Dual Effects (dual + effects)

Distribution by Scientific Domains

Selected Abstracts

Dual effects of NMDA receptor activation on polysialylated neural cell adhesion molecule expression during brainstem postnatal development

Farima Bouzioukh
Abstract Here we show a dual role of N -methyl- d -aspartate receptor (NMDAR) activation in controlling polysialylated neural cell adhesion molecule (PSA-NCAM) dynamic expression in the dorsal vagal complex (DVC), a gateway for many primary afferent fibres. In this structure the overall expression of PSA-NCAM decreases during the first 2 weeks after birth to persist only at synapses in the adult. Electrical stimulation of the vagal afferents causes a rapid increase of PSA-NCAM expression both in vivo and in acute slices before postnatal day (P) 14 whereas a similar stimulation induces a decrease after P15. Inhibition of NMDAR activity in vitro completely prevented these changes. These regulations depend on calmodulin activation and cGMP production at all stages. By contrast, blockade of neuronal nitric oxide synthase (nNOS) prevented these changes only after P10 in agreement with its late expression in the DVC. The pivotal role of NMDAR is also supported by the observation that chronic blockade induces a dramatic decrease in PSA-NCAM expression. [source]

Dual effects of hepatitis C virus Core protein on the transcription of cyclin-dependent kinase inhibitor p21 gene

H. J. Kwun
Summary. Transcription of p21 was activated in hepatitis C virus (HCV) Core-expressing HepG2 cells where its upstream p53 was stabilized. However, this effect was not absolutely required for the activation of p21 by Core, as demonstrated in Hep3B cells. In addition, an opposite effect on the transcription of p21 was observed in NIH3T3 and primary hepatocytes, where p53 was not decreased by Core. To explain the p53-independent regulation of p21 by Core, we identified a Core-responsive element between positions ,74 and ,83 of the p21 promoter, exactly overlapped with a tumour growth factor , (TGF- ,)/butyrate responsive element. Furthermore, we demonstrated that Core could activate the p21 through the element by stimulating a butyrate pathway, whereas this was inhibited through a TGF- , pathway. The opposing effects of Core protein on the transcription of p21 might be important in understanding the progression of hepatic disease in HCV-positive patients. [source]

The changes in neuromuscular excitability with normobaric hyperoxia in humans

Christelle Brerro-Saby
Based on previous observations in hyperbaric hyperoxia, we hypothesized that normobaric hyperoxia, often used during general anaesthesia and resuscitation, might also induce a neuromuscular excitability. In heathy volunteers, we studied the consequences of a 50 min period of pure oxygen breathing on the neuromuscular conduction time (CT), the amplitude of the compound evoked muscle potential (M-wave), the latency and amplitude of the Hoffman reflex (H reflex) and the electromyographic tonic vibratory response (TVR) of the flexor digitorum superficialis muscle to explore the proprioceptive reflex loop. Hyperoxia-induced oxidative stress was measured by the changes in blood markers of lipid peroxidation (thiobarbituric acid reactive substances, TBARS) and antioxidant response (reduced ascorbic acid, RAA). During hyperoxia, the M-wave amplitude increased, both CT and H reflex latency were shortened, and the H reflex amplitude increased. By contrast, TVR significantly decreased. Concomitantly, an oxidative stress was assessed by increased TBARS and decreased RAA levels. This study shows the existence of dual effects of hyperoxia, which facilitates the muscle membrane excitability, nerve conduction and spinal reflexes, but reduces the gain of the proprioceptive reflex loop. The activation of the group IV muscle afferents by hyperoxia and the resulting oxidative stress might explain the TVR depression. [source]

Binding of rat brain hexokinase to recombinant yeast mitochondria

FEBS JOURNAL, Issue 10 2000
Identification of necessary physico-chemical determinants
The association of rat brain hexokinase with heterologous recombinant yeast mitochondria harboring human porin (Yh) is comparable to that with rat liver mitochondria in terms of cation requirements, cooperativity in binding, and the effect of amphipathic compounds. Mg2+, which is required for hexokinase binding to all mitochondria, can be replaced by other cations. The efficiency of hexokinases, however, depends on the valence of hydrophilic cations, or the partition of hydrophobic cations in the membrane, implying that these act by reducing a prohibitive negative surface charge density on the outer membrane rather than fulfilling a specific structural requirement. Macromolecular crowding (using dextran) has dual effects. Dextran added in excess increases hexokinase binding to yeast mitochondria, according to the porin molecule they harbor. This effect, significant with wild-type yeast mitochondria, is only marginal with Yh as well as rat mitochondria. On the other hand, an increase in the number of hexokinase binding sites on mitochondria is also observed. This increase, moderate in wild-type organelles, is more pronounced with Yh. Finally, dextran, which has no effect on the modulation of hexokinase binding by cations, abolishes the inhibitory effect of amphipathic compounds. Thus, while hexokinase binding to mitochondria is predetermined by the porin molecule, the organization of the latter in the membrane plays a critical role as well, indicative that porin must associate with other mitochondrial components to form competent binding sites on the outer membrane. [source]

Tradeoffs and thresholds in the effects of nitrogen addition on biodiversity and ecosystem functioning: evidence from inner Mongolia Grasslands

Abstract Nitrogen (N) deposition is widely considered an environmental problem that leads to biodiversity loss and reduced ecosystem resilience; but, N fertilization has also been used as a management tool for enhancing primary production and ground cover, thereby promoting the restoration of degraded lands. However, empirical evaluation of these contrasting impacts is lacking. We tested the dual effects of N enrichment on biodiversity and ecosystem functioning at different organizational levels (i.e., plant species, functional groups, and community) by adding N at 0, 1.75, 5.25, 10.5, 17.5, and 28.0 g N m,2 yr,1 for four years in two contrasting field sites in Inner Mongolia: an undisturbed mature grassland and a nearby degraded grassland of the same type. N addition had both quantitatively and qualitatively different effects on the two communities. In the mature community, N addition led to a large reduction in species richness, accompanied by increased dominance of early successional annuals and loss of perennial grasses and forbs at all N input rates. In the degraded community, however, N addition increased the productivity and dominance of perennial rhizomatous grasses, with only a slight reduction in species richness and no significant change in annual abundance. The mature grassland was much more sensitive to N-induced changes in community structure, likely as a result of higher soil moisture accentuating limitation by N alone. Our findings suggest that the critical threshold for N-induced species loss to mature Eurasian grasslands is below 1.75 g N m,2 yr,1, and that changes in aboveground biomass, species richness, and plant functional group composition to both mature and degraded ecosystems saturate at N addition rates of approximately 10.5 g N m,2 yr,1. This work highlights the tradeoffs that exist in assessing the total impact of N deposition on ecosystem function. [source]

Inhibition of microsomal triglyceride transfer protein: Another mechanism for drug-induced steatosis in mice

HEPATOLOGY, Issue 1 2003
Philippe Lettéron
Although many steatogenic drugs inhibit mitochondrial fatty acid ,-oxidation, limited information is available on possible effects on hepatic lipoprotein secretion. In the endoplasmic reticulum (ER) lumen, microsomal triglyceride transfer protein (MTP) lipidates apolipoprotein B (Apo B), to form triglyceride (TG)-rich very low density lipoprotein (VLDL) particles, which follow vesicular flow to the plasma membrane to be secreted, whereas incompletely lipidated Apo B particles are partly degraded. We studied hepatic MTP activity, the lipoproteins present in the ER lumen, and hepatic lipoprotein secretion 4 hours after administration of a single dose of amineptine (1 mmol/kg), amiodarone (1 mmol/kg), doxycycline (0.25 mmol/kg), tetracycline (0.25 mmol/kg), tianeptine (0.5 mmol/kg), or pirprofen (2 mmol/kg) in mice. These various doses have been shown previously to markedly inhibit fatty acid oxidation after a single dose, and to trigger steatosis either after repeated doses (doxycycline) or a single dose (other compounds) in mice. In the present study, amineptine, amiodarone, pirprofen, tetracycline, and tianeptine, but not doxycycline, inhibited MTP activity in vitro, decreased ex vivo MTP activity in the hepatic homogenate of treated mice, decreased TG in the luminal VLDL fraction of hepatic microsomes of treated mice, and decreased in vivo hepatic lipoprotein secretion (TG and Apo B). In conclusion, several steatogenic drugs inhibit not only mitochondrial ,-oxidation, as previously shown, but also MTP activity, Apo B lipidation into TG-rich VLDL particles, and hepatic lipoprotein secretion. Drugs with these dual effects may be more steatogenic than drugs acting only on ,-oxidation or only MTP. [source]

Is Leptin the Link Between Fat and Bone Mass?,

Thierry Thomas Ph.D.
Abstract Recently, leptin has emerged as a potential candidate responsible for protective effects of fat on bone tissue. However, it remains difficult to draw a clear picture of leptin effects on bone metabolism because published data are sometimes conflicting or apparently contradictory. Beyond differences in models or experimental procedures, it is tempting to hypothesize that leptin exerts dual effects depending on bone tissue, skeletal maturity, and/or signaling pathway. Early in life, leptin could stimulate bone growth and bone size through direct angiogenic and osteogenic effects on stromal precursor cells. Later, it may decrease bone remodeling in the mature skeleton, when trabecular bone turnover is high, by stimulating osteoprotegerin (OPG) expression. Leptin negative effects on bone formation effected through central nervous system pathway could counterbalance these peripheral and positive effects, the latter being predominant when the blood-brain barrier permeability decreases or the serum leptin level rises above a certain threshold. Thus, the sex-dependent specificity of the relationship between leptin and bone mineral density (BMD) in human studies could be, at least in part, caused by serum leptin levels that are two- to threefold higher in women than in men, independent of adiposity. Although these hypotheses remain highly speculative and require further investigations, existing studies consistently support the role of leptin as a link between fat and bone. [source]

Adipose Tissue Hormones and the Regulation of Food Intake

B. A. Henry
Over the past decade, adipose tissue has been shown to produce numerous factors that act as hormones. Many of these act on the brain to regulate energy balance via dual effects on food intake and energy expenditure. These include well-characterised hormones such as leptin, oestrogen and glucocorticoids and novel factors such as adiponectin and resistin. This review provides a perspective on the role of these factors as lipostats. [source]

Estrogen-mediated immunomodulation involves reduced activation of effector T cells, potentiation of treg cells, and enhanced expression of the PD-1 costimulatory pathway

Magdalena J. Polanczyk
Abstract Estrogen (E2)-induced immunomodulation involves dual effects on antigen-presenting cells (APC) and CD4+CD25+ regulatory T cells (Treg) but not a direct effect on effector T cells. In this report, we further investigated the effects of E2 on APC and Treg function. We found that E2 treatment in vivo strongly reduced recovery of APC from the peritoneal cavity and inhibited induction of the inflammatory cytokines interleukin (IL)-12 and interferon-, but enhanced secretion of IL-10. Moreover, E2-conditioned bone marrow-derived dendritic cells (BM-DC) could both enhance Treg activity and directly inhibit responder T cells in the absence of Treg cells. We examined whether this E2-induced inhibitory activity of BM-DC might involve costimulation through the recently described PD-1 pathway. Both E2 and pregnancy markedly enhanced PD-1 expression in several types of APC, including macrophages, B cells, and especially dendritic cells (DC). Similarly to E2-induced enhancement of FoxP3 expression and experimental autoimmune encephalomyelitis protection, E2-induced enhancement of PD-1+ cells was also mediated through estrogen receptor alpha (Esr1) in DC and macrophages but not in B cells. Based on antibody inhibition studies, PD-1 interaction with its ligands, PDL-1 and especially PDL-2, could mediate either positive or negative regulatory signaling in both mature and immature E2-conditioned DC, depending, respectively, on a relatively high (10:1) or low (1:1) ratio of T cells:BM-DC. These novel findings indicate that E2-induced immunomodulation is mediated in part through potentiation in BM-DC of the PD-1 costimulatory pathway. © 2006 Wiley-Liss, Inc. [source]

Latitude and Incidence of Ocular Melanoma

Guo-Pei Yu
We investigated the associations between latitude and the incidence of two different types of ocular melanoma, external ocular melanoma (exposed to sunlight) and internal melanoma (not exposed to sunlight), separately. Using 1992,2002 data from the Surveillance, Epidemiology, and End Results (SEER) Program of National Cancer Institute, we identified 2142 ocular melanoma cases in non-Hispanic whites, and then regressed the incidences of various types of ocular melanomas with latitude. Our analysis indicated that the higher the latitude (away from the equator, the less sun exposure), the lower the risk of external ocular melanoma (eyelid and conjunctival melanomas) among non-Hispanic whites (P for trend = 0.018). The incidence increased 2.48 fold from 47,48° to 20,22°. This trend is very similar to that of skin melanoma. The incidence of internal ocular melanoma (uveal melanoma) increased significantly with increasing latitudes (the less sun exposure, P for trend < 0.0001), it increased 4.91 fold from 20,22° to 47,48°. The latitudinal patterns of ocular melanomas may reflect the dual effects of sunlight exposure, i.e. a mutagenic effect of direct solar radiation on external ocular melanomas and a protective effect for internal uveal melanoma, which is similar to the sun radiation protective effects for various internal malignant tumors that are not exposed to the sunlight. [source]

Antiangiogenic and Immunomodulatory Effects of Rapamycin on Islet Endothelium: Relevance for Islet Transplantation

V. Cantaluppi
Donor intra-islet endothelial cells contribute to neovascularization after transplantation. Several factors may interfere with this process and ultimately influence islet engraftment. Rapamycin, a central immunosuppressant in islet transplantation, is an mTOR inhibitor that has been shown to inhibit cancer angiogenesis. The aim of this study was to evaluate the effects of rapamycin on islet endothelium. Rapamycin inhibited the outgrowth of endothelial cells from freshly purified human islets and the formation of capillary-like structures in vitro and in vivo after subcutaneous injection within Matrigel plugs into SCID mice. Rapamycin decreased migration, proliferation and angiogenic properties of human and mouse islet-derived endothelial cell lines with appearance of apoptosis. The expression of angionesis-related factors VEGF, ,V,3 integrin and thrombospondin-1 on islet endothelium was altered in the presence of rapamycin. On the other hand, rapamycin decreased the surface expression of molecules involved in immune processes such as ICAM-1 and CD40 and reduced the adhesion of T cells to islet endothelium. Our results suggest that rapamycin exerts dual effects on islet endothelium inducing a simultaneous inhibition of angiogenesis and a down-regulation of receptors involved in lymphocyte adhesion and activation. [source]

Impact of the predatory mite Anystis baccarum (Prostigmata: Anystidae) on apple rust mite Aculus schlechtendali (Prostigmata: Eriophyidae) populations in Northern Ireland Bramley orchards

Summary Anystis baccarum is a common predatory mite in Northern Ireland Bramley orchards. To determine its effect on Aculus schlechtendali populations, sticky traps and sprays of demeton-S-methyl were used to exclude A. baccarum from branches. Out of four trials, exclusion of A. baccarum by sticky traps alone resulted in significantly greater numbers of A. schlechtendali in one trial. In the other trials where A. schlechtendali numbers were lower, there was either no effect, or possible evidence of fewer A. schlechtendali. The combination of demeton-S-methyl treatments and sticky traps to exclude A. baccarum resulted in significantly more A. schlechtendali in two trials out of three in 1998. It seems likely that this resulted from the dual effects of stimulation of A. schlechtendali reproduction by the acaricide and the absence of predation by A. baccarum, because acaricide treatment alone in 1999 resulted in significant reductions in A. schlechtendali numbers at the end of the season. This effect could have resulted from A. baccarum re-invading the treatment branches after the effects of the acaricide had worn off. It is recommended that growers are encouraged to conserve A. baccarum within their orchards. [source]

Likelihood Methods for Treatment Noncompliance and Subsequent Nonresponse in Randomized Trials

BIOMETRICS, Issue 2 2005
A. James O'Malley
Summary While several new methods that account for noncompliance or missing data in randomized trials have been proposed, the dual effects of noncompliance and nonresponse are rarely dealt with simultaneously. We construct a maximum likelihood estimator (MLE) of the causal effect of treatment assignment for a two-armed randomized trial assuming all-or-none treatment noncompliance and allowing for subsequent nonresponse. The EM algorithm is used for parameter estimation. Our likelihood procedure relies on a latent compliance state covariate that describes the behavior of a subject under all possible treatment assignments and characterizes the missing data mechanism as in Frangakis and Rubin (1999, Biometrika86, 365,379). Using simulated data, we show that the MLE for normal outcomes compares favorably to the method-of-moments (MOM) and the standard intention-to-treat (ITT) estimators under (1) both normal and nonnormal data, and (2) departures from the latent ignorability and compound exclusion restriction assumptions. We illustrate methods using data from a trial to compare the efficacy of two antipsychotics for adults with refractory schizophrenia. [source]

Similarity, Isomorphism or Duality?

Recent Survey Evidence on the Human Resource Management Policies of Multinational Corporations
There is considerable debate as to the determinants of the human resource policies of human resource management: do they reflect national institutional or cultural realities, emerging common global practices, parent country effects or the dual effects of transnational and national realities? We use an extensive international database to explore these differences, assessing variations in a range of human resource practices. We find new evidence of national differences in the manner in which indigenous firms manage their people, but also evidence of a similarity in practice amongst multinational corporations. In other words, multinational corporations tend to manage their human resources in ways that are distinct from those of their host country; at the same time, country of origin effects seem relatively weak. Whilst there is some evidence of common global practices, sufficient diversity in practice persists to suggest that duality theories may provide the most appropriate explanation. [source]

Psychopharmacology of substance misuse and comorbid psychiatric disorders

M. T. Abou-Saleh
The common occurrence of comorbid substance misuse and other psychiatric disorders has challenged the diagnostic and therapeutic skills of professionals concerned with the care of patients with these dual disorders. Combined pharmacological and psychological treatment approaches have evolved empirically drawing upon standard treatments with emphasis on psychosocial approaches to substance misuse for psychotic disorders and pharmacological approaches for mood disorders. Advances in the biology of both disorders have started to inform their psychopharmacology. The specific role of atypical antipscychotics is highlighted. Further studies of the biology of comorbidity will impact the use of effective pharmaceuticals such as clozapine with dual effects on schizophrenia and substance misuse. [source]