Membrane Environment Imposes Unique Selection Pressures on Transmembrane Domains of G Protein-Coupled Receptors

We have investigated the influence of the plasma membrane environment on the molecular evolution of G protein-coupled receptors (GPCRs), the largest receptor family in Metazoa. In particular, we have analyzed the site-specific rate variation across the two primary structural partitions, transmembrane (TM) and extramembrane (EM), of these membrane proteins. We find that TM domains evolve more slowly than do EM domains, though TM domains display increased rate heterogeneity relative to their EM counterparts. Although the majority of residues across GPCRs experience strong to weak purifying selection, many GPCRs experience positive selection at both TM and EM residues, albeit with a slight bias towards the EM. Further, a subset of GPCRs, chemosensory receptors (including olfactory and taste receptors), exhibit increased rates of evolution relative to other GPCRs, an effect which is more pronounced in their TM spans. Although it has been previously suggested that the TM’s low evolutionary rate is caused by their high percentage of buried residues, we show that their attenuated rate seems to stem from the strong biophysical constraints of the membrane itself, or by functional requirements. In spite of the strong evolutionary constraints acting on the TM spans of GPCRs, positive selection and high levels of evolutionary rate variability are common. Thus, biophysical constraints should not be presumed to preclude a protein’s ability to evolve.     

Wie Singv?gel auf Feindrufe hassen lernen

Summary The question of how territorial calls of the European pygmy owl come to elicit approach and/or mobbing responses from songbirds was investigated in areas both in and out of the owl's distribution. Great tits learned to respond to an artificial 800 Hz pure tone stimulus in both areas when the sound was presented in conjunction with both a multi-species mobbingchorus playback and a live pygmy owl placed near the nest.By substituting the live owl with a novel, harmless bird, i. e. a live Java sparrow, or by omitting either live bird as a reinforcing stimulus, learning success was significantly diminished, as measured in terms of mobbing incidence. Omission of either live bird during the conditioning process, however, led to the same proportion of Ss responding to the novel 800 Hz tone by silent approach and search behaviour, as when the owl was employed.Coal tits, strangely enough, did not learn to respond in either way to the owl's calls when a stuffed owl was substituted for a live specimen despite their vigorous mobbing during the conditioning.

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Mit Unterstützung der Deutschen Forschungsgemeinschaft, Az. Cu 4/18, Cu 4/19. Herzlich gedankt sei auch für vielfältige Hilfe den Herren Dr.Berndt (Weddell),W. Dehler (Nürnberg), Dr.König (Ludwigsburg), ForstratRaschke (Danndorf), Dr.Scherzinger (Waldhäuser), Dr.M. D. Shalter (Bochum),H. Sternberg (Braunschweig).     

Renal co-morbidity in patients with rheumatic diseases

Renal co-morbidity is common in patients with rheumatic disease based on regular assessment of serum and urine parameters of renal function. When patients present with both arthritis and renal abnormalities the following questions have to be addressed. Is kidney disease a complication of rheumatic disease or its management, or are they both manifestations of a single systemic autoimmune disease? Is rheumatic disease a complication of kidney disease and its management? How do rheumatic disease and kidney disease affect each other even when they are unrelated? The present review provides an overview of how to address these questions in daily practice.     

β1-Integrins in the cartilage matrix

Integrins are cell-surface receptors that mediate cell attachment to extracellular matrix components. The pericellular matrix in cartilage not only is a mechanical framework, but is also important for chondrocyte differentiation and stabilization of the phenotype. The interaction between chondrocytes and pericellular matrix is mediated, in part, by integrin receptors. We have previously demonstrated the presence of beta1-integrins in the cartilage matrix of organoid culture of limb buds from 12-day-old mouse embryos by immunohistological methods. In order to corroborate these findings, we have further investigated the distribution of integrins in the cartilage matrix by immunoelectron microscopy and by immunoprecipitation methods. Cartilage tissue of limb buds of 17-day-old mouse embryos was treated with collagenase and the cell-free and cellular protein-free supernatant was removed and used for immunoprecipitation experiments. Immunoprecipitation with antibodies against beta1-, alpha1-, alpha3-, and alpha5beta1-integrins and collagen type II, followed by immunoblotting with the same antibodies, demonstrated the presence of these integrins and collagen type II in the supernatant. The integrins found in the cartilage matrix could have been either secreted or shed by the cells. The question as to whether they have a function in the cartilage matrix, such as interlinking, in the matrix organization or in the stabilization of matrix components remains to be elucidated.     

Simulating cellular galectin networks by mixing galectins in vitro reveals synergistic activity

BackgroundEven though members of the family of adhesion/growth-regulatory galectins are increasingly detected to be co-expressed, they are still being routinely tested separately. The recent discovery of heterodimer formation among galectins-1, -3, and -7 in mixtures prompts further study of their functional activities in mixtures.MethodsCell agglutination, galectin binding to cells, as well as effects on cell proliferation, onset of apoptosis and migration were determined in assays using various cell types and mixtures of galectins-1, -3, and -7.ResultsEvidence for a more than additive increases of experimental parameters was consistently obtained.ConclusionTesting galectins in mixtures simulates the situation of co-expression in situ and reveals unsuspected over-additive activities. This new insight is relevant for analyzing galectin functionality in (patho)physiological conditions.     

Patterns in the phytochemistry of arctic plants

Ninety-one species of arctic tundra plants were screened for possible chemical defences against herbivory. Tannins were found in one-third of the species, whereas two-thirds of the plants contained alkaloids. Anthraquinones, cyanogenic glycosides and saponins accounted for only 6% of the positive reactions. The results were used to test the apparency hypothesis for the distribution of chemical plant defences which states that rare or unpredictable species should contain qualitative defences (toxins, such as alkaloids) while common or predictable species should contain quantitative defences (digestibility-reducing compounds, such as tannins). Abundance of plant species showed no relationship to chemical content, except that the relatively abundant shrubs more often contained tannins than the relatively rare forbs. Common graminoids (grasses and related taxa) did not contain tannins and data for the other classes of compounds did not support the apparency hypothesis. Graminoids appeared to rely on tolerance to grazing rather than chemical defences and common ericaceous plants produced both digestibility-reducing and toxic compounds.     

Growth of Streptococcus faecalus in dense culture

A fermentation system was designed and constructed to study the growth characteristics of microorganisms at low and high cell concentrations. The technique used to develop high cell densities utilized a rotating microfiltration unit to permit the removal of cell-free product from the fermenter. The fermenter volume and the filter were contained in a single unit composed of a series of concentric cylinders. Annuli contained the fermenter volume while the second outermost cylinder supported a microfiltration membrane. Feed to the system was pumped at constant rates, and the internal pressure built up to a value, which would effect the required filtration rate. The system was operated batchwise and continuously with and without filtration. The anaerobie growth characteristics of Streptococcus faccalus were determined at 37°C and pH 7.0 for batch, continuous, and continuous with filtration modes of operation. The growth characteristics were unchanged when the cell density was increased. Changes in cell yield peer model of glucose consumed were clearly illustrated during thee course of single run by operating the fermenter in the unsteady state with filtration. No consumption of glucose for developed was 40% packed cell volume, a value 45 times larger than could be grown in simple batch culture.