let-7 microRNAs regulate microglial function and suppress glioma growth through Toll-like receptor 7

Microglia express Toll-like receptors (TLRs) that sense pathogen- and host-derived factors, including single-stranded RNA. In the brain, let-7 microRNA (miRNA) family members are abundantly expressed, and some have recently been shown to serve as TLR7 ligands. We investigated whether let-7 miRNA family members differentially control microglia biology in health and disease. We found that a subset of let-7 miRNA family members function as signaling molecules to induce microglial release of inflammatory cytokines, modulate antigen presentation, and attenuate cell migration in a TLR7-dependent manner. The capability of the let-7 miRNAs to control microglial function is sequence specific, mapping to a let-7 UUGU motif. In human and murine glioblastoma/glioma, let-7 miRNAs are differentially expressed and reduce murine GL261 glioma growth in the same sequence-specific fashion through microglial TLR7. Taken together, these data establish let-7 miRNAs as key TLR7 signaling activators that serve to regulate the diverse functions of microglia in health and glioma

Cellular and synaptic diversity of layer 2-3 pyramidal neurons in human individuals

Understanding the functional principles of the human brain requires deep insight into the neuronal and network physiology. To what extent such principles of cellular physiology and synaptic interactions are common across different human individuals is unknown. We characterized the physiology of ~1200 pyramidal neurons and ~1400 monosynaptic connections using advanced multineuron patch-clamp recordings in slices from human temporal cortex. To disentangle within and between individual sources of heterogeneity, we recorded up to 100 neurons per single subject. We found that neuronal, but not synaptic physiology varied with laminar depth. Connection probability was ~15% throughout layer 2-3. Synaptic amplitudes exhibited heavy-tailed distributions with an inverse power law relationship to short term plasticity. Neurons could be classified into four functional subtypes. These general principles of microcircuit physiology were common across individuals. Our study advances the understanding of human neuron and synaptic diversity from an individual and phenotypic perspective

Comparison between a count-based and geometrical approach for the assessment of left ventricular dyssynchrony using myocardial perfusion scintigraphy

Cardiovascular Aspects of Radiolog

Initiating a new national epilepsy surgery program: experiences gathered in Georgia

Surgery is the most effective therapeutic approach for medically refractory epilepsies and a safe and cost-efficient treatment in terms of long-term expenses of direct, indirect, and intangible costs. Georgia is a Caucasian low- to middle-income country with a remarkable effort to deal with epileptic diseases, but without an appropriate epilepsy surgery program. To address the needs for such a service in this country, two joint German-Georgian projects were initiated in 2017 and 2019. In the framework of these projects, a productive exchange program involving German and Georgian experts was undertaken in the past two years. This program included training and mentoring for Georgian clinical colleagues, as well as joint case conferences and workshops with the aim of optimizing presurgical diagnostics and preparing for an epilepsy surgery program in Georgia. Finally, a postsurgical medium- and long-term follow-up scheme was organized as the third component of this comprehensive approach. As a result of our efforts, the first patients underwent anterior temporal lobectomy and all of them remain seizure-free up to the present day. Hence, epilepsy surgery is not only feasible, but also already available in Georgia. In this report, we aim to share our experiences in the initiation and implementation of surgical epilepsy intervention in Georgia and illustrate our recent endeavor and achievements

A new powerful source for coherent VUV radiation: Demonstration of exponential growth and saturation at the TTF free-electron laser

We present experimental evidence that the free-electron laser at the TESLA Test Facility has reached the maximum power gain of 107 in the vacuum ultraviolet (VUV) region at wavelengths between 80 and 120 nm. At saturation the FEL emits short pulses with GW peak power and a high degree of transverse coherence. The radiation pulse length can be adjusted between 30 fs and 100 fs. Radiation spectra and fluctuation properties agree with the theory of high gain, single-pass free-electron lasers starting from shot noise