot Andrew J.
Published: December 2004

The present research was designed to examine hypotheses derived from the proposition that shame is the core of fear of failure. Study 1 was conducted in a naturalistic setting and demonstrated that individuals high in fear of failure reported greater shame upon a perceived failure experience than those low in fear of failure. These findings were obtained controlling for other negative emotions. Study 2 was conducted in a controlled laboratory setting and demonstrated that high fear of failure individuals reported greater shame, overgeneralization, and closeness to their mother (controlling for baseline levels of these variables) than those low in fear of failure. Those high in fear of failure also reported that they would be less likely to tell their mother and father about their failure experience and would be more likely to tell their mother and father about their success experience. The implications of these findings for acquiring a deeper understanding of fear of failure are discussed.
Infrahumanization or Familiarity? Attribution of Uniquely Human Emotions to the Self, the Ingroup, and the Outgroup
Authors: Cortes Brezo P. , Demoulin Stéphanie , Rodriguez Ramon T. , Rodriguez Armando P. , Leyens Jacques-Philippe
Published: December 2004

People attribute more secondary emotions to their ingroup than to outgroups. This effect is interpreted in terms of infrahumanization theory. Familiarity also could explain this differential attribution because secondary emotions are thought to be less visible and intense than primary ones. This alternative explanation to infrahumanization was tested in three studies. In Study 1, participants attributed, in a between-participants design, primary and secondary emotions to themselves, to their ingroup, or to an outgroup. In Study 2, participants answered for themselves and their ingroup or for themselves and an outgroup. In Study 3, participants made attributions to the ingroup or a series of outgroups varying in terms of familiarity. The data do not support an explanation in terms of familiarity. The discussion centers on conditions not conducting to infrahumanization.
Personality Psychology’s Comeback and Its Emerging Symbiosis With Social Psychology
Authors: Swann William B. , Seyle Conor
Published: December 2004

Psychology’s early allegiance to behaviorism and experimental methods led many to disparage personality approaches throughout much of last century. Doubts about personality psychology’s viability culminated in Mischel’s assertion that measures of personality account for modest amounts of variance in behavior. In the years immediately following this critique, interest in personality research waned and many psychology departments dropped their training programs in personality. Throughout the past two decades, however, personality psychology has enjoyed a resurgence. The authors discuss several possible explanations for personality’s comeback and then describe the emergence of a promising symbiosis between personality psychology and its sister discipline, social psychology. The article concludes by noting that although this emerging symbiosis is likely to continue bearing considerable theoretical fruit, the traditional distinction between personal, situational, and interactional determinants of behavior continues to be useful within appropriate contexts.
The Past and the Future of Violence Against Women
Authors: Schwartz Martin D.
Published: December 2004

The most important thing we have learned about violence against women over the past 20 years is that violence is gendered and learned and can only be understood in the context of gender inequality. Most violence is male, and although some violence is done by females, it is far from equal and often done for very different reasons. Among other major findings is that children from violent households tend to grow up to be problematic, which means that a major method of curbing juvenile delinquency in 10 years is to stop violence against women today.
The Biology of Trauma
Authors: Solomon Eldra P. , Heide Kathleen M.
Published: December 2004

During the past 20 years, the development of brain imaging techniques and new biochemical approaches has led to increased understanding of the biological effects of psychological trauma. New hypotheses have been generated about brain development and the roots of antisocial behavior. We now understand that psychological trauma disrupts homeostasis and can cause both short and long-term effects on many organs and systems of the body. Our expanding knowledge of the effects of trauma on the body has inspired new approaches to treating trauma survivors. Biologically informed therapy addresses the physiological effects of trauma, as well as cognitive distortions and maladaptive behaviors. The authors suggest that the most effective therapeutic innovation during the past 20 years for treating trauma survivors has been Eye Movement Desensitization and Reprocessing (EMDR), a therapeutic approach that focuses on resolving trauma using a combination of top-down (cognitive) and bottom-up (affect/body) processing.
Reflections on Partner Violence
Authors: Rhatigan Deborah L. , Moore Todd M. , Street Amy E.
Published: December 2004

The authors reflect on past research and technology as well as their hopes for future innovations within the field of intimate partner violence. They review work that has contributed to current conceptual definitions of partner violence, particularly those that have shaped the field’s broadened perspective. They discuss technological and measurement innovations that have contributed to more accurate assessments of violence prevalence. The authors believe that via these technologies, the true extent of violence within the home has been made known. In conclusion, the authors argue that to reduce violence between partners, there is an overwhelming need for future researchers to build on past data, develop improved theories, and apply those ideas to prevention and intervention techniques and programs. Furthermore, they believe that it is imperative for current and future programs to be extensively evaluated and tested for their effectiveness.
The Zinc Finger Ikaros Transcription Factor Regulates Pituitary Growth Hormone and Prolactin Gene Expression through Distinct Effects on Chromatin Accessibility
Authors: Ezzat Shereen , Yu Shunjiang , Asa Sylvia L.
Published: December 2004

The Ikaros transcription factors perform critical functions in the control of lymphohematopoiesis and immune regulation. Family members contain multiple zinc fingers that mediate DNA binding but have also been implicated as part of a complex chromatin-remodeling network. We show here that Ikaros is expressed in pituitary mammosomatotrophs where it regulates the GH and prolactin (PRL) genes. Ikaros was detected by Northern and Western blotting in GH4 pituitary mammosomatotroph cells. Wild-type Ikaros (Ik1) inhibits GH mRNA and protein expression but stimulates PRL mRNA and protein levels. Ikaros does not bind directly to the proximal GH promoter but abrogates the effect of the histone deacetylation inhibitor trichostatin A on this region. Ikaros selectively deacetylates histone 3 residues on the proximal transfected or endogenous GH promoter and limits access of the Pit1 activator. In contrast, Ikaros acetylates histone 3 on the proximal PRL promoter and facilitates Pit1 binding to this region in the same cells. These data provide evidence for Ikaros-mediated histone acetylation and chromatin remodeling in the selective regulation of pituitary GH and PRL hormone gene expression.
Nouvelles données concernant le lysozyme de blanc d'œuf d'Oie: Teneur en tryptophane, stabilité et spécificité
Authors: Dianoux Anne‐Christine , Jollès Pierre
Published: December 2004

New data concerning the tryptophan content, the stability, and the specificity of goose egg‐white lysozyme are reported. This enzyme occupies a special place among the mammelian lysozymes already studied and the general definition of a lysozyme had to be modified. The mechanism of action is discussed.
Totalsynthese und absolute Konfiguration von natürlichem Multifloramin
Authors: Brossi A. , O'Brien J. , Teitel S.
Published: December 2004

The diphenol 1 was resolved into its antipodes and their absolute configuration was established. The levorotatory isomer R‐(−)‐1 was oxidized to the dienone R‐(−)‐6, which was rearranged to afford natural (−)‐multifloramine (R‐(−)‐7), thus establishing that the latter has the R‐configuration. By the same reaction sequences, the enantiomeric diphenol S‐(+)‐1 was transformed to provide (+)‐multifloramine (S‐(+)‐7) of the S‐configuration.
Indolalkaloide aus Conopharyngia durissima STAPF. 134. Mitteilung über Alkaloide [1]
Authors: Dugan J. J. , Hesse M. , Renner U. , Schmid H.
Published: December 2004

The alkaloids akuammiline (1) and anhydrovobasindiol (6) were isolated from the trunk bark of the Apocynacea Conopharyngia durissima STAPF. The structure of the unknown base anhydrovobasindiol was elucidated and this base was partially synthetised from the alkaloid vobasine. The well‐known akuammiline could be correlated by LiAlH4 reduction to picralinol (4).
Photochemische Reaktionen. 50. Mitteilung [1]. Zur Photochemie von gesättigten β‐Ketosulfiden II. Synthese von 6‐Hydroxy‐2‐thia‐7‐oxa‐isotwistan
Authors: Ganter C. , Moser J.‐F.
Published: December 2004

The results of the ultraviolet irradiation of the saturated β‐ketosulfide 2 are discussed. The photochemistry of 2 is characterized by the occurrence of two primary photoprocesses. Their efficiences depend markedly on the excited transition, (charge‐transfer)‐ or (n → π*)‐excitation, respectively. In methanol solution (charge‐transfer)‐excitation leads almost exclusively to product 7, due to (Cα – S)‐fission, and (n → π*)‐excitation to nearly equal amounts of 7 and of products 4 and 6 which result from α‐cleavage. On solvent sensibilization in benzene products 4, 6, 7 and the still unidentified product 52 are formed.

Compounds 4 and 6 have been described earlier [2]. The structure elucidation of 7 is reported in this paper. Acid‐induced transformation of 7 yields the dihetero‐isotwistane 15.
Crocetindialdehyd und Crocetinhalbaldehyd als Blütenferbstoffe von Jacquinia angustifolia
Authors: Eugster C. H. , Hürlimann H. , Leuenberger H. J.
Published: December 2004

Crocetindialdehyd und Crocetinhalbaldhyd wurden aus den Blüten von Jacquinia angustifolia isoliert.
Sur la composition de l'arôme de tomate
Authors: Viani R. , Bricout J. , Marion J. P. , Müggler‐Chavan F. , Reymond D. , Egli R. H.
Published: December 2004

A gas‐chromatographic investigation of tomato aroma has revealed 46 components of which 32 are new. The isolation and identification of 2‐isobutyl‐thiazole, substance for the first time found in a natural aroma, are given in detail.
Photochemische Umwandlungen. 30. Mitteilung [1]. Zur Kinetik der Norbornadien‐Quadricyclan‐Photocycloaddition
Authors: Kaupp G. , Prinzbach H.
Published: December 2004

Quantum yields for several norbornadiene → quadricyclane conversions have been determined under various experimental conditions (Tab. 1). The data are interpreted in terms of a singlet intermediate of type 15.