Anatomical Characteristics of Cervicomedullary Compression on MRI Scans in Children with Achondroplasia.

This retrospective study assessed anatomical characteristics of cervicomedullary compression in children with achondroplasia. Twelve anatomical parameters were analyzed (foramen magnum diameter and area; myelon area; clivus length; tentorium and occipital angles; brainstem volume outside the posterior fossa; and posterior fossa, cerebellum, supratentorial ventricular system, intracranial cerebrospinal fluid, and fourth ventricle volumes) from sagittal and transversal T1- and T2-weighted magnetic resonance imaging (MRI) scans from 37 children with achondroplasia aged ≤ 4 years (median [range] 0.8 [0.

Distribution of insulin in primate brain following nose-to-brain transport.

Introduction: Nose-to-brain (N2B) insulin delivery has potential for Alzheimer's disease (AD) therapy. However, clinical implementation has been challenging without methods to follow N2B delivery non-invasively. Positron emission tomography (PET) was applied to measure F-18-labeled insulin ([F]FB-insulin) from intranasal dosing to brain uptake in non-human primates following N2B delivery.

Pressure-Induced Dislocations and Their Influence on Ionic Transport in Li-Conducting Argyrodites.

The influence of the microstructure on the ionic conductivity and cell performance is a topic of broad scientific interest in solid-state batteries. The current understanding is that interfacial decomposition reactions during cycling induce local strain at the interfaces between solid electrolytes and the anode/cathode, as well as within the electrode composites. Characterizing the effects of internal strain on ion transport is particularly important, given the significant local chemomechanical effects caused by volumetric changes of the active materials during cycling.

[C]Paraoxon: Radiosynthesis, Biodistribution and In Vivo Positron Emission Tomography Imaging in Rat.

Synthesis of the acetylcholinesterase inhibitor paraoxon (POX) as a carbon-11 positron emission tomography tracer ([C]POX) and profiling in live rats is reported. Naïve rats intravenously injected with [C]POX showed a rapid decrease in parent tracer to ∼1%, with an increase in radiolabeled serum proteins to 87% and red blood cells (RBCs) to 9%. Protein and RBC leveled over 60 minutes, reflecting covalent modification of proteins by [C]POX.

On the Discrepancy between Local and Average Structure in the Fast Na Ionic Conductor NaSbWS.

Aliovalent substitution is a common strategy to improve the ionic conductivity of solid electrolytes for solid-state batteries. The substitution of SbS by WS in NaSbWS leads to a very high ionic conductivity of 41 mS cm at room temperature. While pristine NaSbS crystallizes in a tetragonal structure, the substituted NaSbWS crystallizes in a cubic phase at room temperature based on its X-ray diffractogram.

Adipocyte-derived extracellular vesicles increase insulin secretion through transport of insulinotropic protein cargo.

Adipocyte-derived extracellular vesicles (AdEVs) are membranous nanoparticles that convey communication from adipose tissue to other organs. Here, to delineate their role as messengers with glucoregulatory nature, we paired fluorescence AdEV-tracing and SILAC-labeling with (phospho)proteomics, and revealed that AdEVs transfer functional insulinotropic protein cargo into pancreatic β-cells. Upon transfer, AdEV proteins were subjects for phosphorylation, augmented insulinotropic GPCR/cAMP/PKA signaling by increasing total protein abundances and phosphosite dynamics, and ultimately enhanced 1st-phase glucose-stimulated insulin secretion (GSIS) in murine islets.

Structural characterization of a new fluorophosphotellurite glass system.

While phosphotellurite glasses have superior properties over SiO-based glasses for many applications in optoelectronics and photonic devices, their high hydroxyl content limits their use in the mid-infrared range. This drawback can be overcome by fluoride addition to the formulation. In this work, we report the preparation, optical, and structural characterization of new glasses in the ternary system TeO-NaF-NaPO having the compositions 0.

Three-dimensional adaptive optical nanoscopy for thick specimen imaging at sub-50-nm resolution.

Understanding cellular organization demands the best possible spatial resolution in all three dimensions. In fluorescence microscopy, this is achieved by 4Pi nanoscopy methods that combine the concepts of using two opposing objectives for optimal diffraction-limited 3D resolution with switching fluorescent molecules between bright and dark states to break the diffraction limit. However, optical aberrations have limited these nanoscopes to thin samples and prevented their application in thick specimens.

Targeting Chikungunya Virus Replication by Benzoannulene Inhibitors.

A benzo[6]annulene, 4-(-butyl)--(3-methoxy-5,6,7,8-tetrahydronaphthalen-2-yl) benzamide (), was identified as an inhibitor against Chikungunya virus (CHIKV) with antiviral activity EC = 1.45 μM and viral titer reduction (VTR) of 2.5 log at 10 μM with no observed cytotoxicity (CC = 169 μM) in normal human dermal fibroblast cells.

Radiofrequency catheter ablation in 246 children with supraventricular tachyarrhythmia.

Introduction: Radiofrequency catheter ablation (RFA) is the treatment of choice for a variety of cardiac arrhythmias in adults. RFA is considered effective and is associated with few complications. We aimed to review the characteristics and outcomes of invasive electrophysiological study (EPS) and RFA in children with supraventricular tachyarrhythmia.

Inhibition of the Vesicular Glutamate Transporter (VGLUT) with Congo Red Analogs: New Binding Insights.

The vesicular glutamate transporter (VGLUT) facilitates the uptake of glutamate (Glu) into neuronal vesicles. VGLUT has not yet been fully characterized pharmacologically but a body of work established that certain azo-dyes bearing two Glu isosteres via a linker were potent inhibitors. However, the distance between the isostere groups that convey potent inhibition has not been delineated.

Biological Distribution and Metabolic Profiles of Carbon-11 and Fluorine-18 Tracers of VX- and Sarin-Analogs in Sprague-Dawley Rats.

Organophosphorus esters (OPs) were originally developed as pesticides but were repurposed as easily manufactured, inexpensive, and highly toxic chemical warfare agents. Acute OP toxicity is primarily due to inhibition of acetylcholinesterase (AChE), an enzyme in the central and peripheral nervous system. OP inhibition of AChE can be reversed using oxime reactivators but many show poor CNS penetration, indicating a need for new clinically viable reactivators.

Islet vascularization is regulated by primary endothelial cilia via VEGF-A-dependent signaling.

Islet vascularization is essential for intact islet function and glucose homeostasis. We have previously shown that primary cilia directly regulate insulin secretion. However, it remains unclear whether they are also implicated in islet vascularization.

HtsRC-Mediated Accumulation of F-Actin Regulates Ring Canal Size During Oogenesis.

Ring canals in the female germline of are supported by a robust filamentous actin (F-actin) cytoskeleton, setting them apart from ring canals in other species and tissues. Previous work has identified components required for the expansion of the ring canal actin cytoskeleton, but has not identified the proteins responsible for F-actin recruitment or accumulation. Using a combination of CRISPR-Cas9 mediated mutagenesis and UAS-Gal4 overexpression, we show that HtsRC-a component specific to female germline ring canals-is both necessary and sufficient to drive F-actin accumulation.

Positron emission tomography evaluation of oxime countermeasures in live rats using the tracer O-(2-[ F]fluoroethyl)-O-(p-nitrophenyl)methylphosphonate [ F]-VXS.

Oxime antidotes regenerate organophosphate-inhibited acetylcholinesterase (AChE). Although they share a common mechanism of AChE reactivation, the rate and amount of oxime that enters the brain are critical to the efficacy, a process linked to the oxime structure and charge. Using a platform based on the organophosphate [ F]-VXS as a positron emission tomography tracer for active AChE, the in vivo distribution of [ F]-VXS was evaluated after an LD dose (250 μg/kg) of the organophosphate paraoxon (POX) and following oximes as antidotes.

Glucose homeostasis is regulated by pancreatic β-cell cilia via endosomal EphA-processing.

Diabetes mellitus affects one in eleven adults worldwide. Most suffer from Type 2 Diabetes which features elevated blood glucose levels and an inability to adequately secrete or respond to insulin. Insulin producing β-cells have primary cilia which are implicated in the regulation of glucose metabolism, insulin signaling and secretion.

Divergent synthesis of organophosphate [C]VX- and [C]Sarin-surrogates from a common set of starting materials.

Radiolabeled 1-[C]ethyl, 4-nitrophenyl methylphosphonate (VX surrogate) and 2-[C]-propanyl, 4-nitrophenyl methylphosphonate (sarin surrogate) were developed as organophosphate (OP) tracers. The [C]ethyl- and [C]isopropyl-iodide radiolabeled synthons were obtained by temperature controlled, in loop reactions of [C]CO with MeMgBr followed by reduction with LiAlH, then reaction with HI. Distillation of the [C]alkyl iodides into a solution of hydrogen (4-nitrophenyl)methylphosphonate and cesium carbonate afforded the desired tracers in >95% radiochemical purity, yields from [C]CO of 1-3% and 1.

Metabolic regulation through the endosomal system.

The endosomal system plays an essential role in cell homeostasis by controlling cellular signaling, nutrient sensing, cell polarity and cell migration. However, its place in the regulation of tissue, organ and whole body physiology is less well understood. Recent studies have revealed an important role for the endosomal system in regulating glucose and lipid homeostasis, with implications for metabolic disorders such as type 2 diabetes, hypercholesterolemia and non-alcoholic fatty liver disease.

Positron emission tomography studies of organophosphate chemical threats and oxime countermeasures.

There is a unique in vivo interplay involving the mechanism of inactivation of acetylcholinesterase (AChE) by toxic organophosphorus (OP) compounds and the restoration of AChE activity by oxime antidotes. OP compounds form covalent adducts to this critical enzyme target and oximes are introduced to directly displace the OP from AChE. For the most part, the in vivo inactivation of AChE leading to neurotoxicity and antidote-based therapeutic reversal of this mechanism are well understood, however, these molecular-level events have not been evaluated by dynamic imaging in living systems at millimeter resolution.

Neural network vehicle models for high-performance automated driving.

Automated vehicles navigate through their environment by first planning and subsequently following a safe trajectory. To prove safer than human beings, they must ultimately perform these tasks as well or better than human drivers across a broad range of conditions and in critical situations. We show that a feedforward-feedback control structure incorporating a simple physics-based model can be used to track a path up to the friction limits of the vehicle with performance comparable with a champion amateur race car driver.

Phosphoproteomics Reveals the GSK3-PDX1 Axis as a Key Pathogenic Signaling Node in Diabetic Islets.

Progressive decline of pancreatic beta cell function is central to the pathogenesis of type 2 diabetes. Protein phosphorylation regulates glucose-stimulated insulin secretion from beta cells, but how signaling networks are remodeled in diabetic islets in vivo remains unknown. Using high-sensitivity mass spectrometry-based proteomics, we quantified 6,500 proteins and 13,000 phosphopeptides in islets of obese diabetic mice and matched controls, revealing drastic remodeling of key kinase hubs and signaling pathways.

Decreased Expression of Cilia Genes in Pancreatic Islets as a Risk Factor for Type 2 Diabetes in Mice and Humans.

An insufficient adaptive beta-cell compensation is a hallmark of type 2 diabetes (T2D). Primary cilia function as versatile sensory antennae regulating various cellular processes, but their role on compensatory beta-cell replication has not been examined. Here, we identify a significant enrichment of downregulated, cilia-annotated genes in pancreatic islets of diabetes-prone NZO mice as compared with diabetes-resistant B6-ob/ob mice.