gardel

BACKGROUND: In pharmacoresistant epilepsy, exploration with depth electrodes can be needed to precisely define the epileptogenic zone. Accurate location of these electrodes is thus essential for the interpretation of Stereotaxic EEG (SEEG) signals. As SEEG analysis increasingly relies on signal processing, it is crucial to make a link between these results and patient's anatomy. Our aims were thus to develop a suite of software tools, called "EpiTools", able to i) precisely and automatically localize the position of each SEEG contact and ii) display the results of signal analysis in each patient's anatomy...

The progression of age-related sarcopenia can be accelerated by impaired recovery of muscle mass following periods of disuse due to illness or immobilization. However, the mechanisms underlying poor recovery of aged muscle following disuse remain to be delineated. Recent evidence suggests that mitochondrial energetics play an important role in regulation of muscle mass. Here, we report that 22-24 month old mice with low muscle mass and low glucose clearance rate also display poor early recovery of muscle mass following 10 days of hind limb unloading...

The epidermis is a multi-layered epithelium that serves as a barrier against water loss and environmental insults. Its morphogenesis occurs through a tightly regulated program of biochemical and architectural changes during which basal cells commit to differentiate and move towards the skin's surface. Here, we reveal an unexpected role for the vertebrate cadherin desmoglein 1 (Dsg1) in remodeling the actin cytoskeleton to promote the transit of basal cells into the suprabasal layer through a process of delamination, one mechanism of epidermal stratification...

The ability of adherent cells to sense changes in the mechanical properties of their extracellular environments is critical to numerous aspects of their physiology. It has been well documented that cell attachment and spreading are sensitive to substrate stiffness. Here, we demonstrate that this behavior is actually biphasic, with a transition that occurs around a Young's modulus of ∼7 kPa. Furthermore, we demonstrate that, contrary to established assumptions, this property is independent of myosin II activity...

Understanding the response of complex materials to external force is central to fields ranging from materials science to biology. Here, we describe a novel type of mechanical adaptation in cross-linked networks of F-actin, a ubiquitous protein found in eukaryotic cells. We show that shear stress changes the network's nonlinear mechanical response even long after that stress is removed. The duration, magnitude and direction of forcing history all change this mechanical response. While the mechanical hysteresis is long-lived, it can be simply erased by force application in the opposite direction...

Developing tissues change shape and tumors initiate spreading through collective cell motility. Conserved mechanisms by which tissues initiate motility into their surroundings are not known. We investigated cytoskeletal regulators during collective invasion by mouse tumor organoids and epithelial Madin-Darby canine kidney (MDCK) acini undergoing branching morphogenesis in collagen. Use of the broad-spectrum formin inhibitor SMIFH2 prevented the formation of migrating cell fronts in both cell types. Focusing on the role of the formin Dia1 in branching morphogenesis, we found that its depletion in MDCK cells does not alter planar cell motility either within the acinus or in two-dimensional scattering assays...

The first ever 'Cellular Dynamics' meeting on the membrane-cytoskeleton interface took place in Southbridge, MA on May 21-24, 2017 and was co-organized by Michael Way, Elizabeth Chen, Margaret Gardel and Jennifer Lippincott-Schwarz. Investigators from around the world studying a broad range of related topics shared their insights into the function and regulation of the cytoskeleton and membrane compartments. This provided great opportunities to learn about key questions in various cellular processes, from the basic organization and operation of the cell to higher-order interactions in adhesion, migration, metastasis, division and immune cell interactions in different model organisms...

Achieving control and tunability of lyotropic materials has been a long-standing goal of liquid crystal research. Here we show that the elasticity of a liquid crystal system consisting of a dense suspension of semiflexible biopolymers can be manipulated over a relatively wide range of elastic moduli. Specifically, thin films of actin filaments are assembled at an oil-water interface. At sufficiently high concentrations, one observes the formation of a nematic phase riddled with [Formula: see text] topological defects, characteristic of a two-dimensional nematic system...

OBJECTIVE: Nicotinamide phosphoribosyl transferase (NAMPT) is the rate-limiting enzyme in the salvage pathway that produces nicotinamide adenine dinucleotide (NAD+ ), an essential co-substrate regulating a myriad of signaling pathways. We produced a mouse that overexpressed NAMPT in skeletal muscle (NamptTg) and hypothesized that NamptTg mice would have increased oxidative capacity, endurance performance, and mitochondrial gene expression, and would be rescued from metabolic abnormalities that developed with high fat diet (HFD) feeding...

Molecular motors embedded within collections of actin and microtubule filaments underlie the dynamics of cytoskeletal assemblies. Understanding the physics of such motor-filament materials is critical to developing a physical model of the cytoskeleton and designing biomimetic active materials. Here, we demonstrate through experiments and simulations that the rigidity and connectivity of filaments in active biopolymer networks regulates the anisotropy and the length scale of the underlying deformations, yielding materials with variable contractility...

OBJECTIVES: This study sought to derive and validate plasma metabolite associations with survival in heart failure (HF) patients. BACKGROUND: Profiling of plasma metabolites to predict the course of HF appears promising, but validation and incremental value of these profiles are less established. METHODS: Patients (n = 1,032) who met Framingham HF criteria with a history of reduced ejection fraction were randomly divided into derivation and validation cohorts (n = 516 each)...

Upon recognition of peptide displayed on MHC molecules, Th1 and Th2 cells form distinct immunological synapse structures. Th1 cells have a bull's eye synapse structure with TCR/ MHC-peptide interactions occurring central to a ring of adhesion molecules, while Th2 cells have a multifocal synapse with small clusters of TCR/MHC interactions throughout the area of T cell/antigen-presenting cell interaction. In this study, we investigated whether this structural difference in the immunological synapse affects delivery of T cell help...

Heartwater, or cowdriosis, is a tick-borne disease of domestic and wild ruminants that is endemic in the Caribbean and sub-Saharan Africa. The disease is caused by an intracellular pathogen, Ehrlichia ruminantium and may be fatal within days of the onset of clinical signs with mortality rates of up to 90% in susceptible hosts. Due to the presence of competent tick vectors in North America, there is substantial risk of introduction of heartwater with potentially devastating consequences to the domestic livestock industry...

Here, we present an indoor positioning system (IPS) for detecting mobile agents based on a single Position Sensitive Device sensor (PSD) sited in the environment and InfraRed Emitter Diode (IRED) located on mobile agents. The main goal of the work is to develop an alternative IPS to other sensing technologies, cheaper, easier to install and with a low computational load to obtain a high rate of measurements per second. The proposed IPS has the capacity to accurately determine 3D position from the angle of arrival (AoA) of the signal received at the PSD sensor...

Here, we propose a model to determine the effect of multipath in indoor environments when the shape and characteristics of the environment are known. The main paper goal is to model the multipath signal formation to solve, as much as possible, the negative effects in light communications, as well as the indoor positioning errors due to this phenomenon when using optical signals. The methodology followed was: analyze the multipath phenomenon, establish a theoretical approach and propose different models to characterize the behavior of the channel, emitter and receiver...

This paper describes the theoretical and practical foundations for remote control of a mobile robot for nonlinear trajectory tracking using an external localisation sensor. It constitutes a classical networked control system, whereby event-based techniques for both control and state estimation contribute to efficient use of communications and reduce sensor activity. Measurement requests are dictated by an event-based state estimator by setting an upper bound to the estimation error covariance matrix. The rest of the time, state prediction is carried out with the Unscented transformation...

No abstract text is available yet for this article.

Antiretroviral (ARV) therapy, comprising a backbone of two nucleos(t)ide reverse transcriptase inhibitors (NRTIs) plus another ARV, is the recognized standard of care (SOC), which has helped extend life expectancy in people living with HIV. In a quest to reduce lifelong drug exposure and minimize or avoid the toxicity of NRTIs, "NRTI-reducing" regimens have been investigated. This descriptive review assessing the results of NRTI-reducing strategies from the largest randomized trials focuses on virological efficacy, resistance, regimen safety (in terms of bone mineral density, renal function, lipids and central nervous system function) and simplicity...

Neuropathic pain caused by nerve damage is a common and severe class of chronic pain. Disease-modifying clinical therapies are needed as current treatments typically provide only symptomatic relief; show varying clinical efficacy; and most have significant adverse effects. One approach is targeting either neurotrophic factors or their receptors that normalize sensory neuron function and stimulate regeneration after nerve damage. Two candidate targets are glial cell line-derived neurotrophic factor (GDNF) and artemin (ARTN), as these GDNF family ligands (GFLs) show efficacy in animal models of neuropathic pain (Boucher et al...

Cytoskeletal mechanics regulates cell morphodynamics and many physiological processes. While contractility is known to be largely RhoA-dependent, the process by which localized biochemical signals are translated into cell-level responses is poorly understood. Here we combine optogenetic control of RhoA, live-cell imaging and traction force microscopy to investigate the dynamics of actomyosin-based force generation. Local activation of RhoA not only stimulates local recruitment of actin and myosin but also increased traction forces that rapidly propagate across the cell via stress fibres and drive increased actin flow...