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Dependent
Kinds of Dependent Terms modified by Dependent Selected AbstractsREMATING IN DROSOPHILA MELANOGASTER: ARE INDIRECT BENEFITS CONDITION DEPENDENT?EVOLUTION, Issue 9 2010Tristan A. F. Long By measuring the direct and indirect fitness costs and benefits of sexual interactions, the feasibility of alternate explanations for polyandry can be experimentally assessed. This approach becomes more complicated when the relative magnitude of the costs and/or benefits associated with multiple mating (i.e., remating with different males) vary with female condition, as this may influence the strength and direction of sexual selection. Here, using the model organism Drosophila melanogaster, we test whether the indirect benefits that a nonvirgin female gains by remating ("trading-up") are influenced by her condition (body size). We found that remating by small-bodied, low-fecundity females resulted in the production of daughters of relatively higher fecundity, whereas the opposite pattern was observed for large-bodied females. In contrast, remating had no measurable effect on the relative reproductive success of sons from dams of either body size. These results are consistent with a hypothesis based on sexually antagonistic genetic variation. The implications of these results to our understanding of the evolution and consequences of polyandry are discussed. [source] HIGH GLUCOSE-INDUCED HUMAN UMBILICAL VEIN ENDOTHELIAL CELL HYPERPERMEABILITY IS DEPENDENT ON PROTEIN KINASE C ACTIVATION AND INDEPENDENT OF THE Ca2+,NITRIC OXIDE SIGNALLING PATHWAYCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 9 2005Lei Dang SUMMARY 1.,Endothelial barrier dysfunction plays a pivotal role in the pathogenesis of diabetic vascular complications. The precise molecular mechanisms by which hyperglycaemia causes the increased permeability in endothelial cells are not yet well understood. In the present study, we investigated whether high concentrations of glucose induce endothelial permeability through the activation of protein kinase C (PKC) and/or the calcium,nitric oxide (NO) signalling pathway in human umbilical vein endothelial cells (HUVEC). 2.,Endothelial permeability was measured by albumin diffusion across endothelial monolayers under the stimuli of high glucose (HG; 20 mmol/L), 100 nmol/L phorbol-myristate-acetate (PMA) or 100 nmol/L histamine. The intracellular calcium concentration ([Ca2+]i) was detected in HUVEC using the fluorescent probe fura-2 AM. The effects of PKC inhibitors (LY379196 and hypocrellin A) and the NO synthase (NOS) inhibitor NG -monomethyl- l -arginine (l -NMMA) on endothelial permeability and [Ca2+]i were determined. 3.,High glucose and PMA increased endothelial permeability associated with decreased [Ca2+]i, whereas histamine triggered significant increases in endothelial permeability, accompanied by increases in [Ca2+]i in HUVEC. Hypocrellin A (HA) and LY379196 reversed both HG- and histamine-induced endothelial permeability. The NOS inhibitor l -NMMA only abolished histamine- and not HG-induced endothelial permeability. Neither LY379196, HA nor l -NMMA had any significant effects on alterations in [Ca2+]i caused by HG and histamine. 4.,These results indicate that increased endothelial permeability in HUVEC induced by HG is dependent on PKC activity and is independent of the [Ca2+]i,NO pathway. Increased endothelial permeability due to other inflammatory factors, such as histamine, may also be mediated by the PKC pathway. Thus, PKC inhibitors would be a potential therapeutic approach to endothelial dysfunction induced by hyperglycaemia, as well as other inflammatory factors, in diabetes. [source] Pediatric Interventional Cardiology in the United States is Dependent on the Off-label Use of Medical DevicesCONGENITAL HEART DISEASE, Issue 1 2010Jamie S. Sutherell MD ABSTRACT Objective., A substantial unmet medical device need exists in pediatric care. As a result, the off-label use of approved devices is routine in pediatric interventional cardiology, but the extent and nature of this practice has not been previously described. The purpose of this study, therefore, is to evaluate the prevalence and nature of off-label cardiac device use in an active pediatric interventional program in the United States. Study Design., This study is a retrospective review of all interventional cardiac procedures performed at our institution from July 1, 2005 to June 30, 2008. Diagnostic (noninterventional) catheterizations, myocardial biopsies, invasive electrophysiology studies, and studies involving investigational devices were excluded. Interventions performed were compared with the manufacturer's labeled indications for each device. Results., During this 3-year period, 473 patients (median age 4.1 years) underwent 595 transcatheter interventions. An approved device was utilized for an off-label application in 63% of patients, and in 50% of all interventions performed. The most frequent off-label procedures were stent implantations (99% off-label), balloon dilations (78% off-label), and coil embolizations (29% off-label). In contrast, the off-label use of septal and ductal occluders was relatively uncommon. Conclusions., In our routine (noninvestigational) practice of pediatric interventional cardiology, 63% of patients underwent procedures utilizing medical devices for off-label indications. These data underscore the need to enhance cardiac device review and approval processes in the United States to include pediatric applications. [source] Neuronal differentiation and long-term survival of newly generated cells in the olfactory midbrain of the adult spiny lobster, Panulirus argusDEVELOPMENTAL NEUROBIOLOGY, Issue 3 2001Manfred Schmidt Abstract The fate of continuously generated cells in the soma clusters of the olfactory midbrain of adult spiny lobsters, Panulirus argus, was investigated by in vivo pulse-chase experiments with the proliferation marker 5-bromo-2,-deoxyuridine (BrdU) combined with immunostainings for neuropeptides of mature neurons. A BrdU injection after a survival time (ST) of 14 h labeled about 100 nuclei in the lateral soma clusters (LC), comprised of projection neurons, and about 30 nuclei in the medial soma clusters (MC), comprised of local interneurons. The BrdU-positive nuclei were confined to small regions at the inside of these clusters, which also contain nuclei in different phases of mitosis and thus represent proliferative zones. After STs of 2 weeks or 3 months, the number of BrdU-positive nuclei was doubled, indicating a mitosis of all originally labeled cells. Dependent on ST, the BrdU-positive nuclei were translocated from the proliferative zones towards the outside of the clusters, where somata of mature neurons reside. Immunostainings with antibodies to the neuropeptides FMRFamide and substance P, both of which label a large portion of somata in the MC and a pair of giant neurons projecting into the LC, revealed that in both clusters the proliferative zones are surrounded by, but are themselves devoid of, labeling. In the MC, some BrdU-positive somata were double-labeled by the FMRFamide antibody after an ST of 3 months, and by the substance P antibody after STs of 6 and 11/14 months, but not after 3 months. In the LC, BrdU-positive somata after an ST of 3 months partially and after 6 and 11/14 months widely overlapped with the arborizations of the giant neurons, indicating the establishment of synaptic input. The experiments show that cells generated in proliferative zones in the LC and MC of adult spiny lobsters after a final mitosis differentiate into neurons within months, survive for at least 1 year, and are integrated into the circuitry of the olfactory midbrain. A new hypothesis about the mechanism of adult neurogenesis in the central olfactory pathway of decapod crustaceans is developed, linking it to neurogenesis during embryonic and larval development. © 2001 John Wiley & Sons, Inc. J Neurobiol 48: 181,203, 2001 [source] Maternal Effort is State Dependent: Energetic Limitation or Regulation?ETHOLOGY, Issue 4 2008Anke Rehling Many small altricial rodents have a postpartum oestrus and are often simultaneously pregnant and lactating. Negative influences of concurrent pregnancy and lactation on both lactational performance and the litter in utero are commonly observed and have been interpreted as resulting from high simultaneous energetic demands of gestation and lactation. We studied these effects in the precocial guinea-pig (Cavia aperea f. porcellus) that, like many altricial rodents, has a postpartum oestrus, but in which the peaks of energy expenditure on lactation and gestation are widely separated. This life history allowed to investigate whether physiological regulation other than by energetic limitations may be responsible for allocation conflicts arising when lactation and gestation overlap. By comparing simultaneously pregnant and lactating females with lactating non-pregnant females, we show that females in the former group nurse less and wean earlier than females of the latter group. In a comparison of litter size, litter mass, and pup mortality of females that had not been lactating during pregnancy with females that had been simultaneously pregnant and lactating, we show that the latter do not reduce investment in the following litter. In our study, energetic constraints on ad libitum fed females are unlikely and we therefore suggest that the results must be explained by regulatory constraints on lactational effort. We point out that this explanation has not been excluded for the effects observed in altricial small mammals. [source] Net Shape Reaction Bonded Ceramic Micro Parts by Mechanical MicrostructuringADVANCED ENGINEERING MATERIALS, Issue 10 2006H.-J. Ritzhaupt-Kleissl Net shape ceramic micro components can be realized by mechanical microstructuring green blanks consisting of precursor materials followed by reaction bonding. The precursor material is composed of mainly zirconium silicide as reactive precursor material, organosilicon polymer (PMSS) as low loss binder and zirconium oxide as an inert phase. Shaping in the green state can easily be performed by micro milling, even if different cutting strategies are applied. Subsequently the components are thermally processed for ceramization and for sintering them to full density. Dependent on the material composition and on the green density the dimensions of the sintered components are retained unchanged compared to the dimensions of the green parts. [source] The Secretory Response of the Rat Colon to the Flavonol Quercetin is Dependent on Ca2+ -CalmodulinEXPERIMENTAL PHYSIOLOGY, Issue 3 2000R. Cermak The dietary flavonol quercetin induces chloride secretion in rat intestine. To clarify the underlying mechanisms, experiments were performed in Ussing chambers with tissue from rat proximal and distal colon. Quercetin induced an increase in short-circuit current (Isc), which was largely independent of submucosal neurons, as it was not affected by the neurotoxin tetrodotoxin. The effect of quercetin was blocked by the calmodulin antagonists trifluoperazine and ophiobolin A and was diminished by a blocker of Ca2+ release from intracellular stores (TMB-8), whereas the muscarinic receptor antagonist atropine was ineffective. The quercetin-induced Isc was abolished in Ca2+ -free solution. The flavonol was able to further increase Isc after maximal stimulation of the cAMP pathway by forskolin. The Isc increase by the flavonol was differently affected by two analogous phosphodiesterase inhibitors. Whereas 3-isobutyl-1-methylxanthine (IBMX) antagonized the effect of quercetin, 8-methoxymethyl-IBMX had no effect. Both phosphodiesterase inhibitors similarly influenced the Isc increase induced by forskolin. These results indicate that the chloride secretion induced by quercetin in rat colon depends on Ca2+ and calmodulin. The cAMP pathway and inhibition of phosphodiesterase appear not to be responsible for the secretory activity of the flavonol. [source] Construction of hybrid peptide synthetases for the production of ,- l -aspartyl- l -phenylalanine, a precursor for the high-intensity sweetener aspartameFEBS JOURNAL, Issue 22 2003Thomas Duerfahrt Microorganisms produce a large number of pharmacologically and biotechnologically important peptides by using nonribosomal peptide synthetases (NRPSs). Due to their modular arrangement and their domain organization NRPSs are particularly suitable for engineering recombinant proteins for the production of novel peptides with interesting properties. In order to compare different strategies of domain assembling and module fusions we focused on the selective construction of a set of peptide synthetases that catalyze the formation of the dipeptide ,- l -aspartyl- l -phenylalanine (Asp-Phe), the precursor of the high-intensity sweetener ,- l -aspartyl- l -phenylalanine methyl ester (aspartame). The de novo design of six different Asp-Phe synthetases was achieved by fusion of Asp and Phe activating modules comprising adenylation, peptidyl carrier protein and condensation domains. Product release was ensured by a C-terminally fused thioesterase domains and quantified by HPLC/MS analysis. Significant differences of enzyme activity caused by the fusion strategies were observed. Two forms of the Asp-Phe dipeptide were detected, the expected ,-Asp-Phe and the by-product ,-Asp-Phe. Dependent on the turnover rates ranging from 0.01,0.7 min,1, the amount of ,-Asp-Phe was between 75 and 100% of overall product, indicating a direct correlation between the turnover numbers and the ratios of ,-Asp-Phe to ,-Asp-Phe. Taken together these results provide useful guidelines for the rational construction of hybrid peptide synthetases. [source] The influence of oxygen saturation on the distributional overlap of predator (cod, Gadus morhua) and prey (herring, Clupea harengus) in the Bornholm Basin of the Baltic SeaFISHERIES OCEANOGRAPHY, Issue 1 2002Stefan Neuenfeldt Environmental heterogeneity can create boundary conditions for the co-occurrence of marine predators and their prey. If one or both are spatially constrained by their tolerance to environmental variables, then spatial differences in the availability of possible habitats define the volume of distributional overlap. Cod (Gadus morhua L.) and its prey, herring (Clupea harengus L.), in the vertically stratified Bornholm Basin of the Baltic Sea are presented as an example. A non-linear model was used to estimate oxygen avoidance thresholds for both species. Herring avoided oxygen saturation levels below 50%, while cod tolerated oxygen saturation down to 16%. The threshold of 50% oxygen saturation, below which cod could not encounter its prey, herring, was applied to a time series of vertical oxygen profiles from the centre of the Bornholm Basin to estimate the size of the overlap volume during the winter period from 1958 to 1999. Dependent on the oxygenation of the deep-water, the overlap volume varied between 57 km3 and 250 km3. [source] Interleukin-6 Induction by Helicobacter pylori in Human Macrophages is Dependent on PhagocytosisHELICOBACTER, Issue 3 2006Stefan Odenbreit Abstract Background:, The colonization of the gastric mucosa with Helicobacter pylori is accompanied by elevated levels of proinflammatory cytokines, such as interleukin-1 (IL-1), IL-6, and IL-8. The aim of our study was to determine the mechanisms of IL-6 stimulation in phagocytes upon H. pylori infection. Materials and Methods:, We investigated the secretion of IL-6 by different professional phagocytes from murine and human origin, including granulocyte- and monocyte-like cells and macrophages derived from human peripheral blood monocytes (PBMCs). The influence of viability, phagocytosis, and the impact of different subcellular fractions of H. pylori bacteria were evaluated. Results:, IL-6 levels induced by H. pylori were low in cell lines derived from murine and human monocytes and in human granulocyte-like cells. By contrast, macrophages derived from human PBMCs were highly responsive to both H. pylori and Escherichia coli. IL-6 induction was blocked by inhibition of actin-dependent processes prior to infection with H. pylori, but not with E. coli or E. coli lipopolysaccharide (LPS). Using cell fractionation, the most activity was found in the H. pylori membrane. H. pylori LPS exhibited a 103 - to 104 -fold lower biologic activity than E. coli LPS, suggesting a minor role for toll-like receptor 4 (TLR4)-mediated signalling from the exterior. Conclusions:, From these data, we conclude that macrophages may be a major source of IL-6 in the gastric mucosa upon H. pylori infection. The IL-6 induction by H. pylori in these cells is a multifactorial process, which requires the uptake and presumably degradation of H. pylori bacteria. [source] Effect of the anti-tumor necrosis factor-, antibody infliximab on the ex vivo mucosal matrix metalloproteinase,proteolytic phenotype in inflammatory bowel diseaseINFLAMMATORY BOWEL DISEASES, Issue 2 2007Martin J. Meijer MSc Abstract Background: Previous studies have shown an upregulation of matrix metalloproteinases (MMPs) in intestinal tissue of patients with inflammatory bowel disease (IBD) and significant clinical improvement after administration of the anti-TNF-, antibody infliximab. The aims of our study were to determine expression and secretion of MMP-1, -2, -3, -9, and their inhibitors TIMP-1, -2 by IBD versus control intestinal mucosa ex vivo and to assess the regulatory capacity by infliximab of the proteolytic phenotype. Methods: Intestinal mucosal explants from 20 IBD and 15 control patients were cultured with or without infliximab and/or the T-cell activator pokeweed mitogen (PWM). Explants and culture supernatants were analyzed for MMPs, TIMPs, and TNF-, protein, activity and/or mRNA levels. All patients were genotyped for functional TNF-,, MMP, and TIMP single nucleotide polymorphism (SNP) loci. Results: Expression of MMP and TIMP protein/activity in basal medium was higher in IBD versus control explants. Dependent on genotype at SNP loci, infliximab downregulated MMP-1, -3, and -9 relative to TIMP-1 and -2 and also decreased MMP-1 and -3 activities, while PWM enhanced these levels, partly counteracted again by infliximab. The expression of MMP-2 relative to TIMP did not change by treatment with infliximab and/or PWM. Conclusions: The high expression of MMPs in patients with IBD suggests a role for these proteinases in the pathogenesis of this disease. Infliximab seems to induce a genotype-associated matrix protective phenotype, which may contribute to the observed therapeutic efficacy of this drug in IBD, particularly at the mucosal surface. (Inflamm Bowel Dis 2007) [source] LPS-Induced Inhibition of Osteogenesis Is TNF-, Dependent in a Murine Tooth Extraction Model,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 10 2009Nobuyoshi Tomomatsu Abstract TNF-, is a major etiologic factor of inflammatory bone diseases such as periodontitis and rheumatoid arthritis. In addition, patients with metabolic diseases such as chronic heart disease and diabetes have significantly increased plasma levels of TNF-,. Several lines of evidence show inhibition of osteoblastogenesis by TNF-, in vitro. Therefore, bone formation and osteogenesis in these patients might be inhibited because of TNF-,. However, little is known about the inhibitory role of TNF-, in bone formation/osteogenesis in vivo. The purpose of this study was to investigate the role of TNF-, in osteogenesis using a murine tooth extraction model. Lipopolysaccharide (LPS) was injected subcutaneously into the calvariae of either wildtype (WT) or TNF-,,deficient (KO) mice. The left incisor was extracted 4 days after LPS injection. The measuring area was established as the tooth socket under the mesial root of the first molar. A significant increase in serum TNF-, levels after LPS injection was observed in WT mice. The BMD of the tooth socket was significantly decreased by LPS injection 21 days after extraction in WT but not in KO mice. Histomorphometric analysis showed a significant decrease in the mineral apposition rate after LPS injection, which appeared at an early stage in WT but not in KO mice. Injection of a peptide that blocked the TNF-, signaling pathway by preventing transmission of the NF-,B signal recovered the inhibition of osteogenesis observed after LPS injection. In conclusion, TNF-, might play a major role in LPS-induced inhibition of osteogenesis under inflammatory conditions. [source] Fluid Flow Induction of Cyclo-Oxygenase 2 Gene Expression in Osteoblasts Is Dependent on an Extracellular Signal-Regulated Kinase Signaling Pathway,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 2 2002Sunil Wadhwa Abstract Mechanical loading of bone may be transmitted to osteocytes and osteoblasts via shear stresses at cell surfaces generated by the flow of interstitial fluid. The stimulated production of prostaglandins, which mediates some effects of mechanical loading on bone, is dependent on inducible cyclo-oxygenase 2 (COX-2) in bone cells. We examined the fluid shear stress (FSS) induction of COX-2 gene expression in immortalized MC3T3-E1 osteoblastic cells stably transfected with ,371/+70 base pairs (bp) of the COX-2 5,-flanking DNA (Pluc371) and in primary osteoblasts (POBs) from calvaria of mice transgenic for Pluc371. Cells were plated on collagen-coated glass slides and subjected to steady laminar FSS in a parallel plate flow chamber. FSS, from 0.14 to10 dynes/cm2, induced COX-2 messenger RNA (mRNA) and protein. FSS (10 dynes/cm2) induced COX-2 mRNA within 30 minutes, with peak effects at 4 h in MC3T3-E1 cells and at ,8 h in POBs. An inhibitor of new protein synthesis puromycin blocked the peak induction of COX-2 mRNA by FSS. COX-2 promoter activity, measured as luciferase activity, correlated with COX-2 mRNA expression in both MC3T3-E1 and POB cells. FSS induced phosphorylation of extracellular signal-regulated kinase (ERK) in MC3T3-E1 cells, with peak effects at 5 minutes. Inhibiting ERK phosphorylation with the specific inhibitor PD98059 inhibited FSS induction of COX-2 mRNA by 55-70% and FSS stimulation of luciferase activity by ,80% in both MC3T3-E1 and POB cells. We conclude that FSS transcriptionally induces COX-2 gene expression in osteoblasts, that the maximum induction requires new protein synthesis, and that induction occurs largely via an ERK signaling pathway. [source] BRAF V599E Mutation is Not Age Dependent: It is Present in Common Melanocytic Nevi in Both Children and AdultsJOURNAL OF CUTANEOUS PATHOLOGY, Issue 1 2005J. Cohen BRAF encodes a serine-threonine kinase, which acts in the RAS/RAF/MAPK pathway transducing regulatory signals from RAS to MEK1/2. Somatic mutations in BRAF have been identified in 53,80% of primary melanomas and 70,90% of common melanocytic nevi. More than 90% of these mutations consist of a valine to glutamate substitution at codon 599 (V599E) of exon 15. While a high prevalence of BRAF mutations in common melanocytic nevi has been reported in adults, nevi in children have not been studied. Of interest, we have previously shown that Spitz nevi in children do not harbor mutations in BRAF. To investigate the association of BRAF mutations with patient age, we studied common melanocytic nevi in children for the V599E activating mutation. Tumor cells were microdissected from 6 common melanocytic nevi in children 10 years of age or younger, and analyzed for the V599E mutation in BRAF by allele-specific PCR and gel electrophoresis. In 6 of 6 (100%) nevi, the V599E mutant allele was observed. Our data suggest that similar genetic pathways are involved in the development of common melanocytic nevi in children and adults. The absence of BRAF mutations in Spitz nevi in children is therefore associated with tumor type, not patient age. [source] Dependent and Accountable: Evidence from the Modern Theory of Central BankingJOURNAL OF ECONOMIC SURVEYS, Issue 5 2000Gustavo Piga In this paper we take another look at the literature on central bank independence. We show that the representative-agent approach to monetary policy is seriously flawed and does not provide a sound basis for deriving institutional solutions to the inflationary-bias. We then argue that the political approach to monetary policy provides a better account of the inflationary-bias and that this has important implications for the set-up of institutional arrangements, like central-bank independence, and the role of contractual arrangements, like indexation. Central bank independence, if appropriately modeled, can fail to reduce inflationary pressures in plausible circumstances. We then identify some issues in the theory of central banking that have not been clearly resolved and we offer some intuition as to the way they could be studied. We conclude by showing some potentially worrisome implications for the future of the European Monetary Union. [source] Differential interictal activity of the precuneus/posterior cingulate cortex revealed by resting state functional MRI at 3T in generalized vs.JOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 6 2008Partial seizure Abstract Purpose To characterize, using functional MRI (fMRI), the pattern of active brain regions in the resting state in patients with epilepsy. Materials and Methods We studied 28 patients with epilepsy, divided into a partial seizure (PS; N = 9) and a generalized seizure group (GS; N = 19), and 34 control subjects. Resting state fMRI was performed using a GE 3T scanner by collecting 200 volumes of echo-planar imaging (EPI) images with subjects relaxed, eyes closed. Data were processed using a modification of the method of Fransson (Hum Brain Mapp 2005;26:15,29), which reveals information on regional low-frequency Blood Oxygenation Level Dependent (BOLD) signal oscillations in the resting state without any a priori hypothesis. The significant active areas in brain were identified with both individual and group analysis. Results Controls showed active regions in the precuneus/posterior cingulate cortex (PCC) and medial prefrontal cortex (MPFC)/ventral anterior cingulate cortex (vACC), theregions associated with the brain "default mode." Similar active regions were observed in PS, whereas GS showed no significant activation of precuneus/PCC. Conclusion In GS, the lack of activation in precuneus/PCC may partly account for their more severe interictal deficits, compared to PS, in cognitive functions such as concentration and memory. J. Magn. Reson. Imaging 2008;27:1214,1220. © 2008 Wiley-Liss, Inc. [source] Expression of the Hypothalamic Transcription Factor Nhlh2 is Dependent on Energy AvailabilityJOURNAL OF NEUROENDOCRINOLOGY, Issue 7 2007K. R. Vella Mice with a deletion of the hypothalamic basic helix-loop-helix transcription factor Nhlh2 display adult onset obesity, implicating Nhlh2 in the neuronal circuits regulating energy availability. Nhlh2 colocalises with the hypothalamic thyrotrophin-releasing hormone (TRH) neurones in the paraventricular nucleus (PVN) and pro-opiomelanocortin (POMC) neurones in the arcuate nucleus. We show that Nhlh2 expression is significantly reduced in response to 24-h food deprivation in the arcuate nucleus, PVN, lateral hypothalamus, ventromedial hypothalamus (VMH) and dorsomedial hypothalamus (DMH). Food intake for 2 h following deprivation stimulates Nhlh2 expression in the arcuate nucleus and the PVN, and leptin injection following deprivation results in increased Nhlh2 expression in the arcuate nucleus, PVN, lateral hypothalamus, VMH, and DMH. Hypothalamic Nhlh2 expression in response to leptin injection is maximal by 2 h. Following leptin injection, Nhlh2 mRNA colocalises in POMC neurones in the arcuate nucleus and TRH neurones in the PVN. Nhlh2 mRNA expression in POMC neurones in the arcuate nucleus and TRH neurones in the PVN is reduced with energy deprivation and is stimulated with food intake and leptin injection. Modulation of POMC expression in response to changes in energy availability is not affected in mice with a targeted deletion of Nhlh2. However, deletion of Nhlh2 does result in loss of normal TRH mRNA expression in mice exposed to food deprivation and leptin stimulation. These data implicate Nhlh2 as a regulatory target of the leptin-mediated energy availability network of the hypothalamus, and TRH as a putative downstream target of Nhlh2. [source] The Expression of an Alcohol Deprivation Effect in the High,Alcohol-Drinking Replicate Rat Lines Is Dependent On Repeated DeprivationsALCOHOLISM, Issue 6 2000Zachary A. Rodd-Henricks Background: The alcohol deprivation effect (ADE) is a temporary increase in the ratio of alcohol/total fluid intake and voluntary intake of ethanol (EtOH) solutions over baseline drinking conditions when EtOH access is reinstated after a period of alcohol deprivation. The ADE has been posited to be an animal model for alcohol craving. In the current study, we examined the effects of initial deprivation length and number of deprivation exposures on the ADE in the replicate lines of the high,alcohol-drinking (HAD) rats. Methods: Adult male HAD-1 and HAD-2 rats received 24 hr free-choice access to 10% (v/v) EtOH and water for 6 weeks. Rats were then assigned to groups deprived of EtOH for 0 (control), or 2 to 8 weeks. All deprived groups were then given 24 hr access to EtOH for 2 weeks before being deprived of EtOH for another 2 weeks. This cycle of 2 weeks of access and 2 weeks of deprivation was carried out for a total of four deprivations. Results: After the initial EtOH deprivation period, EtOH consumption in HAD-1 and HAD-2 rats returned to baseline levels but failed to exhibit either an early onset ADE (initial 2 hr) or prolonged ADE (24 hr). An ADE was observed in two of the four deprived groups for the HAD-1 rats (2 week and 6 week groups) and in all deprived groups for the HAD-2 rats after a second deprivation, and in all deprived groups of both lines after a third deprivation. In the HAD-2 line, but not in the HAD-1 line, the duration of the ADE was prolonged into the second reinstatement day after the fourth deprivation. Conclusions: The expression of an ADE was observed only after repeated deprivation periods in the HAD lines. The duration of the ADE was prolonged in the HAD-2 line, but not in the HAD-1 line, with repeated deprivations, which suggests a dissociation between selection for alcohol preference and the effects of repeated deprivations on the duration of the ADE. [source] Mass and lifetime measurements of exotic nuclei in storage ringsMASS SPECTROMETRY REVIEWS, Issue 5 2008Bernhard Franzke Abstract Mass and lifetime measurements lead to the discovery and understanding of basic properties of matter. The isotopic nature of the chemical elements, nuclear binding, and the location and strength of nuclear shells are the most outstanding examples leading to the development of the first nuclear models. More recent are the discoveries of new structures of nuclides far from the valley of stability. A new generation of direct mass measurements which allows the exploration of extended areas of the nuclear mass surface with high accuracy has been opened up with the combination of the Experimental Storage Ring ESR and the FRragment Separator FRS at GSI Darmstadt. In-flight separated nuclei are stored in the ring. Their masses are directly determined from the revolution frequency. Dependent on the half-life two complementary methods are applied. Schottky Mass Spectrometry SMS relies on the measurement of the revolution frequency of electron cooled stored ions. The cooling time determines the lower half-life limit to the order of seconds. For Isochronous Mass Spectrometry IMS the ring is operated in an isochronous ion-optical mode. The revolution frequency of the individual ions coasting in the ring is measured using a time-of-flight method. Nuclides with lifetimes down to microseconds become accessible. With SMS masses of several hundreds nuclides have been measured simultaneously with an accuracy in the 2,×,10,7 -range. This high accuracy and the ability to study large areas of the mass surface are ideal tools to discover new nuclear structure properties and to guide improvements for theoretical mass models. In addition, nuclear half-lives of stored bare and highly charged ions have been measured. This new experimental development is a significant progress since nuclear decay characteristics are mostly known for neutral atoms. For bare and highly charged ions new nuclear decay modes become possible, such as bound-state beta decay. Dramatic changes in the nuclear lifetime have been observed in highly charged ions compared to neutral atoms due to blocking of nuclear decay channels caused by the modified atomic interaction. High ionization degrees prevail in hot stellar matter and thus these experiments have great relevance for the understanding of the synthesis of elements in the universe and astrophysical scenarios in general. © 2008 Wiley Periodicals, Inc., Mass Spec Rev 27: 428,469, 2008 [source] Radiation Sources Providing Increased UVNUVB Ratios Induce Photoprotection Dependent on the UVA Dose in Hairless MicePHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 2 2006Vivienne E. Reeve ABSTRACT In studies involving mice in which doses of UVA (320,400 nm) and UVB (290,320 nm) radiation were administered alone or combined sequentially, we observed a protective effect of UVA against UVB-induced erythemdedema and systemic suppression of contact hypersensitivity. The UVA immunoprotection was mediated by the induction of the stress enzyme heme oxygenase-1 (HO-1) in the skin, protection of the cutaneous Th1 cytokines interferon-gM (IFN-,) and IL-12 and inhibition of the UVB-induced expression of the Th2 cytokine IL-10. In this study, we seek evidence for an immunological waveband interaction when UVA and UVB are administered concurrently to hairless mice as occurs during sunlight exposure in humans. A series of spectra providing varying ratios of UVA/UVB were developed, with the UVA ratio increased to approximately 3.5 times the UVA component in solar simulated UV (SSUV). We report that progressively increasing the UVA component of the radiation while maintaining a constant UVB dose resulted in a reduction of both the erythemdedema reaction and the degree of systemic immunosuppression, as measured as contact hypersensitivity. The UVA-enhanced immunoprotection was abrogated in mice treated with a specific HO enzyme inhibitor. UVA-enhanced radiation also upregulated the expression of cutaneous IFN-, and IL-12 and inhibited expression of both IL-6 and IL-10, compared with the activity of SSUV. The results were consistent with the previously characterized mechanisms of photoprotection by the UVA waveband alone and suggest that the UVA component of solar UV may have beneficial properties for humans. [source] Porphyrin Bleaching and PDT-induced Spectral Changes are Irradiance Dependent in ALA-sensitized Normal Rat Skin In Vivo,PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 1 2001Jarod C. Finlay ABSTRACT Photobleaching kinetics of aminolevulinic acid,induced protoporphyrin IX (PpIX) were measured in the normal skin of rats in vivo using a technique in which fluorescence spectra were corrected for the effects of tissue optical properties in the emission spectral window through division by reflectance spectra acquired in the same geometry and wavelength interval and for changes in excitation wavelength optical properties using diffuse reflectance measured at the excitation wavelength. Loss of PpIX fluorescence was monitored during photodynamic therapy (PDT) performed using 514 nm irradiation. Bleaching in response to irradiances of 1, 5 and 100 mW cm,2 was evaluated. The results demonstrate an irradiance dependence to the rate of photobleaching vs irradiation fluence, with the lowest irradiance leading to the most efficient loss of fluorescence. The kinetics for the accumulation of the primary fluorescent photoproduct of PpIX also exhibit an irradiance dependence, with greater peak accumulation at higher irradiance. These findings are consistent with a predominantly oxygen-dependent photobleaching reaction mechanism in vivo, and they provide spectroscopic evidence that PDT delivered at low irradiance deposits greater photodynamic dose for a given irradiation fluence. We also observed an irradiance dependence to the appearance of a fluorescence emission peak near 620 nm, consistent with accumulation of uroporphyrin/coproporphyrin in response to mitochondrial damage. [source] Effector Functions of Donor-Reactive CD8 Memory T Cells Are Dependent on ICOS Induced During Division in Cardiac GraftsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2009A. D. Schenk Alloreactive T-cell memory is present in every transplant recipient and endangers graft survival. Even in the absence of known sensitizing exposures, heterologous immunity and homeostatic T-cell proliferation generate ,endogenous' memory T cells with donor-reactivity. We have recently shown that endogenous donor-reactive CD8 memory T cells infiltrate murine cardiac allografts within hours of reperfusion and amplify early posttransplant inflammation by producing IFN-,. Here, we have tested the role of ICOS co-stimulation in eliciting effector function from these memory T cells. ICOS is not expressed on the cell surface of circulating CD8 memory T cells but is rapidly upregulated during cell division within the allograft parenchyma. Donor-reactive CD8 memory T-cell infiltration, proliferation and ICOS expression are regulated by donor class I MHC molecule expression. ICOS blockade significantly reduced IFN-, production and other proinflammatory functions of the activated CD8 memory T cells. Our data demonstrate that this induction of ICOS expression within peripheral tissues is an important feature of CD8 memory T-cell activation and identify ICOS as a specific target for neutralizing proinflammatory functions of endogenous CD8 memory T cells. [source] Marginal Models for Dependent, Clustered, and Longitudinal Categorical Data by BERGSMA, W., CROON, M., and HAGENAARS, J. A.BIOMETRICS, Issue 1 2010Ivy Liu No abstract is available for this article. [source] The Anti-tumor Effects of Androstene Steroids Exhibit a Strict Structure,Activity Relationship Dependent upon the Orientation of the Hydroxyl Group on Carbon-17CHEMICAL BIOLOGY & DRUG DESIGN, Issue 6 2009Martin R. Graf Androstene steroids are metabolites of dehydroepiandrosterone and exist as androstene-diols or -triols in ,- and ,-epimeric forms based upon the placement of the hydroxyl groups relative to the plane of the ,5cycloperhydrophenanthrene ring. 5-Androstene-3,,17,-diol (3,,17,-AED) functions to upregulate immunity and the addition of a third hydroxyl group at C-7 in the ,- or ,-orientation (3,,7,,17,-AET and 3,,7,,17,-AET, respectively) enhances the immunological activity of the molecule. In contrast, 5-androstene-3,,17,-diol (3,,17,-AED) possesses potent anti-tumor activity. We synthesized a new androstene by adding a third hydroxyl group at C-7 to make 5-androstene-3,,7,,17,-triol (3,,7,,17,-AET) and compared the anti-tumor activity of this steroid to the four existing androstenes. The results showed that this modification reduced the activity of 3,,17,-AED. The ranking of the anti-tumor activities of these steroids and their IC50 on human glioblastoma and lymphoma cells was: 3,,17,-AED (,10 ,m) > 3,,7,,17,-AET (,30 ,m) >> 3,,7,,17,-AET (,150 ,m)> 3,,7,,17,-AET (not achievable) , 3,,17,-AED (not achievable). 3,,17,-AED and 3,,7,,17,-AET induced autophagy in T98G glioblastoma cells and apoptosis in U937 lymphoma cells. These results indicate that the position of the hydroxyl group on C-17 dictates the anti-tumor activity of the androstenes and must be in the ,-configuration, demonstrating a strict structure,activity relationship. [source] The Activity of Covalently Immobilized Grubbs,Hoveyda Type Catalyst Is Highly Dependent on the Nature of the Support Material.CHEMINFORM, Issue 19 2007Florian Michalek Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF. [source] Solid-State and Solution Studies of {Lnn(SiW11O39)} Polyoxoanions: An Example of Building Block Condensation Dependent on the Nature of the Rare Earth.CHEMINFORM, Issue 24 2003Pierre Mialane Abstract For Abstract see ChemInform Abstract in Full Text. [source] Exploring the Career/Achievement and Personal Life Orientation Differences between Entrepreneurs and Nonentrepreneurs: The Impact of Sex and DependentsJOURNAL OF SMALL BUSINESS MANAGEMENT, Issue 3 2006Richard DeMartino This study explores the career/achievement and personal life orientations of entrepreneurs, specifically the impact of sex and dependent-child status. Although a growing body of research has explored the similarities and uniqueness of women, none have explicitly analyzed entrepreneurs employing a career/achievement and personal life framework. In addition, no studies have sought to explore the career/achievement and personal life orientations of female entrepreneurs with female nonentrepreneurs of similar backgrounds. Consequently, this research explores and compares the career/achievement and personal life orientations of female entrepreneurs with a group of female nonentrepreneurs with similar educational levels, ages, and work experience. It also compares the orientations of male entrepreneurs with a group of male nonentrepreneurs in order to both confirm existing literature and create a means to compare intra-female with intra-male career and personal life orientations. The analysis shows no statistically significant differences in the career/achievement and personal life orientations of women entrepreneurs and similar female nonentrepreneurs. It also finds, confirming existing literature, that male entrepreneurs possess a greater career/achievement orientation as compared with male nonentrepreneurs. [source] Divided justice, different voices: inheritance and family provisionLEGAL STUDIES, Issue 4 2003Fiona Cownie Both the Family Division of the High Court and the Chancery Division of the High Court exercise jurisdiction over the Inheritance (Provision for Family and Dependents) Act 1975, with the applicant being able to elect the Division that they wish to proceed in. Many practitioners believe that the two Divisions have different attitudes towards the Act. This paper argues the structure of the 1975 Act makes it highly likely that the two Divisions will approach in different ways and that a close analysis of judgments shows that there is a discernible difference in the rhetoric that is used in judgments in the two Divisions, that this difference in rhetoric affects the way in which applicants are viewed and that thus sometimes it affects the outcome of cases. Since there is no advantage in practice to having the two jurisdictions and since the difference between the jurisprudences in the two Divisions can result in like cases not being treated alike, an elementary form of injustice. The paper concludes that it would be better if one Division exercised sole jurisdiction over the Act. [source] Liver Transplantation for Methadone-Maintained Opiate Dependents: Making the Case for Cautious OptimismAMERICAN JOURNAL OF TRANSPLANTATION, Issue 10 2003Andrea Di Martini No abstract is available for this article. [source] Kinematics, Dynamics, Biomechanics: Evolution of Autonomy in Game AnimationCOMPUTER GRAPHICS FORUM, Issue 3 2005Steve Collins The believeable portrayal of character performances is critical in engaging the immersed player in interactive entertainment. The story, the emotion and the relationship between the player and the world they are interacting within are hugely dependent on how appropriately the world's characters look, move and behave. We're concerned here with the character's motion; with next generation game consoles like Xbox360TM and Playstation®3 the graphical representation of characters will take a major step forward which places even more emphasis on the motion of the character. The behavior of the character is driven by story and design which are adapted to game context by the game's AI system. The motion of the characters populating the game's world, however, is evolving to an interesting blend of kinematics, dynamics, biomechanics and AI drivenmotion planning. Our goal here is to present the technologies involved in creating what are essentially character automata, emotionless and largely brainless character shells that nevertheless exhibit enough "behavior" to move as directed while adapting to the environment through sensing and actuating responses. This abstracts the complexities of low level motion control, dynamics, collision detection etc. and allows the game's artificial intelligence system to direct these characters at a higher level. While much research has already been conducted in this area and some great results have been published, we will present the particular issues that face game developers working on current and next generation consoles, and how these technologies may be integrated into game production pipelines so to facilitate the creation of character performances in games. The challenges posed by the limited memory and CPU bandwidth (though this is changing somewhat with next generation) and the challenges of integrating these solutions with current game design approaches leads to some interesting problems, some of which the industry has solutions for and some others which still remain largely unsolved. [source] | |||||||||||||||||||||||||||||||||||||