Paxillin and focal adhesion signalling

To facilitate a rapid response to environmental change, cells use scaffolding - or adaptor - proteins to recruit key components of their signal-transduction machinery to specific subcellular locations. Paxillin is a multi-domain adaptor found at the interface between the plasma membrane and the actin cytoskeleton. Here it provides a platform for the integration and processing of adhesion- and growth factor-related signals.     

Evidence use in decision-making on introducing innovations: a systematic scoping review with stakeholder feedback

Background

A range of evidence informs decision-making on innovation in health care, including formal research findings, local data and professional opinion. However, cultural and organisational factors often prevent the translation of evidence for innovations into practice. In addition to the characteristics of evidence, it is known that processes at the individual level influence its impact on decision-making. Less is known about the ways in which processes at the professional, organisational and local system level shape evidence use and its role in decisions to adopt innovations.

Methods

A systematic scoping review was used to review the health literature on innovations within acute and primary care and map processes at the professional, organisational and local system levels which influence how evidence informs decision-making on innovation. Stakeholder feedback on the themes identified was collected via focus groups to test and develop the findings.

Results

Following database and manual searches, 31 studies reporting primary qualitative data met the inclusion criteria: 24 were of sufficient methodological quality to be included in the thematic analysis. Evidence use in decision-making on innovation is influenced by multi-level processes (professional, organisational, local system) and interactions across these levels. Preferences for evidence vary by professional group and health service setting. Organisations can shape professional behaviour by requiring particular forms of evidence to inform decision-making. Pan-regional organisations shape innovation decision-making at lower levels. Political processes at all levels shape the selection and use of evidence in decision-making.

Conclusions

The synthesis of results from primary qualitative studies found that evidence use in decision-making on innovation is influenced by processes at multiple levels. Interactions between different levels shape evidence use in decision-making (e.g. professional groups and organisations can use local systems to validate evidence and legitimise innovations, while local systems can tailor or frame evidence to influence activity at lower levels). Organisational leaders need to consider whether the environment in which decisions are made values diverse evidence and stakeholder perspectives. Further qualitative research on decision-making practices that highlights how and why different types of evidence come to count during decisions, and tracks the political aspects of decisions about innovation, is needed.

     

Modeling interactions between voltage-gated Ca2+ channels and KCa1.1 channels

High voltage-activated (HVA) Cav channels form complexes with KCa1.1 channels, allowing reliable activation of KCa1.1 current through a nanodomain interaction. We recently found that low voltage-activated Cav3 calcium channels also create KCa1.1-Cav3 complexes. While coimmunoprecipitation studies again supported a nanodomain interaction, the sensitivity to calcium chelating agents was instead consistent with a microdomain interaction. A computational model of the KCa1.1-Cav3 complex suggested that multiple Cav3 channels were necessary to activate KCa1.1 channels, potentially causing the KCa1.1-Cav3 complex to be more susceptible to calcium chelators. Here, we expanded the model and compared it to a KCa1.1-Cav2.2 model to examine the role of Cav channel conductance and kinetics on KCa1.1 activation. As found for direct recordings, the voltage-dependent and kinetic properties of Cav3 channels were reflected in the activation of KCa1.1 current, including transient activation from lower voltages than other KCa1.1-Cav complexes. Substantial activation of KCa1.1 channels required the concerted activity of several Cav3.2 channels. Combined with the effect of EGTA, these results suggest that the Ca²⁺ domains of several KCa1.1-Cav3 complexes need to cooperate to generate sufficient [Ca²⁺]_i, despite the physical association between KCa1.1 and Cav3 channels. By comparison, Cav2.2 channels were twice as effective at activating KCa1.1 channels and a single KCa1.1-Cav2.2 complex would be self-sufficient. However, even though Cav3 channels generate small, transient currents, the regulation of KCa1.1 activity by Cav3 channels is possible if multiple complexes cooperate through microdomain interactions.     

Abundance and ecological significance of the clam Rangia cuneata (Sowerby, 1831) in the upper Barataria Estuary (Louisiana,USA)

We proposed that Rangia cuneata (Sowerby, 1831) is an important estuarine bivalve with ecological significance in three coastal lakes in Barataria Bay, Gulf of Mexico—Lake Cataouatche, Lake Salvador and Lac des Allemands. Our goals were to determine the abundance and distribution of Rangia in these lakes and to measure clearance times to elucidate its potential impacts on phytoplankton communities. The estimated average densities of R. cuneata in Lake Cataouatche, Lake Salvador, and Lac des Allemands were 63, 157, and 107 individuals m⁻², respectively, which is 30% lower than that observed in nearby Lake Pontchartrain. The size of clams in Lake Salvador was between 4 and 50 mm, while individuals in Lake Cataouatche and Lac des Allemands were mostly >20 mm. We postulate that a relatively infrequent large tropical storm transported the larvae from Lake Salvador to the other two lakes 1 year before our sampling to create this size difference. The clams were up to 99.9% of the total benthic biomass in Lake Salvador, 15.9% in Lake Cataouatche, and 40.0% in Lac des Allemands. The R. cuneata biomass values were between 16.2 and 27.6 g m⁻² and the clearance times were 1.0–1.5 days. The clearance times are among the highest previously reported for coastal bivalve communities, which were from cooler climates. The results demonstrate that Rangia can be a critical part of the ecological processes in shallow water systems of the Gulf of Mexico.     

An approach to functionally relevant clustering of the protein universe: Active site profile‐based clustering of protein structures and sequences

Protein function identification remains a significant problem. Solving this problem at the molecular functional level would allow mechanistic determinant identification—amino acids that distinguish details between functional families within a superfamily. Active site profiling was developed to identify mechanistic determinants. DASP and DASP2 were developed as tools to search sequence databases using active site profiling. Here, TuLIP (Two‐Level Iterative clustering Process) is introduced as an iterative, divisive clustering process that utilizes active site profiling to separate structurally characterized superfamily members into functionally relevant clusters. Underlying TuLIP is the observation that functionally relevant families (curated by Structure‐Function Linkage Database, SFLD) self‐identify in DASP2 searches; clusters containing multiple functional families do not. Each TuLIP iteration produces candidate clusters, each evaluated to determine if it self‐identifies using DASP2. If so, it is deemed a functionally relevant group. Divisive clustering continues until each structure is either a functionally relevant group member or a singlet. TuLIP is validated on enolase and glutathione transferase structures, superfamilies well‐curated by SFLD. Correlation is strong; small numbers of structures prevent statistically significant analysis. TuLIP‐identified enolase clusters are used in DASP2 GenBank searches to identify sequences sharing functional site features. Analysis shows a true positive rate of 96%, false negative rate of 4%, and maximum false positive rate of 4%. F‐measure and performance analysis on the enolase search results and comparison to GEMMA and SCI‐PHY demonstrate that TuLIP avoids the over‐division problem of these methods. Mechanistic determinants for enolase families are evaluated and shown to correlate well with literature results.     

The Creativity of Everyday Life in Crafting Resilient Food Systems: a Framework and Case from the Atlantic Forest Coast of Brazil

We introduce everyday creativity as an approach to understanding the role of agency in resilience thinking and as a conceptual lens through which to view the ways that people respond to globalized change. Our focus is on the use of biodiversity in crafting responses within food systems of rural and remote communities. We propose a conceptual framework to understand the flow of biological materials across five phases of a food system and how benefits map to actors. This allows us to locate disruptions that arise from globalized change and the factors that enable and constrain responses. We then present an application of the conceptual framework using a case study from the Atlantic Forest Coast of Brazil, that demonstrates that in a world characterized by globalized change our understanding of resilient food systems requires more analysis of the factors that limit everyday creativity at different phases of the food system.     

Influence of fibrillin-1 genotype on the aortic stiffness in men.

Aortic stiffness is a predictor of cardiovascular mortality. The mechanical properties of the arterial wall depend on the connective tissue framework, with variation in fibrillin-1 and collagen I genes being associated with aortic stiffness and/or pulse pressure elevation. The aim of this study was to investigate whether variation in fibrillin-1 genotype was associated with aortic stiffness in men. The mechanical properties of the abdominal aorta of 79 healthy men (range 28-81 yr) were investigated by ultrasonographic phase-locked echo tracking. Fibrillin-1 genotype, characterized by the variable tandem repeat in intron 28, and collagen type I alpha 1 genotype characterized by the 2,064 G>T polymorphism, were determined by using DNA from peripheral blood cells. Three common fibrillin-1 genotypes, 2-2, 2-3, and 2-4, were observed in 50 (64%), 10 (13%), and 11 (14%) of the men, respectively. Those of 2-3 genotype had higher pressure strain elastic modulus and aortic stiffness compared with men of 2-2 or 2-4 genotype (P = 0.005). Pulse pressure also was increased in the 2-3 genotype (P = 0.04). There was no significant association between type 1 collagen genotype and aortic stiffness in this cohort. In conclusion, the fibrillin-1 2-3 genotype in men was associated with increased aortic stiffness and pulse pressure, indicative of an increased risk for cardiovascular disease.     

Rational design of novel glycomimetics: inhibitors of concanavalin A

A virtual screening approach was used to identify new glycomimetics. The National Cancer Institute Diversity Set was docked into the carbohydrate binding site of the lectin concanavalin A (ConA). The resulting poses were analyzed and 19 molecules were tested for inhibition with an enzyme-linked lectin assay (ELLA). Eight of the 19 molecules inhibited ConA-carbohydrate binding. The two most potent inhibitors have IC(50) values that are an order of magnitude smaller than the monosaccharide methyl alpha-D-mannopyranoside.     

Genomic analysis of adaptive differentiation in Drosophila melanogaster

Drosophila melanogaster shows clinal variation along latitudinal transects on multiple continents for several phenotypes, allozyme variants, sequence variants, and chromosome inversions. Previous investigation suggests that many such clines are due to spatially varying selection rather than demographic history, but the genomic extent of such selection is unknown. To map differentiation throughout the genome, we hybridized DNA from temperate and subtropical populations to Affymetrix tiling arrays. The dense genomic sampling of variants and low level of linkage disequilibrium in D. melanogaster enabled identification of many small, differentiated regions. Many regions are differentiated in parallel in the United States and Australia, strongly supporting the idea that they are influenced by spatially varying selection. Genomic differentiation is distributed nonrandomly with respect to gene function, even in regions differentiated on only one continent, providing further evidence for the role of selection. These data provide candidate genes for phenotypes known to vary clinally and implicate interesting new processes in genotype-by-environment interactions, including chorion proteins, proteins regulating meiotic recombination and segregation, gustatory and olfactory receptors, and proteins affecting synaptic function and behavior. This portrait of differentiation provides a genomic perspective on adaptation and the maintenance of variation through spatially varying selection.     

Conifers, angiosperm trees, and lianas: growth, whole-plant water and nitrogen use efficiency, and stable isotope composition ({delta}13C and {delta}18O) of seedlings grown in a tropical environment

Seedlings of several species of gymnosperm trees, angiosperm trees, and angiosperm lianas were grown under tropical field conditions in the Republic of Panama; physiological processes controlling plant C and water fluxes were assessed across this functionally diverse range of species. Relative growth rate, r, was primarily controlled by the ratio of leaf area to plant mass, of which specific leaf area was a key component. Instantaneous photosynthesis, when expressed on a leaf-mass basis, explained 69% of variation in r (P < 0.0001, n = 94). Mean r of angiosperms was significantly higher than that of the gymnosperms; within angiosperms, mean r of lianas was higher than that of trees. Whole-plant nitrogen use efficiency was also significantly higher in angiosperm than in gymnosperm species, and was primarily controlled by the rate of photosynthesis for a given amount of leaf nitrogen. Whole-plant water use efficiency, TE(c), varied significantly among species, and was primarily controlled by c(i)/c(a), the ratio of intercellular to ambient CO(2) partial pressures during photosynthesis. Instantaneous measurements of c(i)/c(a) explained 51% of variation in TE(c) (P < 0.0001, n = 94). Whole-plant (13)C discrimination also varied significantly as a function of c(i)/c(a) (R(2) = 0.57, P < 0.0001, n = 94), and was, accordingly, a good predictor of TE(c). The (18)O enrichment of stem dry matter was primarily controlled by the predicted (18)O enrichment of evaporative sites within leaves (R(2) = 0.61, P < 0.0001, n = 94), with some residual variation explained by mean transpiration rate. Measurements of carbon and oxygen stable isotope ratios could provide a useful means of parameterizing physiological models of tropical forest trees.