Inferring the Effects of Honokiol on the Notch Signaling Pathway in SW480 Colon Cancer Cells.

In a tumor cell, the development of acquired therapeutic resistance and the ability to survive in extracellular environments that differ from the primary site are the result of molecular adaptations in potentially highly plastic molecular networks. The accurate prediction of intracellular networks in a tumor remains a difficult problem in cancer informatics. In order to make truly rational patient-driven therapeutic decisions, it will be critical to develop methodologies that can accurately infer the molecular circuitry in the cells of a specific tumor.

Partial molar enthalpies and reaction enthalpies from equilibrium molecular dynamics simulation.

We present a new molecular simulation technique for determining partial molar enthalpies in mixtures of gases and liquids from single simulations, without relying on particle insertions, deletions, or identity changes. The method can also be applied to systems with chemical reactions. We demonstrate our method for binary mixtures of Weeks-Chandler-Anderson particles by comparing with conventional simulation techniques, as well as for a simple model that mimics a chemical reaction.

Assessment of altered three-dimensional blood characteristics in aortic disease by velocity distribution analysis.

Purpose: To test the feasibility of velocity distribution analysis for identifying altered three-dimensional (3D) flow characteristics in patients with aortic disease based on 4D flow MRI volumetric analysis.

Methods: Forty patients with aortic (Ao) dilation (mid ascending aortic diameter MAA = 40 ± 7 mm, age = 56 ± 17 years, 11 females) underwent cardiovascular MRI. Four groups were retrospectively defined: mild Ao dilation (n = 10; MAA < 35 mm); moderate Ao dilation (n = 10; 35 < MAA < 45 mm); severe Ao dilation (n = 10; MAA > 45 mm); Ao dilation+aortic stenosis AS (n = 10; MAA > 35 mm and peak velocity > 2.

A NOTCH1-driven MYC enhancer promotes T cell development, transformation and acute lymphoblastic leukemia.

Efforts to identify and annotate cancer driver genetic lesions have been focused primarily on the analysis of protein-coding genes; however, most genetic abnormalities found in human cancer are located in intergenic regions. Here we identify a new long range-acting MYC enhancer controlled by NOTCH1 that is targeted by recurrent chromosomal duplications in human T cell acute lymphoblastic leukemia (T-ALL). This highly conserved regulatory element, hereby named N-Me for NOTCH MYC enhancer, is located within a broad super-enhancer region +1.

Supraspinal gene transfer by intrathecal adeno-associated virus serotype 5.

We report the pattern of transgene expression across brain regions after intrathecal delivery of adeno-associated virus serotype 5 (AAV5). Labeling in hindbrain appeared to be primarily neuronal, and was detected in sensory nuclei of medulla, pontine nuclei, and all layers of cerebellar cortex. Expression in midbrain was minimal, and generally limited to isolated neurons and astrocytes in the cerebral peduncles.

Reduced anterior internal capsule white matter integrity in primary insomnia.

Chronic insomnia is one of the most prevalent central nervous system diseases, however, its neurobiology is poorly understood. Up to now, nothing is known about the integrity of white matter tracts in insomnia patients. In this study, diffusion tensor imaging (DTI) was used in a well-characterized sample of primary insomnia (PI) patients and good sleeper controls to fill this void.

Competitive inhibition reaction mechanisms for the two-step model of protein aggregation.

We propose three new reaction mechanisms for competitive inhibition of protein aggregation for the two-step model of protein aggregation. The first mechanism is characterized by the inhibition of native protein, the second is characterized by the inhibition of aggregation-prone protein and the third mechanism is characterized by the mixed inhibition of native and aggregation-prone proteins. Rate equations are derived for these mechanisms, and a method is described for plotting kinetic results to distinguish these three types of inhibitors.

Hartmannibacter diazotrophicus gen. nov., sp. nov., a phosphate-solubilizing and nitrogen-fixing alphaproteobacterium isolated from the rhizosphere of a natural salt-meadow plant.

A phosphate-mobilizing, Gram-negative bacterium was isolated from rhizospheric soil of Plantago winteri from a natural salt meadow as part of an investigation of rhizospheric bacteria from salt-resistant plant species and evaluation of their plant-growth-promoting abilities. Cells were rods, motile, strictly aerobic, oxidase-positive and catalase-negative. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain E19(T) was distinct from other taxa within the class Alphaproteobacteria.

A primary FIsh Gill Cell System (FIGCS) for environmental monitoring of river waters.

Studies were conducted to assess the feasibility of a primary FIsh Gill Cell culture system (FIGCS) for both laboratory and field based environmental monitoring of rivers known to be affected by metal contamination. FIGCS were exposed in the laboratory and in the field to water from the River Hayle, a metal-contaminated system in Cornwall, United Kingdom. Water chemistry, including transition metal concentrations, changes in transepithelial electrical resistance (TEER), cell viability and the expression of metal responsive genes, metallothionein A and B were measured.

Evaluation of aortic stenosis severity using 4D flow jet shear layer detection for the measurement of valve effective orifice area.

Aims: The objective of this study was to evaluate the potential of 4D flow MRI to assess valve effective orifice area (EOA) in patients with aortic stenosis as determined by the jet shear layer detection (JSLD) method.

Methods And Results: An in-vitro stenosis phantom was used for validation and in-vivo imaging was performed in 10 healthy controls and 40 patients with aortic stenosis. EOA was calculated by the JSLD method using standard 2D phase contrast MRI (PC-MRI) and 4D flow MRI measurements (EOAJSLD-2D and EOAJSLD-4D, respectively).

Transcatheter aortic valve replacement program development: recommendations for best practice.

Background: Transcatheter aortic valve replacement (TAVR) is an increasingly available therapy for the management of aortic stenosis in higher risk populations. Beyond addressing the procedural challenges, centers must attend to the unique requirements of developing TAVR programs from referral to follow-up.

Aim: The aim of this article is to outline the recommendations for best practice for program development from centers with early and extensive experience.

4D flow imaging: current status to future clinical applications.

4D flow MRI permits a comprehensive in-vivo assessment of three-directional blood flow within 3-dimensional vascular structures throughout the cardiac cycle. Given the large coverage permitted from a 4D flow acquisition, the distribution of vessel wall and flow parameters along an entire vessel of interest can thus be derived from a single measurement without being dependent on multiple predefined 2D acquisitions. In addition to qualitative 3D visualizations of complex cardiac and vascular flow patterns, quantitative flow analysis can be performed and is complemented by the ability to compute sophisticated hemodynamic parameters, such as wall shear stress or 3D pressure difference maps.

Optimal experimental design to estimate statistically significant periods of oscillations in time course data.

We investigated commonly used methods (Autocorrelation, Enright, and Discrete Fourier Transform) to estimate the periodicity of oscillatory data and determine which method most accurately estimated periods while being least vulnerable to the presence of noise. Both simulated and experimental data were used in the analysis performed. We determined the significance of calculated periods by applying these methods to several random permutations of the data and then calculating the probability of obtaining the period's peak in the corresponding periodograms.

Gill cell culture systems as models for aquatic environmental monitoring.

A vast number of chemicals require environmental safety assessments for market authorisation. To ensure acceptable water quality, effluents and natural waters are monitored for their potential harmful effects. Tests for market authorisation and environmental monitoring usually involve the use of large numbers of organisms and, for ethical, cost and logistic reasons, there is a drive to develop alternative methods that can predict toxicity to fish without the need to expose any animals.

Unraveling intestinal stem cell behavior with models of crypt dynamics.

The definition, regulation and function of intestinal stem cells (ISCs) has been hotly debated. Recent discoveries have started to clarify the nature of ISCs, but many questions remain. This review discusses the current advances and controversies of ISC biology as well as theoretical compartmental models that have been coupled with in vivo experimentation to investigate the mechanisms of ISC dynamics during homeostasis, tumorigenesis, repair and development.

Rheinheimera hassiensis sp. nov. and Rheinheimera muenzenbergensis sp. nov., two species from the rhizosphere of Hordeum secalinum.

Two motile, Gram-staining-negative, aerobic, rod-shaped bacteria designated strains E48(T) and E49(T) were isolated from the rhizosphere of Hordeum secalinum from a natural salt meadow near Münzenberg, Germany. 16S rRNA gene sequence similarity analysis revealed that strains E48(T) and E49(T) shared similarities of 97.6 % with Rheinheimera pacifica KMM 1406(T) and 98.

Bicuspid aortic cusp fusion morphology alters aortic three-dimensional outflow patterns, wall shear stress, and expression of aortopathy.

Background: Aortic 3-dimensional blood flow was analyzed to investigate altered ascending aorta (AAo) hemodynamics in bicuspid aortic valve (BAV) patients and its association with differences in cusp fusion patterns (right-left, RL versus right-noncoronary, RN) and expression of aortopathy.

Methods And Results: Four-dimensional flow MRI measured in vivo 3-dimensional blood flow in the aorta of 75 subjects: BAV patients with aortic dilatation stratified by leaflet fusion pattern (n=15 RL-BAV, mid AAo diameter=39.9±4.

Single-molecule enzymology à la Michaelis-Menten.

Over the past 100 years, deterministic rate equations have been successfully used to infer enzyme-catalysed reaction mechanisms and to estimate rate constants from reaction kinetics experiments conducted in vitro. In recent years, sophisticated experimental techniques have been developed that begin to allow the measurement of enzyme-catalysed and other biopolymer-mediated reactions inside single cells at the single-molecule level. Time-course data obtained using these methods are considerably noisy because molecule numbers within cells are typically quite small.

From unicuspid to quadricuspid: influence of aortic valve morphology on aortic three-dimensional hemodynamics.

Purpose: To assess the impact of aortic valve morphology on aortic hemodynamics between normal tricuspid and congenitally anomalous aortic valves ranging from unicuspid to quadricuspid morphology.

Materials And Methods: Aortic three-dimensional (3D) blood flow was evaluated by 4D flow MRI in 14 healthy volunteers with normal trileaflet valves and 14 patients with unicuspid (n = 3), bicuspid (n = 9, 3 "true" bicuspid, 3 right-left (RL), 3 right-noncoronary (RN) leaflet fusion, and quadricuspid aortic valves (n = 2). Data analysis included the co-registered visualization of aortic valve morphology with systolic 3D blood flow.

White matter microstructure alterations of the medial forebrain bundle in melancholic depression.

Background: The medial forebrain bundle (MFB) is a key structure of the reward system and connects the ventral tegmental area (VTA) with the nucleus accumbens (NAcc), the medial and lateral orbitofrontal cortex (mOFC, lOFC) and the dorsolateral prefrontal cortex (dlPFC). Previous diffusion tensor imaging (DTI) studies in major depressive disorder point to white matter alterations of regions which may be incorporated in the MFB. Therefore, it was the aim of our study to probe white matter integrity of the MFB using a DTI-based probabilistic fibre tracking approach.

Validity of the Michaelis-Menten equation--steady-state or reactant stationary assumption: that is the question.

The Michaelis-Menten equation is generally used to estimate the kinetic parameters, V and K(M), when the steady-state assumption is valid. Following a brief overview of the derivation of the Michaelis-Menten equation for the single-enzyme, single-substrate reaction, a critical review of the criteria for validity of the steady-state assumption is presented. The application of the steady-state assumption makes the implicit assumption that there is an initial transient during which the substrate concentration remains approximately constant, equal to the initial substrate concentration, while the enzyme-substrate complex concentration builds up.

Fronto-parietal dorsal and ventral pathways in the context of different linguistic manipulations.

This study investigates structural connectivity between left fronto-parietal brain regions that were identified in a previous fMRI study which used different linguistic manipulation tasks. Diffusion-weighted images were acquired from 20 volunteers. Structural connectivity between brain regions from the fMRI study was computed using probabilistic fiber tracking.