Morphology and Nanomechanics of Sensory Neurons Growth Cones following Peripheral Nerve Injury

A prior peripheral nerve injury in vivo, promotes a rapid elongated mode of sensory neurons neurite regrowth in vitro. This in vitro model of conditioned axotomy allows analysis of the cellular and molecular mechanisms leading to an improved neurite re-growth. Our differential interference contrast microscopy and immunocytochemistry results show that conditioned axotomy, induced by sciatic nerve injury, did not increase somatic size of adult lumbar sensory neurons from mice dorsal root ganglia sensory neurons but promoted the appearance of larger neurites and growth cones. Using atomic force microscopy on live neurons, we investigated whether membrane mechanical properties of growth cones of axotomized neurons were modified following sciatic nerve injury. Our data revealed that neurons having a regenerative growth were characterized by softer growth cones, compared to control neurons. The increase of the growth cone membrane elasticity suggests a modification in the ratio and the inner framework of the main structural proteins

Online Training of an Opto-Electronic Reservoir Computer

Reservoir Computing is a bio-inspired computing paradigm for processing time dependent signals. Its analog implementations equal and sometimes outperform other digital algorithms on a series of benchmark tasks. Their performance can be increased by switching from offline to online training method. Here we present the first online trained opto-electronic reservoir computer. The system is tested on a channel equalisation task and the algorithm is executed by an FPGA chip. We report performances close to previous implementations and demonstrate the benefits of online training on a non-stationary task that could not be easily solved using offline methods.info:eu-repo/semantics/publishe

Cortical Disinhibition, Attractor Dynamics, and Belief Updating in Schizophrenia

Genetic and pharmacological evidence implicates N-methyl-D-aspartate receptor (NMDAR) dysfunction in the pathophysiology of schizophrenia. Dysfunction of this key receptor – if localised to inhibitory interneurons – could cause a net disinhibition of cortex and increase in ‘noise’. These effects can be computationally modelled in a variety of ways: by reducing the precision in Bayesian models of behaviour, by estimating neuronal excitability changes in schizophrenia from evoked responses, or – as described in detail here – by modelling abnormal belief updating in a probabilistic inference task. Features of belief updating in schizophrenia include greater updating to unexpected evidence, lower updating to consistent evidence, and greater stochasticity in responding. All of these features can be explained by a loss of stability of ‘attractor states’ in cortex and the representations they encode. Indeed, a hierarchical Bayesian model of belief updating indicates that subjects with schizophrenia have a consistently increased ‘belief instability’ parameter. This instability could be a direct result of cortical disinhibition: this hypothesis should be explored in future studies

Ligand-Receptor Interactions

The formation and dissociation of specific noncovalent interactions between a variety of macromolecules play a crucial role in the function of biological systems. During the last few years, three main lines of research led to a dramatic improvement of our understanding of these important phenomena. First, combination of genetic engineering and X ray cristallography made available a simultaneous knowledg of the precise structure and affinity of series or related ligand-receptor systems differing by a few well-defined atoms. Second, improvement of computer power and simulation techniques allowed extended exploration of the interaction of realistic macromolecules. Third, simultaneous development of a variety of techniques based on atomic force microscopy, hydrodynamic flow, biomembrane probes, optical tweezers, magnetic fields or flexible transducers yielded direct experimental information of the behavior of single ligand receptor bonds. At the same time, investigation of well defined cellular models raised the interest of biologists to the kinetic and mechanical properties of cell membrane receptors. The aim of this review is to give a description of these advances that benefitted from a largely multidisciplinar approach

The biomechanical role of periodontal ligament in bonded and replanted vertically fractured teeth under cyclic biting forces

After teeth are replanted, there are two possible healing responses: periodontal ligament healing or ankylosis with subsequent replacement resorption. The purpose of this study was to compare the fatigue resistance of vertically fractured teeth after bonding the fragments under conditions simulating both healing modes. Thirty-two human premolars were vertically fractured and the fragments were bonded together with Super-Bond C&B. They were then randomly distributed into four groups (BP, CP, CA, BA). The BP and CP groups were used to investigate the periodontal ligament healing mode whilst the BA and CA groups simulated ankylosis. All teeth had root canal treatment performed. Metal crowns were constructed for the CP and CA groups. The BP and BA groups only had composite resin restorations in the access cavities. All specimens were subjected to a 260 N load at 4 Hz until failure of the bond or until 2×106 cycles had been reached if no fracture occurred. Cracks were detected by stereomicroscope imaging and also assessed via dye penetration tests. Finally, interfaces of the resin luting agent were examined by scanning electron microscope. The results confirmed that the fatigue resistance was higher in the groups with simulated periodontal ligament healing. Periodontal reattachment showed important biomechanical role in bonded and replanted vertically fractured teeth

Investigating Unique Environmental Contributions to the Neural Representation of Written Words: A Monozygotic Twin Study

The visual word form area (VWFA) is a region of left inferior occipitotemporal cortex that is critically involved in visual word recognition. Previous studies have investigated whether and how experience shapes the functional characteristics of VWFA by comparing neural response magnitude in response to words and nonwords. Conflicting results have been obtained, however, perhaps because response magnitude can be influenced by other factors such as attention. In this study, we measured neural activity in monozygotic twins, using functional magnetic resonance imaging. This allowed us to quantify differences in unique environmental contributions to neural activation evoked by words, pseudowords, consonant strings, and false fonts in the VWFA and striate cortex. The results demonstrate significantly greater effects of unique environment in the word and pseudoword conditions compared to the consonant string and false font conditions both in VWFA and in left striate cortex. These findings provide direct evidence for environmental contributions to the neural architecture for reading, and suggest that learning phonology and/or orthographic patterns plays the biggest role in shaping that architecture

Structure–property relation and relevance of beam theories for microtubules: a coupled molecular and continuum mechanics study

Quasi-one-dimensional microtubules (MTs) in cells enjoy high axial rigidity but large transverse flexibility due to the inter-protofilament (PF) sliding. This study aims to explore the structure–property relation for MTs and examine the relevance of the beam theories to their unique features. A molecular structural mechanics (MSM) model was used to identify the origin of the inter-PF sliding and its role in bending and vibration of MTs. The beam models were then fitted to the MSM to reveal how they cope with the distinct mechanical responses induced by the inter-PF sliding. Clear evidence showed that the inter-PF sliding is due to the soft inter-PF bonds and leads to the length-dependent bending stiffness. The Euler beam theory is found to adequately describe MT deformation when the inter-PF sliding is largely prohibited. Nevertheless, neither shear deformation nor the nonlocal effect considered in the ‘more accurate’ beam theories can fully capture the effect of the inter-PF sliding. This reflects the distinct deformation mechanisms between an MT and its equivalent continuous body

Nutrient regulation of the islet epigenome controls adaptive insulin secretion

Adaptation of the islet β-cell insulin secretory response to changing insulin demand is critical for blood glucose homeostasis, yet the mechanisms underlying this adaptation are unknown. Here, we have shown that nutrient-stimulated histone acetylation plays a key role in adapting insulin secretion through regulation of genes involved in β-cell nutrient sensing and metabolism. Nutrient regulation of the epigenome occurred at sites occupied by the chromatin-modifying enzyme Lysine-specific demethylase 1 (Lsd1) in islets. β-cell-specific deletion of Lsd1 led to insulin hypersecretion, aberrant expression of nutrient response genes, and histone hyperacetylation. Islets from mice adapted to chronically increased insulin demand exhibited shared epigenetic and transcriptional changes. Moreover, we found that genetic variants associated with type 2 diabetes were enriched at LSD1-bound sites in human islets, suggesting that interpretation of nutrient signals is genetically determined and clinically relevant. Overall, these studies revealed that adaptive insulin secretion involves Lsd1-mediated coupling of nutrient state to regulation of the islet epigenome