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The Reconciliatory Approach : How Multilateral Environmental Agreements Can Harmonize International Legal Obligations

Transboundary environmental problems pose a specific challenge to the international legal system, as they often demand instruments providing for collective and far-reaching measures on a global scale. Such measures may interfere with other areas of international law, including trade law, human rights law and international humanitarian law (IHL), which may permit conflicting behaviour. The interfer

Female aggression in the European Starling during the breeding season

Intraspecific female aggression during the breeding season can have several different functions: defence of resources, defence against intraspecific brood parasitism and defence of mating status. The intraspecific aggressive behaviour of breeding female starlings, Sturnus vulgaris, was examined by exposing them to a simulated intrusion of a conspecific bird. A caged male or female starling was pla

Tumor necrosis factor-α-mediated downregulation of the cystic fibrosis transmembrane conductance regulator drives pathological sphingosine-1-phosphate signaling in a mouse model of heart failure

Background-Sphingosine-1-phosphate (S1P) signaling is a central regulator of resistance artery tone. Therefore, S1P levels need to be tightly controlled through the delicate interplay of its generating enzyme sphingosine kinase 1 and its functional antagonist S1P phosphohydrolase-1. The intracellular localization of S1P phosphohydrolase-1 necessitates the import of extracellular S1P into the intra

Preservation of enzyme activity and antigenicity after mutagenesis of the membrane anchoring domain of GAD65

The smaller isoform of glutamic acid decarboxylase, GAD65, is an important autoantigen implicated in the pathogenesis of type 1 diabetes whereas the larger isoform, GAD67 appears to play no major role. The primary difference between the two isoforms resides in the N-terminal part of the molecule including the GAD65 membrane-anchoring domain. The aim of this study was to generate mutants of the mem

BTKbase: the mutation database for X-linked agammaglobulinemia.

X-linked agammaglobulinemia (XLA) is a hereditary immunodeficiency caused by mutations in the gene encoding Bruton tyrosine kinase (BTK). XLA patients have a decreased number of mature B cells and a lack of all immunoglobulin isotypes, resulting in susceptibility to severe bacterial infections. XLA-causing mutations are collected in a mutation database (BTKbase), which is available at http://bioin

Phosphorylation of Shc by Src family kinases is necessary for stem cell factor receptor/c-kit mediated activation of the Ras/MAP kinase pathway and c-fos induction

In this report we show that Tyr568 and Tyr570 are phosphorylated in vivo in the Kit/stem cell factor receptor (Kit/SCFR) following ligand-stimulation. By mutation of Tyr568 and Tyr570 to phenylalanine residues and expression of the mutated receptors in porcine aortic endothelial (PAE) cells, we could demonstrate a loss of activation of members of the Src family of tyrosine kinases when Tyr568 was

Structural determinants in the platelet-derived growth factor alpha-receptor implicated in modulation of chemotaxis

Activation of the platelet-derived growth factor (PDGF) beta-receptor leads to cell growth and chemotaxis. The PDGF alpha-receptor also mediates a mitogenic signal, but fails to induce cell migration in certain cell types. To examine this difference in signal transduction, a series of point-mutated PDGF alpha-receptors were analyzed. Porcine aortic endothelial cells expressing mutant PDGF alpha-re

Application of synthetic peptides for detection of anti-citrullinated peptide antibodies.

Anti-citrullinated protein antibodies (ACPAs) are a hallmark of rheumatoid arthritis (RA) and represent an important tool for the serological diagnosis of RA. In this study, we describe ACPA reactivity to overlapping citrullinated Epstein-Barr virus nuclear antigen-1 (EBNA-1)-derived peptides and analyze their potential as substrates for ACPA detection by streptavidin capture enzyme-linked immunos

Effect of pH on direct electron transfer in the system gold electrode-recombinant horseradish peroxidase

The effect of pH on the kinetics of the bioelectrocatalytic reduction of H2O2 catalysed by horseradish peroxidase (HRP) has been studied at –50 mV vs. AgjAgCl on HRP-modified Au electrodes placed in a wall-jet flow-through electrochemical cell. Native HRP (nHRP) and a nonglycosylated recombinant form containing a six-histidine tag at the C-terminus, CHisrHRP, produced by genetic engineering of non

Analysis and modeling of field data on coastal morphological evolution over yearly and decadal time scales. Part 1: Background and linear techniques

A number of statistical techniques to analyze and model coastal morphological evolution over yearly and decadal (i.e., long-term) time scales based on field data are presented. After a general introduction to long-term morphological modeling, mainly linear methods are discussed, whereas nonlinear methods are treated in a companion paper (SOUTHGATE et al., 2001). The theoretical background to the m

Alterations in regulation of energy homeostasis in cyclic nucleotide phosphodiesterase 3B-null mice

Cyclic nucleotide phosphodiesterase 3B (PDE3B) has been suggested to be critical for mediating insulin/IGF-1 inhibition of cAMP signaling in adipocytes, liver, and pancreatic beta cells. In Pde3b-KO adipocytes we found decreased adipocyte size, unchanged insulin-stimulated phosphorylation of protein kinase B and activation of glucose uptake, enhanced catecholamine-stimulated lipolysis and insulin-

Direct electron transfer between graphite electrodes and ligninolytic peroxidases from Phanerochaete chrysosporium

Electron transfer (ET) of ligninolytic peroxidases was studied in the bioelectrocatalytic reduction reaction of H2O2 at peroxidase-modified graphite electrodes. Specifically, native lignin (LiP) and manganese (MnP) peroxidases secreted by Phanerochaete chrysosporium, as well as a few different recombinant MnP forms were used in the electrochemical studies. The recombinant enzymes included wild-typ

beta-lactamase-producing nontypeable Haemophilus influenzae fails to protect Streptococcus pneumoniae from amoxicillin during experimental acute otitis media

Acute otitis media (AOM) is the most common reason for outpatient antimicrobial therapy. Mixed infections pose a potential problem, since the first-line drug used for the treatment of AOM, amoxicillin, can be neutralized by ß-lactamase-producing pathogens of the upper respiratory tract. To study the effects of a 5-day course of amoxicillin on a mixed middle ear infection, rats were challenged with

CD1-dependent regulation of chronic central nervous system inflammation in experimental autoimmune encephalomyelitis.

The existence of T cells restricted for the MHC I-like molecule CD1 is well established, but the function of these cells is still obscure; one implication is that CD1-dependent T cells regulate autoimmunity. In this study, we investigate their role in experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis, using CD1-deficient mice on a C57BL/6 background. We show t

Short leucine-rich glycoproteins of the extracellular matrix display diverse patterns of complement interaction and activation.

The extracellular matrix consists of structural macromolecules and other proteins with regulatory functions. An important family of the latter class of molecules found in most tissues is the small leucine-rich repeat proteins (SLRPs). We have previously shown that the SLRP fibromodulin binds directly to C1q and activates the classical pathway of complement. In the present study we further examine

Haemophilus influenzae protein E recognizes the C-terminal domain of vitronectin and modulates the membrane attack complex.

Haemophilus influenzae protein E (PE) is a 16 kDa adhesin that induces a pro-inflammatory immune response in lung epithelial cells. The active epithelial binding region comprising amino acids PE 84-108 also interferes with complement-mediated bacterial killing by capturing vitronectin (Vn) that prevents complement deposition and formation of the membrane attack complex (MAC). Here, the interaction

Molecular Mechanisms of Collagen Isotype-Specific Modulation of Smooth Muscle Cell Phenotype.

OBJECTIVE: Smooth muscle cell (SMC) phenotypic modulation, an important component of atherosclerosis progression, is critically regulated by the matrix, with normal components of the healthy SMC matrix limiting modulation and atherosclerosis-associated transitional matrix proteins promoting phenotypic modulation. We sought to determine how collagen IV (which comprises the healthy artery wall) and

Secretory lysosome targeting and induced secretion of human soluble TNF-alpha receptor in murine hematopoietic cells in vivo as a principle for immunoregulation in inflammation and malignancy.

OBJECTIVE: Systemic administration of immunotherapeutics often gives rise to severe side effects. A local deposition, using secretory lysosomes of hematopoietic cells as vehicles for delivery, can overcome this problem. In the present study, the validity of this concept was investigated using retroviral transduction of the human soluble tumor necrosis factor-alpha receptor 1 (hsTNFR1) into murine

C4b-binding protein: The good, the bad and the deadly. Novel functions of an old friend.

C4b-binding protein (C4BP) is best known as a potent soluble inhibitor of the classical and lectin pathways of the complement system. This large 500kDa multimeric plasma glycoprotein is expressed mainly in the liver but also in lung and pancreas. It consists of several identical 75kDa α-chains and often also one 40kDa β-chain, both of which are mainly composed of complement control protein (CCP) d