Search

Detailed simulation of wind generation as driven by weather patterns is required to quantify the impact on the electrical grid of the power fluctuations in offshore wind power fleets. This article focuses on studying the power fluctuations of high installation density offshore fleets since they present a growing challenge to the operation and planning of power systems in Europe. The Belgian offshore fleet is studied because it has the highest density of installation in Europe by 2020 and a new extension is expected to start operations by 2028. Different stages of the future installed capacity, turbine technology and turbine storm shutdown technologies are examined and compared. This paper analyzes the distribution of power fluctuations both overall and during high wind speeds. The simulations presented in this article use a new t-student distributed wind speed fluctuations model that captures the missing spectra from the weather reanalysis-simulations. An updated plant storm shutdown model captures the plant behavior of modern high wind speed turbine operation. Detailed wake modeling is carried out using a calibrated engineering wake model in order to capture the Belgium offshore fleet and its tight farm to farm spacing. Long generation time series based on 37 years of historical weather data in 5 min resolution are simulated in order to quantify the extreme fleet-level power fluctuations. The model validation with respect the operational data of the 2018 fleet shows that the methodology presented in this article is able to capture the distribution of wind power and its spatio-temporal characteristics. The results show that the standardized generation ramps are expected to be reduced towards the 4.4 GW of installations due to the larger distances between plants. The most extreme power fluctuations occur during high wind speeds, with large down-ramps occurring in extreme storm events. Extreme down-ramps are mitigated using modern turbine storm shutdown technologies; while extreme up-ramps can be mitigated by the system operator. Extreme ramping events also occur at bellow rated wind speeds, but mitigation of such ramping events remains a challenge for transmission system operators.

Background: To assess an improved version of sublingual AIT performed by applying a novel short-course oromucosal allergen administration strategy in a translational allergic pig model by prolonged and enhanced tolerogenic presentation of intact allergen with a novel mucoadhesive patch technology. Methods: Newborn piglets sensitized intraperitoneally with the common egg allergen ovalbumin (OVA) were sublingually treated five times using a dose ascending administration schedule with nanofiber-based mucoadhesive patches carrying OVA allergen, formulated with immune tolerogenic particles derived from the probiotic bacterium Lactococcus lactis (TBP). Immunologic assessment was conducted by the use of the intradermal test of immediate allergic reactions to OVA. Results: Five weekly treatments with the mucoadhesive patch carrying OVA alone or OVA and TBP resulted in significant desensitisation, being 8% and 45% respectively, as measured by intradermal testing. Mucoadhesive patch-based administration of OVA together with TBP resulted in the allergen localisation to submucosa tissue and draining lymph nodes and resulted in better desensitization compared with patch containing OVA allergen alone. Conclusion: A first demonstration of short-course SLIT approach which we term Specific Oromucosal Immunotherapy (SOMIT) has been successfully carried out in a new translational therapeutic porcine model of allergy. The results suggest that an improved short-course SLIT approach is feasible by prolonging allergen delivery using a mucoadhesive patch and proper stimulation of a privileged tolerogenic immune compartment by tolerogenic probiotic bacterial particles.

This paper analyses several energy system scenarios towards 2050 for the North Sea region. With focus on offshore wind power, the impacts of meshed offshore grid and sector coupling are studied. First, a project-based scenario, where each offshore wind power plant is connected individually to onshore, is compared to a meshed grid scenario. Both the amount of offshore wind installed and the level of curtailment are assessed. Then, these results are compared to a scenario with sector coupling included. The results show that while the introduction of a meshed grid can increase the amount of offshore wind installed towards 2050, sector coupling is expected to be a more important driver for increasing offshore wind installations. In addition, sector coupling can significantly decrease the level of offshore wind curtailment.

Effects of lowering ambient temperature in the second half of the growth period were studied in 2 broiler strains with different genetic potential for growth (Ross from 1972 and 2004) when given ad libitum access or pre-mixed increasing proportion of whole wheat in their diet. A total of 48 groups of day-old broilers (n = 64) from the 2 strains were housed as hatched in 48 pens in 4 houses and slaughtered at 6 wk of age. Half of the groups had access to pelleted feed pre-mixed with increasing proportion of whole wheat, the other half had access to pelleted feed and whole wheat in separate troughs. Ambient temperature from 28 d of age was either 21 or 15°C. The fast-growing strain had greater (P < 0.001) live weight throughout (mean slaughter weights 2.6 (±0.014) kg and 1.0 (±0.006) kg). When given a choice, the fast-growing strain consumed a lower (P ≤ 0.004) proportion of whole wheat in their diet in weeks 5 and 6 (20 and 26 (±0.9) % whole wheat), and the slow-growing strain chose a higher (P < 0.001) wheat proportion (45 and 56 (±1.7) %) than the pre-mixed inclusion of 25 and 30%, respectively. The slow-growing strain grew slightly faster in the colder ambient temperature, and slower when given a free choice of whole wheat. Both strains drank more water per feed consumed in the warmer ambient temperature treatment. Foot pad dermatitis, only seen in the fast-growing birds, had a higher occurrence in the colder and in the choice feeding treatments. Gait scoring on day 34 showed perfect gait in more than 85% of the slow-growing and less than 1% of the fast-growing birds. Activity was higher and panting levels were lower in the slow-growing strain (P < 0.001) toward the end of the growth period, with no effect of the temperature treatment on panting. Slow-growing strains increase their energy intake, and fast-growing strains increase their protein intake when given a choice.

In the poultry production industry, chickens with access to outdoor areas are exposed to a wide range of parasites e.g. the helminth Ascaridia galli. By real-time quantitative RT-PCR, the relative gene expression of the T helper 1 (Th1) cytokine IFN-γ, the T helper 2 (Th2) cytokine IL-13, the anti-inflammatory cytokines IL-10 and TGF-β4 and the pro-inflammatory cytokine IL-17F were determined over a period of 3 weeks in A. galli and non-A. galli-infected chickens. A characteristic Th2 response was observed in the jejunum of A. galli-infected chickens with increased expression of IL-13 and decreased expression of IFN-γ from day 14 post infection. At the putative time of larvae invasion into the intestinal mucosa (day 7), an increased expression of IFN-γ, IL-10, and TGF-β4 was observed in the spleen. At the putative onset of the innate immune response (day 10), a decreased expression of jejunal IFN-γ and IL-13 was observed. Finally, at the expected period of an adaptive immune response (days 14–21) a general decreased expression of IFN-γ and TGF-β4 in spleen and IFN-γ in jejunum was followed by a decreased expression of IFN-γ and IL-10 at day 21 in caecal tonsils.

Mannose-binding lectin (MBL) plays a major role in the immune response as a soluble pattern-recognition receptor. MBL deficiency and susceptibility to different types of infections have been subject to extensive studies over the last decades. In humans and chickens, several studies have shown that MBL participates in the protection of hosts against virus infections. Infectious bronchitis (IB) is a highly contagious disease of economic importance in the poultry industry caused by the coronavirus infectious bronchitis virus (IBV). MBL has earlier been described to play a potential role in the pathogenesis of IBV infection and the production of IBV-specific antibodies, which may be exploited in optimising IBV vaccine strategies. The present study shows that MBL has the capability to bind to IBV in vitro. Chickens from two inbred lines (L10H and L10L) selected for high or low MBL serum concentrations, respectively, were vaccinated against IBV with or without the addition of the MBL ligands mannan, chitosan and fructooligosaccharide (FOS). The addition of MBL ligands to the IBV vaccine, especially FOS, enhanced the production of IBV-specific IgG antibody production in L10H chickens, but not L10L chickens after the second vaccination. The addition of FOS to the vaccine also increased the number of circulating CD4+ cells in L10H chickens compared to L10L chickens. The L10H chickens as well as the L10L chickens also showed an increased number of CD4−CD8α−γδ T-cells when an MBL ligand was added to the vaccine, most pronouncedly after the first vaccination. As MBL ligands co-administered with IBV vaccine induced differences between the two chicken lines, these results indirectly suggest that MBL is involved in the immune response to IBV vaccination. Furthermore, the higher antibody response in L10H chickens receiving vaccine and FOS makes FOS a potential adjuvant candidate in an IBV vaccine. Mannose-binding lectin (MBL) plays a major role in the immune response as a soluble pattern-recognition receptor. MBL deficiency and susceptibility to different types of infections have been subject to extensive studies over the last decades. In humans and chickens, several studies have shown that MBL participates in the protection of hosts against virus infections. Infectious bronchitis (IB) is a highly contagious disease of economic importance in the poultry industry caused by the coronavirus infectious bronchitis virus (IBV). MBL has earlier been described to play a potential role in the pathogenesis of IBV infection and the production of IBV-specific antibodies, which may be exploited in optimising IBV vaccine strategies. The present study shows that MBL has the capability to bind to IBV in vitro. Chickens from two inbred lines (L10H and L10L) selected for high or low MBL serum concentrations, respectively, were vaccinated against IBV with or without the addition of the MBL ligands mannan, chitosan and fructooligosaccharide (FOS). The addition of MBL ligands to the IBV vaccine, especially FOS, enhanced the production of IBV-specific IgG antibody production in L10H chickens, but not L10L chickens after the second vaccination. The addition of FOS to the vaccine also increased the number of circulating CD4+ cells in L10H chickens compared to L10L chickens. The L10H chickens as well as the L10L chickens also showed an increased number of CD4−CD8α−γδ T-cells when an MBL ligand was added to the vaccine, most pronouncedly after the first vaccination. As MBL ligands co-administered with IBV vaccine induced differences between the two chicken lines, these results indirectly suggest that MBL is involved in the immune response to IBV vaccination. Furthermore, the higher antibody response in L10H chickens receiving vaccine and FOS makes FOS a potential adjuvant candidate in an IBV vaccine.

Potent vaccine efficiency is crucial for disease control in both human and livestock vaccination programmes. Free range chickens and chickens with access to outdoor areas have a high risk of infection with parasites including Ascaridia galli, a gastrointestinal nematode with a potential influence on the immunological response to vaccination against other infectious diseases. The purpose of this study was to investigate whether A. galli infection influences vaccine-induced immunity to Newcastle Disease (ND) in chickens from an MHC-characterized inbred line. Chickens were experimentally infected with A. galli at 4 weeks of age or left as non-parasitized controls. At 10 and 13 weeks of age half of the chickens were ND-vaccinated and at 16 weeks of age, all chickens were challenged with a lentogenic strain of Newcastle disease virus (NDV). A. galli infection influenced both humoral and cell-mediated immune responses after ND vaccination. Thus, significantly lower NDV serum titres were found in the A. galli-infected group as compared to the non-parasitized group early after vaccination. In addition, the A. galli-infected chickens showed significantly lower frequencies of NDV-specific T cells in peripheral blood three weeks after the first ND vaccination as compared to non-parasitized chickens. Finally, A. galli significantly increased local mRNA expression of IL-4 and IL-13 and significantly decreased TGF-ß4 expression in the jejunum two weeks after infection with A. galli. At the time of vaccination (six and nine weeks after A. galli infection) the local expression in the jejunum of both IFN-? and IL-10 was significantly decreased in A. galli-infected chickens. Upon challenge with the NDV LaSota strain, viral genomes persisted in the oral cavity for a slightly longer period of time in A. galli-infected vaccinees as compared to non-parasitized vaccinees. However, more work is needed in order to determine if vaccine-induced protective immunity is impaired in A. galli-infected chickens.

In chickens, the nematode Ascaridia galli is found with prevalences of up to 100% causing economic losses to farmers. No avian nematode vaccines have yet been developed and detailed knowledge about the chicken immune response towards A. galli is therefore of great importance. The objective of this study was to evaluate the induction of protective immune responses to A. galli soluble antigen by different immunization routes. Chickens were immunized with a crude extract of A. galli via an oral or intra-muscular route using cholera toxin B subunit as adjuvant and subsequently challenged with A. galli. Only chickens immunized via the intra-muscular route developed a specific A. galli antibody response. Frequencies of γδ T cells in spleen were higher 7 days after the first immunization in both groups but only significantly so in the intra-muscularly immunized group. In addition, systemic immunization had an effect on both Th1 and Th2 cytokines in caecal tonsils and Meckel's diverticulum. Thus both humoral and cellular immune responses are inducible by soluble A. galli antigen, but in this study no protection against the parasite was achieved.

Mannose-binding lectin (MBL) is a key molecule in innate immunity. MBL binds to carbohydrates on the surface of pathogens, initiating the complement system via the lectin-dependent pathway or facilitates opsonophagocytosis. In vivo studies using inbred chicken lines differing in MBL serum concentration indicate that chicken MBL affects Salmonella resistance; further studies are imperative in conventional broiler chickens. In this study 104 conventional day-old chickens (offspring from a cross between Cobb 500 male and female parent breeders) were orally infected with Salmonella enterica subsp. enterica serovar Montevideo. The chickens were divided into two groups based on polymorphisms in their MBL promoter region, designated L/L for low serum concentrations of MBL and L/H for medium serum concentrations of MBL. A semi-quantitative real-time PCR method for detection of Salmonella in cloacal swabs was used, the log10 CFU quantification was based on a standard curve from artificially spiked cloacal swab samples pre-incubated for 8 h with known concentrations of Salmonella ranging from 10(1) to 10(6) CFU/swabs, with an obtained amplification efficiency of 102% and a linear relationship between the log10 CFU and the threshold cycle Ct values of (R(2) = 0.99). The L/L chickens had significantly higher Log10 CFU/swab at week 5 post infection (pi) than the L/H chickens. A repetition of the study with 86 L/L and 18 L/H chickens, also gave significantly higher log10 CFU ± SEM in cloacal swabs, using the semi-quantitative real-time PCR method from L/L chickens than from the L/H chickens at week 5 pi. These results indicate that genetically determined basic levels of MBL may influence S. Montevideo susceptibility.

We present a theoretical framework for simulating the synaptic accumulation of the costimulatory molecules CD28, CTLA-4, B7-1, and B7-2, based on a system of mean-field, ordinary differential equations, and rigorous biophysical and expression data. The simulations show that binding affinity, stoichiometric properties, expression levels, and, in particular, competition effects all profoundly influence complex formation at cellular interfaces. B7-2 engages 33-fold more CD28 than CTLA-4 at the synapse in contrast to B7-1, which ligates ∼7-fold more CTLA-4 than CD28. Although B7-1 completely dominates interactions with CTLA-4, forming linear arrays of 7-18 receptor-ligand pairs, CTLA-4 is fully engaged by B7-2 when B7-1 is absent. Additional simulations reveal the sensitivity of CD28 interactions to modeled transport processes. The results support the concept that B7-2 and B7-1 are the dominant ligands of CD28 and CTLA-4, respectively, and indicate that the inability of B7-2 to recruit CTLA-4 to the synapse cannot be due to the differential binding properties of B7-1 and B7-2 only. We discuss the apparent redundancy of B7-1 in the context of a potentially dynamic synaptic microenvironment, and in light of functions other than the direct enhancement of T cell inhibition by CTLA-4.

The roles of the c-Jun N-terminal kinases (JNKs) in inflammatory arthritis have been investigated; however, the roles of each isotype (ie, JNK1 and JNK2) in rheumatoid arthritis and conclusions about whether inhibition of one or both is necessary for amelioration of disease are unclear. By using JNK1- or JNK2-deficient mice in the collagen-induced arthritis and the KRN T-cell receptor transgenic mouse on C57BL/6 nonobese diabetic (K/BxN) serum transfer arthritis models, we demonstrate that JNK1 deficiency results in protection from arthritis, as judged by clinical score and histological evaluation in both models of inflammatory arthritis. In contrast, abrogation of JNK2 exacerbates disease. In collagen-induced arthritis, the distinct roles of the JNK isotypes can, at least in part, be explained by altered regulation of CD86 expression in JNK1- or JNK2-deficient macrophages in response to microbial products, thereby affecting T-cell-mediated immunity. The protection from K/BxN serum-induced arthritis in Jnk1(-/-) mice can also be explained by inept macrophage function because adoptive transfer of wild-type macrophages to Jnk1(-/-) mice restored disease susceptibility. Thus, our results provide a possible explanation for the modest therapeutic effects of broad JNK inhibitors and suggest that future therapies should selectively target the JNK1 isoform.

Mannose-binding lectin (MBL) is a C-type serum lectin of importance in innate immunity. Low serum concentrations of MBL have been associated with greater susceptibility to infections. In this study, binding of purified chicken MBL (cMBL) to Salmonella enterica subsp. enterica (S. enterica) serotypes B, C1 and D was investigated by flow cytometry, and Staphylococcus aureus (S. aureus) was used for comparison. For S. enterica the C1 serotypes were the only group to exhibit binding to cMBL. Furthermore, functional studies of the role of cMBL in phagocytosis and complement activation were performed. Spiking with cMBL had a dose-dependent effect on the HD11 phagocytic activity of S. enterica subsp. enterica serovar Montevideo, and a more pronounced effect in a carbohydrate competitive assay. This cMBL dose dependency of opsonophagocytic activity by HD11 cells was not observed for S. aureus. No difference in complement-dependent bactericidal activity in serum with high or low cMBL concentrations was found for S. Montevideo. On the other hand, serum with high concentrations of cMBL exhibited a greater bactericidal activity to S. aureus than serum with low concentrations of cMBL. The results presented here emphasise that chicken cMBL exhibits functional similarities with its mammalian counterparts, i.e. playing a role in opsonophagocytosis and complement activation.

GM-CSF (granulocyte-macrophage colony stimulating factor) plays a central role in inflammatory processes. Treatment with antibodies neutralizing murine GM-CSF showed significant therapeutic effects in mouse models of inflammatory diseases. We constructed by phage display technology a human scFv, which could potently neutralize human GM-CSF. At first, a human V(L) repertoire was combined with the V(H) domain of a parental GM-CSF-neutralizing rat antibody. One dominant rat/human scFv clone was selected, neutralizing human GM-CSF with an IC50 of 7.3 nM. The human V(L) of this clone was then combined with a human V(H) repertoire. The latter preserved the CDR 3 of the parental rat V(H) domain to retain binding specificity. Several human scFvs were selected, which neutralized human GM-CSF at low nanomolar concentrations (IC50 > or = 2.6 nM). To increase serum half-life, a branched 40 kDa PEG-polymer was coupled to the most potent GM-CSF-neutralizing scFv (3077) via an additional C-terminal cysteine. PEG conjugation had a negligible effect on the in vitro neutralizing potential of the scFv, although it caused a significant drop in binding affinity owing to a reduced on-rate. It also significantly increased the stability of the scFv at elevated temperatures. In mouse experiments, the PEGylated scFv 3077 showed a significantly prolonged elimination half-life of 59 h as compared with 2 h for the unconjugated scFv version. PEGylated scFv 3077 is a potential candidate for development of a novel antibody therapy to treat pro-inflammatory human diseases.

The B7 ligands CD80 and CD86 on APCs deliver either costimulatory or inhibitory signals to the T cell when interacting with their counter-receptors CD28 and CD152 (CTLA-4) on the T cell surface. Although crucial for lymphocyte regulation, the structural basis of these interactions is still not completely understood. Using multivalent presentation and conditions mimicking clustering, believed to be essential for signaling through these receptors, and by applying a combined differential mass spectrometry and structural mapping approach to these conditions, we were able to identify a putative contact area involving hydrophilic regions on both CD28 and CD80 as well as a putative CD28 oligomerization interface induced by B7 ligation. Analysis of the CD80-CD28 interaction site reveals a well-defined interface structurally distinct from that of CD80 and CD152 and thus provides valuable information for therapeutic intervention targeted at this pathway, suggesting a general approach for other receptors.

Mannose-binding lectin (MBL) is a key protein in innate immunity. MBL binds to carbohydrates on the surface of pathogens, where it initiates complement activation via the lectin-dependent pathway or facilitates opsonophagocytosis. In vitro studies have shown that human MBL is able to bind to Salmonella, but knowledge in relation to chicken MBL and Salmonella is lacking. In order to study this relation day-old chickens from two selected lines L10H and L10L, differing in MBL serum concentration, were either orally infected with S. Infantis (S.123443) or kept as non-infected controls. The differences between healthy L10H and L10L chicken sublines were more profound than differences caused by the S. Infantis infection. The average daily body weight was higher for L10H than for L10L, regardless of infection, indicating beneficial effects of MBL selection on growth. Salmonella was detected in cloacal swabs and the number of Salmonella positive chickens during the experiment was significantly higher in L10L than L10H, indicating that MBL may affect the magnitude of Salmonella colonisation in day-old chickens. MBL expression was determined in ceca tissue by real-time RT-PCR. L10H chickens showed a significantly higher relative expression than L10L at days 1 and 41 pi, regardless of infection. Finally, flow cytometric analysis of whole blood from infected chickens showed that L10H had a significantly higher count of all assessed leucocyte subsets on day 5 pi, and also a higher count of monocytes on day 12 pi than L10L. No difference was observed between infected and non-infected L10L chicken.

Chickens from two inbred lines selected for high (L10H) or low (L10L) mannose-binding lectin (MBL) serum concentrations were infected with infectious bronchitis virus (IBV), and innate as well as adaptive immunological parameters were measured throughout the experimental period. Chickens with high MBL serum concentrations were found to have less viral load in the trachea than chickens with low MBL serum concentrations indicating that these chickens were less severely affected by the infection. This study is the first to show that MBL expression is present in the lungs of healthy chickens and that the expression is upregulated at days 3 postinfection (p.i.) in L10H chickens. Furthermore, in the liver of infected chickens, the MBL expression was upregulated at day 7 p.i., despite the fact that the MBL serum concentrations were decreased below baseline at that time point. The number of TCR gamma delta+CD8 alpha+ cells in the blood of noninfected chickens increased from week 0 to 3 p.i. However, the number of cells was higher in L10H chickens than in L10L chickens throughout the experiment. No increase was observed in the number of TCR gamma delta+CD8 alpha+ cells in the blood of the infected L10H and L10L chickens. The numbers of B cells at week 3 p.i. were higher for noninfected L10L chickens than for the other chickens. No differences were observed between the infected and noninfected L10H chickens or between the infected L10H and L10L chickens. Furthermore, at week 3 p.i., the number of monocytes was higher in infected and noninfected L10H chickens than in the infected and noninfected L10L chickens. Thus, these results indicate that MBL is produced locally and may be involved in the regulation of the cellular immune response after an IBV infection. However, MBL did not appear to influence the humoral immune response after IBV infection in this study.

Organic Meat Production and Processing describes the challenges of production, processing and food safety of organic meat. The editors and international collection of authors explore the trends in organic meats and how the meat industry is impacted. Commencing with chapters on the economics, market and regulatory aspects of organic meats, coverage then extends to management issues for organically raised and processed meat animals. Processing, sensory and human health aspects are covered in detail, as are the incidences of foodborne pathogens in organic beef, swine, poultry and other organic meat species. The book concludes by describing pre-harvest control measures for assuring the safety of organic meats.Organic Meat Production and Processing serves as a unique resource for fully understanding the current and potential issues associated with organic meats

The loop region of chymotrypsin inhibitor 2 from barley has been employed as a scaffold for testing the intrinsic propensity of a peptide fragment to form a secondary structure. The helix formation of the nine amino acid residue segment Lys-Gln- Ala-Val- Asp- Asn- Ala-Tyr-Ala of helix E from subtilisin Carlsberg has been studied by the construction of a hybrid consisting of chymotrypsin inhibitor 2 (CI2) where part of the active loop has been replaced by the nonapeptide. An expression system for a truncated form of C12 where the 19 structureless residues of the N-terminus have been removed and Leu20 replaced by methionyl was constructed from the entire 83-residue wild-type C12 gene by polymerase chain reaction methodology. The gene encoding the hybrid was constructed from the truncated inhibitor gene. The stability of the truncated inhibitor and of the hybrid toward guanidinium chloride denaturation was examined. From these measurements, the energy of unfolding in pure water was extrapolated to 30.5 1.0 kJ/mol for the truncated inhibitor and 10.9 f 0.3 kJ/mol for the hybrid. These energies show that the stability of C12 is unaffected by the N-terminal truncation but severely decreased by the loop mutations. The three-dimensional structure of the hybrid protein has been determined in solution by nuclear magnetic resonance spectroscopy using 893 distance restraints and 84 torsional angle restraints. The average rootmean-square deviation (rmsd) of 15 structures compared to their geometrical average was 0.8 f 0.2 A for heavy backbone atoms and 1.3 * 0.2 A for all heavy atoms. The inserted peptide segment does not form an a-helix in the new structural context whereas the structure of the C12 scaffold turns out to be amazingly conserved. (Less)

[EN] An experiment using Magnetic Resonance lmaging (MRI) tomography were done inwlving 87 rabbits el four genotypes, 12 or 16 weeks old. MRI was applied on the day before slaughter. The slices were taken in three orthogonal planes. The resufting pictures indicate that MRI provides very detailed slices. The volume of the fat deposit around the kldneys, the tml body fat volume of the body and the muscle el the hind part was collected from the MRI pictures. Correlation coefficients were computad between the volume of the perirenal fat ancl its weight, the muscle volume el the hind part ancl its weight, the tctal body fat volume and the crude fat content. The correlation values were found to be very high (O. n to 0.94) in the group of age 16 proving that the MRI tomograph is a excellent In vivo method to determine the volumes of fat and muscle. The la.ver correlation values in the group el age 12 (0.39 to 0.76) indicate that the MRI tomography is sensitiva to the digital sampling errors., [FR] Un total de 87 laplns appartensnt lt 4 génotypes ~s de 12 lt 16 semalnes ont été étudlés par lmsgerie en résonance magnétique (IRM). Les laplns ont été ana/ysés par IRM Is vei//e de fsbattage. Les "coupes• ont été réalisées dans 3 p/Bns orthogonaux. Les images obtenues pour chaque coupe sont tres détaillées. Le volume de la masse adipeuse p(riénBle, de fensemble des masses adipeuses du COITJS et ce/ui des masses musculaires de farrilJre de fanimal ont été détermlnées par analyse de coupes. Les coefficients de corrélation entre ces volumes détermlnés par IRM et /eur poids mesuré par dissection aprés abattage sont de O, 77 lt 0,94 chez les laplns de 16 semalnes. Ceci atieste que f/RM est une bonne méthode pour la mesure in vivo des volumes de tissu adipeux ou musculaire. Les vBleurs beaucoup plus faibles des corrélations obtenues chez les laplns de 12 semalnes, (0,39 it O, 76) montrent la limite de f/RM pour ce type d'étude (faible masse des tissus adipeux) en raison de se sensibilité aux erreurs d'analyse des images infonnatiques numérlsées, This work was supported by the E.C. (Copernicus) as a part of project CIPA-CT93-0206. The authors gratefully ackowledge E. Biro-Németh, L. Radnai and the staff of the CT Biological Centre of the Pannon Agricultural University for their expert assistance

[EN] The two rabbit meat breeds, Danish White (D), represented by a 3-way cross of 3 lines from the Danish lnstitute of Animal Science (DIAS), and Pannon White (H), represen_ted by a synthetic breed from the Pannon Agricultura! University (PAU) were used in a diallel crossing experiment carried out simultaneously at the two locations. In the four combinations: DD, DH, HD, and HH the male breed is mentioned first. The length of gestation and the number of young at birth were the same for the does from the two breeds, but the number of days between kindlings was smaller in H-does than in Ddoes. Litter number five was the largest at birth. From weaning to the test end, the mortality for all 1, 147 weaned young rabbits was only 2.7%. The largest number was seen in group (DD) with 5.4% and the smallest in group (HD) with 1.2%. The growth rate was recorded from weaning to an age of 70 days. Highest daily gain from weaning to an age of 70 days averaged 46.1 g in group (HD). A slightly smaller growth rate, 44.2 g, was obtained in group (DD). In group (OH), the growth rate averaged 43.9 g, and in group (HH) 41.2 g. Both crossbred groups grew faster than group (HH), but only group (HD) showed a crossbred effect., [FR] L'essai a porté sur le croisement dial/ele de deux /apins de races a viande : le Danois Blanc (D) issu d'un croisement a 3 trois voies entre trois lignées provenant du Danish lnstitute of Animal Science et Je Japin Pannon White (H) issu d'une race synthétique provenant de la Pannon Agricultura/ University (Hongrie), essai qui fut mené simultanément dans les deux lieux d'origine. Dans les quatre combinaisons : DD, DH, HD et HH le mlJ/e est nommé en premier. La durée de la gestation et Je nombre de /apereaux a la naissance sont identiques pour les lapines des deux races, mais le nombre de jours entre deux mise bas consécutives est plus faible pour les lapines H que pour les lapines D. La plus forte taille de portée a la naissance est enregistrée a la cinquieme portée. Du sevrage jusqu'a Ja fin de l'expérimentation, la mortalité pour /'ensemble des 1 147 lapereaux sevrés est seulement de 2, 7% (la plus importante conceme le groupe DD : 5,4% et la plus faib/e le groupe HD: 1,2%). La vitesse de croissance a été enregistrée du sevrage a 38 jours jusqu'a 70 jours d'IJge. Le plus fort gain de poids moyen quotidien pendant cette période est de 46, 1g pour Je groupe HD. Un gain légérement plus faible, 44,2g, est enregistré pour le groupe DD. Dans Je groupe DH le gain moyen est de 43,9g, et dans le groupe HH de 41,2g. Les deux groupes issus du croisement grossissent plus vite que le groupe HH, mais seul Je groupe HD montre un effet croisement., The experiment was partly financed by the EU-project for co-operation in Science and Technology with Central and Eastern European Countries, project no. ERB 3511 PL 922921.

We consider the problem of detecting and estimating the strength of association between a trait of interest and alleles or haplotypes in a small genomic region (e.g. a gene or a gene complex), when no direct information on that region is available but the values of neighbouring DNA-markers are at hand. We argue that the effects of the non-observable haplotypes of the genomic regions can and should be represented by factors representing disjoint groups of marker-alleles. A theoretical argument based on a hypothetical phylogenetic tree supports this general claim. The techniques described allow to identify and to infer the number of detectable haplotypes in the genomic region that are associated with a trait. The methods proposed use an exhaustive combinatorial search coupled with the maximization of a version of the likelihood function penalized for the number of parameters. This procedure can easily be implemented with standard statistical methods for a moderate number of marker-alleles., 21 pages, 7 figures

Application of humanized xenotransplantation disease models and experimental clinical studies in the context of translational research in drug discovery in dermatology is an opportunity to reduce failure due to lack of efficacy in clinical development stage.

The pro-inflammatory cytokine GM-CSF is aberrantly produced in many autoimmune and chronic inflammatory human diseases. GM-CSF neutralization by antibodies has been shown to have a profound therapeutic effect in animal models of rheumatoid arthritis, inflammatory lung diseases, psoriasis and multiple sclerosis. Moreover, the absence of GM-CSF in null mutant mice ameliorates or prevents certain of these diseases. Here we describe the biophysical and biological properties of a human anti-GM-CSF IgG1 antibody designated MT203, which was derived by phage display guided selection. MT203 bound with picomolar affinity to an epitope on human and macaque GM-CSF involved in high-affinity receptor interaction. As a consequence, the antibody potently prevented both GM-CSF-induced proliferation of TF-1 cells with a sub-nanomolar IC50 value and the production of the chemokine IL-8 by U937 cells. MT203 neutralized equally well recombinant (r) human (h) GM-CSF from Escherichia coli and yeast, and also normally glycosylated GM-CSF secreted by human lung epithelial cells in response to IL-1β stimulation. Furthermore, MT203 significantly reduced both survival and activation of peripheral human eosinophils as may be required for effective treatment of inflammatory lung diseases. The antibody did not show a detectable loss of neutralizing activity after 5 days in human serum at 37 °C. Based on its favorable properties, MT203 has been selected for development as a novel anti-inflammatory human monoclonal antibody with therapeutic potential in a multitude of human autoimmune and inflammatory diseases.

Over the last two decades, more and more farmers converted from conventional to organic farming systems. The few breeds and genetic lines which are intensively used in conventional production systems are not necessarily well adapted to the conditions in organic farming, because genotype * environment interactions may cause individual genotypes performing well in one environment to do poorly in another surrounding. An example in poultry is given, illustrating that laying hens which were selected for high egg production in a cage, had a considerable decrease in number of eggs laid in a free-range system and furthermore developed unfavourable behaviour patterns like feather pecking. The range of phenotypes produced by one genotype can be determined by variation in the environment and visually demonstrated in reaction norm curves. As one example for this phenomenon, reaction norm curves depicting the environmental sensitivity for fertility in dairy cattle were shown. It is suggested to develop new selection indices and to apply them to the existing stock. Different possibilities for these new indices which contain production as well as functional or fitness traits are given. Summing up, organic farming systems may crave a different type of livestock which can be accounted for in a breeding context.

Udgivelsesdato: 2000-Aug The intermolecular contact regions between monomers of the homodimeric DNA binding protein ParR and the interaction between the glycoproteins CD28 and CD80 were investigated using a strategy that combined chemical cross-linking with differential MALDI-MS analyses. ParR dimers were modified in vitro with the thiol-cleavable cross-linker 3,3'-dithio-bis(succinimidylproprionate) (DTSSP), proteolytically digested with trypsin and analyzed by MALDI-MS peptide mapping. Comparison of the peptide maps obtained from digested cross-linked ParR dimers in the presence and absence of a thiol reagent strongly supported a "head-to-tail" arrangement of the monomers in the dimeric complex. Glycoprotein fusion constructs CD28-IgG and CD80-Fab were cross-linked in vitro by DTSSP, characterized by nonreducing SDS-PAGE, digested in situ with trypsin and analyzed by MALDI-MS peptide mapping (+/- thiol reagent). The data revealed the presence of an intermolecular cross-link between the receptor regions of the glycoprotein constructs, as well as a number of unexpected but nonetheless specific interactions between the fusion domains of CD28-IgG and the receptor domain of CD80-Fab. The strategy of chemical cross-linking combined with differential MALDI-MS peptide mapping (+ thiol reagent) enabled localization of the interface region(s) of the complexes studied and clearly demonstrates the utility of such an approach to obtain structural information on interacting noncovalent complexes.

Plasma growth hormone (GH) secretory profiles of 8-week-old male and female broiler chickens selected for high body weight at 42 days of age (GL line) or for improved food efficiency between 18 and 39 days of age (FCR line) were compared. A pulsatile GH secretory pattern was still present for all the 8-week-old chickens examined. Overall mean GH levels, and to a lesser extent GH baseline and GH amplitude values, were higher for FCR chickens compared with GL chickens. Mean GH concentrations, baseline and amplitudes were slightly, but not significantly, superior in males. Length and frequency of pulses were not influenced by line or sex. In view of the current knowledge on age- and sex-related changes in pulsatile GH secretion, it is argued that the line and sex differences would have been more pronounced in younger chickens. Based on this, the hypothesis that the amplitude of the pulsatile GH release is related to protein conversion efficiency and protein deposition rather than to average body wei...

NMR pulse sequences for measuring coupling constants in 13C, 15N-labeled proteins are presented. These pulse sequences represent improvements over earlier experiments with respect to resolution and number of radiofrequency pulses. The experiments are useful for measuring JNH β, JNCO, JNC α, JH N CO and JH N H α. Applications to chymotrypsin inhibitor 2 (CI-2) are shown.

I. Biochemistry and Genetics of Denitrification.- 1. Bio-inorganic Aspects of Denitrification: Structures and Reactions of NxOy Compounds and their Interaction with Iron and Copper Proteins.- 2. Distribution and Diversity of Dissimilatory NO2- Reductases in Denitrifying Bacteria.- 3. Metabolism of Nitrous Oxide.- 4. Physiology, Biochemistry and Genetics of Nitrate Dissimilation to Ammonia.- II. Ecophysiology of Denitrification.- 5. Role of Environmental Factors in Regulating Nitrate Respiration in Intertidal Sediments.- 6. Physiological and Ecological Aspects of Aerobic Denitrification, a Link with Heterotrophic Nitrification?.- III. Emission of NxOy Compounds.- 7. Flux of NOx between Soil and Atmosphere: Importance and Soil Microbial Metabolism.- 8. Emissions of N2O from Various Environments - the Use of Stable Isotope Composition of N2O as a Tracer for the Studies of N2O Biogeochemical Cycling.- IV. Denitrification in Soil.- 9. Acetylene Inhibition Technique: Development, Advantages and Potential Problems.- 10. The Use of Acetylene for the Quantification of N2 and N2O Production from Biological Processes in Soil.- 11. Measuring Denitrification in Soils Using 15N Techniques.- 12. Rhizosphere Denitrification a Minor Process but Indicator of Decomposition Activity.- 13. Characterizing the Variability of Soil Denitrification.- 14. Anaerobic Zones and Denitrification in Soil: Modeling and Measurement.- 15. Diffusion-Reaction Models of Denitrification in Soil Microsites.- V. Denitrification in Biofilm and Sediment.- 16. Combined Use of the Acetylene Inhibition Technique and Microsensors for Quantification of Denitrification in Sediments and Biofilms.- 17. Denitrification in Stream Biofilm and Sediment: In Situ Variation and Control Factors.- 18. Measurement of Sediment Denitrification Using 15N Tracer Method.- 19. Denitrification in Aquatic Sediments.- 20. Denitrification Model for Marine Sediment.- Contributors.

Background Histone deacetylase inhibitors (HDACIs) induce hyperacetylation of core histones modulating chromatin structure and affecting gene expression. These compounds are also able to induce growth arrest, cell differentiation, and apoptotic cell death of tumor cells in vitro as well as in vivo. Even though several genes modulated by HDAC inhibition have been identified, those genes clearly responsible for the biological effects of these drugs have remained elusive. We investigated the pharmacological effect of the HDACI and potential anti-cancer agent Trichostatin A (TSA) on primary T cells. Methods To ascertain the effect of TSA on resting and activated T cells we used a model system where an enriched cell population consisting of primary T-cells was stimulated in vitro with immobilized anti-CD3/anti-CD28 antibodies whilst exposed to pharmacological concentrations of Trichostatin A. Results We found that this drug causes a rapid decline in cytokine expression, accumulation of cells in the G1 phase of the cell cycle, and induces apoptotic cell death. The mitochondrial respiratory chain (MRC) plays a critical role in the apoptotic response to TSA, as dissipation of mitochondrial membrane potential and reactive oxygen species (ROS) scavengers block TSA-induced T-cell death. Treatment of T cells with TSA results in the altered expression of a subset of genes involved in T cell responses, as assessed by microarray gene expression profiling. We also observed up- as well as down-regulation of various costimulatory/adhesion molecules, such as CD28 and CD154, important for T-cell function. Conclusions Taken together, our findings indicate that HDAC inhibitors have an immunomodulatory potential that may contribute to the potency and specificity of these antineoplastic compounds and might be useful in the treatment of autoimmune disorders.