Molecular basis and species specificity of high affinity binding of vasoactive intestinal polypeptide by the rat secretin receptor

The affinity and specificity of the binding interaction between ligands and their receptors are key for appropriate hormonal regulation of target tissues. However, it is now apparent that vasoactive intestinal polypeptide (VIP) binds to the rat secretin receptor with similar affinity to that for its natural ligand, secretin (Holtmann et al., 1995). In this report, we establish that this is not a characteristic of the human secretin receptor, and use rat-human secretin receptor chimeras, site mutants and truncated receptor constructs to establish the molecular basis for this unusual binding interaction. Of note, isolated N-terminal domains of the rat secretin and the VIP receptors are capable of high affinity binding of VIP. In the recently recognized secretin family of receptors, this domain has six conserved cysteine residues and disulfide bonds that are likely important to achieve the complex conformation critical for this binding. A single acidic residue (Asp98) present in the rat secretin receptor appears to be critical, because a site-mutant changing this to the polar, but uncharged residue present in that position in the human receptor (Asn) eliminates the high affinity binding of VIP. Of interest, a previously identified critical basic residue in VIP (Lys15) provides a candidate for charge-pairing with this residue, potentially aligning the peptide ligand in a nonproductive orientation within this receptor.     

Reinigung lösungsmittelhaltiger Abluft – alternative Möglichkeiten

Purification of solvents containing air – Alternative methods. Different processes are used for the purification of solvents containing air: condensation, absorption, adsorption, combustion, membrane permeation, and biofilters or bioscrubbers. The processes will be explained by examples. The specifications required by “TA Luft” often cannot be reached only by condensation and membrane permeation. The success of absorption depends on the scrubbing liquid. Glycol ethers are useful scrubbing liquids – especially for chlorinated hydrocarbons. The choice of the process depends on the volume flow rate, the solvent concentration, and the kind of solvent. Recycling of the solvents reduces the costs of the process.     

Photocrosslinking of stilbene-modified polymers

The reactions of trans-2,5-dimethoxy-4′-aminostilbene with poly(maleic anhydride-co-methylvinyl ether) and trans-2,5-dimethoxy-4′-isocyanatostilbene with poly(oxy-1,4-phenyleneisopropylidene:1,4-phenyleneoxy-2-hydroxytrimethylene) yield polymeric systems which undergo rapid crosslinking upon short exposure to ultraviolet light. The extent of photocrosslinking as a function of exposure time was determined by the decrease of the trans-stilbene ultraviolet absorption at 350 nm.     

Molecular interaction networks in the analyses of sequence variation and proteomics data

Protein–protein interaction networks are typically generated in standard cell lines or model organisms as it is prohibitively difficult to record large interaction datasets from specific tissues or disease models at a reasonable pace. Although the interaction data are of high confidence, they thus do not reflect in vivo relationships as such. A wealth of physiologically relevant protein information, obtained under different conditions and from different systems, is available including information on genetic variation, protein levels, and PTMs. However, these data are difficult to assess comprehensively because the relationships between the entities remain elusive from the measurements. Here, we exemplarily highlight recent studies that gained deeper insight from genetic variation, protein, and PTM measurements using interaction information pointing toward the importance and potential of interaction networks for the interpretation of sequencing and proteomics data.     

Zeolite based trace humidity sensor for high temperature applications in hydrogen atmosphere

We present a humidity sensor based on H-ZSM-5 type zeolite that is suitable to detect traces of humidity (10–110 ppm_V) under harsh conditions, e.g. reducing atmosphere (H₂) and high temperature (up to 600 °C). By means of complex impedance spectroscopy (IS) we show that the zeolite sensor responds linearly towards minimal changes in humidity. Therefore this result indicates that the zeolite sensor is capable to detect traces of humidity in processes where high temperatures in a hydrogen environment are required.     

Immunoglobulin 1 (IgG1) Fc-glycosylation profiling of anti-citrullinated peptide antibodies from human serum

In several autoimmune disorders, including rheumatoid arthritis (RA), autoantibodies are thought to be the driving force of pathogenicity. Glycosylation of the Fc-part of human Igs is known to modulate biological activity. Hitherto, glycosylation of human IgG-Fc has been analyzed predominantly at the level of total serum IgG, revealing reduced galactosylation in RA. Given the pathogenic relevance of autoantibodies in RA, we wished, in the present study, to address the question whether distinct Fc-glycosylation features are observable at the level of antigen-specific IgG subpopulations. For this purpose, we have developed a method for the microscale purification and Fc-glycosylation analysis of anti-citrullinated peptide antibodies (ACPA). ACPA represent a group of autoantibodies that occur with unique specificity in RA patients. Their presence is associated with increased inflammatory disease activity and rapid joint destruction. Results indicate that ACPA of the IgG1 subclass vary considerably from total serum IgG1 with respect to Fc-galactosylation, with galactosylation being higher on ACPA than on serum IgG1 for some patients, while other patients show higher galactosylation on serum IgG1 than on ACPA. Using this method, studies can be performed on the biological and clinical relevance of ACPA glycosylation within RA patient cohorts.