Concise Review: Induced Pluripotent Stem Cell-Based Drug Discovery for Mitochondrial Disease.

High attrition rates and loss of capital plague the drug discovery process. This is particularly evident for mitochondrial disease that typically involves neurological manifestations and is caused by nuclear or mitochondrial DNA defects. This group of heterogeneous disorders is difficult to target because of the variability of the symptoms among individual patients and the lack of viable modeling systems.

Photochemical Properties of the Red-shifted Channelrhodopsin Chrimson.

Color-tuned variants of channelrhodopsins allow for selective optogenetic manipulation of different host cell populations. Chrimson is the channelrhodopsin with the longest wavelength absorbance maximum. We characterize its photochemical properties at different pH values corresponding to two protonation states of the counterion for the protonated Schiff base.

Nano-sized Al2O3 reduces acute toxic effects of thiacloprid on the non-biting midge Chironomus riparius.

This study focuses on interactions between nanoparticles and a pesticide. The aim was to investigate how nano-sized aluminum oxide (410 nm) can alter the toxic effects of thiacloprid, even if no sorption between particles and the insecticide takes place. Thus, our study investigated a rather unexplored interaction.

Nonequilibrium generalised Langevin equation for the calculation of heat transport properties in model 1D atomic chains coupled to two 3D thermal baths.

We use a generalised Langevin equation scheme to study the thermal transport of low dimensional systems. In this approach, the central classical region is connected to two realistic thermal baths kept at two different temperatures [H. Ness et al.

Endocrine disruption by environmental gestagens in amphibians - A short review supported by new in vitro data using gonads of Xenopus laevis.

Endocrine disruption caused by various anthropogenic compounds is of persisting concern, especially for aquatic wildlife, because surface waters are the main sink of these so-called endocrine disruptors (ED). In the past, research focused on (anti)estrogenic, (anti)androgenic, and (anti)thyroidal substances, affecting primarily reproduction and development in vertebrates; however, other endocrine systems might be also targeted by ED. Environmental gestagens, including natural progestogens (e.

tRNA Modifications: Impact on Structure and Thermal Adaptation.

Transfer RNAs (tRNAs) are central players in translation, functioning as adapter molecules between the informational level of nucleic acids and the functional level of proteins. They show a highly conserved secondary and tertiary structure and the highest density of post-transcriptional modifications among all RNAs. These modifications concentrate in two hotspots-the anticodon loop and the tRNA core region, where the D- and T-loop interact with each other, stabilizing the overall structure of the molecule.

Cardiolipin Supports Respiratory Enzymes in Plants in Different Ways.

In eukaryotes the presence of the dimeric phospholipid cardiolipin (CL) is limited to the mitochondrial membranes. It resides predominantly in the inner membrane where it interacts with components of the mitochondrial electron transfer chain. CL deficiency has previously been shown to affect abundances of the plant NADH-dehydrogenase complex and its association with dimeric cyctochrome c reductase.

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The guideline "The Acute Scrotum in Children and Adolescents" has been developed by representatives of the German Society of Pediatric Surgery, the German Society for Urology, and the German Society for Pediatric Radiology confirmed by the German Society for Pediatric and Adolescent Medicine. It went online in December 2015. The core statements of the guideline will be summarised.

Salt Interactions in Solution Prevent Direct Association of Urea with a Peptide Backbone.

There is an ongoing debate as to how urea denatures proteins in solution. Using a combination of neutron scattering and computer simulation of a model peptide, KGPGK, it was found that the ionic strength and pH have a significant impact on the urea-peptide interaction. From the work presented here, it appears that urea first and foremost decreases the charge-based interactions in solution, such as the TFA-TFA association, before interacting with the peptide backbone via hydrogen bonds.

Human iPSC-Derived Neural Progenitors Are an Effective Drug Discovery Model for Neurological mtDNA Disorders.

Mitochondrial DNA (mtDNA) mutations frequently cause neurological diseases. Modeling of these defects has been difficult because of the challenges associated with engineering mtDNA. We show here that neural progenitor cells (NPCs) derived from human induced pluripotent stem cells (iPSCs) retain the parental mtDNA profile and exhibit a metabolic switch toward oxidative phosphorylation.

Quantification of fibrous spatial point patterns from single-molecule localization microscopy (SMLM) data.

Motivation: Unlike conventional microscopy which produces pixelated images, SMLM produces data in the form of a list of localization coordinates-a spatial point pattern (SPP). Often, such SPPs are analyzed using cluster analysis algorithms to quantify molecular clustering within, for example, the plasma membrane. While SMLM cluster analysis is now well developed, techniques for analyzing fibrous structures remain poorly explored.

From by-product to valuable components: Efficient enzymatic conversion of lactose in whey using β-galactosidase from .

β-Galactosidase from was overexpressed in a food-grade organism, WCFS1. Laboratory cultivations yielded 11,000 U of β-galactosidase activity per liter of culture corresponding to approximately 170 mg of enzyme. Crude cell-free enzyme extracts obtained by cell disruption and subsequent removal of cell debris showed high stability and were used for conversion of lactose in whey permeate.

Antimicrobial Peptide Potency is Facilitated by Greater Conformational Flexibility when Binding to Gram-negative Bacterial Inner Membranes.

The interaction of antimicrobial peptides (AMPs) with the inner membrane of Gram-negative bacteria is a key determinant of their abilities to exert diverse bactericidal effects. Here we present a molecular level understanding of the initial target membrane interaction for two cationic α-helical AMPs that share structural similarities but have a ten-fold difference in antibacterial potency towards Gram-negative bacteria. The binding and insertion from solution of pleurocidin or magainin 2 to membranes representing the inner membrane of Gram-negative bacteria, comprising a mixture of 128 anionic and 384 zwitterionic lipids, is monitored over 100 ns in all atom molecular dynamics simulations.

Differential proteomics analysis of Frankliniella occidentalis immune response after infection with Tomato spotted wilt virus (Tospovirus).

Tomato spotted wilt virus (TSWV) is mainly vectored by Frankliniella occidentalis Pergande, and it potentially activates the vector's immune response. However, molecular background of the altered immune response is not clearly understood. Therefore, using a proteomic approach, we investigated the immune pathways that are activated in F.

Specific effects of monovalent counterions on the structural and interfacial properties of dodecyl sulfate monolayers.

A series of molecular dynamics simulations have been conducted in order to study the specific ion effects of Li, Na, Cs and NH cations on dodecyl sulfate (DS) monolayers. Varying the counterion had no appreciable effect on the structure of the surfactant molecules within the different monolayers. However, the different counterions have a significant effect on the interfacial properties of the monolayer.

Transcriptional Responses of Escherichia coli to a Small-Molecule Inhibitor of LolCDE, an Essential Component of the Lipoprotein Transport Pathway.

Unlabelled: In Gram-negative bacteria, a dedicated machinery consisting of LolABCDE components targets lipoproteins to the outer membrane. We used a previously identified small-molecule inhibitor of the LolCDE complex of Escherichia coli to assess the global transcriptional consequences of interference with lipoprotein transport. Exposure of E.

Usefulness of ultrasonography is the evaluation of thyroid nodules.

Objective: To evaluate the diagnostic capacity of ultrasonography (US) for differentiating between malignant and benign thyroid nodules and its usefulness in obviating unnecessary invasive procedures.

Patients And Methods: From January 2012 through December 2014, a total of 321 fine-needle aspiration biopsy (FNAB) procedures were done in 302 patients selected according to the criteria recommended by the American Association of Clinical Endocrinology guidelines and the American Thyroid Association guidelines. We analyzed the following characteristics on US: location, size, morphology, contour, consistency, echostructure, echogenicity, calcifications, and vascularization.

A movement disorder with dystonia and ataxia caused by a mutation in the HIBCH gene.

Background: Recessive mutations in the 3-hydroxyisobutyryl-CoA hydrolase gene (HIBCH) are associated with a rare neurodegenerative disease that affects the basal ganglia. Most patients die during infancy or early childhood. Here we describe 5 adolescent and adult patients from 2 unrelated families, who presented with a movement disorder and MRI features suggestive of Leigh syndrome.

Four challenges in medical image analysis from an industrial perspective.

Today's medical imaging systems produce a huge amount of images containing a wealth of information. However, the information is hidden in the data and image analysis algorithms are needed to extract it, to make it readily available for medical decisions and to enable an efficient work flow. Advances in medical image analysis over the past 20 years mean there are now many algorithms and ideas available that allow to address medical image analysis tasks in commercial solutions with sufficient performance in terms of accuracy, reliability and speed.

Comparative atomic-scale hydration of the ceramide and phosphocholine headgroup in solution and bilayer environments.

Previous studies have used neutron diffraction to elucidate the hydration of the ceramide and the phosphatidylcholine headgroup in solution. These solution studies provide bond-length resolution information on the system, but are limited to liquid samples. The work presented here investigates how the hydration of ceramide and phosphatidylcholine headgroups in a solution compares with that found in a lipid bilayer.

The synthetic gestagen levonorgestrel directly affects gene expression in thyroid and pituitary glands of Xenopus laevis tadpoles.

The synthetic gestagen levonorgestrel (LNG) was previously shown to perturb thyroid hormone-dependent metamorphosis in Xenopus laevis. However, so far the mechanisms underlying the anti-metamorphic effects of LNG remained unknown. Therefore, a series of in vivo and ex vivo experiments was performed to identify potential target sites of LNG action along the pituitary-thyroid axis of X.

Design and Synthesis of Fsp(3)-Rich, Bis-Spirocyclic-Based Compound Libraries for Biological Screening.

The exploration of innovative chemical space is a critical step in the early phases of drug discovery. Bis-spirocyclic frameworks occur in natural products and other biologically relevant metabolites and show attractive features, such as molecular compactness, structural complexity, and three-dimensional character. A concise approach to the synthesis of bis-spirocyclic-based compound libraries starting from readily available commercial reagents and robust chemical transformations has been developed.