121 research outputs found
Training abusive parents in the use of anger control procedures for improving parent-child interactions
The purpose of the present study was to evaluate the effectiveness of a home-based multicomponent anger management program utilizing self-control procedures for: (a) decreasing frequencies of aversive parent behaviors directed toward target children and (b) altering parents\u27; angry feelings and subjective urges to physically harm their children in provocation situations. Abusive parents from three at-risk families were trained in the use of anger management skills tb aid them in coping with arousal on cognitive, somatic, and behavioral levels, simultaneously. Results indicated that the training procedures were successful in significantly reducing rates of aversive parent behavior exhibited in the home across all treated family units. The program also appeared successful for decreasing parents\u27 angry urges and their daily rates of feeling angry when provoked by their children. These reductions in the parents\u27 rates of aversive behavior and angry feelings following anger control training were maintained at stable levels over a 6 month follow-up period
Aging Effects on Acute Lung Inflammation After Burn Injury
The risk of complications and death after a moderate sized burn injury is significantly higher in persons over the age of 65, while almost non-existant in young, healthy individuals. The studies outlined below use a murine model to determine the mechanisms behind the development of pulmonary complications that frequently occur in aged individuals following burn injury. We hypothesized that, since aged mice maintain an elevated proinflammatory state prior to injury, they are at an even greater risk of pulmonary inflammation than young mice given a comparable sized wound. We found that neutrophils continue to accumulate in the lungs of aged mice at 24 hours after burn injury, but do not migrate into the alveoli. We also showed that neutrophil migration towards KC--a dominant neutrophil chemokine--in a transwell chemotaxis assay is robust in neutrophils from young mice, but blunted in those from aged mice. These differences are likely due to intracellular signaling defects, as levels of the receptor for KC, CXCR2, is not different on neutrophils between age groups. In addition, we found that burn injury causes a significant decrease in CXCR2 on the surface of neutrophils, indicating that these cells are more susceptible to receptor desensitization. When anti-CXCR2 antibody is injected immediately post-burn, the aberrant pulmonary inflammation is completely abolished in aged mice compared to those receiving a control antibody, suggesting that targeting this pathway in the acute stages of burn help dampen the inflammatory response of the aged mice. In a separate set of experiments, we demonstrated that expression of the cell adhesion molecule, ICAM-1, on pulmonary vasculature and non-specific neutrophil adhesion is increased in aged mice following burn injury. In sum, we concluded that neutrophils accumulate in the lungs of aged mice as a result of sequestration in the pulmonary vasculature due to defective CXCR2-mediated migration and increased adhesion. These studies are critical to understanding why aged patients are at such a higher risk for pulmonary complications after burn injury and reveal targets for new and better therapeutic regimens that could potentially help older patients reach full recovery
Acquisizione della Croce di Ruthwell: creazione e possibili utilizzi di un modello 3D fedele di un reperto storico
Nella presente tesi si analizzano le tecniche di acquisizione 3D applicate in ambiti umanistici, mostrandone i possibili vantaggi. In particolare si descrive il progetto di acquisizione della Croce di Ruthwell, con esempi di suo utilizzo
Effective Visible Light Exploitation by Copper Molybdo-tungstate Photoanodes
The need for stable oxide-based semiconductors with a narrow band gap, able to maximize the exploitation of the visible light portion of the solar spectrum, is a challenging issue for photoelectrocatalytic (PEC) applications. In the present work, CuW1 12xMoxO4 (Eg = 2.0 eV for x = 0.5), which exhibits a significantly reduced optical band gap Eg compared with isostructural CuWO4 (Eg = 2.3 eV), was investigated as a photoactive material for the preparation of photoanodes. CuW0.5Mo0.5O4 electrodes with different thicknesses (80 12530 nm), prepared by a simple solution-based process in the form of multilayer films, effectively exhibit visible light photoactivity up to 650 nm (i.e., extended compared with CuWO4 photoanodes prepared by the same way). Furthermore, the systematic investigation on the effects on photoactivity of the CuW0.5Mo0.5O4 layer thickness evidenced that long-wavelength photons can better be exploited by thicker electrodes. PEC measurements in the presence of NaNO2, acting as a suitable hole scavenger ensuring enhanced photocurrent generation compared with that of water oxidation while minimizing dark currents, allowed us to elucidate the role that molybdenum incorporation plays on the charge separation efficiency in the bulk and on the charge injection efficiency at the photoanode surface. The adopted Mo for W substitution increases the visible light photoactivity of copper tungstate toward improved exploitation and storage of visible light into chemical energy via photoelectrocatalysis
Transcriptional regulation of the S-layer protein type I secretion system in Caulobacter crescentus
The Gram-negative Caulobacter crescentus exports RsaA, the crystalline S-layer subunit protein using a dedicated type I secretion system. The protein and two transporter genes (rsaADE) are located together, comparable to the Escherichia coli type I hemolysin hlyCABD operon, where read through of a stem loop following hlyCA results in reduced transcription of the hlyBD. Using two genetic approaches and a direct assessment of transcription from regions 5′ to the genes we learned that rsaD and rsaE were transcribed together as a separate transcript from rsaA. These results are contrary to previous assumptions about the rsaADE type I secretion gene control and add another theme to the area of type I secretion transcription regulation. It may be that to accommodate the high levels of RsaA secretion, the type I transporters must be transcribed independently from rsa
Development of an HIV-1 Specific Microbicide Using Caulobacter crescentus S-Layer Mediated Display of CD4 and MIP1α
The development of alternative strategies to prevent HIV infection is a global public health priority. Initial efforts in anti-HIV microbicide development have met with poor success as the strategies have relied on a non-specific mechanism of action. Here, we report the development of a microbicide aimed at specifically blocking HIV entry by displaying molecular components of the HIV/host cell attachment complex on the surface of Caulobacter crescentus, a harmless aquatic bacterium. This bacterium can be readily manipulated to present heterologous proteins at high density on its surface by genetic insertion into its crystalline surface layer protein [1], [2]. In separate constructions, we generated bacteria displaying domain 1 of CD4 and MIP1α. Each moiety reacted with specific antibodies by Western immunoblot and immuno-fluorescence microscopy. Microbicide functionality was assessed using an HIV pseudotype virus assay system representing Clade B subtypes. Bacteria displaying MIP1α reduced infectivity by 35–78% depending on the specific subtype while CD4 display reduced infection by as much as 56%. Combinations of both constructs reduced infectivity by nearly 98%. We demonstrated that HIV infection could be inhibited using a strategy aimed at HIV-specific molecular interactions with Caulobacter surface protein display, and that sufficient protein folding and conformation could be mimicked to bind and block entry. Further, this is the first demonstration that Caulobacter surface protein display may be a useful approach to preventing HIV infection or other viruses as a microbicide. We propose that this harmless bacterium, which is inexpensive to produce and formulate, might be suitable for topical applications as a viable alternative in the search for effective microbicides to counteract the world wide incidence of HIV infection
MIF-induced stromal PKCβ/IL8 is essential in human acute myeloid leukemia
Acute myeloid leukemia (AML) cells exhibit a high level of spontaneous apoptosis when cultured in vitro but have a prolonged survival time in vivo, indicating that tissue microenvironment plays a critical role in promoting AML cell survival. In vitro studies have shown that bone marrow-mesenchymal stromal cells (BM-MSC) protect AML blasts from spontaneous and chemotherapy-induced apoptosis. Here we report a novel interaction between AML blasts and BM-MSC which benefits AML proliferation and survival. We initially examined the cytokine profile in cultured human AML compared to AML cultured with BMMSC and found that macrophage-migration inhibitory factor (MIF) was highly expressed by primary AML, and that interleukin-8 (IL-8) was increased in AML/BM-MSC co-cultures. Recombinant MIF increased IL-8 expression in BM-MSC via its receptor CD74. Moreover, the MIF inhibitor ISO-1 inhibited AML-induced IL-8 expression by BM-MSC as well as BMMSC- induced AML survival. Protein kinase C β (PKCβ) regulated MIF-induced IL-8 in BMMSC. Finally, targeted IL-8 shRNA inhibited BM-MSC-induced AML survival. These results describe a novel, bidirectional, pro-survival mechanism between AML blasts and BM-MSC. Furthermore, they provide biologic rationale for therapeutic strategies in AML targeting the microenvironment, specifically MIF and IL-8
Contact-Dependent Killing by Caulobacter Crescentus via Cell Surface-Associated, Glycine Zipper Proteins
Most bacteria are in fierce competition with other species for limited nutrients. Some bacteria can kill nearby cells by secreting bacteriocins, a diverse group of proteinaceous antimicrobials. However, bacteriocins are typically freely diffusible, and so of little value to planktonic cells in aqueous environments. Here, we identify an atypical two-protein bacteriocin in the α-proteobacterium Caulobacter crescentus that is retained on the surface of producer cells where it mediates cell contact-dependent killing. The bacteriocin-like proteins CdzC and CdzD harbor glycine-zipper motifs, often found in amyloids, and CdzC forms large, insoluble aggregates on the surface of producer cells. These aggregates can drive contact-dependent killing of other organisms, or Caulobacter cells not producing the CdzI immunity protein. The Cdz system uses a type I secretion system and is unrelated to previously described contact-dependent inhibition systems. However, Cdz-like systems are found in many bacteria, suggesting that this form of contact-dependent inhibition is common.United States. National Institutes of Health (R01GM082899
Anesthetic Propofol Reduces Endotoxic Inflammation by Inhibiting Reactive Oxygen Species-regulated Akt/IKKβ/NF-κB Signaling
BACKGROUND: Anesthetic propofol has immunomodulatory effects, particularly in the area of anti-inflammation. Bacterial endotoxin lipopolysaccharide (LPS) induces inflammation through toll-like receptor (TLR) 4 signaling. We investigated the molecular actions of propofol against LPS/TLR4-induced inflammatory activation in murine RAW264.7 macrophages. METHODOLOGY/PRINCIPAL FINDINGS: Non-cytotoxic levels of propofol reduced LPS-induced inducible nitric oxide synthase (iNOS) and NO as determined by western blotting and the Griess reaction, respectively. Propofol also reduced the production of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-10 as detected by enzyme-linked immunosorbent assays. Western blot analysis showed propofol inhibited LPS-induced activation and phosphorylation of IKKβ (Ser180) and nuclear factor (NF)-κB (Ser536); the subsequent nuclear translocation of NF-κB p65 was also reduced. Additionally, propofol inhibited LPS-induced Akt activation and phosphorylation (Ser473) partly by reducing reactive oxygen species (ROS) generation; inter-regulation that ROS regulated Akt followed by NF-κB activation was found to be crucial for LPS-induced inflammatory responses in macrophages. An in vivo study using C57BL/6 mice also demonstrated the anti-inflammatory properties against LPS in peritoneal macrophages. CONCLUSIONS/SIGNIFICANCE: These results suggest that propofol reduces LPS-induced inflammatory responses in macrophages by inhibiting the interconnected ROS/Akt/IKKβ/NF-κB signaling pathways
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