808 research outputs found
Nonmyocytes as electrophysiological contributors to cardiac excitation and conduction.
Although cardiac action potential (AP) generation and propagation have traditionally been attributed exclusively to cardiomyocytes (CM), other cell types in the heart are also capable of forming electrically conducting junctions. Interactions between CM and nonmyocytes (NM) enable and modulate each other's activity. This review provides an overview of the current understanding of heterocellular electrical communication in the heart. Although cardiac fibroblasts were initially thought to be electrical insulators, recent studies have demonstrated that they form functional electrical connections with CM in situ. Other NM, such as macrophages, have also been recognized as contributing to cardiac electrophysiology and arrhythmogenesis. Novel experimental tools have enabled the investigation of cell-specific activity patterns in native cardiac tissue, which is expected to yield exciting new insights into the development of novel or improved diagnostic and therapeutic strategies.A.S.-C. received financial support via a “la Caixa” Foundation
under ID 100010434 and PhD Fellowship LCF/BQ/DR19/11740029.S
New insights into solvent-induced structural changes of C-13 labelled metal-organic frameworks by solid state NMR
Selective C-13-labelling of carboxylate carbons in the linker molecules of flexible metal-organic frameworks (MOFs) makes solid-state NMR spectroscopy very powerful to investigate solvent-induced local structural changes as demonstrated by C-13 and H-1 NMR spectroscopy on the pillared layer MOF DUT-8(Ni). Selective identification of polar solvent-node interactions becomes feasible
JNK inhibition sensitises hepatocellular carcinoma cells but not normal hepatocytes to the TNF-related apoptosis-inducing ligand.
Background: cJun terminal kinase (JNK) is constitutively
activated in most hepatocellular carcinomas (HCCs), yet
its exact role in carcinogenesis remains controversial.
While tumour necrosis factor (TNF)-related apoptosisinducing
ligand (TRAIL) is known as a major mediator of
acquired immune tumour surveillance, and is currently
being tested in clinical trials as a novel cancer therapy,
the resistance of many tumours to TRAIL and concerns
about its toxicity in vivo represent obstacles to its clinical
application. In this study we investigated whether JNK
activity in HCC could contribute to the resistance to
apoptosis in these tumours.
Methods: The effect of JNK/Jun inhibition on receptormediated
apoptosis was analysed by pharmacological
inhibition or RNA interference in cancer cells and nontumour
cells isolated from human liver or transgenic mice
lacking a phosphorylation site for Jun.
Results: JNK inhibition caused cell cycle arrest,
enhanced caspase recruitment, and greatly sensitised
HCC cells but not normal hepatocytes to TRAIL. TRAILinduced
activation of JNK could be effectively interrupted
by administration of the JNK inhibitor SP600125.
Conclusions: Expression and TRAIL-dependent feedback
activation of JNK likely represent a mechanism by which
cancer cells escape TRAIL-mediated tumour surveillance.
JNK inhibition might represent a novel strategy for
specifically sensitising HCC cells to TRAIL thus opening
promising therapeutic perspectives for safe and effective
use of TRAIL in cancer treatment
Impact of Defects and Crystal Size on Negative Gas Adsorption in DUT-49 Analyzed by in Situ <sup>129</sup>Xe NMR Spectroscopy
The origin of crystal-size-dependent adsorption behavior of flexible metal-organic frameworks is increasingly studied. In this contribution, we probe the solid-fluid interactions of DUT-49 crystals of different size by in situ 129Xe NMR spectroscopy at 200 K. With decreasing size of the crystals, the average solid-fluid interactions are found to decrease reflected by a decrease in chemical shift of adsorbed xenon from 230 to 200 ppm, explaining the lack of adsorption-induced transitions for smaller crystals. However, recent studies propose that these results can also originate from the presence of lattice defects. To investigate the influence of defects on the adsorption behavior of DUT-49, we synthesized a series of samples with tailored defect concentrations and characterized them by in situ 129Xe NMR. In comparison to the results obtained for crystals with different size, we find pronounced changes of the adsorption behavior and influence of the chemical shift only for very high concentrations of defects, which further emphasizes the important role of particle size phenomena
Assessing Drivers’ Fatigue State Under Real Traffic Conditions Using EEG Alpha Spindles
The effectiveness of EEG alpha spindles, defined by short narrowband bursts in the alpha band, as an objective measure for assessing driver fatigue under real driving conditions was examined using an algorithm for the identification of alpha spindles. The method is applied to data recorded under real traffic conditions and compared with the performance of the traditional EEG fatigue measure alpha band power. Statistical analysis revealed significant increases from the first to the last driving section of alpha band power; with larger effect sizes for the alpha spindle based measures. An increased level of fatigue for drop-outs, as compared to participants who did not abort the drive, was observed only by means of alpha spindle parameters. EEG alpha spindle parameters increase both fatigue detection sensitivity and specificity as compared to EEG alpha band power. It is demonstrated that alpha spindles are superior to EEG band power measures for assessing driver fatigue under real traffic conditions
High-Resolution Spectroscopy of the Planetary Host HD 13189: Highly-Evolved and Metal-Poor
We report on the abundances of 13 elements in the planetary host HD 13189, a
massive giant star. Abundances are found to be sub-solar, with [Fe/H] = -0.58
+/- 0.04$; HD 13189 is one of the most metal-poor planetary hosts yet
discovered. Abundance ratios relative to Fe show no peculiarities with respect
to random field stars. A census of metallicities of the seven currently known
planet-harboring giants results in a distribution that is more metal-poor than
the well-known metal-rich distribution of main sequence (MS) planetary hosts.
This finding is discussed in terms of accretion of H-depleted material, one of
the possible mechanisms responsible for the high-metallicity distribution of MS
stars with planets. We estimate the mass of the HD 13189 progenitor to be 3.5
M_sun but cannot constrain this value to better than 2-6 M_sun. A stellar mass
of 3.5 M_sun implies a planetary mass of m sin i = 14.0 +/- 0.8 M_J, placing
the companion at the planet/brown dwarf boundary. Given its physical
characteristics, the HD 13189 system is potentially unique among planetary
systems, and its continued investigation should provide invaluable data to
extrasolar planetary research.Comment: 14 pages, 2 figures; Accepted for publication in ApJ Letter
Correlation of Isotope Count With Sentinel Node Positivity in Vulvar Cancer
Objective: Sentinel node biopsy (SNB) has become standard of care in early stage vulvar cancer. As the correlation of isotope count with the presence of metastases remains unclear, often several active nodes are excised per groin. This can result in increased morbidity in node-negative disease despite of SNB. In the current analysis, we assess whether resection of the hottest node could be sufficient to detect sentinel lymph node (SLN) metastasis. Methods: Patients with primary vulvar cancer receiving an SNB with radioactive tracer at the University Medical Center Hamburg-Eppendorf between 2008 and 2015 were evaluated. Results: A total of 145 patients with SNB were analyzed;thereof, 144 underwent bilateral SNB, resulting in 289 analyzed groins. A median of 2 SLNs (range, 1-7) per groin were removed. From 94 (32.5%) of 289 groins, more than 2 SLNs were excised. Median overall SLN isotope count was 1400 cps. In 50 groins, a positive SLN was detected (unilateral in 38 patients, bilateral in 6). The median number of positive SLN per groin was 1 (range, 1-4). The SLN with the highest isotope count carried metastases in 36 (78.3%) of 46 groins (in 4 cases, the highest count was unknown). In 10 (21.7%) of 46 positive groins, the SLN with the highest count was not the metastatic SLN (9/10 second highest count). Median count of these 10 SLN was 60% of the highest count with a range from 11.0% to 74.0%. Conclusions: The highest isotope count does not reliably detect the positive SLN in vulvar cancer. To prevent mostly fatal groin recurrences, surgeons should continue to remove all SLN accumulating relevant radioactive tracer over background activity
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