Complementary Effects of Two Growth Factors in Multifunctionalized Silk Nanofibers for Nerve Reconstruction

With the aim of forming bioactive guides for peripheral nerve regeneration, silk fibroin was electrospun to obtain aligned nanofibers. These fibers were functionalized by incorporating Nerve Growth Factor (NGF) and Ciliary NeuroTrophic Factor (CNTF) during electrospinning. PC12 cells grown on the fibers confirmed the bioavailability and bioactivity of the NGF, which was not significantly released from the fibers. Primary neurons from rat dorsal root ganglia (DRGs) were grown on the nanofibers and anchored to the fibers and grew in a directional fashion based on the fiber orientation, and as confirmed by growth cone morphology. These biofunctionalized nanofibers led to a 3-fold increase in neurite length at their contact, which was likely due to the NGF. Glial cell growth, alignment and migration were stimulated by the CNTF in the functionalized nanofibers. Organotypic culture of rat fetal DRGs confirmed the complementary effect of both growth factors in multifunctionalized nanofibers, which allowed glial cell migration, alignment and parallel axonal growth in structures resembling the ‘bands of Bungner’ found in situ. Graftable multi-channel conduits based on biofunctionalized aligned silk nanofibers were developed as an organized 3D scaffold. Our bioactive silk tubes thus represent new options for a biological and biocompatible nerve guidance conduit.     

Integrated Proteomics Identified Up-Regulated Focal Adhesion-Mediated Proteins in Human Squamous Cell Carcinoma in an Orthotopic Murine Model

Understanding the molecular mechanisms of oral carcinogenesis will yield important advances in diagnostics, prognostics, effective treatment, and outcome of oral cancer. Hence, in this study we have investigated the proteomic and peptidomic profiles by combining an orthotopic murine model of oral squamous cell carcinoma (OSCC), mass spectrometry-based proteomics and biological network analysis. Our results indicated the up-regulation of proteins involved in actin cytoskeleton organization and cell-cell junction assembly events and their expression was validated in human OSCC tissues. In addition, the functional relevance of talin-1 in OSCC adhesion, migration and invasion was demonstrated. Taken together, this study identified specific processes deregulated in oral cancer and provided novel refined OSCC-targeting molecules.     

Insulin Resistance is Associated with MCP1-Mediated Macrophage Accumulation in Skeletal Muscle in Mice and Humans

Inflammation is now recognized as a major factor contributing to type 2 diabetes (T2D). However, while the mechanisms and consequences associated with white adipose tissue inflammation are well described, very little is known concerning the situation in skeletal muscle. The aim of this study was to investigate, in vitro and in vivo, how skeletal muscle inflammation develops and how in turn it modulates local and systemic insulin sensitivity in different mice models of T2D and in humans, focusing on the role of the chemokine MCP1. Here, we found that skeletal muscle inflammation and macrophage markers are increased and associated with insulin resistance in mice models and humans. In addition, we demonstrated that intra-muscular TNFα expression is exclusively restricted to the population of intramuscular leukocytes and that the chemokine MCP1 was associated with skeletal muscle inflammatory markers in these models. Furthermore, we demonstrated that exposure of C2C12 myotubes to palmitate elevated the production of the chemokine MCP1 and that the muscle-specific overexpression of MCP1 in transgenic mice induced the local recruitment of macrophages and altered local insulin sensitivity. Overall our study demonstrates that skeletal muscle inflammation is clearly increased in the context of T2D in each one of the models we investigated, which is likely consecutive to the lipotoxic environment generated by peripheral insulin resistance, further increasing MCP1 expression in muscle. Consequently, our results suggest that MCP1-mediated skeletal muscle macrophages recruitment plays a role in the etiology of T2D.     

Underlying impacts of invasive cats on islands: not only a question of predation

The domestic cat has been introduced on most islands worldwide, where it has established feral populations and is currently known to be one of the worst invasive mammalian predators. Predation is the strongest deleterious effect of cats on wildlife, inducing a direct negative impact on population size and dynamics, breeding success and changes in species assemblages. Direct predation is not the only damaging impact on native wildlife, since cats can be responsible for other poorly-documented underlying ecological impacts, like competition, hybridization, disease transmission, ecological process alteration, and behavioral change. Here, we pinpoint relevant examples of these ecological impacts, by searching for accurate data from published literature. We used electronic databases covering most of the world islands where the effects of cats were documented. Knowledge of these impacts can be of great importance to preserve insular ecosystem functions and persistence of endangered native species. We emphasize that direct predation processes should not be the only factor considered in the management of invasive cats on islands.     

Collision avoidance during group evasive manoeuvres: a comparison of real versus simulated swarms with manipulated vision and surface wave detectors

Coordinated group motion has been studied extensively both in real systems (flocks, swarms and schools) and in simulations (self-propelled particle (SPP) models using attraction and repulsion rules). Rarely are attraction and repulsion rules manipulated, and the resulting emergent behaviours of real and simulation systems are compared. We compare swarms of sensory-deprived whirligig beetles with matching simulation models. Whirligigs live at the water''s surface and coordinate their grouping using their eyes and antennae. We filmed groups of beetles in which antennae or eyes had been unilaterally obstructed and measured individual and group behaviours. We then developed and compared eight SPP simulation models. Eye-less beetles formed larger diameter resting groups than antenna-less or control groups. Antenna-less groups collided more often with each other during evasive group movements than did eye-less or control groups. Simulations of antenna-less individuals produced no difference from a control (or a slight decrease) in group diameter. Simulations of eye-less individuals produced an increase in group diameter. Our study is important in (i) differentiating between group attraction and repulsion rules, (ii) directly comparing emergent properties of real and simulated groups, and (iii) exploring a new sensory modality (surface wave detection) to coordinate group movement.     

FAK Acts as a Suppressor of RTK-MAP Kinase Signalling in Drosophila melanogaster Epithelia and Human Cancer Cells

Receptor Tyrosine Kinases (RTKs) and Focal Adhesion Kinase (FAK) regulate multiple signalling pathways, including mitogen-activated protein (MAP) kinase pathway. FAK interacts with several RTKs but little is known about how FAK regulates their downstream signalling. Here we investigated how FAK regulates signalling resulting from the overexpression of the RTKs RET and EGFR. FAK suppressed RTKs signalling in Drosophila melanogaster epithelia by impairing MAPK pathway. This regulation was also observed in MDA-MB-231 human breast cancer cells, suggesting it is a conserved phenomenon in humans. Mechanistically, FAK reduced receptor recycling into the plasma membrane, which resulted in lower MAPK activation. Conversely, increasing the membrane pool of the receptor increased MAPK pathway signalling. FAK is widely considered as a therapeutic target in cancer biology; however, it also has tumour suppressor properties in some contexts. Therefore, the FAK-mediated negative regulation of RTK/MAPK signalling described here may have potential implications in the designing of therapy strategies for RTK-driven tumours.