Acid ceramidase is a novel drug target for pediatric brain tumors.

Pediatric brain tumors are the most common solid tumors in children and are also a leading culprit of cancer-related fatalities in children. Pediatric brain tumors remain hard to treat. In this study, we demonstrated that medulloblastoma, pediatric glioblastoma, and atypical teratoid rhabdoid tumors express significant levels of acid ceramidase, where levels are highest in the radioresistant tumors, suggesting that acid ceramidase may confer radioresistance.

Trends of PM concentrations in China: A long term approach.

The fast economic growth of China along the last two decades has created a strong impact on the environment. The occurrence of heavy haze pollution days is the most visible effect. Although many researchers have studied such problem, a high number of spatio-temporal limitations in the recent studies were identified.

Adhesion of ligand-conjugated biosynthesized magnetite nanoparticles to triple negative breast cancer cells.

This paper presents the results of an experimental study of the adhesion forces between components of model conjugated magnetite nanoparticle systems for improved selectivity in the specific targeting of triple negative breast cancer. Adhesion forces between chemically synthesized magnetite nanoparticles (CMNPs), biosynthesized magnetite nanoparticles (BMNPs), as well as their conjugated systems and triple negative breast cancer cells (MDA-MB-231) or normal breast cells (MCF 10A) are elucidated at a nanoscale. In all cases, the BMNPs had higher adhesion forces (to breast cancer cells and normal breast cells) than CMNPs.

Mitochondria-regulated formation of endothelium-derived extracellular vesicles shifts the mediator of flow-induced vasodilation.

To examine the effect of endothelium-derived extracellular vesicles (eEVs) on the mediator of flow-induced dilation (FID), composition, formation, and functional effects on the mediator of FID were examined from two different eEV subtypes, one produced from ceramide, while the other was produced from plasminogen-activator inhibitor 1 (PAI-1). Using video microscopy, we measured internal-diameter changes in response to increases in flow in human adipose resistance arteries acutely exposed (30 min) to eEVs derived from cultured endothelial cells exposed to ceramide or PAI-1. FID was significantly impaired following exposure to 500K/ml (K = 1,000) of ceramide-induced eEVs (Cer-eEVs) but unaffected by 250K/ml.

Proteomic Screen for Cellular Targets of the Vaccinia Virus F10 Protein Kinase Reveals that Phosphorylation of mDia Regulates Stress Fiber Formation.

Vaccinia virus, a complex dsDNA virus, is unusual in replicating exclusively within the cytoplasm of infected cells. Although this prototypic poxvirus encodes >200 proteins utilized during infection, a significant role for host proteins and cellular architecture is increasingly evident. The viral B1 kinase and H1 phosphatase are known to target cellular proteins as well as viral substrates, but little is known about the cellular substrates of the F10 kinase.

Whole Body Coordination and Knee Movement Control During Five Rehabilitation Exercises.

Knee rehabilitation exercises to improve motor control, target movement fluency, and displacement variability. Although knee movement in the frontal plane during exercise is routinely assessed in clinical practice, optimal knee control remains poorly understood. In this study, 29 healthy participants (height: 1.

LVAD Outflow Graft Angle and Thrombosis Risk.

This study quantifies thrombogenic potential (TP) of a wide range of left ventricular assist device (LVAD) outflow graft anastomosis angles through state-of-the-art techniques: 3D imaged-based patient-specific models created via virtual surgery and unsteady computational fluid dynamics with Lagrangian particle tracking. This study aims at clarifying the influence of a single parameter (outflow graft angle) on the thrombogenesis associated with flow patterns in the aortic root after LVAD implantation. This is an important and poorly-understood aspect of LVAD therapy, because several studies have shown strong inter and intrapatient thrombogenic variability and current LVAD implantation strategies do not incorporate outflow graft angle optimization.

Computational Study of Fracture Characteristics in Infant Skulls Using a Simplified Finite Element Model.

Skull fracture characteristics are associated with loading conditions (such as the impact point and impact velocity) and could provide indication of abuse or accident-induced head injuries. However, correlations between fracture characteristics and loading conditions in infant and toddler are ill-understood. A simplified computational model representing an infant head was built to simulate skull responses to blunt impacts.

Creation of an idealized nasopharynx geometry for accurate computational fluid dynamics simulations of nasal airflow in patient-specific models lacking the nasopharynx anatomy.

Virtual surgery planning based on computational fluid dynamics (CFD) simulations has the potential to improve surgical outcomes for nasal airway obstruction patients, but the benefits of virtual surgery planning must outweigh the risks of radiation exposure. Cone beam computed tomography (CT) scans represent an attractive imaging modality for virtual surgery planning due to lower costs and lower radiation exposures compared with conventional CT scans. However, to minimize the radiation exposure, the cone beam CT sinusitis protocol sometimes images only the nasal cavity, excluding the nasopharynx.

Association of TMTC2 With Human Nonsyndromic Sensorineural Hearing Loss.

Importance: Sensorineural hearing loss (SNHL) is commonly caused by conditions that affect cochlear structures or the auditory nerve, and the genes identified as causing SNHL to date only explain a fraction of the overall genetic risk for this debilitating disorder. It is likely that other genes and mutations also cause SNHL.

Objective: To identify a candidate gene that causes bilateral, symmetric, progressive SNHL in a large multigeneration family of Northern European descent.

Hippocampal proteomics defines pathways associated with memory decline and resilience in normal aging and Alzheimer's disease mouse models.

Alzheimer's disease (AD), the most common form of dementia in the elderly, has no cure. Thus, the identification of key molecular mediators of cognitive decline in AD remains a top priority. As aging is the most significant risk factor for AD, the goal of this study was to identify altered proteins and pathways associated with the development of normal aging and AD memory deficits, and identify unique proteins and pathways that may contribute to AD-specific symptoms.

Numerical simulations of the 10-year-old head response in drop impacts and compression tests.

Background And Objective: Studies on traumatic injuries of children indicate that impact to the head is a major cause of severe injury and high mortality. However, regulatory and ethical concerns very much limit development and validation of computer models representing the pediatric head. The purpose of this study was to develop a child head finite element model with high-biofidelity to be used for studying pediatric head injury mechanisms.

Image-based quantification of 3D morphology for bifurcations in the left coronary artery: Application to stent design.

Background: Improved strategies for stent-based treatment of coronary artery disease at bifurcations require a greater understanding of artery morphology.

Objective: We developed a workflow to quantify morphology in the left main coronary (LMCA), left anterior descending (LAD), and left circumflex (LCX) artery bifurcations.

Methods: Computational models of each bifurcation were created for 55 patients using computed tomography images in 3D segmentation software.

Tepidibacillus infernus sp. nov., a moderately thermophilic, selenate- and arsenate-respiring hydrolytic bacterium isolated from a gold mine, and emended description of the genus Tepidibacillus.

A novel aerotolerant anaerobic, moderately thermophilic, organotrophic bacterium, strain MBL-TLPT, was isolated from a sample of microbial mat, developed under the flow of subsurface water in TauTona gold mine, South Africa. Cells of the new isolate were flagellated, spore-forming rods, 0.25-0.

HyCCAPP as a tool to characterize promoter DNA-protein interactions in Saccharomyces cerevisiae.

Currently available methods for interrogating DNA-protein interactions at individual genomic loci have significant limitations, and make it difficult to work with unmodified cells or examine single-copy regions without specific antibodies. In this study, we describe a physiological application of the Hybridization Capture of Chromatin-Associated Proteins for Proteomics (HyCCAPP) methodology we have developed. Both novel and known locus-specific DNA-protein interactions were identified at the ENO2 and GAL1 promoter regions of Saccharomyces cerevisiae, and revealed subgroups of proteins present in significantly different levels at the loci in cells grown on glucose versus galactose as the carbon source.

Impact of Middle versus Inferior Total Turbinectomy on Nasal Aerodynamics.

Objectives: This computational study aims to (1) use virtual surgery to theoretically investigate the maximum possible change in nasal aerodynamics after turbinate surgery, (2) quantify the relative contributions of the middle and inferior turbinates to nasal resistance and air conditioning, and (3) quantify to what extent total turbinectomy impairs the nasal air-conditioning capacity.

Study Design: Virtual surgery and computational fluid dynamics.

Setting: Academic tertiary medical center.

Semi-supervised clustering of fractionated electrograms for electroanatomical atrial mapping.

Background: Electrogram-guided ablation procedures have been proposed as an alternative strategy consisting of either mapping and ablating focal sources or targeting complex fractionated electrograms in atrial fibrillation (AF). However, the incomplete understanding of the mechanism of AF makes difficult the decision of detecting the target sites. To date, feature extraction from electrograms is carried out mostly based on the time-domain morphology analysis and non-linear features.

The relationship between nasal resistance to airflow and the airspace minimal cross-sectional area.

The relationship between nasal resistance (R) and airspace minimal cross-sectional area (mCSA) remains unclear. After the introduction of acoustic rhinometry, many otolaryngologists believed that mCSA measurements would correlate with subjective perception of nasal airway obstruction (NAO), and thus could provide an objective measure of nasal patency to guide therapy. However, multiple studies reported a low correlation between mCSA and subjective nasal patency, and between mCSA and R.

Pharmacological Modulation of Hemodynamics in Adult Zebrafish In Vivo.

Introduction: Hemodynamic parameters in zebrafish receive increasing attention because of their important role in cardiovascular processes such as atherosclerosis, hematopoiesis, sprouting and intussusceptive angiogenesis. To study underlying mechanisms, the precise modulation of parameters like blood flow velocity or shear stress is centrally important. Questions related to blood flow have been addressed in the past in either embryonic or ex vivo-zebrafish models but little information is available for adult animals.

Effect of encapsulation on plasminogen activator delivery to the microcirculation and its implications for bleeding.

Background And Purpose: It is known that encapsulation can alter the delivery of plasminogen activators by flow to accelerate fibrinolysis while other experimental studies suggest encapsulation may reduce the risk of hemorrhage with administration of the agent. The aim of this research is to resolve the effect of encapsulation on fibrinolysis and bleeding in the microcirculation.

Methods: An established rabbit model of fibrinolytic hemorrhage was utilized to explore the potential of encapsulation to limit bleeding.

Impact of a cytomegalovirus kinase inhibitor on infection and neuronal progenitor cell differentiation.

Human cytomegalovirus (HCMV) is the leading cause of congenital infections. Symptomatic newborns present with a range of sequelae including disorders of the CNS such as visual impairment, microcephaly, mental retardation and hearing loss. HCMV congenital infection causes gross changes in brain morphology and disturbances in glial and neuronal distribution, number and migration.

Tumor Necrosis Factor α Regulates Endothelial Progenitor Cell Migration via CADM1 and NF-kB.

Shortly after the discovery of endothelial progenitor cells (EPCs) in 1997, many clinical trials were conducted using EPCs as a cellular based therapy with the goal of restoring damaged organ function by inducing growth of new blood vessels (angiogenesis). Results were disappointing, largely because the cellular and molecular mechanisms of EPC-induced angiogenesis were not clearly understood. Following injection, EPCs must migrate to the target tissue and engraft prior to induction of angiogenesis.

Mg(2+) differentially regulates two modes of mitochondrial Ca(2+) uptake in isolated cardiac mitochondria: implications for mitochondrial Ca(2+) sequestration.

The manner in which mitochondria take up and store Ca(2+) remains highly debated. Recent experimental and computational evidence has suggested the presence of at least two modes of Ca(2+) uptake and a complex Ca(2+) sequestration mechanism in mitochondria. But how Mg(2+) regulates these different modes of Ca(2+) uptake as well as mitochondrial Ca(2+) sequestration is not known.

Mechanical Characterization of Immature Porcine Brainstem in Tension at Dynamic Strain Rates.

Background: Many brain injury cases involve pediatric road traffic accidents, and among these, brainstem injury causes disastrous outcomes. A thorough understanding of the tensile characterization of immature brainstem tissue is crucial in modeling traumatic brain injury sustained by children, but limited experimental data in tension is available for the immature brain tissue at dynamic strain rates.

Material And Methods: We harvested brainstem tissue from immature pigs (about 4 weeks old, and at a developmental stage similar to that of human toddlers) as a byproduct from a local slaughter house and very carefully prepared the samples.