295 research outputs found
Analyzing consumer-related nitrogen flows: A case study on food and material use in Austria
Nitrogen budgets cover pools and flows of nitrogen (N) contained in human-made goods and compounds, wich may potentially affect the global nitrogen cycle and in consequence the human environment. Acknowledging the importance of food and other agricultural products, this paper additionally investigates frequently neglected flows of N related to consumers and estimates their magnitude, using Austria in 2010 as an example. Specifically, N in non-food industrial products (synthetic & natural polymers, wood & paper products, waste), and N related to pets, gardens, and energy use is considered. Over the last five decades, both food and material consumption have increased distinctly. While food supply accounts for 52% of total directly consumer-related nitrogen inflows covered in this study (66,000t Na^1), also material products account for a considerable share of 28% (36,000t Na^1). N application in gardens (12%) and N in pet food (7%) do also play a role. Quantified outflows are human excretion (54%), food waste (13%), garden waste (16%), material waste (7%) and waste from pets (10%). The detected balance surplus of 34,000t Na^1, corresponding to 27% of total inflows, points to some accumulation of N in the form of durable consumer goods and to potentially missing flows. The analysis focusses on the apparent knowledge gaps. Especially flows involving material products are poorly understood and would require better understanding of nitrogen contents of products and of waste. This indicates that improvements may be possible by providing more complete nitrogen budgets in the future that cover all environmental pools
One-stage versus two-stage lymph node dissection after investigation of sentinel lymph node in cutaneous melanoma: a comparison of complications, costs, hospitalization times, and operation times
The aim of the study was to evaluate whether complication rate, costs, operation times, and hospitalization times differed in two different patient groups: in group 1, frozen section analysis of the sentinel lymph node and lymph node dissection were carried out in the same operation. In group 2, normal investigation of the sentinel lymph node and lymph node dissection were done in a second operation. One hundred thirty-five patients with cutaneous melanoma were included. Hospitalization times, costs, complication rates, and operation times of two-stage and one-stage lymph node dissection of the draining area after detection of metastases in the sentinel lymph node were retrospectively compared. Lymph node metastasis in the sentinel lymph node was found in 23 patients. In 11 patients, removal of the sentinel lymph node and dissection of the lymph node basin was performed in the same operation. In 12 patients, a two-stage procedure was the treatment of choice. Operation times were not different in the two groups (p=0.87) while two-stage operation patients were hospitalized significantly longer (14.2±9.7 vs 23.9±24days; p=0.01) and costs were significantly higher (7,836.90±2,397.95 Swiss francs vs 5,279.40±1,994.90 Swiss francs). In addition, more complications were found in the two-stage grou
Optimizing the parameters for hydro-jet dissection in fatty tissue — A morphological Ex Vivo analysis
Summary: Background: The advantage of water-jet dissection is the preservation of vessels and nerves. Especially in liver surgery, blood loss can be significantly decreased. The use of water-jet dissectors in other fields of surgery is currently under investigation. The preparation of vessels in fatty tissue is of special interest for plastic surgeons. The optimal technical parameters were investigated. Methods: Abdominal fat tissue of fresh cadavers was cut under standardized conditions with different parameters of the water-jet dissector. Results: One single pass at a cutting pressure between 20 and 60 Bar makes an incision of 8 mm. Deeper cuts can be achieved by repeated application on the same cut. Five passes at 40 Bar results in a depth of 1.7 cm without vessel damage. If the applied pressure is 50 or 60 Bar, up to 7% damaged vessels can be found. The water-jet dissection leads to a water uptake of the cut tissue. Conclusions: The optimal pressure for water-jet dissection of fatty tissue lies between 30 and 40 Bar. The effect of the mechanical irritation of the vessels has to be investigatedin vivo before using the water-jet dissector for preparation of blood vessels in humans, e.g. for flap dissectio
Discovery and Validation of a New Class of Small Molecule Toll-Like Receptor 4 (TLR4) Inhibitors
Many inflammatory diseases may be linked to pathologically elevated signaling via the receptor for lipopolysaccharide (LPS), toll-like receptor 4 (TLR4). There has thus been great interest in the discovery of TLR4 inhibitors as potential anti-inflammatory agents. Recently, the structure of TLR4 bound to the inhibitor E5564 was solved, raising the possibility that novel TLR4 inhibitors that target the E5564-binding domain could be designed. We utilized a similarity search algorithm in conjunction with a limited screening approach of small molecule libraries to identify compounds that bind to the E5564 site and inhibit TLR4. Our lead compound, C34, is a 2-acetamidopyranoside (MW 389) with the formula C17H27NO9, which inhibited TLR4 in enterocytes and macrophages in vitro, and reduced systemic inflammation in mouse models of endotoxemia and necrotizing enterocolitis. Molecular docking of C34 to the hydrophobic internal pocket of the TLR4 co-receptor MD-2 demonstrated a tight fit, embedding the pyran ring deep inside the pocket. Strikingly, C34 inhibited LPS signaling ex-vivo in human ileum that was resected from infants with necrotizing enterocolitis. These findings identify C34 and the β-anomeric cyclohexyl analog C35 as novel leads for small molecule TLR4 inhibitors that have potential therapeutic benefit for TLR4-mediated inflammatory diseases. © 2013 Neal et al
Potential role of fibroblast-like synoviocytes in joint damage induced by Brucella abortus infection through production and induction of matrix metalloproteinases
Arthritis is one of the most common complications of human brucellosis, but its pathogenic mechanisms have not been elucidated. Fibroblast-like synoviocytes (FLS) are known to be central mediators of joint damage in inflammatory arthritides through the production of matrix metalloproteinases (MMPs) that degrade collagen and of cytokines and chemokines that mediate the recruitment and activation of leukocytes. In this study we show that Brucella abortus infects and replicates in human FLS (SW982 cell line) in vitro and that infection results in the production of MMP-2 and proinflammatory mediators (interleukin-6 [IL-6], IL-8, monocyte chemotactic protein 1 [MCP-1], and granulocyte-macrophage colony-stimulating factor [GM-CSF]). Culture supernatants from Brucella-infected FLS induced the migration of monocytes and neutrophils in vitro and also induced these cells to secrete MMP-9 in a GM-CSF- and IL-6-dependent fashion, respectively. Reciprocally, culture supernatants from Brucella-infected monocytes and neutrophils induced FLS to produce MMP-2 in a tumor necrosis factor alpha (TNF-α)-dependent fashion. The secretion of proinflammatory mediators and MMP-2 by FLS did not depend on bacterial viability, since it was also induced by heat-killed B. abortus (HKBA) and by a model Brucella lipoprotein (L-Omp19). These responses were mediated by the recognition of B. abortus antigens through Toll-like receptor 2. The intra-articular injection of HKBA or L-Omp19 into the knee joint of mice resulted in the local induction of the proinflammatory mediators MMP-2 and MMP-9 and in the generation of a mixed inflammatory infiltrate. These results suggest that FLS, and phagocytes recruited by them to the infection focus, may be involved in joint damage during brucellar arthritis through the production of MMPs and proinflammatory mediators.Fil: Scian, Romina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "Profesor R. A. Margni"; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Barrionuevo, Paula. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "Profesor R. A. Margni"; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Giambartolomei, Guillermo Hernan. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "Profesor R. A. Margni"; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: de Simone, Emilio Adrian. Universidad de Buenos Aires. Facultad de Cs.veterinarias. Catedra de Fisiologia Animal; Argentina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "Profesor R. A. Margni"; ArgentinaFil: Vanzulli, Silvia I.. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Fossati, Carlos Alberto. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "Profesor R. A. Margni"; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Baldi, Pablo Cesar. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "Profesor R. A. Margni"; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Delpino, María Victoria. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "Profesor R. A. Margni"; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentin
Two novel human cytomegalovirus NK cell evasion functions target MICA for lysosomal degradation
NKG2D plays a major role in controlling immune responses through the regulation of natural killer (NK) cells, αβ and γδ T-cell function. This activating receptor recognizes eight distinct ligands (the MHC Class I polypeptide-related sequences (MIC) A andB, and UL16-binding proteins (ULBP)1–6) induced by cellular stress to promote recognition cells perturbed by malignant transformation or microbial infection. Studies into human cytomegalovirus (HCMV) have aided both the identification and characterization of NKG2D ligands (NKG2DLs). HCMV immediate early (IE) gene up regulates NKGDLs, and we now describe the differential activation of ULBP2 and MICA/B by IE1 and IE2 respectively. Despite activation by IE functions, HCMV effectively suppressed cell surface expression of NKGDLs through both the early and late phases of infection. The immune evasion functions UL16, UL142, and microRNA(miR)-UL112 are known to target NKG2DLs. While infection with a UL16 deletion mutant caused the expected increase in MICB and ULBP2 cell surface expression, deletion of UL142 did not have a similar impact on its target, MICA. We therefore performed a systematic screen of the viral genome to search of addition functions that targeted MICA. US18 and US20 were identified as novel NK cell evasion functions capable of acting independently to promote MICA degradation by lysosomal degradation. The most dramatic effect on MICA expression was achieved when US18 and US20 acted in concert. US18 and US20 are the first members of the US12 gene family to have been assigned a function. The US12 family has 10 members encoded sequentially through US12–US21; a genetic arrangement, which is suggestive of an ‘accordion’ expansion of an ancestral gene in response to a selective pressure. This expansion must have be an ancient event as the whole family is conserved across simian cytomegaloviruses from old world monkeys. The evolutionary benefit bestowed by the combinatorial effect of US18 and US20 on MICA may have contributed to sustaining the US12 gene family
Differences in B cell regulation in DRB1 shared epitope positive and negative rheumatoid arthritis
Adapting feeding methods for less nitrogen pollution from pig and dairy cattle farming: abatement costs and uncertainties
This study assesses abatement costs of three measures aimed at reducing nitrogen (N) emissions from livestock production: two protein-adjusted feeding strategies for pigs, and higher-quality forage for dairy cattle. In a partial cost approach, we quantified the effect of different measures on N losses and production costs. We accounted for emissions of NH3, N2O and NO from animal housing, manure storage, manure application, and from soils. Uncertainties related to volatile prices and assumptions about excretion rates and emission factors were assessed in a Monte Carlo simulation. Covering variability of individual input parameters, this uncertainty assessment addresses a fundamental gap in current decision support on N loss reduction measures. For the scenarios investigated, average N abatement costs at farm level were negative and represented net benefits to farmers: In pig husbandry, adapting feeding practices in most individual situations resulted in net benefits, both for three-phase feeding (min −35, max +5, mean −14 €/kg N abated) and optimised single-phase feeding (min −52, max +4, mean −21 €/kg N abated). In dairy production, N abatement by improved forage quality proved invariably more economic than current practice (min −40, max −11, mean −21 €/kg N abated). As shown in this study, N abatement costs can serve as a framework for comparing the cost-effectiveness and feasibility of N loss reduction measures within and between livestock production systems. This is in turn critical when informing practitioners and providing policy support on workable strategies for reducing the N footprint of animal husbandry
- …
