Molecular Motion in Viscous DGEBA with Nanoparticles as Seen by Quasi‐Elastic Neutron Scattering

Pure and filled epoxies are widely used in industry. Nanocomposites especially are affected by interphase regions where properties deviate from bulk. The study of molecular mobility in epoxy monomers is a first step to understanding the molecular dynamics in nanocomposites and their effect on crosslinking in epoxy networks. Here, quasi‐elastic neutron scattering is used to disentangle the molecular motions of monomeric diglycidylether of Bisphenol A (DGEBA) and a suspension of zeolite nanoparticles in DGEBA on a timescale from 2 ps to 5.5 ns. Regarding molecular transport of DGEBA inside the suspension, the particles have no impact on the faster rotational motions. A combination of neutron time‐of‐flight and backscattering spectroscopy reveals a pronounced hindrance of DGEBA molecular dynamics on/in the zeolite particles along with a new type of molecular motion occurring on intermediate timescales. That localized motion is attributed to jump diffusion motions, emanating from interphase effects at the zeolite particles.     

A novel slow-inactivation-specific ion channel modulator attenuates neuropathic pain

Voltage-gated ion channels are implicated in pain sensation and transmission signaling mechanisms within both peripheral nociceptors and the spinal cord. Genetic knockdown and knockout experiments have shown that specific channel isoforms, including Na_V1.7 and Na_V1.8 sodium channels and Ca_V3.2 T-type calcium channels, play distinct pronociceptive roles. We have rationally designed and synthesized a novel small organic compound (Z123212) that modulates both recombinant and native sodium and calcium channel currents by selectively stabilizing channels in their slow-inactivated state. Slow inactivation of voltage-gated channels can function as a brake during periods of neuronal hyperexcitability, and Z123212 was found to reduce the excitability of both peripheral nociceptors and lamina I/II spinal cord neurons in a state-dependent manner. In vivo experiments demonstrate that oral administration of Z123212 is efficacious in reversing thermal hyperalgesia and tactile allodynia in the rat spinal nerve ligation model of neuropathic pain and also produces acute antinociception in the hot-plate test. At therapeutically relevant concentrations, Z123212 did not cause significant motor or cardiovascular adverse effects. Taken together, the state-dependent inhibition of sodium and calcium channels in both the peripheral and central pain signaling pathways may provide a synergistic mechanism toward the development of a novel class of pain therapeutics.     

Endogenous testosterone density is an independent predictor of pelvic lymph node invasion in high-risk prostate cancer: results in 201 consecutive patients treated with radical prostatectomy and extended pelvic lymph node dissection

International Urology and Nephrology - To evaluate the influence of endogenous testosterone density (ETD) on pelvic lymph node invasion (PLNI) in high risk (HR) prostate cancer (PCa) treated with...     

DNA degradation test predicts success in whole-genome amplification from diverse clinical samples

The need to apply modern technologies to analyze DNA from diverse clinical samples often stumbles on suboptimal sample quality. We developed a simple approach to assess DNA fragmentation in minute clinical samples of widely different origin and the likelihood of success of degradation-tolerant whole genome amplification (restriction and circularization-aided rolling circle amplification, RCA-RCA) and subsequent polymerase chain reaction (PCR). A multiplex PCR amplification of four glyceraldehyde-3-phosphate dehydrogenase amplicons of varying sizes was performed using genomic DNA from clinical samples, followed by size discrimination on agarose gel or fluorescent denaturing high-performance liquid chromatography (dHPLC). RCA-RCA followed by real-time PCR was also performed, for correlation. Even minimal quantities of longer PCR fragments ( approximately 300 to 400 bp), visible via high-sensitivity fluorescent dHPLC or agarose gel, were essential for the success of RCA-RCA and subsequent PCR-based assays. dHPLC gave a more accurate correlation between DNA fragmentation and sample quality than agarose gel electrophoresis. Multiplex-PCR-dHPLC predicted correctly the likelihood of assay success in formalin-fixed, paraffin-embedded samples fixed under controlled conditions and of different ages, in laser capture microdissection samples, in tissue print micropeels, and plasma-circulating DNA. Estimates of the percent information retained relative to snap-frozen DNA are derived for real-time PCR analysis. The assay is rapid and convenient and can be used widely to characterize DNA from any clinical sample of unknown quality.     

Aβ neurotoxicity depends on interactions between copper ions, prion protein, and N-methyl-D-aspartate receptors

N-methyl-d-aspartate receptors (NMDARs) mediate critical CNS functions, whereas excessive activity contributes to neuronal damage. At physiological glycine concentrations, NMDAR currents recorded from cultured rodent hippocampal neurons exhibited strong desensitization in the continued presence of NMDA, thus protecting neurons from calcium overload. Reducing copper availability by specific chelators (bathocuproine disulfonate, cuprizone) induced nondesensitizing NMDAR currents even at physiologically low glycine concentrations. This effect was mimicked by, and was not additive with, genetic ablation of cellular prion protein (PrP(C)), a key copper-binding protein in the CNS. Acute ablation of PrP(C) by enzymatically cleaving its cell-surface GPI anchor yielded similar effects. Biochemical studies and electrophysiological measurements revealed that PrP(C) interacts with the NMDAR complex in a copper-dependent manner to allosterically reduce glycine affinity for the receptor. Synthetic human Aβ(1-42) (10 nM-5 μM) produced an identical effect that could be mitigated by addition of excess copper ions or NMDAR blockers. Taken together, Aβ(1-42), copper chelators, or PrP(C) inactivation all enhance the activity of glycine at the NMDAR, giving rise to pathologically large nondesensitizing steady-state NMDAR currents and neurotoxicity. We propose a physiological role for PrP(C), one that limits excessive NMDAR activity that might otherwise promote neuronal damage. In addition, we provide a unifying molecular mechanism whereby toxic species of Aβ(1-42) might mediate neuronal and synaptic injury, at least in part, by disrupting the normal copper-mediated, PrP(C)-dependent inhibition of excessive activity of this highly calcium-permeable glutamate receptor.     

Presentation and interpretation of food intake data: Factors affecting comparability across studies

Non-uniform, unclear, or incomplete presentation of food intake data limits interpretation, usefulness, and comparisons across studies. In this contribution, we discuss factors affecting uniform reporting of food intake across studies. The amount of food eaten can be reported as mean portion size, number of servings or total amount of food consumed per day; the absolute intake value for the specific study depends on the denominator used because food intake data can be presented as per capita intake or for consumers only. To identify the foods mostly consumed, foods are reported and ranked according to total number of times consumed, number of consumers, total intake, or nutrient contribution by individual foods or food groups. Presentation of food intake data primarily depends on a study's aim; reported data thus often are not comparable across studies. Food intake data further depend on the dietary assessment methodology used and foods in the database consulted; and are influenced by the inherent limitations of all dietary assessments. Intake data can be presented as either single foods or as clearly defined food groups. Mixed dishes, reported as such or in terms of ingredients and items added during food preparation remain challenging. Comparable presentation of food consumption data is not always possible; presenting sufficient information will assist valid interpretation and optimal use of the presented data. A checklist was developed to strengthen the reporting of food intake data in science communication.