Desmosome Assembly and Disassembly Are Membrane Raft-Dependent

Strong intercellular adhesion is critical for tissues that experience mechanical stress, such as the skin and heart. Desmosomes provide adhesive strength to tissues by anchoring desmosomal cadherins of neighboring cells to the intermediate filament cytoskeleton. Alterations in assembly and disassembly compromise desmosome function and may contribute to human diseases, such as the autoimmune skin blistering disease pemphigus vulgaris (PV). We previously demonstrated that PV auto-antibodies directed against the desmosomal cadherin desmoglein 3 (Dsg3) cause loss of adhesion by triggering membrane raft-mediated Dsg3 endocytosis. We hypothesized that raft membrane microdomains play a broader role in desmosome homeostasis by regulating the dynamics of desmosome assembly and disassembly. In human keratinocytes, Dsg3 is raft associated as determined by biochemical and super resolution immunofluorescence microscopy methods. Cholesterol depletion, which disrupts rafts, prevented desmosome assembly and adhesion, thus functionally linking rafts to desmosome formation. Interestingly, Dsg3 did not associate with rafts in cells lacking desmosomal proteins. Additionally, PV IgG-induced desmosome disassembly occurred by redistribution of Dsg3 into raft-containing endocytic membrane domains, resulting in cholesterol-dependent loss of adhesion. These findings demonstrate that membrane rafts are required for desmosome assembly and disassembly dynamics, suggesting therapeutic potential for raft targeting agents in desmosomal diseases such as PV.     

The Southern Megalopolis: Using the Past to Predict the Future of Urban Sprawl in the Southeast U.S

The future health of ecosystems is arguably as dependent on urban sprawl as it is on human-caused climatic warming. Urban sprawl strongly impacts the urban ecosystems it creates and the natural and agro-ecosystems that it displaces and fragments. Here, we project urban sprawl changes for the next 50 years for the fast-growing Southeast U.S. Previous studies have focused on modeling population density, but the urban extent is arguably as important as population density per se in terms of its ecological and conservation impacts. We develop simulations using the SLEUTH urban growth model that complement population-driven models but focus on spatial pattern and extent. To better capture the reach of low-density suburban development, we extend the capabilities of SLEUTH by incorporating street-network information. Our simulations point to a future in which the extent of urbanization in the Southeast is projected to increase by 101% to 192%. Our results highlight areas where ecosystem fragmentation is likely, and serve as a benchmark to explore the challenging tradeoffs between ecosystem health, economic growth and cultural desires.     

Evidence That Multiple Defects in Lipid Regulation Occur before Hyperglycemia during the Prodrome of Type-2 Diabetes

Background

Blood-vessel dysfunction arises before overt hyperglycemia in type-2 diabetes (T2DM). We hypothesised that a metabolomic approach might identify metabolites/pathways perturbed in this pre-hyperglycemic phase. To test this hypothesis and for specific metabolite hypothesis generation, serum metabolic profiling was performed in young women at increased, intermediate and low risk of subsequent T2DM.

Methods

Participants were stratified by glucose tolerance during a previous index pregnancy into three risk-groups: overt gestational diabetes (GDM; n = 18); those with glucose values in the upper quartile but below GDM levels (UQ group; n = 45); and controls (n = 43, below the median glucose values). Follow-up serum samples were collected at a mean 22 months postnatally. Samples were analysed in a random order using Ultra Performance Liquid Chromatography coupled to an electrospray hybrid LTQ-Orbitrap mass spectrometer. Statistical analysis included principal component (PCA) and multivariate methods.

Findings

Significant between-group differences were observed at follow-up in waist circumference (86, 95%CI (79–91) vs 80 (76–84) cm for GDM vs controls, p<0.05), adiponectin (about 33% lower in GDM group, p = 0.004), fasting glucose, post-prandial glucose and HbA_1c, but the latter 3 all remained within the ‘normal’ range. Substantial differences in metabolite profiles were apparent between the 2 ‘at-risk’ groups and controls, particularly in concentrations of phospholipids (4 metabolites with p≤0.01), acylcarnitines (3 with p≤0.02), short- and long-chain fatty acids (3 with p< = 0.03), and diglycerides (4 with p≤0.05).

Interpretation

Defects in adipocyte function from excess energy storage as relatively hypoxic visceral and hepatic fat, and impaired mitochondrial fatty acid oxidation may initiate the observed perturbations in lipid metabolism. Together with evidence from the failure of glucose-directed treatments to improve cardiovascular outcomes, these data and those of others indicate that a new, quite different definition of type-2 diabetes is required. This definition would incorporate disturbed lipid metabolism prior to hyperglycemia.     

Camera Traps Can Be Heard and Seen by Animals

Camera traps are electrical instruments that emit sounds and light. In recent decades they have become a tool of choice in wildlife research and monitoring. The variability between camera trap models and the methods used are considerable, and little is known about how animals respond to camera trap emissions. It has been reported that some animals show a response to camera traps, and in research this is often undesirable so it is important to understand why the animals are disturbed. We conducted laboratory based investigations to test the audio and infrared optical outputs of 12 camera trap models. Camera traps were measured for audio outputs in an anechoic chamber; we also measured ultrasonic (n = 5) and infrared illumination outputs (n = 7) of a subset of the camera trap models. We then compared the perceptive hearing range (n = 21) and assessed the vision ranges (n = 3) of mammals species (where data existed) to determine if animals can see and hear camera traps. We report that camera traps produce sounds that are well within the perceptive range of most mammals’ hearing and produce illumination that can be seen by many species.     

Fashioning the Immunological Self: The Biological Individuality of F. Macfarlane Burnet

During the 1940s and 1950s, the Australian microbiologist F. Macfarlane Burnet sought a biologically plausible explanation of antibody production. In this essay, we seek to recover the conceptual pathways that Burnet followed in his immunological theorizing. In so doing, we emphasize the influence of speculations on individuality, especially those of philosopher Alfred North Whitehead; the impact of cybernetics and information theory; and the contributions of clinical research into autoimmune disease that took place in Melbourne. We point to the influence of local experimental and intellectual currents on Burnet’s work. Accordingly, this essay describes an arc distinct from most other tracings of Burnet’s conceptual development, which focus on his early bacteriophage research, his fascination with the work of Julian Huxley and other biologists in the 1920s, and his interest in North Atlantic experimental investigations in the life sciences. No doubt these too were potent influences, but they seem insufficient to explain, for example, Burnet’s sudden enthusiasm in the 1940s for immunological definitions of self and not-self. We want to demonstrate here how Burnet’s deep involvement in philosophical biology – along with attention to local clinical research – provided him with additional theoretic tools and conceptual equipment, with which to explain immune function.     

Inhibition of Personally-Relevant Angry Faces Moderates the Effect of Empathy on Interpersonal Functioning

While empathy is typically assumed to promote effective social interactions, it can sometimes be detrimental when it is unrestrained and overgeneralized. The present study explored whether cognitive inhibition would moderate the effect of empathy on social functioning. Eighty healthy young adults underwent two assessments six months apart. Participants’ ability to suppress interference from distracting emotional stimuli was assessed using a Negative Affective Priming Task that included both generic and personally-relevant (i.e., participants’ intimate partners) facial expressions of emotion. The UCLA Life Stress Interview and Empathy Quotient were administered to measure interpersonal functioning and empathy respectively. Multilevel modeling demonstrated that higher empathy was associated with worse concurrent interpersonal outcomes for individuals who showed weak inhibition of the personally-relevant depictions of anger. The effect of empathy on social functioning might be dependent on individuals’ ability to suppress interference from meaningful emotional distractors in their environment.