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Timing of ARDS Solution (TARU): Any Realistic Medical Assessment involving ARDS Quality from the ICU.
Perceptual decisions are informed by the accumulation of sensory evidence over time, but the form of this fundamental temporal computation is not fully understood. Characterizations of the temporal integration of sensory stimuli in behavior and neural activity are usually conceived with separate stages for sensory encoding and downstream integration for accumulating the sensory evidence. Sensory and decision stages can each have their own temporal dynamics that affect the time course of perception and action. Here, we discuss recent work using temporal signatures of behavior in the context of traditional two-stage models. This discussion highlights shortcomings of two stage sensory/decision frameworks, points towards how modern techniques can provide more realistic characterizations of temporal integration, and in turn motivates a richer philosophical framework for building models of how sensory data might be interpreted by the brain to produce actions.Given the prevalence of sleep in early development, any satisfactory account of infant brain activity must consider what happens during sleep. Only recently, however, has it become possible to record sleep-related brain activity in newborn rodents. Using such methods in rat pups, it is now clear that sleep, more so than wake, provides a critical context for the processing of sensory input and the expression of functional connectivity throughout the sensorimotor system. In addition, sleep uniquely reveals functional activity in the developing primary motor cortex, which establishes a somatosensory map long before its role in motor control emerges. These findings will inform our understanding of the developmental processes that contribute to the nascent sense of embodiment in human infants.Diabetes is a major worldwide health problem which results from the loss and/or dysfunction of pancreatic insulin-producing β cells in the pancreas. Therefore, there is great interest in understanding the endogenous capacity of β cells to regenerate under normal or pathological conditions, with the goal of restoring functional β cell mass in patients with diabetes. Here, we summarize the current status of β cell regeneration research, which has been broadly divided into three in vivo mechanisms 1. proliferation of existing β cells; 2. neogenesis of β cells from adult ductal progenitors; and 3. transdifferentiation of other cell types into β cells. We discuss the evidence and controversies for each mechanism in mice and humans, as well as the prospect of using these approaches for the treatment of diabetes.Preterm birth and postpartum hemorrhage are the leading causes of neonatal and maternal morbidities worldwide, respectively. Current clinically utilized tocolytics and uterotonics to manage these obstetric conditions are limited due to their off-target effects and/or lack of efficacy. Thus, an ideal tocolytic or uterotonic would be uterine-selective with rapid onset and long-duration efficacy. Here, we discuss strategies for the discovery of new therapeutic targets and compounds that regulate uterine contractility with the aforementioned properties.Today there are extensive maps of the molecular heterogeneity of primary afferents and dorsal horn interneurons, yet there is a dearth of molecular and functional information regarding the projection neurons that transmit pain and itch information to the brain. Additionally, most contemporary research into the spinal cord and medullary projection neurons focuses on neurons in the superficial dorsal horn; the contribution of deep dorsal horn and even ventral horn projection neurons to pain and itch processing is often overlooked. In the present review we integrate conclusions from classical as well as contemporary studies and provide a more balanced view of the diversity of projection neurons. A major question addressed is the extent to which labeled-lines are maintained in these different populations or whether the brain generates distinct pain and itch percepts by decoding complex convergent inputs that engage projection neurons.Neurodegenerative diseases compromise the quality of life of increasing numbers of the world's aging population. While diagnosis is possible no effective treatments are available. Strong efforts are needed to develop new therapeutic approaches, namely in the areas of tissue engineering and deep brain stimulation (DBS). Conductive polymers are the ideal material for these applications due to the positive effect of conducting electricity on neural cell's differentiation profile. This novel study assessed the biocompatibility of polybenzimidazole (PBI), as electrospun fibers and after being doped with different acids. Firstly, doped films of PBI were used to characterize the materials' contact angle and electroconductivity. After this, fibers were electrospun and characterized by SEM, FTIR and TGA. Neural Stem Cell's (NSC) proliferation was assessed and their growth rate and morphology on different samples was determined. Differentiation of NSCs on PBI - CSA fibers was also investigated and gene expression (SOX2, NES, GFAP, Tuj1) was assessed through Immunochemistry and qPCR. All the samples tested were able to support neural stem cell (NSC) proliferation without significant changes on the cell's typical morphology. Reversan ic50 Successfully differentiation of NSCs towards neural cells on PBI - CSA fibers was also achieved. This promising PBI fibrous scaffold material is envisioned to be used in neural cell engineering applications, including scaffolds, in vitro models for drug screening and electrodes.Central nervous system damage in mammals leads to neuronal cell death, axonal degeneration, and formation of a glial scar resulting in functional and behavioral defects. Other vertebrates, like fish and salamanders, have retained the ability to functionally regenerate after central nervous system injury. To date research from many research organisms has led to a more concise understanding of the response of local neural cells to injury. However, it has become clear that non-neural cells of the immune system play an important role in determining the tissue response to injury. In this review we briefly consider the mammalian response to injury compared to organisms with the natural ability to regenerate. We then discuss similarities and differences in how cells of the innate and adaptive immune system respond and contribute to tissue repair in various species.The extracellular matrix (ECM) is a heterogeneous mixture of proteoglycans and fibrous proteins that form the non-cellular component of tissues and organs. During normal development, homeostasis, and disease progression, the ECM provides dynamic structural and molecular signals that influence the form and function of individual cells and multicellular tissues. Here, we review recent developments in the design and fabrication of engineered ECMs and the application of these systems to study the morphogenesis of epithelial tissues. We emphasize emerging techniques for reproducing the structural and molecular complexity of native ECM, and we highlight how these techniques may be used to decouple the different signals that drive epithelial morphogenesis. Engineered models of native ECM will enable further investigation of the dynamic mechanisms by which the microenvironment influences tissue morphogenesis.Offering high temporal resolution, voltage imaging is an important and essential technique in neuroscience. Among different optical imaging approaches, the label-free approach remains attractive due to its unique value coming from free of exogenous chromophores. The intrinsic voltage-indicating signals arising from membrane deformation, membrane spectral change, phase shift, light scattering, and membrane hydration haven been reported. First demonstrated 70 years ago, label-free optical imaging of membrane potential is still at an early stage and the field is challenged by the relatively small signals generated by the intrinsic optical properties. We review major contrast mechanisms used for label-free voltage imaging and discuss several recent exciting advances that could potentially enable membrane potential imaging in mammalian neurons at high speed and high sensitivity.Genetically encoded voltage indicators report membrane voltage with high spatiotemporal resolution. Extensive recent efforts to improve the GEVIs' brightness, sensitivity, and kinetics have greatly increased the GEVIs' signal-to-noise performance over ten-fold and lowered their response time to the sub-millisecond regime. Such capabilities have broadened the GEVIs' ability to measure membrane voltage of neural populations at cellular resolution in vitro and in vivo, all at high speeds. The GEVIs' high voltage fidelity and fast response have revealed novel physiological phenomena in multiple neuroscientific applications. Such applications portend future targeted studies of voltage activity that take advantage of the GEVIs' ability to report rapid dynamics from genetically-targeted neural populations.Nearly all cellular processes are sensitive to mechanical inputs, and this plays a major role in diverse physiological processes. Mechanical stimuli are thought to be primarily detected through force-induced changes in protein structure. Approximately a decade ago, molecular tension sensors were created to measure forces across proteins within cells. Since then, an impressive assortment of sensors has been created and provided key insights into mechanotransduction, but comparisons of measurements between various sensors are challenging. In this review, we discuss the different types of molecular tension sensors, provide a system of classification based on their molecular-scale mechanical properties, and highlight how new applications of these sensors are enabling measurements beyond the magnitude of tensile load. We suggest that an expanded understanding of the functionality of these sensors, as well as integration with other techniques, will lead to consensus amongst measurements as well as critical insights into the underlying mechanisms of mechanotransduction.The detection of action potentials and the characterization of their waveform represent basic benchmarks for evaluating optical sensors of voltage. The effectiveness of a voltage sensor in reporting action potentials will determine its usefulness in voltage imaging experiments designed for the study of neural circuitry. The hybrid voltage sensor (hVOS) technique is based on a sensing mechanism with a rapid response to voltage changes. hVOS imaging is thus well suited for optical studies of action potentials. This technique detects action potentials in intact brain slices with an excellent signal-to-noise ratio. These optical action potentials recapitulate voltage recordings with high temporal fidelity. In different genetically-defined types of neurons targeted by cre-lox technology, hVOS recordings of action potentials recapitulate the expected differences in duration. Furthermore, by targeting an hVOS probe to axons, imaging experiments can follow action potential propagation and document dynamic changes in waveform resulting from use-dependent plasticity.Mathematical models of biological systems need to both reflect and manage the inherent complexities of biological phenomena. Through their versatility and ability to capture behavior at multiple scales, multi-scale models offer a valuable approach. Due to the typically nonlinear and stochastic nature of multi-scale models as well as unknown parameter values, various types of uncertainty are present; thus, effective assessment and quantification of such uncertainty through sensitivity analysis is important. In this review, we discuss global sensitivity analysis in the context of multi-scale and multi-compartment models and highlight its value in model development and analysis. We present an overview of sensitivity analysis methods, approaches for extending such methods to a multi-scale setting, and examples of how sensitivity analysis can inform model reduction. Through schematics and references to past work, we aim to emphasize the advantages and usefulness of such techniques.
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