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Reduced Levels (reduced + level)
Selected AbstractsAn evaluation of a visual biofeedback intervention in dyslexic adultsDYSLEXIA, Issue 1 2005Elizabeth Liddle Abstract A prototype of a biofeedback system designed to treat dyslexia by improving heart-rate variability was evaluated in a single blind study of dyslexic adults. Treatment consisted of four 15 minute exposures to a visual display synchronized with either the participant's own cardiac cycle (intervention condition), or of a synthesized cardiac cycle (placebo condition). Repeated measures were made of picture naming speed, single word reading speed and accuracy, copying speed, heart-rate variability and performance on a lateralized visual temporal order judgement task. Small but significant improvements were found in reading and naming speed in the treatment group relative to the placebo group. No significant improvements were found in unspeeded reading measures. Results from heart-rate measures indicated that treatment had effected a shift in the ratio between parameters reflecting the influence of the sympathetic and parasympathetic autonomic nervous systems (ANS), respectively, in favour of the parasympathetic. In the temporal order judgement task, participants who received treatment showed a reduced level of overall improvement relative to that seen in those who received placebo, coupled with evidence of a shift in visual attention from left to right hemifield in their pattern of performance. The results are interpreted as indicating that the treatment induces a shift in autonomic balance in favour of the parasympathetic ANS, and that this shift is also reflected in increased efficiency of left cerebral hemisphere circuits implicated in the perceptual-motor processes required for naming and reading fluency. Conversely, it is also reflected in lower spatial awareness of peripheral visual stimuli, particularly those presented to left hemifield. Copyright © 2004 John Wiley & Sons, Ltd. [source] Withdrawal symptoms in abstinent methamphetamine-dependent subjectsADDICTION, Issue 10 2010Todd Zorick ABSTRACT Aims Withdrawal symptoms have been linked to a propensity for relapse to drug abuse. Inasmuch as this association applies to methamphetamine (MA) abuse, an understanding of the course of MA withdrawal symptoms may help to direct treatment for MA dependence. Previous studies of symptoms manifested during abstinence from MA have been limited in size and scope. We asked (i) whether debilitating psychological and/or physical symptoms appear during the first several weeks of MA abstinence, (ii) how craving for MA evolves and (iii) whether psychiatric symptoms (e.g. depression, psychosis) persist beyond a month of abstinence. Design A study of MA-dependent participants, who initiated and maintained abstinence from the drug for up to 5 weeks, compared to a matched healthy comparison group. Setting In-patient research hospital ward (MA-dependent subjects) and out-patient (comparison subjects). Participants Fifty-six MA-dependent and eighty-nine comparison subjects. Measurements Rater-assessed MA withdrawal questionnaire and self-report assessment of craving (MA-dependent subjects) and self-report assessment of psychiatric symptoms (both groups). Findings At study entry, MA-dependent subjects exhibited a wide range in severity of depressive symptoms, with the average score at a mild,moderate level of severity. Symptoms of psychosis were also prevalent. While depressive and psychotic symptoms largely resolved within a week of abstinence, craving did not decrease significantly from the time of initiating abstinence until the second week, and then continued at a reduced level to the fifth week. Conclusions Depressive and psychotic symptoms accompany acute withdrawal from methamphetamine but resolve within 1 week. Craving is also present and lasts at least 5 weeks. [source] A preliminary report on the implication of RT,PCR detection of DAZ, RBMY1, USP9Y and Protamine-2 mRNA in testicular biopsy samples from azoospermic menINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 1 2002A. Friel In this study, reverse transcription,polymerase chain reaction (RT,PCR) was optimized to analyse the presence of DAZ, RBMY1, USP9Y, protamine-2, SRY and actin messenger RNA (mRNA) in testicular cells of men suffering from idiopathic azoospermia. All samples (n=28), including five controls, showed normal expression of actin, SRY and USP9Y. Sperm was not recovered from eight patients after testicular biopsy. Of these, four patients showed altered mRNA levels for the fertility genes, DAZ, RBMY1 and protamine-2. One patient, who was previously shown to be azoospermia factor region (AZF)b deleted, lacked RBM mRNA and presented with reduced amplification of protamine-2 mRNA. This correlated with previous studies, which proposed that RBM expression is exclusive to AZFb and that the lack of testicular RBMY1 mRNA results in suppressed spermatogenesis. Two patients were each lacking DAZ mRNA but did show expression of RBMY1 mRNA at a reduced level, suggesting that there might be residual spermatogenesis in the absence of DAZ expression. Protamine-2 mRNA was detected in one patient and was absent in the second patient. Finally, one patient lacked DAZ, RBMY1 and protamine-2 mRNA. The 19 remaining azoospermic patients presented with normal expression patterns for each of the fertility genes studied. This study demonstrates that the expression of spermatogenesis-specific genes varies in azoospermia. The study of the expression of such genes in a larger number of patients might be useful in characterizing and identifying subpopulations of azoospermic men. [source] Alterations in the expression of intestinal enzymes in rats exposed to nickelJOURNAL OF APPLIED TOXICOLOGY, Issue 5 2006Amika Singla Abstract The effect of feeding nickel (50 mg kg,1 body weight) daily for 7 days was studied on the development of various brush border enzymes across the crypt,villus axis. The activities of brush border maltase (P < 0.05), lactase (P < 0.05), alkaline phosphatase (P < 0.05) and leucine amino peptidase (P < 0.05) were augmented in purified brush borders, whereas sucrase, trehlase (P < 0.01) and glutamyl transpeptidase (P < 0.05) were reduced in nickel fed animals compared with controls. Kinetic and heat inactivation studies with brush border sucrase and alkaline phosphatase confirmed these findings. Western blot analysis of alkaline phosphatase showed a strong signal for the enzyme protein but a reduced level of sucrase antigen in nickel fed rat intestine compared with the controls. These findings suggest that the expression of various brush border enzymes along the crypt,villus axis is modulated in rat intestine exposed to nickel, which may disrupt the digestive functions of the intestinal tissue. Copyright © 2006 John Wiley & Sons, Ltd. [source] Involvement of ,1,1 integrin in insulin-like growth factor-1-mediated protection of PC12 neuronal processes from tumor necrosis factor-,-induced injuryJOURNAL OF NEUROSCIENCE RESEARCH, Issue 1 2006Jin Ying Wang Abstract Insulin-like growth factor 1 receptor (IGF-1R) supports neuronal survival against a wide variety of insults. This includes tumor necrosis factor-, (TNF,)-mediated neuronal damage, which represents one of the factors suspected to play a role in HIV-associated dementia (HAD). PC12 neurons engineered to express human IGF-1R (PC12/IGF-1R) maintain neuronal processes on collagen IV for several weeks. However, prolonged treatment with TNF, caused degeneration of neuronal processes, with no apparent signs of apoptosis. In this process, TNF, did not affect IGF-1-mediated phosphorylation of IRS-1, IRS-2, Akt, or Erks. In addition, PC12/IGF-1R cells were found to express predominantly ,1,1 integrin, which has high affinity to collagen IV. The treatment of PC12/IGF-1R neurons with a specific ,1,1 integrin inhibitor, obtustatin, also caused loss of neuronal processes, accompanied by a quick cell detachment and extensive apoptosis. In the presence of IGF-1, both TNF,-induced and obtustatin-induced degeneration of neuronal processes were effectively inhibited. Furthermore, TNF,-mediated neuronal degeneration correlated with decreased attachment of PC12/IGF-1R cells to collagen IV and with a reduced level of ,1,1 integrin, consistent with a role for this surface protein in the maintenance of neuronal processes. Thus the neuroprotective effects of IGF-1 are not restricted to its antiapoptotic properties but also involve an additional neuroprotective mechanism, by which IGF-1 counteracts the negative effect of TNF, on ,1,1 integrin-mediated attachment to collagen IV. © 2005 Wiley-Liss, Inc. [source] Effect of Repeated Doses of Ethanol on Hepatic Mg2+ Homeostasis and MobilizationALCOHOLISM, Issue 7 2007Andrew Young The acute administration of a first dose of ethanol (EtOH) to rat liver cells reduces the amount of Mg2+ extruded by a second dose of EtOH or the subsequent addition of adrenergic agonists. In contrast, the Mg2+ extrusion normally elicited by the ,1 -adrenergic or , -adrenergic agonist does not impair the Mg2+ mobilization induced by the subsequent addition of EtOH. Inhibition of EtOH metabolism by 4-methylpyrazole abolishes almost completely the Mg2+ extrusion induced by the first dose of EtOH, and partially enlarges that elicited by the second dose of alcohol or the subsequent adrenergic stimulation. Ethanol-treated liver cells stimulated by the adrenergic agonist show a reduced level of membrane-bound G,s as well as a reduced cellular cAMP content. Analysis of cellular Mg2+ distribution indicates that EtOH administration decreases the Mg2+ content of the cytoplasm, mitochondria, and endoplasmic reticulum to a comparable extent. These data indicate that acute EtOH administration directly impairs cellular Mg2+ homeostasis and also prevents a further Mg2+ mobilization by additional doses of alcohol or ,1 -adrenoceptor and , -adrenoceptor agonist by decreasing cytosolic and intraorganelle Mg2+ content and by affecting G-protein membrane distribution/signaling. [source] Patterns of performance degradation and restoration during sleep restriction and subsequent recovery: a sleep dose-response studyJOURNAL OF SLEEP RESEARCH, Issue 1 2003Gregory Belenky SUMMARY Daytime performance changes were examined during chronic sleep restriction or augmentation and following subsequent recovery sleep. Sixty-six normal volunteers spent either 3 (n = 18), 5 (n= 16), 7 (n = 16), or 9 h (n = 16) daily time in bed (TIB) for 7 days (restriction/augmentation) followed by 3 days with 8 h daily TIB (recovery). In the 3-h group, speed (mean and fastest 10% of responses) on the psychomotor vigilance task (PVT) declined, and PVT lapses (reaction times greater than 500 ms) increased steadily across the 7 days of sleep restriction. In the 7- and 5-h groups speed initially declined, then appeared to stabilize at a reduced level; lapses were increased only in the 5-h group. In the 9-h group, speed and lapses remained at baseline levels. During recovery, PVT speed in the 7- and 5-h groups (and lapses in the 5-h group) remained at the stable, but reduced levels seen during the last days of the experimental phase, with no evidence of recovery. Speed and lapses in the 3-h group recovered rapidly following the first night of recovery sleep; however, recovery was incomplete with speed and lapses stabilizing at a level comparable with the 7- and 5-h groups. Performance in the 9-h group remained at baseline levels during the recovery phase. These results suggest that the brain adapts to chronic sleep restriction. In mild to moderate sleep restriction this adaptation is sufficient to stabilize performance, although at a reduced level. These adaptive changes are hypothesized to restrict brain operational capacity and to persist for several days after normal sleep duration is restored, delaying recovery. [source] Preferential localization of recombinant factor VIIa to platelets activated with a combination of thrombin and a glycoprotein VI receptor agonistJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 4 2007M. KJALKE Summary., Background:, Activation of platelets with a combination of collagen and thrombin generates a subpopulation of highly procoagulant ,coated' platelets characterized by high surface expression of fibrinogen and other procoagulant proteins. Objectives:, To analyze the interaction of recombinant factor VIIa (rFVIIa) with coated platelets. Methods and results:, rFVIIa localized to the coated platelets in flow cytometry experiments, while minimal rFVIIa was found on platelets activated with adenosine diphosphate, thrombin or via glycoprotein VI individually, and essentially no rFVIIa was found on non-stimulated platelets. Removal of the , -carboxyglutamic acid (Gla) domain of rFVIIa, and addition of EDTA, annexin V or excess prothrombin inhibited rFVIIa localization to the coated platelets, indicating that the interaction was mediated by the calcium-dependent conformation of the Gla domain and platelet exposure of negatively charged phospholipids. A reduced level of platelet fibrinogen exposure was observed at hemophilia A-like conditions in a model system of cell-based coagulation, indicating that coated platelet formation in hemophilia may be diminished. Addition of rFVIIa dose-dependently enhanced thrombin generation and partly restored platelet fibrinogen exposure. Conclusions:, The data suggest that rFVIIa localized preferentially on platelets activated with dual agonists, thereby ensuring enhanced thrombin generation localized at the site of injury where both collagen and tissue factor are exposed, the latter ensuring the formation of thrombin necessary for coated platelet formation. [source] Genetic structure of the European polecat (Mustela putorius) and its implication for conservation strategiesJOURNAL OF ZOOLOGY, Issue 1 2006C. Pertoldi Abstract During the last century, the European polecat Mustela putorius populations in most of Europe declined and survived in fragmented patches, because of habitat alterations and direct persecution. To assess the genetic consequences of the demographic decline and to describe the spatial pattern of genetic diversity, 250 polecats sampled at seven localities from five European countries , Poland, Denmark (southern Denmark and northern Denmark), Spain, Belgium (eastern and western) and the Netherlands , were screened by means of nine microsatellite loci. Genetic diversity estimated by mean expected heterozygosity (HE) and allelic richness (AR) were moderately high within populations [range: 0.50 (northern Denmark) ,HE,0.64 (Poland) and 1.33,AR,7.80] as compared with other carnivores and mustelids. Bottleneck tests suggested that polecat populations in southern Denmark and Poland have declined recently and populations from northern Denmark and the Netherlands have expanded recently, whereas the remaining populations did not show any sign of demographic change. Recent demographic changes could suggest that some of the populations are still not in equilibrium, which could partly explain the relatively high genetic variability observed in polecat populations despite the drastic decline in population size observed in several European countries. A significant heterozygote deficiency [FIS=0.19; 0.01,95% confidence interval (CI),0.32] suggests substructuring within the total European sample. Partitioning of the genetic variation among sampling locations (FST=0.14; 0.06,95% CI,0.23) and pairwise FST between localities (range: 0.01,FST,0.37) without any correlation with the geographic distances between localities were found, suggesting a recent divergence and a restriction of gene flow between populations and the action of genetic drift. An assignment test showed that the Polish and the northern Danish populations were the most unique, whereas the other populations were partially admixed. Factorial component analysis tests indicate a subdivision of the total sample into two distinct groups: one including the samples from Poland and the two Danish localities and the second group comprising the remaining localities investigated. The observed pattern of genetic differentiation is suggested to be due to two main routes of recolonization after the last glacial period. To compare the results obtained with microsatellite data, the most variable region of the mitochondrial DNA (d-loop) was sequenced and different phylogenetic reconstructions and genetic diversity analyses based on nucleotide (,) and haplotype diversity (h) measures within populations were performed using a subsample of populations. The lack of well-defined geographical structure, as well as the reduced level of mitochondrial DNA variability (,: 0.00274±0.00038; h: 0.876±0.028) that was found, has been previously reported in several studies on different carnivores and supports the hypothesis of post-glacial recolonization from southern or eastern refugees of Europe as suggested by the microsatellite data. Implications for conservation strategies of the polecat at the European level are discussed. [source] Molecularly Imprinted Multi-Layer Core-Shell Nanoparticles , A Surface Grafting ApproachMACROMOLECULAR RAPID COMMUNICATIONS, Issue 22 2007Natalia Pérez-Moral Abstract Surface initiated living-radical polymerization (SIP) based on dithiocarbamate iniferters has been used to create molecularly imprinted core-shell (CS) nanoparticles. Using this approach, propranolol, morphine and naproxen have been successfully imprinted in particle shells (the latter could not be imprinted using conventional aqueous-based CS methods). Rebinding properties of the imprinted particles appear to be similar to those made by alternative methods. The living radical initiation mechanism makes it possible to build complex multi-layer particles sequentially. As a demonstration, multi-layer propranolol-imprinted particles were generated. Two additional functional shells were grown over the imprinted shell, while the propranolol binding was retained, albeit at a reduced level. [source] Use of Botulinum Toxin Type A Injection for Neuropathic Pain after Trigeminal Nerve InjuryPAIN MEDICINE, Issue 4 2010Seung Hyun Yoon DDS Abstract Objective., To present a case that neuropathic pain following traumatic injury of the inferior alveolar nerve, which was relieved by the injection of BTX-A. Design., Case report. Setting., Tertiary care University hospital. Subject., A 62-year-old female was referred by her general dentist to our clinic due to numbness and pain over the left side of her lower lip and chin region. Intervention., Botulinum toxin type A injected into the middle of chin area subcutaneously. Results., At 1 month after BTX-A injection, the affected area had decreased in size. And at 2 months, the patient reported a slight decreased in pain, and CPT differences being sustained at a reduced level. Conclusions., This case report suggests an effective new modality for treating neuropathic pain after trigeminal nerve injury. A further randomized controlled study involving a large number of patients is needed. [source] The effect of short-term low-temperature treatments on gene expression in Arabidopsis correlates with changes in intracellular Ca2+ levelsPLANT CELL & ENVIRONMENT, Issue 4 2003K. NORDIN HENRIKSSON ABSTRACT The role of changes in intracellular calcium ion concentration ([Ca2+]i) in low-temperature signal transduction in plants has lately been supported by several studies. An analysis to determine whether the low-temperature-induced increase in cytosolic Ca2+ concentration ([Ca2+]cyt) could be correlated with a downstream response such as gene expression was carried out. The induction of the low-temperature-regulated gene LTI78 was used as an end point marker of the signal transduction pathway. It was found that this gene is induced by very brief low-temperature exposures and that the induction does not depend on a continuous exposure to low temperature. By altering the cooling rate, different patterns of the Ca2+ response were obtained which could be correlated with different patterns of LTI78 induction. Furthermore, reducing the Ca2+ transients by pre-treatment with the Ca2+ channel blocker La3+ also led to a reduced level of gene induction. The results show that brief exposures to low temperature results in the onset of a signalling pathway that leads to the induction of gene expression. This indicates the involvement of changes in [Ca2+]cyt in low-temperature signalling leading to LTI78 expression but the presence of multiple signalling pathways is suggested. [source] Role of IscS in Fe-S cluster assembly in Trypanosoma bruceiTHE JOURNAL OF EUKARYOTIC MICROBIOLOGY, Issue 2 2005O. SMÍD Despite the significance of proteins containing iron-sulfur cluster (Fe,S proteins), the processes of Fe,S cluster assembly and maturation of Fe,S proteins are poorly understood. However, several key proteins involved in the assembly have been identified, notably IscS, a cystein desulfurase, which provides sulfur for Fe,S cluster and IscU, a metallochaperone acting as a scaffold for cluster assembly. In this work, we studied the process of Fe,S cluster biosynthesis in Trypanosoma brucei by identifying the homologue of IscS in the T. brucei (TbIscS). To address the function of TbIscS, we inhibited its expression by means of RNA interference (RNAi). After RNAi induction, generation time of the TbIscS knock-down cell line was significantly prolonged. All types of mitochondrial ATP production in the cells were severely affected. Analysis of glucose metabolism end products determined pyruvate as major excreted metabolite of the induced cells, while the uninduced cells produced only small amount of this glycolytic end product. These data demonstrate that mitochondrial metabolism is impaired in cells with TbIscS knocked down. To test whether the observed phenomena were results of Fe,S cluster assembly disruption, we examined the Fe,S cluster-dependent activity of aconitase. This enzyme is localized in its active form in mitochondrion as well as in cytosol of T. brucei. After RNAi induction we observed the reduction of aconitase activity in both compartments (approx. 70% reduction in cytosol, approx. 30% in mitochondria). Western blots together with the EPR analysis showed that the reduction in cytosolic activity was due to impaired Fe,S cluster formation, while decrease in aconitase activity in mitochondria corresponded to the reduced level of the protein. [source] Self-poisoning with lamotrigine and pregabalinANAESTHESIA, Issue 5 2007A. J. Braga Summary We report a case of intentional overdose in a 29-year-old male with two of the newer anti-epileptic agents, lamotrigine and pregabalin. To our knowledge, this case report details the highest plasma levels of lamotrigine ever recorded in the literature. The patient presented with seizures and a reduced level of consciousness. Management of these and subsequent complications centres on supportive care in the high dependency and intensive therapy units. [source] C-reactive protein, its role in inflammation, Type 2 diabetes and cardiovascular disease, and the effects of insulin-sensitizing treatment with thiazolidinedionesDIABETIC MEDICINE, Issue 8 2004R. Nesto Abstract Increased concentrations of the marker of inflammation, C-reactive protein (CRP), are associated with insulin resistance, Type 2 diabetes and the development of cardiovascular disease. In particular, inflammation is closely associated with endothelial dysfunction and is recognized as one of the cardiovascular risk factors clustering in the Insulin Resistance Syndrome or Metabolic Syndrome. The exact mechanisms linking insulin resistance and inflammation remain unclear. However, the close association between insulin resistance and inflammation in atherogenesis suggests that therapies that address both parameters may have benefits in reducing diabetes-related macrovascular complications. The thiazolidinedione class of oral anti-diabetic agents are powerful insulin sensitizers that also have anti-inflammatory properties. Treatment with these agents has a range of anti-atherogenic effects, including reduced levels of CRP, plasminogen activator inhibitor-1 (PAI-1), TNF-, and reactive oxygen species. Additionally, the insulin-sensitizing effect of thiazolidinediones improves other factors of the Insulin Resistance Syndrome, including dyslipidaemia and hypertension. Outcome studies are underway to determine if the effects of improving insulin sensitivity and reducing inflammation will translate into clinical benefits and reduce the cardiovascular morbidity and mortality associated with insulin resistance and Type 2 diabetes. [source] Screening for the calstabin-ryanodine receptor complex stabilizers JTV-519 and S-107 in doping control analysisDRUG TESTING AND ANALYSIS, Issue 1 2009Mario Thevis Abstract Recent studies outlined the influence of exercise on the stability of the skeletal muscle calstabin1-ryanodine receptor1-complex, which represents a major Ca2+ release channel. The progressive modification of the type-1 skeletal muscle ryanodine receptor (RyR1) combined with reduced levels of calstabin1 and phosphodiesterase PDE4D3 resulted in a Ca2+ leak that has been a suggested cause of muscle damage and impaired exercise capacity. The use of 1,4-benzothiazepine derivatives such as the drug candidates JTV-519 and S-107 enhanced rebinding of calstabin1 to RyR1 and resulted in significantly improved skeletal muscle function and exercise performance in rodents. Due to the fact that the mechanism of RyR1 remodelling under exercise conditions were proven to be similar in mice and humans, a comparable effect of JTV-519 and S-107 on trained athletes is expected, making the compounds relevant for doping controls. After synthesis of JTV-519, S-107, and a putative desmethylated metabolite of S-107, target compounds were characterized using nuclear magnetic resonance spectroscopy and electrospray ionization (ESI),high-resolution/high-accuracy Orbitrap mass spectrometry. Collision-induced dissociation pathways were suggested based on the determination of elemental compositions of product ions and H/D-exchange experiments. The most diagnostic product ion of JTV-519 was found at m/z 188 (representing the 4-benzyl-1-methyl piperidine residue), and S-107 as well as its desmethylated analog yielded characteristic fragments at m/z 153 and 138 (accounting for 1-methoxy-4-methylsulfanyl-benzene and 4-methoxy-benzenethiol residues, respectively). The analytes were implemented in existing doping control screening procedures based on liquid chromatography, multiple reaction monitoring and simultaneous precursor ion scanning modes using a triple quadrupole mass spectrometer. Validation items such as specificity, recovery (68,92%), lower limit of detection (0.1,0.2 ng/mL), intraday (5.2,18.5%) and interday (8.7,18.8%) precision as well as ion suppression/enhancement effects were determined. Copyright © 2009 John Wiley & Sons, Ltd. [source] Impaired nutritional status in common variable immunodeficiency patients correlates with reduced levels of serum IgA and of circulating CD4+ T lymphocytesEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 6 2001M. Muscaritoli Background Common variable immunodeficiency (CVI) is a primary defect of the immune system. Infections, persistent diarrhoea and malabsorption may result in malnutrition, which may in turn contribute to increased morbidity. In this paper, the prevalence of malnutrition in CVI was evaluated. Patients and methods Forty CVI patients (20 male, 20 female, aged 17,75 years) underwent anthropometric measurements from which body mass index, arm fat and muscle area were calculated. Body mass index values <,18·5 and arm fat and muscle area values <,10th percentile were considered indicative of malnutrition. Patients were divided into four groups according to circulating CD4+ T cells (lower or greater than 300 µL,1) and serum immunoglobulin A (IgA) levels (detectable and undetectable). Results Body mass index <,18·5, arm fat and muscle area <,10th percentile were observed in 23%, 58% and 44%, respectively, of patients. Lower values of body mass index, arm fat and muscle area were more frequent in patients with low CD4+ cells and undetectable IgA. Low arm fat values were more frequent in patients with diarrhoea (P = 0·03). Infectious episodes were more frequent in undetectable IgA than in detectable IgA patients (P = 0·04). Conclusions Anthropometric measurements revealed an increased rate of malnutrition in CVI patients, particularly in those with low CD4+ and undetectable IgA, suggesting that selected CVI subjects could be considered for standard or specialized nutritional support. [source] Impaired B-1 and B-2 B,cell development and atypical splenic B,cell structures in IL-7 receptor-deficient miceEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 12 2004Lena Erlandsson Abstract The cytokine IL-7 and its receptor are essential for normal B and T,lymphopoiesis. We have analyzed the role of this receptor in B,cell development throughout ontogeny in IL-7 receptor,,-deficient mice. We demonstrate that the IL-7 receptor becomes progressively more important with age. B,lymphopoiesis takes place, albeit at reduced levels, in fetal liver and bone marrow of young mice, but is arrested in adults. The outcome is a severe reduction, from an early age, in peripheral B,cells including follicular, marginal zone and B-1 B,cells as well as perturbed splenic B,cell structures, which are restored after adoptive transfer of normal spleen cells. We conclude that in the absence of the IL-7 receptor, the residual B,lymphopoiesis occurring early in ontogeny must be facilitated by another component, whereas the IL-7 receptor is the key factor in adults. The impairment of marginal zone and B-1 B,cells in IL-7 receptor- but not IL-7-deficient mice suggests non-redundant functions for the IL-7 receptor ligands, IL-7 and thymic stromal lymphopoietin. [source] Chronic interleukin-6 alters the level of synaptic proteins in hippocampus in culture and in vivoEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2007Elly J. F. Vereyken Abstract There is now considerable evidence that the level of expression of the proinflammatory cytokine, interleukin-6 (IL-6), is increased in the central nervous system (CNS) during neuroinflammatory conditions such as occurs in neurological disorders and in disease and injury. However, our understanding of the consequences of increased expression of IL-6 on the CNS is still limited, especially with respect to the developing nervous system, which is known to be particularly vulnerable to environmental factors. To address this issue, we investigated the properties of cultured hippocampal neurons exposed chronically to IL-6 during the main period of morphological and physiological development, which occurs during the first 2 weeks of culture. IL-6 was tested at 500 U/mL, considered to reflect a pathophysiologic concentration. The morphological features of neuronal development in the control and IL-6-treated cultures appeared similar. However, Western blot analysis showed a significant reduction in the level of Group-II metabotropic receptors (mGluR2/3) and L-type Ca2+ channels in the IL-6-treated cultures. A similar reduction in mGluR2/3 and L-type Ca2+ channel protein was observed in transgenic mice that over-express IL-6 in the CNS through astrocyte production starting early in development. Analysis of Ca2+ signals produced by spontaneous synaptic network activity in the hippocampal cultures and effects of a mGluR2/3 agonist and antagonist showed that the reduced levels of mGluR2/3 impact on the functional properties of hippocampal synaptic network activity. These results have important implications relative to the mechanisms responsible for altered CNS function during conditions associated with increased levels of IL-6 in the CNS. [source] DIVERGENCE WITH GENE FLOW IN THE ROCK-DWELLING CICHLIDS OF LAKE MALAWIEVOLUTION, Issue 5 2000Patrick D. Danley Abstract Within the past two million years, more than 450 species of haplochromine cichlids have diverged from a single common ancestor in Lake Malawi. Several factors have been implicated in the diversification of this monophyletic clade, including changes in lake level and low levels of gene flow across limited geographic scales. The objectives of this study were to determine the effect of recent lake-level fluctuations on patterns of allelic diversity in the genus Metriaclima, to describe the patterns of population structure within this genus, and to identify barriers to migration. This was accomplished through an analysis of allele frequencies at four microsatellite loci. Twelve populations spanning four species within Metriaclima were surveyed. The effect of lake-level fluctuations can be seen in the reduced genetic diversity of the most recently colonized sites; however, genetic diversity is not depressed at the species level. Low levels of population structure exist among populations, yet some gene flow persists across long stretches of inhospitable habitat. No general barrier to migration was identified. The results of this study are interpreted with respect to several speciation models. Divergence via population bottlenecks is unlikely due to the large allelic diversity observed within each species. Genetic drift and microallopatric divergence are also rejected because some gene flow does occur between adjacent populations. However, the reduced levels of gene flow between populations does suggest that minor changes in the selective environment could cause the divergence of populations. [source] Precautionary Savings Behavior of Maritally Stressed CouplesFAMILY & CONSUMER SCIENCES RESEARCH JOURNAL, Issue 3 2006Michael S. Finke According to precautionary savings theory, households tend to save more when future income is less certain. Divorce often results in reduced levels of household income and individual consumption comparable to other potential income shocks. Households that will divorce or separate in 5 years are identified from the Panel Study of Income Dynamics (1994,1999) to determine whether these households maintain greater wealth holdings in anticipation of divorce. When spouses earn comparable incomes, divorce-prone households have significantly higher wealth levels (p < .01) than households that remain married. When there is a higher-earning spouse, households have significantly lower wealth levels (p < .01) than households that remain married. Results suggest that spouses with comparable earnings treat divorce as a wealth shock, whereas higher-earning spouses rationally dissave when divorce is imminent. Equitable wealth allocation for lower-earning spouses may require a more detailed investigation of predivorce wealth changes. [source] The effect of focal adhesion kinase gene silencing on 5-fluorouracil chemosensitivity involves an Akt/NF-,B signaling pathway in colorectal carcinomasINTERNATIONAL JOURNAL OF CANCER, Issue 1 2010Yuying Chen Abstract Multicellular resistance (MCR) is produced because multicellular spheroids (MCSs) are formed with a broad cell,cell connection when cultured in three-dimensions, which limits the clinical treatment efficacy in solid tumors. Focal adhesion kinase (FAK) plays an important role in apoptosis, survival and cell adhesion between cells and their extracellular matrix. In this study, we investigated the expressions of FAK, Akt and NF-,B in human colorectal cancer (CRC), and the effects of FAK gene silencing on MCSs formation and 5-fluorouracil (5-FU) chemosensitivity in colon carcinoma MCSs culture cells. In CRC samples, FAK, Akt and NF-,B were overexpressed. The positive expression of FAK correlated notably with lymph node metastasis and cellular differentiation. Positive expressions of Akt and NF-,B were significantly related to cellular differentiation and lymph node metastasis, respectively. Furthermore, positive expression of FAK correlated with that of Akt and NF-,B. The expression of FAK was inhibited significantly by a small hairpin RNA targeting FAK. Knockdown of FAK reversed the formation and aggregation of MCSs, significantly decreased the 50% inhibitory concentration of 5-FU, and markedly increased MCS culture cells apoptosis. These effects were associated with reduced levels of Akt and NF-,B. These results indicate that suppressing FAK expression potentiated 5-FU-induced cytotoxicity and contributed to its chemosensitizing effect by suppressing Akt/NF-,B signaling in colon carcinoma MCS culture cells. These data also imply that FAK mediates MCR of CRC through the survival signaling pathway FAK/Akt/NF-,B. [source] Nmi (N-Myc interactor) inhibits Wnt/,-catenin signaling and retards tumor growthINTERNATIONAL JOURNAL OF CANCER, Issue 3 2009Rebecca A. Fillmore Abstract We found that the expression levels of N-Myc interactor (Nmi) were low in aggressive breast cancer cell lines when compared with less aggressive cell lines. However, the lower levels in the aggressive lines were inducible by interferon-, (IFN-,). Because Nmi has been reported to be a transcription cofactor that augments IFN-, induced transcription activity, we decided to test whether Nmi regulates expression of Dkk1, which is also inducible by IFN-,. We established stable clones constitutively expressing Nmi in MDA-MB-231 (breast) and MDA-MB-435 (melanoma) cell lines. Dkk1 was significantly up-regulated in the Nmi expressing clones concurrent with reduced levels of the critical transcription cofactor of Wnt pathway, ,-catenin. Treatment of the Nmi expressors with blocking antibody to Dkk1 restored ,-catenin protein levels. c-Myc is a known downstream target of activated ,-catenin signaling. Treatment of Nmi expressors with the proteosome inhibitor MG132, resulted in elevated ,-catenin levels with concomitant elevation of c-Myc levels. Our functional studies showed that constitutive expression of Nmi reduced the ability of tumor cells for the invasion, anchorage independent growth and tumor growth in vivo. Collectively, the data suggest that overexpression of Nmi inhibits the Wnt/,-catenin signaling via up-regulation of Dkk1 and retards tumor growth. © 2009 UICC [source] The von Hippel-Lindau tumor suppressor gene expression level has prognostic value in neuroblastomaINTERNATIONAL JOURNAL OF CANCER, Issue 3 2006Jasmien Hoebeeck Abstract Deletions of the short arm of chromosome 3 are often observed in a specific subset of aggressive neuroblastomas (NBs) with loss of distal 11q and without MYCN amplification. The critical deleted region encompasses the locus of the von Hippel-Lindau gene (VHL, 3p25). Constitutional loss of function mutations in the VHL gene are responsible for the VHL syndrome, a dominantly inherited familial cancer syndrome predisposing to a variety of neoplasms, including pheochromocytoma. Pheochromocytomas are, like NB, derived from neural crest cells, but, unlike NB, consist of more mature chromaffin cells instead of immature neuroblasts. Further arguments for a putative role of VHL in NB are its function as oxygen sensitizer and the reported relation between hypoxia and dedifferentiation of NB cells, leading to a more aggressive phenotype. To test the possible involvement of VHL in NB, we did mRNA expression analysis and sought evidence for VHL gene inactivation. Although no evidence for a classic tumor suppressor role for VHL in NB could be obtained, a strong correlation was observed between reduced levels of VHL mRNA and low patient survival probability (p = 0.013). Furthermore, VHL appears to have predictive power in NTRK1 (TRKA) positive tumor samples with presumed favorable prognosis, which makes it a potentially valuable marker for more accurate risk assessment in this subgroup of patients. The significance of the reduced VHL expression levels in relation to NB tumor biology remains unexplained, as functional analysis demonstrated no clear effect of the reduction in VHL mRNA expression on protein stability of its downstream target hypoxia-inducible factor ,. © 2006 Wiley-Liss, Inc. [source] Field efficacy of transgenic cotton containing single and double toxin genes against the Asian corn borer (Lep., Pyralidae)JOURNAL OF APPLIED ENTOMOLOGY, Issue 9-10 2004K. He Abstract:, Insect resistant transgenic cotton (Gossypium hirsutum L.) is expected to provide satisfactory control of lepidopteran species in the cotton field. The Asian corn borer, Ostrinia furnacalis (Guenée) (Lep., Pyralidae), is an important component of the lepidopteran pest complex of cotton in China. Insect resistant transgenic cotton cultivars GK2, carrying cry1A gene, and SGK321, carrying both cry1A and CpTI genes, were evaluated for resistance to Asian corn borer. Field trials were conducted with artificial infestation of Asian corn borer at squaring, flowering and flowering-boll cotton plants, which coincided with the generations of natural Asian corn borer occurrence. Damage ratings were significantly reduced in transgenic cotton cultivars both GK2 and SGK321 compared with their parental non-transgenic cotton cultivars Simian3 and Shiyuan321, respectively. In addition, percentage of plants stem bored and number of tunnels per plant were significantly higher on GK2 than on SGK321 in the second generation. Laboratory bioassays were carried out by exposing neonates to plant tissues collected from the field. Tissues assayed included the new leaves, match-head squares and white flowers, which are the tissues initially attacked by the neonates in the field. Low larval survival rates were observed on SGK321 and GK2, contrasting greatly to the high number of survivors found on their non-transgenic cotton tissue isolated throughout the season. However, larval survival was higher on new leaves isolated from late-season transgenic cotton plants and fruit tissues than on early-season. In addition, higher larval survival was observed on GK2 than SGK321 in assays with the late season tissues. This may be associated with reduced levels of available toxin in plant tissues as they age. Both laboratory and field data indicated that SGK321 and GK2 were highly resistant to Asian corn borer. The high level of efficacy for insect resistant transgenic cotton against Asian corn borer offers the potential for season-long control. [source] miR-20b modulates VEGF expression by targeting HIF-1, and STAT3 in MCF-7 breast cancer cells,JOURNAL OF CELLULAR PHYSIOLOGY, Issue 1 2010Sandra Cascio MicroRNAs (miRNAs) are small non-coding RNAs that regulate the expression of different genes, including genes involved in cancer progression. A functional link between hypoxia, a key feature of the tumor microenvironment, and miRNA expression has been documented. We investigated whether and how miR-20b can regulate the expression of vascular endothelial growth factor (VEGF) in MCF-7 breast cancer cells under normoxic and hypoxia-mimicking conditions (CoCl2 exposure). Using immunoblotting, ELISA, and quantitative real-time PCR, we demonstrated that miR-20b decreased VEGF protein levels at 4 and 24,h following CoCl2 treatment, and VEGF mRNA at 4,h of treatment. In addition, miR-20b reduced VEGF protein expression in untreated cells. Next, we investigated the molecular mechanism by which pre-miR-20b can affect VEGF transcription, focusing on hypoxia inducible factor 1 (HIF-1) and signal transducer and activator of transcription 3 (STAT3), transcriptional inducers of VEGF and putative targets of miR-20b. Downregulation of VEGF mRNA by miR-20b under a 4,h of CoCl2 treatment was associated with reduced levels of nuclear HIF-1, subunit and STAT3. Chromatin immunoprecipitation (ChIP) assays revealed that HIF-1,, but not STAT3, was recruited to the VEGF promoter following the 4,h of CoCl2 treatment. This effect was inhibited by transfection of cells with pre-miR-20b. In addition, using siRNA knockdown, we demonstrated that the presence of STAT3 is necessary for CoCl2 -mediated HIF-1, nuclear accumulation and recruitment on VEGF promoter. In summary, this report demonstrates, for the first time, that the VEGF expression in breast cancer cells is mediated by HIF-1 and STAT3 in a miR-20b-dependent manner. J. Cell. Physiol. 224:242,249, 2010 © 2010 Wiley-Liss, Inc. [source] Do personality characteristics and beliefs predict intra-group bullying between prisoners?AGGRESSIVE BEHAVIOR, Issue 4 2010Polly Turner Abstract This study assesses how beliefs about aggression and personality can predict engagement in intra-group bullying among prisoners. A sample of 213 adult male prisoners completed the DIPC-SCALED (bullying behavior), the EXPAGG (beliefs toward aggression), and the IPIP (a five-factor measure of personality). It was predicted that bullies would hold greater instrumental beliefs supporting the use of aggression than the other categories, with perpetrators reporting lower scores on agreeableness, conscientiousness, and openness to experience, and higher scores on neuroticism (i.e. low scores on emotional stability) than the remaining sample. Bullies and bully-victims endorsed greater instrumental aggressive beliefs than the victim category. Only one perpetrator group, bullies were predicted by reduced levels of agreeableness and increased levels of neuroticism, whereas bully/victims were predicted by decreased levels of neuroticism. Limitations of this study and directions for future research are discussed. Aggr. Behav. 36:261,270, 2010. © 2010 Wiley-Liss, Inc. [source] THE INFLUENCE OF SAE LOCUS KNOCKOUT ON EXOPROTEINS IN STAPHYLOCOCCUS AUREUSJOURNAL OF FOOD SAFETY, Issue 3 2010JUNNI TANG ABSTRACT The sae operon is a key regulator in Staphylococcus aureus, which is known as an important infective and toxigenic bacterial pathogen. For the exploration of virulence factors expressed in the secreted exoprotein fraction are being controlled by sae operon, the relationship between the sae locus and exoproteins was investigated in this study. The homologous recombination vector pBT2,sae was constructed and the sae deletion mutant strain was successfully obtained. The results showed that the sae locus played an important role in the production of thermonucleases and other exoproteins. Sodium dodecyl sulfate polyacrylamide gel electrophoresis showed different exoprotein profiles between parent strain and mutant strain, in which three bands were visibly weakened. The results revealed that sae locus was involved in the regulation on exoproteins, some of which play a known fundamental role in the virulence of S. aureus. PRACTICAL APPLICATIONS This study presents that knocking out the sae gene locus in a specific Staphylococcus aureus strain results in reduced thermonuclease action, and also in reduced levels of proteins in the vicinity of 42 and 32 kDa molecular weight in sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis (PAGE) gels, indicating that their production is dependent on the sae locus. Practically, these proteins are associated with virulence traits, and with the pathogen's response to the environment and in potential hosts, which could be helpful for understanding the pathogenicity of S. aureus and also for further studies on the role of selected genes in the pathogenicity of S. aureus. [source] Neuroserpin regulates neurite outgrowth in nerve growth factor-treated PC12 cellsJOURNAL OF NEUROCHEMISTRY, Issue 6 2002Parmjeet K. Parmar Abstract Neuroserpin is a serine protease inhibitor widely expressed in the developing and adult nervous systems and implicated in the regulation of proteases involved in processes such as synaptic plasticity, neuronal migration and axogenesis. We have analysed the effect of neuroserpin on growth factor-induced neurite outgrowth in PC12 cells. We show that small changes in neuroserpin expression result in changes to the number of cells extending neurites and total neurite length following NGF treatment. Increased expression of neuroserpin resulted in a decrease in the number of cells extending neurites and a reduction in total free neurite length whereas reduced levels of neuroserpin led to a small increase in the number of neurite extending cells and a significant increase in total free neurite length compared to the parent cell line. Neuroserpin also altered the response of PC12 cells to bFGF and EGF treatment. Neuroserpin was localised to dense cored secretory vesicles in PC12 cells but was unable to complex with its likely enzyme target, tissue plasminogen activator at the acidic pH found in these vesicles. These data suggest that modulation of neuroserpin levels at the extending neurite growth cone may play an important role in regulating axonal growth. [source] Suppression of the Febrile Response in Late Gestation: Evidence, Mechanisms and OutcomesJOURNAL OF NEUROENDOCRINOLOGY, Issue 4 2008A. Mouihate Fever is a beneficial host defence response. However, fever caused by the immune stimulant, lipopolysaccharide (LPS), are attenuated in many species during pregnancy, particularly near term. A number of parallel mechanisms may be responsible, and these vary in magnitude according to the time of gestation, type of inflammatory stimulus and species of animal. Some studies report a reduction in the plasma levels of circulating pro-inflammatory cytokines such as tumour necrosis factor-,, interleukin-1, and interleukin-6 along with increased levels of anti-inflammatory cytokines such as interleukin-1 receptor antagonist. Associated with the attenuated febrile response to LPS is a reduction in the activation of the prostaglandin synthesising enzyme, cyclo-oxygenase 2, resulting in reduced levels of the obligatory prostaglandin mediators of the febrile response in the brain. There is also a reduction in the sensitivity of the brain to the pyrogenic action of prostaglandins, which does not appear to be due to a change in the levels of hypothalamic EP3 prostaglandin receptors. The suppression of fever at term may be important for the health of the neonate because fever in pregnant mothers may be harmful to the late-term foetus and neonate. [source] | |||||||||||||||||||||||||||||||||||||