Transcranial focused ultrasound is an emerging form of non-invasive neuromodulation that uses acoustic energy to affect neuronal excitability. The effect of ultrasound on human motor cortical ...excitability and behavior is currently unknown. We apply ultrasound to the primary motor cortex in humans using a novel simultaneous transcranial ultrasound and magnetic stimulation paradigm that allows for concurrent and concentric ultrasound stimulation with transcranial magnetic stimulation (TMS). This allows for non-invasive inspection of the effect of ultrasound on motor neuronal excitability using the motor evoked potential (MEP). We test the effect of ultrasound on single pulse MEP recruitment curves and paired pulse protocols including short interval intracortical inhibition (SICI) and intracortical facilitation (ICF). In addition, we test the effect of ultrasound to motor cortex on a stimulus response reaction time task. Results show ultrasound inhibits the amplitude of single-pulse MEPs and attenuates intracortical facilitation but does not affect intracortical inhibition. Ultrasound also reduces reaction time on a simple stimulus response task. This is the first report of the effect of ultrasound on human motor cortical excitability and motor behavior and confirms previous results in the somatosensory cortex that ultrasound results in effective neuronal inhibition that confers a performance advantage.
Transcranial focused ultrasound (tFUS) is a new non-invasive neuromodulation technique that uses mechanical energy to modulate neuronal excitability with high spatial precision. tFUS has been shown ...to be capable of modulating EEG brain activity in humans that is spatially restricted, and here, we use 7T MRI to extend these findings. We test the effect of tFUS on 7T BOLD fMRI signals from individual finger representations in the human primary motor cortex (M1) and connected cortical motor regions. Participants (N = 5) performed a cued finger tapping task in a 7T MRI scanner with their thumb, index, and middle fingers to produce a BOLD signal for individual M1 finger representations during either tFUS or sham neuromodulation to the thumb representation.
Results demonstrated a statistically significant increase in activation volume of the M1 thumb representation for the tFUS condition as compared to sham. No differences in percent BOLD changes were found. This effect was spatially confined as the index and middle finger M1 finger representations did not show similar significant changes in either percent change or activation volume. No effects were seen during tFUS to M1 in the supplementary motor area or the dorsal premotor cortex.
Single element tFUS can be paired with high field MRI that does not induce significant artifact. tFUS increases activation volumes of the targeted finger representation that is spatially restricted within M1 but does not extend to functionally connected motor regions. Trial registration ClinicalTrials.gov NCT03634631 08/14/18.
Recent studies have indicated that visually embellished charts such as infographics have the ability to engage viewers and positively affect memorability. Fueled by these findings, researchers have ...proposed a variety of infographic design tools. However, these tools do not cover the entire design space. In this work, we identify a subset of infographics that we call infomages. Infomages are casual visuals of data in which a data chart is embedded into a thematic image such that the content of the image reflects the subject and the designer's interpretation of the data. Creating an effective infomage, however, can require a fair amount of design expertise and is thus out of reach for most people. In order to also afford non‐artists with the means to design convincing infomages, we first study the principled design of existing infomages and identify a set of key chart embedding techniques. Informed by these findings we build a design tool that links web‐scale image search with a set of interactive image processing tools to empower novice users with the ability to design a wide variety of infomages. As the embedding process might introduce some amount of visual distortion of the data our tool also aids users to gauge the amount of this distortion, if any. We experimentally demonstrate the usability of our tool and conclude with a discussion of infomages and our design tool.
Non-invasive biomarker analysis has made repetitive and painless sampling over time possible. Exosomes are being released from a parent cell and their cargo mirrors the cell micromilieu of the parent ...cell. Therefore, exosomes are promising surrogates for their parent cells. That is also why exosomes provide an improved signal-to-noise ratio. Current studies have identified valid non-invasive biomarkers that may be able to monitor disease severity. Exosomes are suggested to play an important role in interepithelial communication and are suggested to play a role in the initiation and maintenance of inflammation in CRS. They are, however, also involved simultaneously in several immunological processes including immune protection and immunosuppression. As the isolation of exosomes is time-consuming their value in everyday routine diagnostics has yet to be determined.
Carbon hydrogen bonds between Cα-H donors and carbonyl acceptors are frequently observed between transmembrane helices (Cα-H···O=C). Networks of these interactions occur often at helix-helix ...interfaces mediated by GxxxG and similar patterns. Cα-H hydrogen bonds have been hypothesized to be important in membrane protein folding and association, but evidence that they are major determinants of helix association is still lacking. Here we present a comprehensive geometric analysis of homodimeric helices that demonstrates the existence of a single region in conformational space with high propensity for Cα-H···O=C hydrogen bond formation. This region corresponds to the most frequent motif for parallel dimers, GASright, whose best-known example is glycophorin A. The finding suggests a causal link between the high frequency of occurrence of GASright and its propensity for carbon hydrogen bond formation. Investigation of the sequence dependency of the motif determined that Gly residues are required at specific positions where only Gly can act as a donor with its "side chain" Hα. Gly also reduces the steric barrier for non-Gly amino acids at other positions to act as Cα donors, promoting the formation of cooperative hydrogen bonding networks. These findings offer a structural rationale for the occurrence of GxxxG patterns at the GASright interface. The analysis identified the conformational space and the sequence requirement of Cα-H···O=C mediated motifs; we took advantage of these results to develop a structural prediction method. The resulting program, CATM, predicts ab initio the known high-resolution structures of homodimeric GASright motifs at near-atomic level.
We focused on human-animal interaction (HAI) as an important aspect of social functioning at the individual level, framing this emerging field from a public health perspective.
Using data from the ...Health and Retirement Study (HRS) 2012 HAI module, we describe the characteristics of pet ownership in a population of older adults, and examine the relation between pet ownership and multiple mental and physical health indicators such as health status, depression, and physical activity.
Of the 1657 participants in our subsample, approximately half (51.5%) reported being pet owners; the majority owned dogs or cats, and most had only one pet. Pet ownership was significantly associated with a higher likelihood of ever having had depression, with pet owners being 1.89 times more likely to have experienced depression. However, pet ownership was not associated with having experienced depression within the last week.
The findings from this study could indicate a relationship between pet ownership and depression, but it is impossible to determine the directionality of that relationship. It is possible that owning a pet may put a person at an increased risk of developing depression, or individuals who are at risk, or who have already developed depression, may acquire a pet as a way of managing their depressive symptoms. The findings of this study provide an initial step in contributing to our understanding of the relationship between companion animals and the social, physical, and mental well-being of the HRS study population. Future research should include measures of HAI in longitudinal, population-based surveys.
Rho kinases (ROCKs), the first Rho effectors to be described, are serine/threonine kinases that are important in fundamental processes of cell migration, cell proliferation and cell survival. ...Abnormal activation of the Rho/ROCK pathway has been observed in various disorders of the central nervous system. Injury to the adult vertebrate brain and spinal cord activates ROCKs, thereby inhibiting neurite growth and sprouting. Inhibition of ROCKs results in accelerated regeneration and enhanced functional recovery after spinal-cord injury in mammals, and inhibition of the Rho/ROCK pathway has also proved to be efficacious in animal models of stroke, inflammatory and demyelinating diseases, Alzheimer's disease and neuropathic pain. ROCK inhibitors therefore have potential for preventing neurodegeneration and stimulating neuroregeneration in various neurological disorders.
Although originally discovered as neuronal growth cone-collapsing factors, repulsive guidance molecules (RGMs) are now known as key players in many fundamental processes, such as cell migration, ...differentiation, iron homeostasis, and apoptosis, during the development and homeostasis of many tissues and organs, including the nervous, skeletal, and immune systems. Furthermore, three RGMs (RGMa, RGMb/DRAGON, and RGMc/hemojuvelin) have been linked to the pathogenesis of various disorders ranging from multiple sclerosis (MS) to cancer and juvenile hemochromatosis (JHH). While the molecular details of these (patho)biological effects and signaling modes have long remained unknown, recent studies unveil several exciting and novel aspects of RGM processing, ligand–receptor interactions, and downstream signaling. In this review, we highlight recent advances in the mechanisms-of-action and function of RGM proteins.
The task of reconstructing an object from its projections via tomographic methods is a time-consuming process due to the vast complexity of the data. For this reason, manufacturers of equipment for ...medical computed tomography (CT) rely mostly on special application specified integrated circuits (ASICs) to obtain the fast reconstruction times required in clinical settings. Although modern CPUs have gained sufficient power in recent years to be competitive for two-dimensional (2D) reconstruction, this is not the case for three-dimensional (3D) reconstructions, especially not when iterative algorithms must be applied. The recent evolution of commodity PC computer graphics boards (GPUs) has the potential to change this picture in a very dramatic way. In this paper we will show how the new floating point GPUs can be exploited to perform both analytical and iterative reconstruction from X-ray and functional imaging data. For this purpose, we decompose three popular three-dimensional (3D) reconstruction algorithms (Feldkamp filtered backprojection, the simultaneous algebraic reconstruction technique, and expectation maximization) into a common set of base modules, which all can be executed on the GPU and their output linked internally. Visualization of the reconstructed object is easily achieved since the object already resides in the graphics hardware, allowing one to run a visualization module at any time to view the reconstruction results. Our implementation allows speedups of over an order of magnitude with respect to CPU implementations, at comparable image quality.
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