Structural insights into the basis and evolution of interactions in multi-subunit protein assemblies. tryptophan synthase and titin FNIII-repeats

Cellular processes benefit from evolutionary shaping when optimized protein-protein interactions result in enhanced functionality. In fact, most cellular proteins are tightly embedded into biological networks that function following a modularity principle. Modularity, whether based on components as parts of stable protein complexes or as dynamic units that interact only transiently (as in signalling and metabolic cascades), facilitates the combinatorial generation of complexity in protein networks through the re-wiring of modules in addition to the diversification of individual proteins – thereby increasing the “evolvability” of the system. The mechanisms that drive the emergence and evolution of molecular recognition in protein networks remain unclear. It is difficult to justify such evolution on the basis of organismic advantage, since the latter might only be noticeable once full pathways and cascades have evolved. It is then likely that the evolution of protein-protein interactions is in the first instance driven by a molecular principle of local advantage to the protein system itself - for example, molecular stability. Unfortunately, it is difficult to gain insights into the evolution of protein-protein interactions since the pathways of evolutionary shaping normally let intermediates of evolution disappear. Subsequently, conclusions are more usually drawn from the comparison of proteins between different species and by mutagenesis probing. In the current study, we aim at gaining an insight into the evolutionary shaping of proteins surfaces for hetero-complex formation by studying two systems at an early stage of development: Tryptophan Synthase B2b (TrpB2b) from S. solfataricus and the modular interfaces of the poly-FNIII tandems in the muscle filament titin. In the case of TrpB2b, the evolution of inter-subunit communication is addressed in addition. Both structures have been elucidated using X-ray crystallography and a comparative analysis of their surfaces has been carried out. The architectural elements subjected to evolutionary pressure have been identified and conclusions on their relation to function and evolution have been drawn

Thermochemistry and photochemistry of spiroketals derived from indan-2-one: stepwise processes versus coarctate fragmentations

Coarctate reactions are defined as reactions that include atoms at which two bonds are made and two bonds are broken simultaneously. In the pursuit of the discovery of new coarctate reactions we investigate the fragmentation reactions of cyclic ketals. Three ketals with different ring sizes derived from indan-2-one were decomposed by photolysis and pyrolysis. Particularly clean is the photolysis of the indan-2-one ketal 1, which gives o-quinodimethane, carbon dioxide and ethylene. The mechanism formally corresponds to a photochemically allowed coarctate fragmentation. Pyrolysis of the five-ring ketal yields a number of products. This is in agreement with the fact that coarctate fragmentation observed upon irradiation would be thermochemically forbidden, although this exclusion principle does not hold for chelotropic reactions. In contrast, fragmentation of the seven-ring ketal 3 is thermochemically allowed and photochemically forbidden. Upon pyrolysis of 3 several products were isolated that could be explained by a coarctate fragmentation. However, the reaction is less clean and stepwise mechanisms may compete

Bildungspastoral: zur notwendigen Kirchlichkeit katholischer Erwachsenenbildung

Die katholische Erwachsenenbildung wird in diesem Beitrag als "Bildungspastoral" beschrieben, als wichtiger kirchlicher Vollzug in der modernen Gesellschaft

„Opfern und geopfert werden, ist des Priesters Los auf Erden.“ Aktuelle Verflüssigungsprozesse des katholischen Amts-Priestertums

Nach einer Skizze der Entwicklungen, die das statische Gehorsamsmodell der neuzeitlichenkatholischen Kirche auflösten, wird als die entscheidende Frage für das zukünftige Laien-Priester-Verhältnis in einer „liquid church“ im Kontext einer „liquid modernity“ das Problemrekonstruiert, wie das katholische Weihepriestertum seine Aufgabe im Volk Gottes jenseitsseiner bisherigen, massiv macht- und sanktionsgestützten Form erfüllen kann. Ob die katholischeKirche darauf eine Antwort findet, scheint offen.After describing the changes that brought with them a dissolution of the former static „modelof obedience“, which has characterized the Catholic Church in modern times, the articleanalyses the relationship between laity and clergy in a „liquid church“ within the context of a„liquid modernity“. The crucial question in this relationship is how the Catholic clergy will beable to fulfil their function for and within the people of God without recourse to hitherto accustomedstructures of power and sanctions. It remains uncertain whether the Catholic Churchwill find an answer to this challenge

Influence of Soil Type on the Effects of Elevated Atmospheric CO2 and N Deposition on the Water Balance and Growth of a Young Spruce and Beech Forest

Sixteen open-top chambers, each equipped with two non-weighablegravity-drained lysimeter compartments, were used to investigate the impacts of elevated atmospheric carbon dioxide (CO2) concentration and nitrogen (N) deposition on the water relations and growth of young model forest ecosystems on two different types of soils. The same vegetation of a mixed spruce and beech overstorey and various herbs in the understorey was planted in all treatments on both soils. The soils were repacked on top of a drainage layer. Four combinations of treatments were applied in four replicates each: ambient (370 cm3 m-3) CO2 + low (7 kg N ha-1 a-1) N deposition, ambient CO2 + high(70 kg N ha-1 a-1) N deposition, elevated (590 cm3 m-3) CO2 + low N deposition, and elevated CO2 + high N deposition. After canopy closure, treatment effects on evapotranspiration and growth during the third year of study were very different for the two soils.On the acidic sandy loam, elevated CO2 enhanced growth(leaf biomass +21%, roots +27%) at reduced evapotranspiration (-9%). High N deposition increased aboveground growth even more strongly (+50%), but also increased evapotranspiration (+16%). Together, elevated CO2 and high N had a more than additive fertilizer effect on growth, while their effects on evapotranspirationcompensated. On the calcareous loamy sand, elevated CO2not only tended to enhance growth (leaf biomass +17%, roots +20%), but also increased evapotranspiration (+5%).On this soil, aboveground growth was stimulated by N only incombination with elevated CO2, but less than on the acidic soil, while evapotranspiration (-6.5%) and root growth into the subsoil (-54%) were decreased by increased N deposition at both CO2 concentrations, in contrast to the N treatments on the acidic sandy loam. The influence of the soil on the observed ecosystem responses canbe interpreted in terms of the concept of optimal resource allocatio

Unsafe Sex and Increased Incidence of Hepatitis C Virus Infection among HIV-Infected Men Who Have Sex with Men: The Swiss HIV Cohort Study

Background. Data on the incidence of hepatitis C virus (HCV) infection among human immunodeficiency virus (HIV)-infected persons are sparse. It is controversial whether and how frequently HCV is transmitted by unprotected sexual intercourse. Methods. We assessed the HCV seroprevalence and incidence of HCV infection in the Swiss HIV Cohort Study between 1988 and 2004. We investigated the association of HCV seroconversion with mode of HIV acquisition, sex, injection drug use (IDU), and constancy of condom use. Data on condom use or unsafe sexual behavior were prospectively collected between 2000 and 2004. Results. The overall seroprevalence of HCV infection was 33% among a total of 7899 eligible participants and 90% among persons reporting IDU. We observed 104 HCV seroconversions among 3327 participants during a total follow-up time of 16,305 person-years, corresponding to an incidence of 0.64 cases per 100 person-years. The incidence among participants with a history of IDU was 7.4 cases per 100 person-years, compared with 0.23 cases per 100 person-years in patients without such a history (P < .001). In men who had sex with men (MSM) without a history of IDU who reported unsafe sex, the incidence was 0.7 cases per 100 person-years, compared with 0.2 cases per 100 person-years in those not reporting unsafe sex (P = .02), corresponding to an incidence rate ratio of 3.5 (95% confidence interval, 1.2-10.0). The hazard of acquiring HCV infection was elevated among younger participants who were MSM. Conclusions. HCV infection incidence in the Swiss HIV Cohort Study was mainly associated with IDU. In HIV-infected MSM, HCV infection was associated with unsafe se

Perivascular Tumor-Infiltrating Leukocyte Scoring for Prognosis of Resected Hepatocellular Carcinoma Patients

Liver resection is a curative treatment for hepatocellular carcinoma (HCC). Tumor-infiltrating leukocytes (TILs) are important players in predicting HCC recurrence. However, the invasive margin could not be confirmed as relevant for HCC. The migration of immune cells into HCC may originate from intratumoral vessels. No previous study has examined perivascular (PV) infiltration. Tumors from 60 patients were examined. Immunohistochemistry was performed against CD3, CD8, CD20, and CD66b. TILs were counted in the PV regions using an algorithm for quantification of the tumor immune stroma (QTiS). The results were correlated with overall (OS) and disease-free survival (DFS), clinical parameters, and laboratory values. PV infiltration of TILs was predominant in resected HCC. Higher PV infiltration of CD3(+) (p = 0.016) and CD8(+) (p = 0.028) independently predicted better OS and DFS, respectively. CD20(+) showed a trend towards better DFS (p = 0.076). Scoring of CD3(+), CD8(+), and CD20(+) independently predicted OS and DFS (p < 0.01). The amount of perivascular-infiltrating CD3(+) cells is an independent predictor of better OS, and CD8(+) cells independently predict prolonged DFS. Our novel perivascular infiltration scoring (PVIS) can independently predict both DFS and OS in resected HCC patients