Lambertsendreier9023

Cardiac diseases are the most frequent causes of death in industrialized countries. Pathological remodeling of the heart muscle is caused by several etiologies such as prolonged hypertension or injuries that can lead to myocardial infarction and in serious cases also the death of the patient. The micro-RNA miR-132 has been identified as a master-switch in the development of cardiac hypertrophy and adverse remodeling. In this study, MALDI-TOF mass spectrometry (MS) was utilized to establish a robust and fast method to sensitively detect and accurately quantify anti-microRNA (antimiR) oligonucleotides in blood plasma. An antimiR oligonucleotide isolation protocol containing an ethanol precipitation step with glycogen as oligonucleotide carrier as well as a robust and reproducible MS-analysis procedure has been established. https://www.selleckchem.com/products/e-7386.html Proteinase K treatment was crucial for releasing antimiR oligonucleotides from plasma- as well as cellular proteins and reducing background derived from biological matrices. AntimiR oligonucleotide detection was achieved from samples of studies in different animal models such as mouse and pig where locked nucleic acids-(LNA)-modified antimiR oligonucleotides have been used to generate pharmacokinetic data. Copyright © 2020 Herkt, Foinquinos, Batkai, Thum and Pich.Currently, there is a lack of biomarkers to identify individuals in the early stages of Alzheimer's disease (AD). A preponderance of evidence suggests that neurodegenerative processes that affect the brain, may also affect the retina. Using optical coherence tomography (OCT), a non-invasive approach, many have shown thinning of the retina in AD and the developmental precursor to AD, mild cognitive impairment (MCI). However, the relationship between retinal thickness and cognitive function is not entirely clear. This is likely due to the disparity in diagnostic criteria used to determine MCI that does not fully probe the cognitive domains that are particularly vulnerable to aging. This study used a comprehensive neuropsychological assessment involving multiple domains of cognition to determine if retinal thickness correlates with cognitive performance in a normal aged population. In this study, 20 healthy individuals between 60 and 90 years of age were administered neuropsychological assessments probing various domains of cognitive function, and OCT to measure peripapillary retinal nerve fiber layer (RNFL) thickness. We found that RNFL thickness is correlated with neuropsychological performance in multiple cognitive domains (e.g., working memory, psychomotor speed, and executive function). Our work demonstrates a positive correlation between RNFL thickness and several, but not all, domains of cognitive function in a normative aging population. By determining which cognitive domains retinal thickness can predict, this work can help identify individuals at risk or in preclinical stages of AD and other neurodegenerative diseases. Copyright © 2020 Mammadova, Neppl, Denburg and West Greenlee.Purpose We present a case of voltage-gated potassium channel (VGKC) complex antibody-positive limbic encephalitis (LE) harboring autoantibodies against Kv1.2. Since the patient responded well to immunotherapy, the autoantibodies were regarded as pathogenic. We aimed to characterize the pathophysiological role of this antibody in comparison to an antibody against the VGKC-associated protein contactin-associated protein-2 (CASPR2). Methods Stereotactic injection of patient sera (anti-Kv1.2-associated LE or anti-CASPR2 encephalopathy) and a control subject was performed into the hippocampus of the anesthetized rat in vivo, and hippocampal slices were prepared for electrophysiological purposes. Using extra- and intracellular techniques, synaptic transmission, long-term potentiation (LTP) and vulnerability to pro-epileptic conditions were analyzed. Results We observed that the slope of the field excitatory postsynaptic potential (fEPSP) was significantly increased at Schaffer collateral-CA1 synapses in anti-Kv1.2-ates presynaptic transmitter release as well as postsynaptic depolarization at the Schaffer-collateral-CA1 synapse, but not in the dentate gyrus. As a consequence, both synaptic transmission and LTP in CA1 are facilitated and action potential firing is altered. In contrast, anti-CASPR2 leads to increased postsynaptic potentials, but without changing LTP or firing properties suggesting that anti-Kv1.2 and anti-CASPR2 differ in their cellular effects. Both patient sera alter susceptibility to epileptic conditions, but presumably by different mechanisms. Copyright © 2020 Kirschstein, Sadkiewicz, Hund-Göschel, Becker, Guli, Müller, Rohde, Hübner, Brehme, Kolbaske, Porath, Sellmann, Großmann, Wittstock, Syrbe, Storch and Köhling.Mathematical models for excitable cells are commonly based on cable theory, which considers a homogenized domain and spatially constant ionic concentrations. Although such models provide valuable insight, the effect of altered ion concentrations or detailed cell morphology on the electrical potentials cannot be captured. In this paper, we discuss an alternative approach to detailed modeling of electrodiffusion in neural tissue. The mathematical model describes the distribution and evolution of ion concentrations in a geometrically-explicit representation of the intra- and extracellular domains. As a combination of the electroneutral Kirchhoff-Nernst-Planck (KNP) model and the Extracellular-Membrane-Intracellular (EMI) framework, we refer to this model as the KNP-EMI model. Here, we introduce and numerically evaluate a new, finite element-based numerical scheme for the KNP-EMI model, capable of efficiently and flexibly handling geometries of arbitrary dimension and arbitrary polynomial degree. Moreover, we compare the electrical potentials predicted by the KNP-EMI and EMI models. Finally, we study ephaptic coupling induced in an unmyelinated axon bundle and demonstrate how the KNP-EMI framework can give new insights in this setting. Copyright © 2020 Ellingsrud, Solbrå, Einevoll, Halnes and Rognes.Reality monitoring is defined as the ability to distinguish internally self-generated information from externally-derived information. Functional imaging studies have consistently found that the medial prefrontal cortex (mPFC) is a key brain region subserving reality monitoring. This study aimed to determine a causal role for mPFC in reality monitoring using navigated repetitive transcranial magnetic stimulation (nrTMS). In a subject-blinded sham-controlled crossover design, healthy individuals received either active or sham nrTMS targeting mPFC. Active modulation of mPFC using nrTMS at a frequency of 10 Hz, significantly improved identification of both self-generated and externally-derived information during reality monitoring, when compared to sham or baseline. Targeted excitatory modulation of mPFC also improved positive mood, reduced negative mood, and increased overall alertness/arousal. These results establish optimal nrTMS dosing parameters that maximized tolerability/comfort and induced significant neuromodulatory effects in the mPFC target.