Computational studies of biomembrane systems: Theoretical considerations, simulation models, and applications

This chapter summarizes several approaches combining theory, simulation and experiment that aim for a better understanding of phenomena in lipid bilayers and membrane protein systems, covering topics such as lipid rafts, membrane mediated interactions, attraction between transmembrane proteins, and aggregation in biomembranes leading to large superstructures such as the light harvesting complex of green plants. After a general overview of theoretical considerations and continuum theory of lipid membranes we introduce different options for simulations of biomembrane systems, addressing questions such as: What can be learned from generic models? When is it expedient to go beyond them? And what are the merits and challenges for systematic coarse graining and quasi-atomistic coarse grained models that ensure a certain chemical specificity

Group affective tone and team performance: A week level study in project teams

Group affective tone is an emergent state that can be shared by group members during interdependent tasks. Groups can experience positive group affective tone (PGAT), a shared feeling of, e.g., excitement, enthusiasm, or activation, as well as negative group affective tone (NGAT), a shared feeling of, e.g., distress, anxiety, and hostility. So far, previous cross-sectional research suggests that PGAT and NGAT are related to team performance outcomes. However, little is known about how the dynamic and fluctuating group affective states are related to team performance over an extended period of time. Therefore, the current study investigated the relation between PGAT, NGAT, and performance over the course of 34 software engineering projects. We hypothesized that PGAT is positively related to team performance, whereas NGAT is negatively related to team performance. Based on the punctuated equilibrium model and the feeling-as-information theory, we expected that these associations become stronger in the second half of the project. Using week-level design with 165 participants in 34 software engineering teams, we repeatedly assessed PGAT, NGAT, and team performance over 14 weeks. Data were analyzed using multilevel structural equation modeling. As expected, PGAT was positively related to team performance, whereas NGAT was negatively related to team performance – between teams over the course of the projects as well as within teams over time. More importantly, the weekly relationships were stronger in the second half of the project. Our study indicates that weekly variations in group affective tone are more relevant after projects reach a temporal midpoint. We discuss theoretical and practical implications for project teams

Klimagase und deren Minderung bei der Milchproduktion

Sources of greenhouse gas (GHG) emission of milk production were analysed on organic and conventional dairy farms from cradle to farm gate and resulted in a mean of ca. 1 kg CO2 eq kg ECM-1 independent of the farm system. When calculated according to dry matter intake of the cows, mean percentages of GHG emissions from enteric fermentation on organic or conventional farms were 31 or 42 % from the complete product related emissions from milk production from cradle to farm gate, respectively. When feed quality parameters were considered in calculation, enteric methane production increased considerably with higher fibre contents in feedstuffs. This was especially important at lower milk yields. On the 44 farms that were analysed, minimal potential GHG emissions from enteric fermentation on the herd level were 0.39 (organic farm) and 0.32 kg CO2 eq kg ECM-1 (conventional farm). This is proposed as unavoidable range for milk from intensive conventional and organic dairy production. GHG emissions from replacement animals and from feedstuff production are also part of the dairy systems. These emissions can only partly be reduced by feedstuff man-agement, manure management and technical measures, e.g. slurry cover, biogas production. Efficiency gains in all steps of the process chain by appropriate manage-ment appear to be most important for (reliably) reducing GHG emissions, e.g., by optimal feed quality and its related good milk yields and healthy and long living cows

Interdependence of Inhibitor Recognition in HIV-1 Protease

Molecular recognition is a highly interdependent process. Subsite couplings within the active site of proteases are most often revealed through conditional amino acid preferences in substrate recognition. However, the potential effect of these couplings on inhibition and thus inhibitor design is largely unexplored. The present study examines the interdependency of subsites in HIV-1 protease using a focused library of protease inhibitors, to aid in future inhibitor design. Previously a series of darunavir (DRV) analogs was designed to systematically probe the S1\u27 and S2\u27 subsites. Co-crystal structures of these analogs with HIV-1 protease provide the ideal opportunity to probe subsite interdependency. All-atom molecular dynamics simulations starting from these structures were performed and systematically analyzed in terms of atomic fluctuations, intermolecular interactions, and water structure. These analyses reveal that the S1\u27 subsite highly influences other subsites: the extension of the hydrophobic P1\u27 moiety results in 1) reduced van der Waals contacts in the P2\u27 subsite, 2) more variability in the hydrogen bond frequencies with catalytic residues and the flap water, and 3) changes in the occupancy of conserved water sites both proximal and distal to the active site. In addition, one of the monomers in this homodimeric enzyme has atomic fluctuations more highly correlated with DRV than the other monomer. These relationships intricately link the HIV-1 protease subsites and are critical to understanding molecular recognition and inhibitor binding. More broadly, the interdependency of subsite recognition within an active site requires consideration in the selection of chemical moieties in drug design; this strategy is in contrast to what is traditionally done with independent optimization of chemical moieties of an inhibitor

Optimierungsansätze zur Verbesserung von Nachhaltigkeit, Ressourceneffizienz und Tierwohl in ökologischen und konventionellen Betrieben im Netzwerk Pilotbetriebe

In a network of organic and conventional pilot farms with dairy and/or arable production in Germany (www.pilotbetriebe.de) aspects of sustainability, resource efficiency, animal health and welfare and economic aspects are analysed. This is based on on-farm assessments and on whole farm modelling. In the first interdisciplinary workshops on the project farms results were presented and scenarios were developed in a participatory approach by scientists, consultants and farmers to improve N, P and land use efficiency as well as dairy health and welfare. Typical areas of action to optimize sustainability in these aspects were identified on the farms, e.g., complete accounting of manure N (N balance), enrichment of crop rotations with clover grass and cover crops (humus balance), improving forage quality (productivity, nutritional imbalances), improvement of housing conditions and grazing access (animal health and welfare). Systematic integration and detection of interconnectedness of environmental performance of production, animal welfare, resource efficiency and productivity result in a new quality in development of farm concepts

Food for Thought : Eastern Baltic cod in distress: biological changes and challenges for stock assessment

The eastern Baltic (EB) cod (Gadus morhua) stock was depleted and overexploited for decades until the mid-2000s, when fishing mortality rapidly declined and biomass started to increase, as shown by stock assessments. These positive developments were partly assigned to effective management measures, and the EB cod was considered one of the most successful stock recoveries in recent times. In contrast to this optimistic view, the analytical stock assessment failed in 2014, leaving the present stock status unclear. Deteriorated quality of some basic input data for stock assessment in combination with changes in environmental and ecological conditions has led to an unusual situation for cod in the Baltic Sea, which poses new challenges for stock assessment and management advice. A number of adverse developments such as low nutritional condition and disappearance of larger individuals indicate that the stock is in distress. In this study, we (i) summarize the knowledge of recent changes in cod biology and ecosystem conditions, (ii) describe the subsequent challenges for stock assessment, and (iii) highlight the key questions where answers are urgently needed to understand the present stock status and provide scientifically solid support for cod management in the Baltic Sea

Trefoil factor 2 rapidly induces interleukin 33 to promote type 2 immunity during allergic asthma and hookworm infection

The molecular mechanisms that drive mucosal T helper type 2 (T[subscript H]2) responses against parasitic helminths and allergens remain unclear. In this study, we demonstrate in mice that TFF2 (trefoil factor 2), an epithelial cell–derived repair molecule, is needed for the control of lung injury caused by the hookworm parasite Nippostrongylus brasiliensis and for type 2 immunity after infection. TFF2 is also necessary for the rapid production of IL-33, a T[subscript H]2-promoting cytokine, by lung epithelia, alveolar macrophages, and inflammatory dendritic cells in infected mice. TFF2 also increases the severity of allergic lung disease caused by house dust mite antigens or IL-13. Moreover, TFF2 messenger RNA expression is significantly increased in nasal mucosal brushings during asthma exacerbations in children. These experiments extend the biological functions of TFF2 from tissue repair to the initiation and maintenance of mucosal T[subscript H]2 responses

Global proteome changes in the rat diaphragm induced by endurance exercise training

Mechanical ventilation (MV) is a life-saving intervention for many critically ill patients. Unfor- tunately, prolonged MV results in the rapid development of diaphragmatic atrophy and weakness. Importantly, endurance exercise training results in a diaphragmatic phenotype that is protected against ventilator-induced diaphragmatic atrophy and weakness. The mechanisms responsible for this exercise-induced protection against ventilator-induced dia- phragmatic atrophy remain unknown. Therefore, to investigate exercise-induced changes in diaphragm muscle proteins, we compared the diaphragmatic proteome from sedentary and exercise-trained rats. Specifically, using label-free liquid chromatography-mass spectrome- try, we performed a proteomics analysis of both soluble proteins and mitochondrial proteins isolated from diaphragm muscle. The total number of diaphragm proteins profiled in the sol- uble protein fraction and mitochondrial protein fraction were 813 and 732, respectively. Endurance exercise training significantly (P<0.05, FDR <10%) altered the abundance of 70 proteins in the soluble diaphragm proteome and 25 proteins of the mitochondrial proteome. In particular, key cytoprotective proteins that increased in relative abundance following exer- cise training included mitochondrial fission process 1 (Mtfp1; MTP18), 3-mercaptopyruvate sulfurtransferase (3MPST), microsomal glutathione S-transferase 3 (Mgst3; GST-III), and heat shock protein 70 kDa protein 1A/1B (HSP70). While these proteins are known to be cytoprotective in several cell types, the cyto-protective roles of these proteins have yet to be fully elucidated in diaphragm muscle fibers. Based upon these important findings, future experiments can now determine which of these diaphragmatic proteins are sufficient and/or required to promote exercise-induced protection against inactivity-induced muscle atrophy

Familievold og tilrettelagte samtaler i konfliktråd

-​Rapporten sammenfatter funn fra evaluering av tiltak 22 og 23 i Handlingsplan mot vold i nære relasjoner 2008-2011: Vendepunkt, som forskere ved NTNU Samfunnsforskning AS har gjennomført på oppdrag fra Justis- og beredskaps-departementet. Målet med prosjektet har i hovedsak vært å undersøke hvorvidt intensjonen med tiltakene er oppnådd, slik det fremgår av formål, mål og delmål i de to tiltakene