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Reduced Ability (reduced + ability)

Distribution by Scientific Domains

Medical Sciences	42%
Life Sciences	35%
Psychology	7%
3 Other Domains	16%

Selected Abstracts

MicroReview: Impact of the bacterial type I cytochrome c maturation system on different biological processes

MOLECULAR MICROBIOLOGY, Issue 6 2005
Nicholas P. Cianciotto
Summary In the ,-, ,- and ,- Proteobacteria, the so-called cytochrome c maturation (Ccm) system is known to promote the covalent attachment of the haem to periplasmic apocytochrome c. However, in species of Pseudomonas, Rhizobium, Paracoccus and Legionella, mutations in ccm genes result in phenotypes that cannot be readily explained by the simple loss of a c -type cytochrome. These phenotypes include loss of siderophore production and utilization, reduced abilities to grow in low-iron conditions and in mammalian and protozoan host cells, and alterations in copper sensitivity and manganese oxidation. These various data suggest that Ccm proteins may perform one or more functions in addition to Ccm, which are critical for bacterial physiology and growth. Novel hypotheses that should be explored include the utilization of Ccm-associated haem for processes besides attachment to apocytochrome c, the export of a non-haem compound through the Ccm system, and the negative effects of protoporphyrin IX accumulation. [source]

Antagonistic lipopolysaccharides block E. coli lipopolysaccharide function at human TLR4 via interaction with the human MD-2 lipopolysaccharide binding site

CELLULAR MICROBIOLOGY, Issue 5 2007
Stephen R. Coats
Summary Lipopolysaccharides containing underacylated lipid A structures exhibit reduced abilities to activate the human (h) Toll-like receptor 4 (TLR4) signalling pathway and function as potent antagonists against lipopolysaccharides bearing canonical lipid A structures. Expression of underacylated lipopolysaccharides has emerged as a novel mechanism utilized by microbial pathogens to modulate host innate immune responses. Notably, antagonistic lipopolysaccharides are prime therapeutic candidates for combating Gram negative bacterial sepsis. Penta-acylated msbB and tetra-acylated Porphyromonas gingivalis lipopolysaccharides functionally antagonize hexa-acylated Escherichia coli lipopolysaccharide-dependent activation of hTLR4 through the coreceptor, hMD-2. Here, the molecular mechanism by which these antagonistic lipopolysaccharides act at hMD-2 is examined. We present evidence that both msbB and P. gingivalis lipopolysaccharides are capable of direct binding to hMD-2. These antagonistic lipopolysaccharides can utilize at least two distinct mechanisms to block E. coli lipopolysaccharide-dependent activation of hTLR4. The main mechanism consists of direct competition between the antagonistic lipopolysaccharides and E. coli lipopolysaccharide for the same binding site on hMD-2, while the secondary mechanism involves the ability of antagonistic lipopolysaccharide,hMD-2 complexes to inhibit E. coli lipopolysaccharide,hMD-2 complexes function at hTLR4. It is also shown that both hTLR4 and hMD-2 contribute to the species-specific recognition of msbB and P. gingivalis lipopolysaccharides as antagonists at the hTLR4 complex. [source]

Nerve growth factor increases airway responses and decreases levels of exhaled nitric oxide during histamine challenge in an in vivo guinea-pig model

ACTA PHYSIOLOGICA, Issue 2 2001
S. G. Friberg
There is a growing body of evidence supporting the idea that nerve growth factor (NGF) may be involved in the development of asthma-associated symptoms, such as airway hyper-responsiveness. Increased levels of NGF have recently been described in serum and in the airways of asthmatics. We have examined whether exhaled nitric oxide (NO) levels might be altered during the increased airway responses upon NGF treatment in guinea-pigs in vivo. Intravenous (i.v.) administration of histamine normally elicits a rapid peak in insufflation pressure (IP) and in exhaled NO, followed by a period of decreased concentrations of exhaled NO. Anaesthetized guinea-pigs were pre-treated intravenously with either saline, 4 or 80 ng kg,1 NGF 30 min before i.v. challenge with 16 ,g kg,1 histamine. At 80 ng kg,1 NGF significantly enhanced the airway obstruction caused by histamine, whereas the peak acute increase in exhaled NO was not enhanced. Following the increase, came a rapid drop, an effect enforced in the NGF treated animals. Subsequently, the time to return to 90% of resting exhaled NO was increased, from 12 min in saline-treated animals to 48 min in NGF-treated animals. Our data confirm that NGF can enhance airway responses to histamine. Moreover, our study shows a decrease in exhaled NO following a histamine challenge, an effect enhanced by NGF. A reduced ability to release exhaled NO may be a mechanism for increased airway responses during elevated NGF levels. The interaction between NGF and airway NO formation, and its relation to airway responses, merit further investigation. [source]

Out-patient behaviour therapy in alcoholism: treatment outcome after 2 years

ACTA PSYCHIATRICA SCANDINAVICA, Issue 3 2002
W. Burtscheidt
Burtscheidt W, Wölwer W, Schwarz R, Strauss W, Gaebel W. Out-patient behaviour therapy in alcoholism: treatment outcome after 2 years. Acta Psychiatr Scand 2002: 106: 227,232. © Blackwell Munksgaard 2002. Objective:,The main aim of the study was the evaluation of out-patient behavioural approaches in alcohol dependence. Additionally, the persistence of treatment effects and the impact of psychiatric comorbidity in long-term follow-up was examined. Method:,A total of 120 patients were randomly assigned to non-specific supportive therapy or to two different behavioural therapy programmes (coping skills training and cognitive therapy) each comprising 26 weekly sessions; the follow-up period lasted 2 years. Results:,Patients undergoing behavioural therapy showed a consistent trend towards higher abstinence rates; significant differences between the two behavioural strategies could not be established. Moreover, the results indicate a reduced ability of cognitive impaired patients to cope with short-time abstinence violations and at a reduced benefit from behavioural techniques for patients with severe personality disorders. Conclusion:,Behavioural treatment yielded long-lasting effects and met high acceptance; yet, still in need of improvement is the development of specific programmes for high-risk patients. [source]

Whole sediment toxicity identification evaluation tools for pyrethroid insecticides: III.

ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 1 2009
Temperature manipulation
Abstract Since the toxicity of pyrethroid insecticides is known to increase at low temperatures, the use of temperature manipulation was explored as a whole-sediment toxicity identification evaluation (TIE) tool to help identify sediment samples in which pyrethroid insecticides are responsible for observed toxicity. The amphipod Hyalella azteca is commonly used for toxicity testing of sediments at a 23°C test temperature. However, a temperature reduction to 18°C doubled the toxicity of pyrethroids, and a further reduction to 13°C tripled their toxicity. A similar response, though less dramatic, was found for 1,1-bis(p -chlorophenyl)-2,2,2-trichloroethane (DDT), and dissimilar temperature responses were seen for cadmium and the insecticide chlorpyrifos. Tests with field-collected sediments containing pyrethroids and/or chlorpyrifos showed the expected thermal dependency in nearly all instances. The inverse relationship between temperature and toxicity provides a simple approach to help establish when pyrethroids are the principal toxicant in a sediment sample that could be used as a supplemental tool in concert with chemical analysis or other TIE manipulations. The phenomenon appears to be, in part, a consequence of a reduced ability to biotransform the toxic parent compound at cooler temperatures. The strong dependence of pyrethroid toxicity on temperature has important ramifications for predicting their environmental effects, and the standard test temperature of 23°C dramatically underestimates risk to resident fauna during the cooler months. [source]

After Cancún: what next for agricultural subsidies?

EUROCHOICES, Issue 3 2003
Tim Josling
Summary After Cancún: what next for agriculturalsubsidies? The collapse of the Ministerial in Cancún highlighted the enhanced role of the developing countries in the WTO and the reduced ability of the US and the EU to manage the trade system. One aspect of these changes has been that developing countries have taken much more interest in the level of domestic support in developed countries. Developed countries believe that the shift of support from production-linked to decoupled instruments has had a positive impact on trade. Developing countries maintain that this reform has not helped them, and has perpetuated inequities in the trade system. Research suggests that the output effect of decoupled support is limited, if not negligible. Such decoupling may be necessary to reform domestic polices. Additionally, domestic policies are being challenged by developing countries using the trade litigation of the WTO. But such challenges risk undermining support for the WTO. Until agreement is reached on these issues there will be little progress in further agricultural trade reform. A political solution must be found that continues the slow process of improvement of domestic farm policies and at the same time offers hope to developing countries that they will benefit from the improvement in the trade conditions for agricultural products. Après Cancún:quel avenir pour les subventions? L'échec de la conférence ministérielle de Cancun met en évidence !e rôle accru des pays en voie de développement à l'OMC, ainsi que la faible aptitude des Etats-Unis et de l'Europe à gérer le système des échanges internationaux. Ces changements impliquent que les pays en voie de développement s'intéressent de plus en plus aux niveaux de protection internes des pays développés. Les pays développés croient que le glissement des aides vers plus de découplage aura eu un effet positif sur les échanges. Mais les pays en voie de développement continuent à penser que ces réformes ne les ont pas aidés, et qu'elles ont perpétué les inégalités du commerce mondial. Le travail présenté ici semble montrer que l'effet du découplage sur l'offre est très faible, voire nul. Peut-être le decouplage est-il utile pour la réforme des politiques internes. Mais, au delà, ces politiques internes sont mises en cause par les pays en voie de développement, qui utilisent à leur encontre les ressources de procédure mises à leur disposition par l'OMC. De telles mises en cause sont de nature à détruire le soutien de l'opinion à l'OMC. II ne faut pas s'attendre à beaucoup de progrès dans les réformes du commerce international agricole tant qu'on n'aura pas trouve un accord sur ces questions. II est done necessaire d'élaborer des solutions qui confortent le lent progrès des politiques internes des pays developpes, tout en offrant aux pays en voie de développement 1, espoir de bénéficier de l'amélioration des conditions des échanges agricoles. Nach Cancún: Was geschieht als nächstes mitAgrarsubventionen? Das Scheitern des Ministerialtreffensin Cancún hob die verbesserte Position der Entwicklungsländer in der WTO und die verminderte Fähigkeit der USA und der EU hervor, das Handelssystem zu lenken. Finer der Aspekte dieser Veränderungen bestand darin, dass die Entwicklungsländer ein sehr viel größeres Interesse am Ausmaß der Inlandsstützung in Industrieländern gezeigt haben. Die Industrieländer glauben, dass sich der Schritt von einer produktionsgebundenen Inlandsstützung hin zu einer entkoppelten Inlandsstützung positiv auf den Handel ausgewirkt hat. Die Entwicklungsländer behaupten jedoch, dass ihnen diese Reform nicht geholfen habe und dass so Ungerechtigkeiten im Handelssystem aufrecht erhalten würden. Forschungsergebnisse legen es nahe, dass sich die entkoppelte Inlandsstützung sehr begrenzt, möglicherweise nur geringfügig, auf die Produktion auswirkt. Eine solche Entkopplung ist möglicherweise notwendig, urn inländische Politikmaßnahmen zu reformieren. Zusátzlich werden die inländischen Politikmaßnahmen von den Entwicklungsländern zur Zeit im Rahmen der WTO-Verfahren zur Beilegung von Handelsstreitigkeiten angefochten. Solche Anfechtungen bergen jedoch immer das Risiko einer abgeschwächten Unterstützung für die WTO. Bis in diesen Punkten Einigkeit herrscht, wird es nur geringe Fortschritte für die Agrarhandelsreformen geben. Es muss eine politische Lösung gefunden werden, welche den langsamen Verbesserungsprozess bei den inländischen Agrarpolitikmaßnahmen voran treibt und welche die Entwicklungsländer zugleich hoffen lässt, von der Verbesserung der Handelsbedingungen für landwirtschaftliche Erzeugnisse profitieren zu können. [source]

IL-10 modulates cytokine gene transcription by protein synthesis-independent and dependent mechanisms in lipopolysaccharide-treated neutrophils

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 11 2007
Marzia Rossato
Abstract We have recently reported that the ability of IL-10 to rapidly exert its anti-inflammatory effects on human neutrophils is dependent upon exposure of these cells to LPS for at least 3,4,h. Here, we demonstrate that, in neutrophils "preconditioned" by LPS, IL-10 primarily targets the transcription of TNF-,, CXCL8 and IL-1ra genes, as revealed by primary transcript real-time RT-PCR. We also show that IL-10-induced transcriptional repression of TNF-, and CXCL8 genes consists of two distinct phases: an early one, occurring rapidly and in a protein synthesis-independent manner, followed by a second phase, more delayed and dependent on protein synthesis. Interestingly, the protein synthesis dependence of the latter phase coincides with a reduced ability of IL-10 to induce STAT3 tyrosine phosphorylation. Importantly, inhibition of IL-10-induced STAT3 activation and IL-10-suppressive action by a prolonged exposure to cycloheximide (CHX) was observed to occur also in human monocytes and was caused by a defective IL-10-mediated activation of Jak1 and Tyk2 kinases. Taken together, our findings suggest that CHX interferes with the IL-10-mediated intracellular signaling pathway by interrupting events upstream of STAT3 activation. These data question the concept of the requirement of an IL-10-induced mediator as the unique mechanism to execute IL-10 anti-inflammatory program. [source]

Functional impairment of cytotoxic T cells in the lung airways following respiratory virus infections

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 6 2006
Simone Vallbracht
Abstract We investigated the differentiation phenotype and function of virus-specific and non-specific CTL that were recruited to the lung parenchyma and the bronchoalveolar space after respiratory virus infections. Soon after virus elimination, we observed functional impairment of CTL isolated from the airways in their ability to produce IFN-, and TNF-, and to lyse target cells. Impaired cytotoxicity was due to a reduced content of granzyme B and a reduced ability to mobilize lytic granules. This impairment in effector functions (a) was largely restricted to CTL in the lung airways, (b) affected both CTL specific for the infecting virus as well as those that were recruited non-specifically to the inflamed lung, (c) was independent of contact between CTL and their specific viral antigen, (d) was not restricted to terminally differentiated CTL but also affected resting memory CTL and (e) could be elicited by both respiratory syncytial virus and influenza virus and thus seemed to be largely independent of the infecting virus. These observations suggest that functional impairment of antiviral T cells in the lung is not the consequence of a viral escape strategy. It may rather result from the particular milieu in the bronchoalveolar space and reflect a host mechanism to prevent excessive pulmonary inflammation. [source]

Fermentative lifestyle in yeasts belonging to the Saccharomyces complex

FEBS JOURNAL, Issue 4 2007
Annamaria Merico
The yeast Saccharomyces cerevisiae is characterized by its ability to: (a) degrade glucose or fructose to ethanol, even in the presence of oxygen (Crabtree effect); (b) grow in the absence of oxygen; and (c) generate respiratory-deficient mitochondrial mutants, so-called petites. How unique are these properties among yeasts in the Saccharomyces clade, and what is their origin? Recent progress in genome sequencing has elucidated the phylogenetic relationships among yeasts in the Saccharomyces complex, providing a framework for the understanding of the evolutionary history of several modern traits. In this study, we analyzed over 40 yeasts that reflect over 150 million years of evolutionary history for their ability to ferment, grow in the absence of oxygen, and generate petites. A great majority of isolates exhibited good fermentation ability, suggesting that this trait could already be an intrinsic property of the progenitor yeast. We found that lineages that underwent the whole-genome duplication, in general, exhibit a fermentative lifestyle, the Crabtree effect, and the ability to grow without oxygen, and can generate stable petite mutants. Some of the pre-genome duplication lineages also exhibit some of these traits, but a majority of the tested species are petite-negative, and show a reduced Crabtree effect and a reduced ability to grow in the absence of oxygen. It could be that the ability to accumulate ethanol in the presence of oxygen, a gradual independence from oxygen and/or the ability to generate petites were developed later in several lineages. However, these traits have been combined and developed to perfection only in the lineage that underwent the whole-genome duplication and led to the modern Saccharomyces cerevisiae yeast. [source]

Calcium modulates endopeptidase 24.15 (EC 3.4.24.15) membrane association, secondary structure and substrate specificity

FEBS JOURNAL, Issue 12 2005
Vitor Oliveira
The metalloendopeptidase 24.15 (EP24.15) is ubiquitously present in the extracellular environment as a secreted protein. Outside the cell, this enzyme degrades several neuropeptides containing from 5 to 17 amino acids (e.g. gonadotropin releasing hormone, bradykinin, opioids and neurotensin). The constitutive secretion of EP24.15 from glioma C6 cells was demonstrated to be stimulated linearly by reduced concentrations of extracellular calcium. In the present report we demonstrate that extracellular calcium concentration has no effect on the total amount of the extracellular (cell associated + medium) enzyme. Indeed, immuno-cytochemical analyses by confocal and electron microscopy suggested that the absence of calcium favors the enzyme shedding from the plasma membrane into the medium. Two putative calcium-binding sites on EP24.15 (D93 and D159) were altered by site-directed mutagenesis to investigate their possible contribution to binding of the enzyme at the cell surface. These mutated recombinant proteins behave similarly to the wild-type enzyme regarding enzymatic activity, secondary structure, calcium sensitivity and immunoreactivity. However, immunocytochemical analyses by confocal microscopy consistently show a reduced ability of the D93A mutant to associate with the plasma membrane of glioma C6 cells when compared with the wild-type enzyme. These data and the model of the enzyme's structure as determined by X-ray diffraction suggest that D93 is located at the enzyme surface and is consistent with membrane association of EP24.15. Moreover, calcium was also observed to induce a major change in the EP24.15 cleavage site on distinctive fluorogenic substrates. These data suggest that calcium may be an important modulator of ep24.15 cell function. [source]

Anaerobic culture conditions favor biofilm-like phenotypes in Pseudomonas aeruginosa isolates from patients with cystic fibrosis

FEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 3 2006
Che Y. O'May
Abstract Pseudomonas aeruginosa causes chronic infections in the lungs of cystic fibrosis (CF) individuals and remains the leading cause of morbidity and mortality associated with the disease. Biofilm growth and phenotypic diversification are factors thought to contribute to this organism's persistence. Most studies have focused on laboratory isolates such as strain PAO1, and there are relatively few reports characterizing the properties of CF strains, especially under decreased oxygen conditions such as occur in the CF lung. This study compared the phenotypic and functional properties of P. aeruginosa from chronically infected CF adults with those of strain PAO1 and other clinical non-CF isolates under aerobic and anaerobic culture conditions. The CF isolates overall displayed a reduced ability to form biofilms in standard in vitro short-term models. They also grew more slowly in culture, and exhibited decreased adherence to glass and decreased motilities (swimming, swarming and twitching). All of these characteristics were markedly accentuated by anaerobic growth conditions. Moreover, the CF strain phenotypes were not readily reversed by culture manipulations designed to encourage planktonic growth. The CF strains were thus inherently different from strain PAO1 and most of the other non-CF clinical P. aeruginosa isolates tested. In vitro models used to research CF isolate biofilm growth need to take the above properties of these strains into account. [source]

Reduced fertility of mouse epididymal sperm lacking Prss21/Tesp5 is rescued by sperm exposure to uterine microenvironment

GENES TO CELLS, Issue 10 2008
Misuzu Yamashita
Although the acrosome reaction and subsequent penetration of sperm through the egg zona pellucida (ZP) are essential for mammalian fertilization, the molecular mechanism is still controversial. We have previously identified serine protease Tesp5 identical to Prss21 on the mouse sperm surface as a candidate enzyme involved in sperm penetration through the ZP. Here we show that despite normal fertility of male mice lacking Prss21/Tesp5, the epididymal sperm penetrates the ZP only at a very low rate in vitro, presumably owing to the reduced ability to bind the ZP and undergo the ZP-induced acrosome reaction. The ability of Prss21-null sperm to fuse with the egg in vitro was also impaired severely. Intriguingly, the reduced fertility of Prss21-null epididymal sperm was rescued by exposure of the sperm to the uterine microenvironment and by in vitro treatment of the sperm with uterine fluids. These data suggest the physiological importance of sperm transport through the uterus. [source]

The impact of mineralocorticoid receptor ISO/VAL genotype (rs5522) and stress on reward learning

GENES, BRAIN AND BEHAVIOR, Issue 6 2010
R. Bogdan
Research suggests that stress disrupts reinforcement learning and induces anhedonia. The mineralocorticoid receptor (MR) determines the sensitivity of the stress response, and the missense iso/val polymorphism (Ile180Val, rs5522) of the MR gene (NR3C2) has been associated with enhanced physiological stress responses, elevated depressive symptoms and reduced cortisol-induced MR gene expression. The goal of these studies was to evaluate whether rs5522 genotype and stress independently and interactively influence reward learning. In study 1, participants (n = 174) completed a probabilistic reward task under baseline (i.e. no-stress) conditions. In study 2, participants (n = 53) completed the task during a stress (threat-of-shock) and no-stress condition. Reward learning, i.e. the ability to modulate behavior as a function of reinforcement history, was the main variable of interest. In study 1, in which participants were evaluated under no-stress conditions, reward learning was enhanced in val carriers. In study 2, participants developed a weaker response bias toward a more frequently rewarded stimulus under the stress relative to no-stress condition. Critically, stress-induced reward learning deficits were largest in val carriers. Although preliminary and in need of replication due to small sample size, findings indicate that psychiatrically healthy individuals carrying the MR val allele, gene, which has been recently linked to depression, showed a reduced ability to modulate behavior as a function of reward when facing an acute, uncontrollable stressor. Future studies are warranted to evaluate whether rs5522 genotype interacts with naturalistic stressors to increase the risk of depression and whether stress-induced anhedonia might moderate such risk. [source]

Chromosomal fragile sites FRA3B and FRA16D show correlated expression and association with failure of apoptosis in lymphocytes from patients with thyroid cancer

GENES, CHROMOSOMES AND CANCER, Issue 5 2006
Isabella Sbrana
It has been suggested that common fragile sites (cFSs) are related to cancer development. This appears to be the case for FRA3B and FRA16D, localized in two tumor-suppressor genes (FHIT and WWOX, respectively) that are altered by deletions or loss of heterozygosity (LOH) in many cancers. The features responsible for fragility have not yet been identified. Furthermore, it is still unclear whether instability at these regions causes chance deletions and loss of function of the associated genes, or whether the gene function itself is related to the appearance of fragility. In this study, we analyzed cFS expression in lymphocytes from 20 healthy or thyroid cancer,affected subjects exposed to radiation after the Chernobyl accident. The same cells were examined for apoptosis, a principal function of both the FHIT and WWOX genes. Exceptionally elevated chromosome fragility was observed, particularly in cancer patients, affecting FRA3B, FRA16D, and a cluster of less highly expressed cFSs; levels of chromosome fragility were found to be correlated among these cFSs. Interestingly, most expressed cFSs were sites of LOH reported for thyroid tumors; moreover, cells with the highest fragility also had a reduced ability to undergo apoptosis. These findings reveal previously unknown genetic interactions affecting fragile loci, suggestive of a shared function inside mitotic cells. Attenuation of checkpoint control and apoptosis resistance seem to be the cell phenotypes associated with unusual chromosome fragility. We propose that breakage at specific cFS could derive from early epigenetic events at loci involved in radiation carcinogenesis. This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1045-2257/suppmat. © 2006 Wiley-Liss, Inc. [source]

Cost-effectiveness analysis based on the number-needed-to-treat: common sense or non-sense?

HEALTH ECONOMICS, Issue 1 2004
Ivar Sønbø Kristiansen
Abstract This paper explores and critically discusses some of the methodological limitations of using the number-needed-to-treat (NNT) in economic evaluation. We argue that NNT may be a straightforward measure of benefit when the effect of an intervention is immediate, but that serious problems arise when the effect is delay rather than avoidance of an adverse event. In this case, NNT is not a robust or accurate measure of effect, but will vary considerably and inconsistently over time. This weakness will naturally spill over onto any CEA based on NNT. A literature review demonstrated that CEAs based on NNT were all published within the last five years, and that all studies suffered from important limitations. A major weakness of using NNT is the imposed restrictions on the outcome measure, which can only be strictly uni-dimensional and non-generic. Using NNT in economic evaluations is obtained at a cost in terms of both methodological shortcomings, and a reduced ability for such evaluations to serve as a useful tool in decision making processes. The use of NNT in economic evaluations might be better avoided. To every complicated question, there is a simple, straightforward, easy , and probably wrong answer (Occam's Sledgehammer). Copyright © 2003 John Wiley & Sons, Ltd. [source]

First missense mutation in the SOST gene causing sclerosteosis by loss of sclerostin function,

HUMAN MUTATION, Issue 7 2010
Elke Piters
Abstract Sclerosteosis is a rare bone dysplasia characterized by greatly increased bone mass, especially of the long bones and the skull. Patients are tall, show facial asymmetry and often have syndactyly. Clinical complications are due to entrapment of cranial nerves. The disease is thought to be due to loss-of-function mutations in the SOST gene. The SOST gene product, sclerostin, is secreted by osteocytes and transported to the bone surface where it inhibits osteoblastic bone formation by antagonizing Wnt signaling. In a small Turkish family with sclerosteosis, we identified a missense mutation (c.499T>C; p.Cys167Arg) in exon 2 of the SOST gene. This type of mutation has not been previously reported and using different functional approaches, we show that it has a devastating effect on the biological function of sclerostin. The affected cysteine is the last cysteine residue of the cystine-knot motif and loss of this residue leads to retention of the mutant protein in the ER, possibly as a consequence of impaired folding. Together with a significant reduced ability to bind to LRP5 and inhibit Wnt signaling, the p.Cys167Arg mutation leads to a complete loss of function of sclerostin and thus to the characteristic sclerosteosis phenotype. © 2010 Wiley-Liss, Inc. [source]

DEC-205lo Langerinlo neonatal Langerhans' cells preferentially utilize a wortmannin-sensitive, fluid-phase pathway to internalize exogenous antigen

IMMUNOLOGY, Issue 4 2003
Bernadette M. Bellette
Summary Antigen treatment of neonatal epidermis results in antigen-specific immune suppression. Compared with adult counterparts, neonatal Langerhans' cells (LC) demonstrate an impaired ability to transport antigen to the lymph node (LN). As it is possible that neonatal LC have a reduced ability to endocytose antigen, we evaluated the acquisition of endocytic function, the expression of uptake receptors and the internalization of soluble and small particulate antigens in neonatal, juvenile and adult mice. Although LC from 4-day-old mice were weakly positive for the mannose-type receptor, Langerin, they were capable of internalizing fluorescein isothiocyanate (FITC)-dextran, but to a lesser extent than LC from 6-week-old mice. However, when ratio data were calculated to account for variations in fluorescence intensity at 4°, it was demonstrated that neonatal LC continued to internalize antigen over a longer period of time than adult mice and, as the ratios were much higher, that neonatal cells were also relatively more efficient in antigen uptake. When receptors for mannan and mannose were competitively blocked, LC from neonatal mice, but not adult mice, could still efficiently internalize FITC,dextran. Consequently, the uptake of FITC,dextran, in part, occurred via alternative receptors or a receptor-independent fluid-phase pathway. A feasible pathway is macropinocytosis, as LC from 4-day-old mice demonstrated a reduction in FITC,dextran internalization by the macropinocytosis inhibitor, wortmannin. Evidence of a functional macropinocytosis pathway in neonatal LC was further supported by internalization of the soluble tracer Lucifer Yellow (LY). We conclude that neonatal LC preferentially utilize a wortmannin-sensitive, fluid-phase pathway, rather than receptor-mediated endocytosis, to internalize antigen. As neonatal LC are capable of sampling their environment without inducing immunity, this may serve to avoid inappropriate immune responses during the neonatal period. [source]

Differing Risk Factors for Falls in Nursing Home and Intermediate-Care Residents Who Can and Cannot Stand Unaided

JOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 11 2003
Stephen R. Lord PhD
Objectives: To determine fall risk factors in nursing home and intermediate-care residents who can and cannot stand unaided. Design: Prospective cohort study. Setting: Residential elderly care facilities in Sydney, Australia. Participants: One thousand people aged 65 to 103 (mean age ± standard deviation: 85.0 ± 7.4). Measurements: Accidental falls. Results: Fall rates were highest in those with fair standing balance, intermediate in those with the best standing balance, and lowest in those with the worst standing balance. This nonlinear pattern was even more striking when subjects were categorized according to their standing balance and ability to rise from a chair. Using this dual classification, fall rates were highest in those who could rise from a chair but could not stand unaided (81%) and lowest in those who could neither rise from a chair nor stand unaided (48%). In residents who could stand unaided, risk factors included increased age, male sex, higher care classifications, incontinence, psychoactive medication use, previous falls, and slow reaction times. In contrast, quite different risk factors were evident in residents who could not stand unaided, with a number of known fall risk factors (previous stroke, reduced ability to rise from a chair, slow reaction times) being associated with fewer falls. In this group, risk factors were intermediate versus nursing home care, poor health status, psychoactive medication use, Parkinson's disease, previous falls, and being able to get out of a chair. Conclusion: The findings indicate that there are different risk factors for falls for people living in residential aged care facilities who can and cannot stand unaided. These findings provide important information for developing fall-prevention strategies and suggest that those who can stand unaided but have multiple falls risk factors constitute the highest priority group for such interventions. [source]

Counteracting the effects of invisibility in work with lesbian patients

JOURNAL OF CLINICAL PSYCHOLOGY, Issue 5 2001
Carolyn SaariArticle first published online: 9 APR 200
Lesbian women frequently experience "invisibility," the failure of others to recognize the significance of their sexuality and partnership relations. Such invisibility can have deleterious effects, such as a reduced ability to relate life stories to others and thereby to extend and integrate aspects of identity and its healthy complexity. Although this invisibility often is intertwined with coming-out phenomena, it continues to exist in many social contexts throughout life. Therefore, it is important for psychotherapists to recognize and understand the concept of invisibility so that they do not perpetuate it within the therapy. Several case vignettes are used as examples of how invisibility can affect a woman's life and functioning and can be counteracted in therapy. © 2001 John Wiley & Sons, Inc. J Clin Psychol/In Session 57: 645,654, 2001. [source]

Innate immune responses of gingival epithelial cells to nonperiodontopathic and periodontopathic bacteria

JOURNAL OF PERIODONTAL RESEARCH, Issue 6 2007
S. Ji
Background and Objective:, We have previously reported different susceptibilities of periodontopathic and nonperiodontopathic bacteria to antimicrobial peptides and phagocytosis by neutrophils. Differences between the two groups of bacteria may exist also in their ability to induce immune responses from the host. Therefore, we evaluated the effects of various oral bacteria on innate immune responses by gingival epithelial cells. Material and Methods:, HOK-16B cells were cocultured with live or lysed nonperiodontopathic (n = 3) and periodontopathic (n = 5) bacterial species. The levels of human beta defensin-1, -2 and -3, and of the cathelicidin, LL-37, were examined by real-time reverse transcription-polymerase chain reaction, and the accumulated interleukin-8 and interleukin-1, were measured by enzyme-linked immunosorbent assay. Results:, Nonperiodontopathic bacteria up-regulated some antimicrobial peptides without affecting the levels of cytokines. In the periodontopathic group, the orange-complex bacteria induced antimicrobial peptides and interleukin-8 efficiently, but the red-complex bacteria often demonstrated suppressive effects. In contrast to live bacteria, bacterial lysates had no suppressive effects. In addition, some bacterial lysates demonstrated a reduced ability to induce antimicrobial peptides compared with live bacteria. Conclusion:, The nonperiodontopathic, the orange-complex, and the red-complex bacteria had different effects on the innate immune responses from gingival epithelial cells, which may affect the outcome of their host,microbial interaction in gingival sulcus. [source]

Self-Assembly of Rod-Like Copolymers into Monolayers: A Simple Theoretical Estimate of Molecular Recognition Quality

MACROMOLECULAR THEORY AND SIMULATIONS, Issue 7-8 2008
Anatoly V. Berezkin
Abstract A discrete model of a monolayer, consisting of identical rod-like copolymer molecules, is suggested. The influence of the copolymer's composition and sequence on its self-assembly was studied. Thermodynamic quantities of monolayers were calculated. It is shown that the system undergoes an "order-disorder" transition upon temperature increase. The most regular monolayers are formed by copolymers with quasi-random sequences. Nevertheless, the monomer composition of such "good" sequences can vary over a wide range. It is shown that homopolymers, copolymers with a predominance of one-type monomer units and copolymers consisting of a small number of large blocks have a reduced ability to self-assembly. [source]

Primary sex ratios in birds: problems with molecular sex identification of undeveloped eggs

MOLECULAR ECOLOGY, Issue 12 2003
Kathryn E. Arnold
Abstract Sex allocation studies seek to ascertain whether mothers manipulate offspring sex ratio prior to ovulation. To do so, DNA for molecular sexing should be collected as soon after conception as possible, but instead neonates are usually sampled. Here, we aim to identify and quantify some of the problems associated with using molecular techniques to identify the sex of newly laid avian eggs. From both fertilized and unfertilized chicken (Gallus gallus) eggs, we sampled (1) the blastoderm/disc, (2) vitelline membrane and (3) a mixture of (1) and (2). Thus, we replicated scenarios under which contaminated samples are taken and/or unfertilized eggs are not identified as such and are sampled. We found that two commonly used molecular sexing tests, based on the CHD-1 genes, differed in sensitivity, but this did not always predict their ability to sex egg samples. The vitelline membrane was a considerable source of maternal and probably paternal contamination. Fertile eggs were regularly assigned the wrong sex when vitelline membrane contaminated the blastoderm sample. The membrane of unfertilized eggs was always female, i.e. maternal DNA had been amplified. DNA was amplified from 47 to 63% of unfertilized blastodiscs, even though it was highly unlikely that DNA from a single haploid cell could be amplified reliably using these polymerase chain reaction (PCR) techniques. Surprisingly, the blastodiscs were identified as both males and females. We suggest that in these cases only maternal DNA was amplified, and that ,false' males, Z not ZZ, were detected. This was due to the reduced ability of both sets of primers to anneal to the W chromosome compared to the Z chromosome at low DNA concentrations. Overall, our data suggested that estimates of primary sex ratios based on newly laid eggs will be appreciably inaccurate. [source]

Comparison of breathing tube connectors during invasive bronchial procedures,

ANAESTHESIA, Issue 6 2009
N. Rahe-Meyer
Summary Bronchoscopy and bronchial suctioning during intra-operative artificial ventilation often causes leakage from the ventilation circuit with a decrease in ventilatory parameters and possible workplace contamination with anaesthetic gases. Different connectors have been developed to reduce gas leakage. We evaluated the following connectors : VBM 2 mm, 3 mm and 5 mm, Bodai Suction-Safe, Bodai Bronch-Safe and Bodai Trach-Safe, as well as the BE 105-7, BE 105-8 and SH 7-45. Invasive bronchial instruments (catheters, bronchoscopes and bronchial blockers) with 1.67,7.33 mm diameter were used. Pressure-controlled ventilation was performed on a test lung using a ventilator. Sevoflurane concentration in the room was measured 0.2 and 1.5 m from the connector using a photo-acoustic infrared-spectroscope. The VBM connectors caused the least gas leak and ensured stability of ventilation parameters even at peak pressures when combined with smaller instruments. With instruments > 6 mm, BE 105-7, BE 105-8 and SH 7-45 connectors performed best. The Bodai connectors showed a reduced ability to prevent leakage and to keep ventilatory parameters stable. All connectors, excluding the Bodai Trach-Safe, prevented exposure to anaesthetic gases beyond the current safety recommendations when combined with the fitting instruments. The connectors showed different ranges of tightness, equivalent to different ranges of compatibility with the instruments used. [source]

Ultrafiltration and Dry Weight,What Are the Cardiovascular Effects?

ARTIFICIAL ORGANS, Issue 3 2003
Article first published online: 2 APR 200, Bernd G. Stegmayr
Abstract: Long-term prognosis in dialysis is poor compared to that in healthy control persons. A worsening of the prognosis is noted especially for patients who at initiation of dialysis have congestive heart failure, ischemic heart disease, or left ventricular dysfunction or hypertrophy. This is the main reason that cardiovascular causes are the most common for morbidity in these patients. The weight obtained when normal urine output is present is the dry weight. With reduced ability to excrete the volume by the kidneys in end-stage renal disease (ESRD), the body will retain water and the patient will gain weight. This extra weight is due to volume overload. While volume overload may induce a rise in blood pressure, if the heart is in acceptable condition, a fast removal of fluid by ultrafiltration (UF) during dialysis may instead cause hypotension. Ultrafiltration failure in peritoneal dialysis (PD) patients may lead to successive water retention and overhydration with subsequent cardiac failure, while volume overload may occur over a few days in hemodialysis (HD) patients. Anemia or even too-high hematocrit may impair cardiac function further and worsen conditions caused by wrong dry weight. Thus, during long-term and sustained volume overload, left ventricular (LV) hypertrophy will occur in an eccentric manner. A sustained overload then may lead to cell death and LV dilatation and, eventually, systolic dysfunction. Once a severe left ventricular dilatation has developed, the blood pressure may decrease during volume overload. A worsened prognosis is seen if malnutrition and low albumin levels are present. Volume overload necessitates ultrafiltration to achieve dry weight. Thereby, volume contraction contributes to exaggerated stimulation of or response to activation of the RAS and alpha-adrenergic sympathetic systems. If ultrafiltration goes beyond these compensatory mechanisms, hypotension will occur and increase the risk for hypoperfusion of vital organs. Such episodes may cause cardiac morbidity, aspiration pneumonia, vascular access closure, or neurological complications (seizures, cerebral infarction), besides a more rapid lowering of residual renal function. Preventive measures are, first, finding the right dry weight; second, minimizing interdialytic weight gain; third, optimizing the target for hemoglobin (110,120 g/l); fourth, lowering dialysate calcium (1.25 mmol/l); and fifth, eventually using higher dialysate potassium if long dialyses are performed. [source]

Neurobiology of empathy and callousness: Implications for the development of antisocial behavior

BEHAVIORAL SCIENCES & THE LAW, Issue 2 2009
Elizabeth A. Shirtcliff Ph.D.
Information on the neurobiology of empathy and callousness provides clinicians with an opportunity to develop sophisticated understanding of mechanisms underpinning antisocial behavior and its counterpart, moral decision-making. This article provides an integrated in-depth review of hormones (e.g. peripheral steroid hormones such as cortisol) and brain structures (e.g. insula, anterior cingulate cortex, and amygdala) implicated in empathy, callousness, and psychopathic-like behavior. The overarching goal of this article is to relate these hormones and brain structures to moral decision-making. This review will begin in the brain, but will then integrate information about biological functioning in the body, specifically stress-reactivity. Our aim is to integrate understanding of neural processes with hormones such as cortisol, both of which have demonstrated relationships to empathy, psychopathy, and antisocial behavior. The review proposes that neurobiological impairments in individuals who display little empathy are not necessarily due to a reduced ability to understand the emotions of others. Instead, evidence suggests that individuals who show little arousal to the distress of others likewise show decreased physiological arousal to their own distress; one manifestation of reduced stress reactivity may be a dysfunction in empathy, which supports psychopathic-like constructs (e.g. callousness). This integration will assist in the development of objective methodologies that can inform and monitor treatment interventions focused on decreasing antisocial behavior. Copyright © 2009 John Wiley & Sons, Ltd. [source]

Measles virus nucleocapsid transport to the plasma membrane requires stable expression and surface accumulation of the viral matrix protein

CELLULAR MICROBIOLOGY, Issue 5 2007
Nicole Runkler
Summary In measles virus (MV)-infected cells the matrix (M) protein plays a key role in virus assembly and budding processes at the plasma membrane because it mediates the contact between the viral surface glycoproteins and the nucleocapsids. By exchanging valine 101, a highly conserved residue among all paramyxoviral M proteins, we generated a recombinant MV (rMV) from cloned cDNA encoding for a M protein with an increased intracellular turnover. The mutant rMV was barely released from the infected cells. This assembly defect was not due to a defective M binding to other matrix- or nucleoproteins, but could rather be assigned to a reduced ability to associate with cellular membranes, and more importantly, to a defective accumulation at the plasma membrane which was accompanied by the deficient transport of nucleocapsids to the cell surface. Thus, we show for the first time that M stability and accumulation at intracellular membranes is a prerequisite for M and nucleocapsid co-transport to the plasma membrane and for subsequent virus assembly and budding processes. [source]

Expression of a Porphyromonas gingivalis lipid A palmitylacyltransferase in Escherichia coli yields a chimeric lipid A with altered ability to stimulate interleukin-8 secretion

CELLULAR MICROBIOLOGY, Issue 1 2006
Brian W. Bainbridge
Summary In Escherichia coli the gene htrB codes for an acyltransferase that catalyses the incorporation of laurate into lipopolysaccharide (LPS) as a lipid A substituent. We describe the cloning, expression and characterization of a Porphyromonas gingivalis htrB homologue. When the htrB homologue was expressed in wild-type E. coli or a mutant strain deficient in htrB, a chimeric LPS with altered lipid A structure was produced. Compared with wild-type E. coli lipid A, the new lipid A species contained a palmitate (C16) in the position normally occupied by laurate (C12) suggesting that the cloned gene performs the same function as E. coli htrB but preferentially transfers the longer-chain palmitic acid that is known to be present in P. gingivalis LPS. LPS was purified from wild-type E. coli, the E. coli htrB mutant strain and the htrB mutant strain expressing the P. gingivalis acyltransferase. LPS from the palmitate bearing chimeric LPS as well as the htrB mutant exhibited a reduced ability to activate human embryonic kidney 293 (HEK293) cells transfected with TLR4/MD2. LPS from the htrB mutant also had a greatly reduced ability to stimulate interleukin-8 (IL-8) secretion in both endothelial cells and monocytes. In contrast, the activity of LPS from the htrB mutant bacteria expressing the P. gingivalis gene displayed wild-type activity to stimulate IL-8 production from endothelial cells but a reduced ability to stimulate IL-8 secretion from monocytes. The intermediate activation observed in monocytes for the chimeric LPS was similar to the pattern seen in HEK293 cells expressing TLR4/MD2 and CD14. Thus, the presence of a longer-chain fatty acid on E. coli lipid A altered the activity of the LPS in monocytes but not endothelial cell assays and the difference in recognition does not appear to be related to differences in Toll-like receptor utilization. [source]

In-vitro and in-vivo evidence of dose-dependent decrease of uropathogenic Escherichia coli virulence after consumption of commercial Vaccinium macrocarpon (cranberry) capsules

CLINICAL MICROBIOLOGY AND INFECTION, Issue 4 2008
J.-P. Lavigne
Abstract This study evaluated the antibacterial efficacy of the consumption of cranberry capsules vs. placebo in the urine of healthy volunteers. A first double-blind, randomised, crossover trial involved eight volunteers who had followed three regimens, with or without cranberry, with a wash-out period of at least 6 days between each regimen. Twelve hours after consumption of cranberry or placebo hard capsules, the first urine of the morning was collected. Different Escherichia coli strains were cultured in the urine samples. Urinary antibacterial adhesion activity was measured in vitro using the human T24 epithelial cell-line, and in vivo using the Caenorhabditis elegans killing model. With the in-vitro model, 108 mg of cranberry induced a significant reduction in bacterial adherence to T24 cells as compared with placebo (p <0.001). A significant dose-dependent decrease in bacterial adherence in vitro was noted after the consumption of 108 and 36 mg of cranberry (p <0.001). The in-vivo model confirmed that E. coli strains had a reduced ability to kill C. elegans after growth in the urine of patients who consumed cranberry capsules. Overall, these in-vivo and in-vitro studies suggested that consumption of cranberry juice represents an interesting new strategy to prevent recurrent urinary tract infection. [source]