F-FDOPA PET/CT Combined with MRI for Gross Tumor Volume Delineation in Patients with Skull Base Paraganglioma.

In this simulation study, we assessed differences in gross tumor volume (GTV) in a series of skull base paragangliomas (SBPGLs) using magnetic resonance imaging (MRI), F-dihydroxyphenylalanine (F-FDOPA) combined positron emission tomography/computed tomography (PET/CT), and F-FDOPA PET/MRI images obtained by rigid alignment of PET and MRI. GTV was delineated in 16 patients with SBPGLs on MRI (GTV), F-FDOPA PET/CT (GTV), and combined PET/MRI (GTV). GTV was the union of GTV and GTV after visual adjustment.

Fluorescence Enhancement of a Microbial Rhodopsin via Electronic Reprogramming.

The engineering of microbial rhodopsins with enhanced fluorescence is of great importance in the expanding field of optogenetics. Here we report the discovery of two mutants (W76S/Y179F and L83Q) of a sensory rhodopsin from the cyanobacterium Anabaena PCC7120 with opposite fluorescence behavior. In fact, while W76S/Y179F displays, with respect to the wild-type protein, a nearly 10-fold increase in red-light emission, the second is not emissive.

The Multifaceted Antibacterial Mechanisms of the Pioneering Peptide Antibiotics Tyrocidine and Gramicidin S.

Cyclic β-sheet decapeptides from the tyrocidine group and the homologous gramicidin S were the first commercially used antibiotics, yet it remains unclear exactly how they kill bacteria. We investigated their mode of action using a bacterial cytological profiling approach. Tyrocidines form defined ion-conducting pores, induce lipid phase separation, and strongly reduce membrane fluidity, resulting in delocalization of a broad range of peripheral and integral membrane proteins.

Lipid-Mediated Interactions between the Antimicrobial Peptides Magainin 2 and PGLa in Bilayers.

A synergistic enhancement of activities has been described for the amphipathic cationic antimicrobial peptides magainin 2 and PGLa when tested in antimicrobial assays or in biophysical experiments using model membranes. In the presence of magainin 2, PGLa changes from an in-planar alignment parallel to the membrane surface to a more transmembrane orientation when investigated in membranes made from fully saturated PC or PC/PG, but not when one of the fatty acyl chains is unsaturated. Such lipid-mediated changes in the membrane topology of polypeptide domains could provide an interesting mechanism for the regulation of membrane proteins.

Can Mitochondrial DNA be CRISPRized: Pro and Contra.

Mitochondria represent a chimera of macromolecules encoded either in the organellar genome, mtDNA, or in the nuclear one. If the pathway of protein targeting to different sub-compartments of mitochondria was relatively well studied, import of small noncoding RNAs into mammalian mitochondria still awaits mechanistic explanations and its functional issues are often not understood thus raising polemics. At the same time, RNA mitochondrial import pathway has an obvious attractiveness as it appears as a unique natural mechanism permitting to address nucleic acids into the organelles.

Diagnostic performance of choline PET for detection of hyperfunctioning parathyroid glands in hyperparathyroidism: a systematic review and meta-analysis.

Purpose: Hyperparathyroidism (HPT) is a common endocrine disorder caused by hyperfunctioning parathyroid glands (HP). The correct detection and localization of HP is challenging but crucial, as it may guide surgical treatment, particularly in patients with primary HPT. There is a growing body of data regarding the role of radiolabelled choline positron emission tomography (PET) in this setting.

Lack of anticipatory behavior in Gpr88 knockout mice showed by automatized home cage phenotyping.

Mouse models are widely used to understand genetic bases of behavior. Traditional testing typically requires multiple experimental settings, captures only snapshots of behavior and involves human intervention. The recent development of automated home cage monitoring offers an alternative method to study mouse behavior in their familiar and social environment, and over weeks.

Scalable 9-Step Synthesis of the Splicing Modulator NVS-SM2.

NVS-SM2, the first activator of pre-mRNA splicing, displays remarkable pharmacological in vivo activities in models of spinal muscular atrophy. Herein we describe an improved approach to the synthesis of this compound, which features a convenient introduction of sterically encumbered amine moiety onto a fluoropyridazine intermediate.

Metabolomic characterization of human hippocampus from drug-resistant epilepsy with mesial temporal seizure.

Objective: Within a complex systems biology perspective, we wished to assess whether hippocampi with established neuropathological features have distinct metabolome. Apparently normal hippocampi with no signs of sclerosis (noHS), were compared to hippocampal sclerosis (HS) type 1 (HS1) and/or type 2 (HS2). Hippocampus metabolome from patients with epilepsy-associated neuroepithelial tumors (EANTs), namely, gangliogliomas (GGs) and dysembryoplastic neuroepithelial tumors (DNTs), was also compared to noHS epileptiform tissue.

Identifying mitotane-induced mitochondria-associated membranes dysfunctions: metabolomic and lipidomic approaches.

Mitotane (o,p'DDD), the most effective drug in adrenocortical carcinoma, concentrates into the mitochondria and impacts mitochondrial functions. To address the molecular mechanisms of mitotane action and to identify its potential target, metabolomic and lipidomic approaches as well as imaging analyses were employed in human adrenocortical H295R cells allowing identification of Mitochondria-Associated Membranes dysfunction as a critical impact of mitotane. Study of intracellular energetic metabolites by NMR spectroscopy showed that mitotane significantly decreased aspartate while concomitantly increased glutamate content in a time- and concentration-dependent manner.

The Added Diagnostic Value of F-Fluorodihydroxyphenylalanine PET/CT in the Preoperative Work-Up of Small Bowel Neuroendocrine Tumors.

Background: The precise localization of the primary tumor and/or the identification of multiple primary tumors improves the preoperative work-up in patients with small bowel (SB) neuroendocrine tumor (NET). The present study assesses the diagnostic value of F-fluorodihydroxyphenylalanine (F-FDOPA) positron emission tomography/computed tomography (PET/CT) during the preoperative wok-up of SB NETs.

Methods: Between January 2010 and June 2017, all consecutive patients with SB NETs undergoing preoperative F-FDOPA PET/CT and successive resection were analyzed.

Metabolomics approaches in experimental allergic encephalomyelitis.

A myelin basic protein (MBP)-induced experimental allergic encephalomyelitis (EAE) involves paraplegia due to a reversible thoracolumbar spinal cord impairment. The aims of this study were thus to find significant metabolic biomarkers of inflammation and identify the site of inflammation in the central nervous system (CNS) during the acute signs in of the disease using metabolomics. All the EAE samples were associated with higher levels of lactate, ascorbate, glucose and amino acids, and decreased level of N-acetyl-aspartate (NAA) compared to the control group.

Structural Characterization of the Amyloid Precursor Protein Transmembrane Domain and Its γ-Cleavage Site.

Alzheimer's disease is the most common form of dementia that affects about 50 million of sufferers worldwide. A major role for the initiation and progression of Alzheimer's disease has been associated with the amyloid β-peptide (Aβ), which is a protease cleavage product of the amyloid precursor protein. The amyloid precursor protein is an integral membrane protein with a single transmembrane domain.

Role of positron emission tomography in thyroid and neuroendocrine tumors.

Positron emission tomography (PET) is an established imaging method in oncology. PET/computed tomography (PET/CT) and PET/magnetic resonance imaging (PET/MRI) are hybrid techniques which combine morphological information obtained by CT and MRI with functional data provided by PET. Several PET radiotracers evaluating different metabolic pathways or receptor status can be used to assess endocrine tumors such as thyroid tumors or neuroendocrine neoplasms (NENs).

Membrane perturbing activities and structural properties of the frog-skin derived peptide Esculentin-1a(1-21)NH and its Diastereomer Esc(1-21)-1c: Correlation with their antipseudomonal and cytotoxic activity.

Antimicrobial peptides (AMPs) represent new alternatives to cope with the increasing number of multi-drug resistant microbial infections. Recently, a derivative of the frog-skin AMP esculentin-1a, Esc(1-21), was found to rapidly kill both the planktonic and biofilm forms of the Gram-negative bacterium Pseudomonas aeruginosa with a membrane-perturbing activity as a plausible mode of action. Lately, its diastereomer Esc(1-21)-1c containing two d-amino acids i.

Design and Fabrication of Highly Reducible PtCo Particles Supported on Graphene-Coated ZnO.

Cobalt particles dispersed on an oxide support form the basis of many important heterogeneous catalysts. Strong interactions between cobalt and the support may lead to irreducible cobalt oxide formation, which is detrimental for the catalytic performance. Therefore, several strategies have been proposed to enhance cobalt reducibility, such as alloying with Pt or utilization of nonoxide supports.

Remodeling of Sensorimotor Brain Connectivity in Gpr88-Deficient Mice.

Recent studies have demonstrated that orchestrated gene activity and expression support synchronous activity of brain networks. However, there is a paucity of information on the consequences of single gene function on overall brain functional organization and connectivity and how this translates at the behavioral level. In this study, we combined mouse mutagenesis with functional and structural magnetic resonance imaging (MRI) to determine whether targeted inactivation of a single gene would modify whole-brain connectivity in live animals.

The histidine-rich peptide LAH4-L1 strongly promotes PAMAM-mediated transfection at low nitrogen to phosphorus ratios in the presence of serum.

Non-viral vectors are widely used and investigated for the delivery of genetic material into cells. However, gene delivery barriers like lysosomal degradation, serum inhibition and transient gene expression so far still limit their clinical applications. Aiming to overcome these limitations, a pH-sensitive hybrid gene vector (PSL complex) was designed by self-assembly of poly(amidoamine) (PAMAM) dendrimers, the histidine-rich peptide LAH4-L1 and the sleeping beauty transposon system (SB transposon system, a plasmid system capable of efficient and precise genomic insertion).

Interfacial charge distributions in carbon-supported palladium catalysts.

Controlling the charge transfer between a semiconducting catalyst carrier and the supported transition metal active phase represents an elite strategy for fine turning the electronic structure of the catalytic centers, hence their activity and selectivity. These phenomena have been theoretically and experimentally elucidated for oxide supports but remain poorly understood for carbons due to their complex nanoscale structure. Here, we combine advanced spectroscopy and microscopy on model Pd/C samples to decouple the electronic and surface chemistry effects on catalytic performance.

3D Super-Resolution Optical Profiling Using Microsphere Enhanced Mirau Interferometry.

We present quantitative three dimensional images of grooves on a writable Blu-ray Disc based on a single objective Mirau type interferometric microscope, enhanced with a microsphere which is considered as a photonic nanojet source. Along the optical axis the resolution of this microsphere assisted interferometry system is a few nanometers while the lateral resolution is around 112 nm. To understand the physical phenomena involved in this kind of imaging we have modelled the interaction between the photonic jet and the complex disc surface.

Comparison between isotropic linear-elastic law and isotropic hyperelastic law in the finite element modeling of the brachial plexus.

Augmented reality could help the identification of nerve structures in brachial plexus surgery. The goal of this study was to determine which law of mechanical behavior was more adapted by comparing the results of Hooke's isotropic linear elastic law to those of Ogden's isotropic hyperelastic law, applied to a biomechanical model of the brachial plexus. A model of finite elements was created using the ABAQUS from a 3D model of the brachial plexus acquired by segmentation and meshing of MRI images at 0°, 45° and 135° of shoulder abduction of a healthy subject.

Dual-light control of nanomachines that integrate motor and modulator subunits.

A current challenge in the field of artificial molecular machines is the synthesis and implementation of systems that can produce useful work when fuelled with a constant source of external energy. The first experimental achievements of this kind consisted of machines with continuous unidirectional rotations and translations that make use of 'Brownian ratchets' to bias random motions. An intrinsic limitation of such designs is that an inversion of directionality requires heavy chemical modifications in the structure of the actuating motor part.