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Act Synergistically (act + synergistically)
Selected AbstractsDo woodlice and earthworms interact synergistically in leaf litter decomposition?FUNCTIONAL ECOLOGY, Issue 1 2005MARTIN ZIMMER Summary 1In laboratory microcosms, we investigated the influence of diversity of both leaf litter and detritivores on decomposition processes. Either woodlice or earthworms, or a combination of woodlice and earthworms, fed on leaf litter of either oak or alder, or oak and alder for 8 weeks. Mass loss of leaf litter, soil microbial respiration and soil nutrient concentrations were determined every 2 weeks. 2For four out of seven decomposition parameters, the joint effects of woodlice and earthworms were stronger than the sum of single-species effects when they had fed on alder litter. When feeding on oak litter, however, woodlice and earthworms together revealed lower decomposition rates than predicted from their single effects. Joint effects of detritivores on decomposition of mixed litter were always lower than predicted from the sum of their effects. 3In mixed-litter assays, we obtained intermediate values of decomposition parameters, indicating that doubling the species richness of leaf litter from one to two species did not promote decomposition processes. Effects of mixing litter were, thus, mostly additive; essentially only when earthworms fed on mixed litter we observed, mostly positive, non-additive effects of diverse litter. 4Our findings provide evidence for a potential effect on ecosystem functioning through joint action of detritivores even at low species diversity, while litter diversity seems to be less significant. On high-quality litter, isopods and earthworms are not functionally redundant but act synergistically on litter decomposition. The effects of detritivore diversity on ecosystem processes, however, are context-specific and depend on the quality and diversity of the available food sources, and on species-specific characteristics of the detritivores. [source] Combination therapy with lamivudine and famciclovir for chronic hepatitis B,infected Chinese patients: A viral dynamics studyHEPATOLOGY, Issue 2 2000George Ka Lau M.D. In vitro studies have shown that lamivudine and penciclovir (the active metabolite of famciclovir) act synergistically to inhibit hepatitis B virus (HBV) replication. We compared the effectiveness of HBV viral suppression by lamivudine monotherapy versus lamivudine plus famciclovir combination therapy in Chinese patients with chronic HBV infection. Twenty-one Chinese hepatitis B e antigen (HBeAg)-positive patients, with detectable HBV DNA (Digene Hybrid Capture II), were randomized to receive either lamivudine 150 mg/d orally (group 1, 9 patients) or lamivudine 150 mg/d plus famciclovir 500 mg 3 times a day orally (group 2, 12 patients) for 12 weeks, with a follow-up period of at least 16 weeks. Serial serum HBV-DNA levels were determined and a mathematical model with provision for incomplete inhibition of virus production during therapy was applied to analyze the dynamics of viral clearance. The mean antiviral efficacy was significantly greater in group 2 than in group 1 (0.988 ± 0.012 vs. 0.94 ± 0.03, P = .0012). HBV DNA returned to pretreatment level within 16 weeks after the end of initial treatment in 4 patients (66.7%) in group 1 and none in group 2 (P = .08), who remained HBeAg positive and received no further treatment after week 12. Hence, in Chinese chronic HBeAg-positive patients, combination therapy using lamivudine and famciclovir was superior to lamivudine monotherapy in inhibiting HBV replication. Further studies of longer duration are needed to define whether combination therapy will increase the HBeAg seroconversion rate and decrease the rate of emergence of lamivudine-resistant variants. [source] Synergistic inhibitory effect of ascorbic acid and acetylsalicylic acid on prostaglandin E2 release in primary rat microgliaJOURNAL OF NEUROCHEMISTRY, Issue 1 2003Bernd L. Fiebich Abstract Ascorbic acid (vitamin C) has been suggested to protect cerebral tissue in a variety of pathophysiological situations such as head trauma, ischemia or Alzheimer's disease. Most of these protective actions have been attributed to the antioxidative capacity of ascorbic acid. Besides the presence of elevated levels of oxygen radicals, prostaglandins produced by neurones and microglial cells seem to play an important role in prolonged tissue damage. We investigated whether ascorbic acid alone inhibits prostaglandin E2 (PGE2) synthesis and may augment the inhibitory effect of acetylsalicylic acid on prostaglandin synthesis. Ascorbic acid dose-dependently inhibited PGE2 synthesis in lipopolysaccharide-treated primary rat microglial cells (IC50 = 3.70 µm). In combination with acetylsalicylic acid (IC50 = 1.85 µm), ascorbic acid augmented the inhibitory effect of acetylsalicylic acid on PGE2 synthesis (IC50 = 0.25 µm in combination with 100 µm ascorbic acid). Ascorbic acid alone or in combination with acetylsalicylic acid did not inhibit cyclooxygenase-2 (COX-2) protein synthesis but inhibited COX-2 enzyme activity. Our results show that ascorbic acid and acetylsalicylic acid act synergistically in inhibiting PGE2 synthesis, which may help to explain a possible protective effect of ascorbic acid in various brain diseases. [source] Orthotopic liver transplantation using low-dose tacrolimus and sirolimusLIVER TRANSPLANTATION, Issue 8 2001Vivian C. McAlister MB Although sirolimus (SRL) binds the immunophilin FK506-binding protein-12 (FKBP-12) with greater avidity than tacrolimus (TAC), animal studies have shown that SRL and TAC act synergistically to prevent rejection. Dose-related toxicity is more often the cause of TAC discontinuation than rejection. We hypothesized that SRL would allow for a substantial reduction in the concomitant dose of TAC after liver transplantation to levels less than the threshold for toxicity. A series of 56 liver transplant recipients were administered a combination of SRL and TAC (target trough levels, 7 and 5 ng/mL, respectively). Planned weaning of steroids commenced after 3 months. Pharmacokinetic (PK) studies were undertaken. Patient and graft survival were 52 patients (93%) and 51 grafts (91%), with a follow-up of 23 months (range, 6 to 35 months). One episode (1.8%) of hepatic artery thrombosis was seen. The rate of acute cellular rejection was 14%. No extra treatment was administered in 3 of 8 patients, and the other 5 episodes responded to a single course of steroids. Cytomegalovirus infection occurred in 4 patients (7%). Renal function, glucose control, and lipid metabolism are near normal in 47 patients (84%) without additional medication. Steroid elimination is completed in 51 patients (91%). Bioavailability of SRL and TAC varied between transplant recipients, but trough levels strongly correlated with the area under the curve (r2 = 0.82 and r2 = 0.84, respectively). Simultaneous administration did not affect the PK profile of the drugs at this dose. The ratio of trough level to daily dose correlated between SRL and TAC. The synergistic effect seen in animal models also occurs in clinical liver transplant recipients on SRL-TAC combination immunosuppression. A low-dose combination of SRL and TAC should be compared with conventional immunosuppression in a multicenter, randomized, controlled trial. [source] Flame retardancy study on magnesium hydroxide associated with clays of different morphology in polypropylene matrixPOLYMERS FOR ADVANCED TECHNOLOGIES, Issue 6 2008B. B. Marosfoi Abstract Fire retardancy behavior of polypropylene,magnesium hydroxide,clay composites of different morphologies is presented. Layer- and needle-like clay nanoparticles in natural and organically surface modified form have been compared. Fire retardant performance of the composites was evaluated by conical combustor and by horizontal burning test, while the structure was characterized by SEM. Rheological analysis of varied temperature provided further information about the strength of the formed combustion residue. The results confirm that fibrous and layered clay nanofillers act synergistically and can be combined with MH microfillers advantageously for improving the flame retardancy of PP composites. Significant improvements were observed in combustion parameters, as well as in flammability classifications. Combination of montmorillonite and sepiolite type of clays resulted in the increased time to ignition, and markedly decreased heat release rate. These advancements are ascribed to the char stabilizer effect of nanofillers leading to increased strength of the residue. It is also concluded that not only the interaction between micro- and nanofillers, but also the nanofillers,nanofillers interaction plays a key role in fire retardant mechanism. Copyright © 2008 John Wiley & Sons, Ltd. [source] Spatial and temporal variability in predation on rainforest primates: do forest fragmentation and predation act synergistically?ANIMAL CONSERVATION, Issue 3 2009M. T. Irwin Abstract Predation is a constant risk for most primates, impacting demography, population dynamics, activity patterns and social behaviour. Data are limited on both the rates of predation and its spatial and temporal variability. We present long-term observations of Cryptoprocta ferox predation on rainforest sifakas in Madagascar, Propithecus diadema at Tsinjoarivo (22 group years) and Propithecus edwardsi at Ranomafana (73 group years), derived from intensive observations based on ongoing behavioural studies. Average per capita offtake rates are relatively low (0.06,0.07), but temporal variability is high (kills are clumped in time). This is consistent with Cryptoprocta ecology; individual home ranges are much larger than sifaka ranges, and individuals may hunt in a subsection of their range until prey density is decreased, then move on. These results have broad implications. First, in terms of the evolution of anti-predator strategies, it now becomes important to ask: (1) whether average or peak predation rates determine the strength of selection and (2) whether antipredator strategies (e.g. vigilance, sleeping site selection) fluctuate interannually, reflecting recent experience. Second, in terms of population ecology, Cryptoprocta may have disproportionately large impacts on the (small) sifaka groups, even driving groups to extinction (as observed at both sites). Third, the disappearance of groups has important implications for conservation. When this happens in continuous forest (as at Ranomafana), home ranges will likely be re-filled over time, whereas in isolated forest fragments (as at Tsinjoarivo), recolonization is less likely. Thus, conservation planners should consider predation as a potentially important proximate cause of extirpation in fragmented landscapes, even when resource density and quality could otherwise sustain populations. Considering the effects of predation can be useful in (1) decisions regarding the allocation of limited conservation resources, including which landscapes to invest resources in and (2) investigating ways to increase resilience of prey species. [source] Immunohistochemical expression of CD95 (Fas), c-myc and epidermal growth factor receptor in hepatitis C virus infection, cirrhotic liver disease and hepatocellular carcinoma,APMIS, Issue 6 2006A. EL-BASSIOUNI Gene product expression in normal and chronic hepatitis C virus infection was determined in an attempt to improve our understanding of the molecular events leading to the development of cirrhosis and liver carcinoma. Activation of CD95 (Fas) causes apoptosis of cells and liver failure in mice and has been associated with human liver disorders. c-myc is involved in cell proliferation and EGFR in regeneration of cells. The material of the current study included 50 cases of chronic hepatitis C (CHC) (and negative hepatitis B virus infection), 29 cases of liver cirrhosis and HCV (LC), and 19 cases of hepatocellular carcinoma and HCV (HCC) admitted to the Theodor Bilharz Research Institute (TBRI) during the years 2003,2004. Ten wedge liver biopsies , taken during laparoscopic cholecystectomy , were included in the study as normal controls. Laboratory investigations, including liver function tests, serological markers for viral hepatitis and serum alpha fetoprotein level (,-FP), were determined for all cases. Histopathological study and immunohistochemistry using monoclonal antibodies for CD95, c-myc and EGFR were also done. In CHC cases, the histological activity index (HAI) revealed more expression of Fas antigen in liver tissues with active inflammation than in those without active inflammation (p<0.01). EGFR and c-myc act synergistically in liver tumorigenesis. Upregulation of Fas in chronic hepatitis C infection and of c-myc & EGFR in malignant transformation was concluded from this study. c-myc expression may obstruct the induction of apoptosis of HCC cells and lead to uncontrolled cell growth. [source] Krüppel-Like Zinc Finger Protein Glis3 Promotes Osteoblast Differentiation by Regulating FGF18 Expression,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 8 2007Ju Youn Beak Abstract The zinc finger protein Glis3 is highly expressed in human osteoblasts and acts synergistically with BMP2 and Shh in enhancing osteoblast differentiation in multipotent C3H10T1/2 cells. This induction of osteoblast differentiation is at least in part caused by the induction of FGF18 expression. This study supports a regulatory role for Glis3 in osteoblast differentiation. Introduction: Gli-similar 3 (Glis3) is closely related to members of the Gli subfamily of Krüppel-like zinc finger proteins, transcription factors that act downstream of sonic hedgehog (Shh). In this study, we analyzed the expression of Glis3 in human osteoblasts and mesenchymal stem cells (MSCs). Moreover, we examined the regulatory role of Glis3 in the differentiation of multipotent C3H10T1/2 cells into osteoblasts and adipocytes. Materials and Methods: Microarray analysis was performed to identify genes regulated by Glis3 in multipotent C3H10T1/2 cells. Reporter and electrophoretic mobility shift assays were performed to analyze the regulation of fibroblast growth factor 18 (FGF18) by Glis3. Results: Glis3 promotes osteoblast differentiation in C3H10T1/2 cells as indicated by the induction of alkaline phosphatase activity and increased expression of osteopontin, osteocalcin, and Runx2. In contrast, Glis3 expression inhibits adipocyte differentiation. Glis3 acts synergistically with BMP2 and Shh in inducing osteoblast differentiation. Deletion analysis indicated that the carboxyl-terminal activation function of Glis3 is needed for its stimulation of osteoblast differentiation. Glis3 is highly expressed in human osteoblasts and induced in MSCs during differentiation along the osteoblast lineage. Microarray analysis identified FGF18 as one of the genes induced by Glis3 in C3H10T1/2 cells. Promoter analysis and electrophoretic mobility shift assays indicated that a Glis3 binding site in the FGF18 promoter flanking region is important in its regulation by Glis3. Conclusions: Our study showed that Glis3 positively regulates differentiation of C3H10T1/2 cells into osteoblasts and inhibits adipocyte differentiation. Glis3 acts synergistically with BMP2 and Shh in inducing osteoblast differentiation. The promotion of osteoblast differentiation by Glis3 involves increased expression of FGF18, a positive regulator of osteogenesis. This, in conjunction with the induction of Glis3 expression during osteoblast differentiation in MSCs and its expression in osteoblasts, suggests that Glis3 is an important modulator of MSC differentiation. [source] Epidermal growth factor receptor and claudin-2 participate in A549 permeability and remodeling: Implications for non-small cell lung cancer tumor colonizationMOLECULAR CARCINOGENESIS, Issue 6 2009Yakov Peter Abstract Tumor colonization involves changes in cell permeability and remodeling. Paracellular permeability is regulated by claudins, integrated tight junction (TJ) proteins, located on the apicolateral portion of epithelial cells. Epidermal growth factor (EGF) was reported to modify cellular claudin levels and induce remodeling. To investigate a role for EGF receptor (EGFR) activation in tumor colonization we studied the effect of EGF and claudin-2 overexpression on permeability and cell reorganization in the human A549 non-small cell lung cancer (NSCLC) cell line. Our data demonstrated that A549 cells possess functional TJs and that EGF treatment increased levels of claudin-2 expression by 46%. Furthermore, EGFR signaling reduced monolayer permeability to choline and triggered cellular remodeling. The mitogen-activated protein kinase inhibitor PD98059 blocked the effect on A549 permeability and remodeling. EGF stimulation also exacerbated a fourfold increase in cell colonization elicited by claudin-2 upregulation. Our findings are consistent with the hypothesis that EGFR signaling plays an important role in A549 cell physiology and acts synergistically with claudin-2 to accelerate tumor colonization. Understanding the influence of EGF on A549 cell permeability and reorganization will help shed light on NSCLC tumor colonization and contribute to the development of novel anti-cancer treatments. © 2008 Wiley-Liss, Inc. [source] Expression, regulation, and signaling of the pattern-recognition receptor nucleotide-binding oligomerization domain 2 in rheumatoid arthritis synovial fibroblastsARTHRITIS & RHEUMATISM, Issue 2 2009Caroline Ospelt Objective Since pattern-recognition receptors (PRRs), in particular Toll-like receptors (TLRs), were found to be overexpressed in the synovium of rheumatoid arthritis (RA) patients and to play a role in the production of disease-relevant molecules, we sought to determine the expression, regulation, and function of the PRR nucleotide-binding oligomerization domain 2 (NOD-2) in RA. Methods Expression of NOD-2 in synovial tissues was analyzed by immunohistochemistry. Expression and induction of NOD-2 in RA synovial fibroblasts (RASFs) were measured by conventional and real-time polymerase chain reaction (PCR) analyses. Levels of interleukin-6 (IL-6) and IL-8 were measured by enzyme-linked immunosorbent assay (ELISA) and expression of matrix metalloproteinases (MMPs) by ELISA and/or real-time PCR. NOD-2 expression was silenced with small interfering RNA. Western blotting with antibodies against phosphorylated and total p38, JNK, and ERK, as well as inhibitors of p38, JNK, and ERK was performed. Activation of NF-,B was measured by electrophoretic mobility shift assay. Results NOD-2 was expressed by fibroblasts and macrophages in the synovium of RA patients, predominantly at sites of invasion into articular cartilage. In cultured RASFs, no basal expression of messenger RNA for NOD-2 was detectable, but was induced by poly(I-C), lipopolysaccharide, and tumor necrosis factor ,. After up-regulation of NOD-2 by TLR ligands, its ligand muramyl dipeptide (MDP) increased the expression of IL-6 and IL-8 via p38 and NF-,B. Stimulation with MDP further induced the expression of MMP-1, MMP-3, and MMP-13. Conclusion Not only TLRs, but also the PRR NOD-2 is expressed in the synovium of RA patients, and activation of NOD-2 acts synergistically with TLRs in the production of proinflammatory and destructive mediators. Therefore, NOD-2 might contribute to the initiation and perpetuation of chronic, destructive inflammation in RA. [source] | |||||||||||||