Uptake and turnover of mono-iodinated thyroid hormone metabolites by PCCL3 thyrocytes

Tyrosine and phenolic ring de-iodination of thyroid hormones (TH) is crucial for regulating their physiological activity. Furthermore, reactions such as de-carboxylation to thyronamines (TAM) and de-amination to thyroacetic acids (TAc) produce TH metabolites (THM) with distinct biological properties. This needs to be considered when studying effects of TH and THM. The accurate and precise quantitative analysis of TH and THM in cell culture supernatants and cell lysates are key procedures required for studying the in vitro metabolism of TH. We report here the development of a liquid-liquid extraction/isotope dilution-liquid chromatography-electrospray tandem mass spectrometry (LC- MS/MS) method for the quantification of 9 thyronines (TN) and 6 TAM in human hepatocellular carcinoma Hep G2 cell lysate extracts. In addition, we adapted the method to quantify TH, TAM and TAc, in cell lysates of FBS-depleted rat thyroid epithelium PCCL3 cells. The methods for both cell lines were validated by rigorous assessment of linearity, limits of quantification and detection (LLOQ and LLOD respectively), intra- and inter-day accuracy, precision, process efficiency (PE), matrix effect (ME) and relative recovery (RE). Calibration curves covering 11 concentrations (based on 400 μl of lysate) were linear in the range 0.016–50 nM and 0.010–50 nM for Hep G2 and PCCL3 cells respectively. The lower limits of quantification were in the range 0.031 to 1 nM. We applied the PCCL3 version of the LC-MS/MS method to the analysis of lysed cell extracts from PCCL3 cells that had been incubated with 3-iodo-L-thyronine (T1), 3-iodothyronamine (3-T1AM) and 3-iodothyroacetic acid (3-T1Ac). Over the course of 30 minutes incubation 3-T1AM was de-iodinated to 4-[4-(2-aminoethylphenoxy)]phenol (thyronamine, T0AM) and de-aminated to 3-T1Ac respectively, whilst T1 underwent de-iodination to T0. This data indicates avid metabolism of these mono-iodinated compounds and the utility of LC-MS/MS to quantify such cellular metabolism

The Calogero-Moser equation system and the ensemble average in the Gaussian ensembles

From random matrix theory it is known that for special values of the coupling constant the Calogero-Moser (CM) equation system is nothing but the radial part of a generalized harmonic oscillator Schroedinger equation. This allows an immediate construction of the solutions by means of a Rodriguez relation. The results are easily generalized to arbitrary values of the coupling constant. By this the CM equations become nearly trivial. As an application an expansion for in terms of eigenfunctions of the CM equation system is obtained, where X and Y are matrices taken from one of the Gaussian ensembles, and the brackets denote an average over the angular variables.Comment: accepted by J. Phys.

Impurity effects on the band structure of one-dimensional photonic crystals: Experiment and theory

We study the effects of single impurities on the transmission in microwave realizations of the photonic Kronig-Penney model, consisting of arrays of Teflon pieces alternating with air spacings in a microwave guide. As only the first propagating mode is considered, the system is essentially one dimensional obeying the Helmholtz equation. We derive analytical closed form expressions from which the band structure, frequency of defect modes, and band profiles can be determined. These agree very well with experimental data for all types of single defects considered (e.g. interstitial, substitutional) and shows that our experimental set-up serves to explore some of the phenomena occurring in more sophisticated experiments. Conversely, based on the understanding provided by our formulas, information about the unknown impurity can be determined by simply observing certain features in the experimental data for the transmission. Further, our results are directly applicable to the closely related quantum 1D Kronig-Penney model.Comment: 16 pages, 7 figure

Geometry-dependent scattering through quantum billiards: Experiment and theory

We present experimental studies of the geometry-specific quantum scattering in microwave billiards of a given shape. We perform full quantum mechanical scattering calculations and find an excellent agreement with the experimental results. We also carry out the semiclassical calculations where the conductance is given as a sum of all classical trajectories between the leads, each of them carrying the quantum-mechanical phase. We unambiguously demonstrate that the characteristic frequencies of the oscillations in the transmission and reflection amplitudes are related to the length distribution of the classical trajectories between the leads, whereas the frequencies of the probabilities can be understood in terms of the length difference distribution in the pairs of classical trajectories. We also discuss the effect of non-classical "ghost" trajectories that include classically forbidden reflection off the lead mouths.Comment: 4 pages, 4 figure

Pressure-sensitive paint measurements in a shock tube

Abstract Surface pressures were measured in the shortduration, transient flow environment of a small-scale, low pressure-ratio shock tube using thin-film pressure-sensitive paint (PSP). Issues regarding coating formulation, measurement uncertainty, optical system design, and temperature and illumination compensation are discussed. The pressure measurements were acquired during steady flow conditions following the passage of normal shocks and expansion regions along a flat sidewall and a wedge sidewall. The PSP characteristic response time was 3 to 6 ms. Overall pressure uncertainty for the shock tube measurements ranged up to 5% over one atmosphere and compared well with theoretical estimates of uncertainty

Corrigendum: Valenced action/inhibition learning in humans is modulated by a genetic variant linked to dopamine D2 receptor expression

Motivational salience plays an important role in shaping human behavior, but recent studies demonstrate that human performance is not uniformly improved by motivation. Instead, action has been shown to dominate valence in motivated tasks, and it is particularly difficult for humans to learn the inhibition of an action to obtain a reward, but the neural mechanism behind this behavioral specificity is yet unclear. In all mammals, including humans, the monoamine neurotransmitter dopamine is particularly important in the neural manifestation of appetitively motivated behavior, and the human dopamine system is subject to considerable genetic variability. The well-studied TaqIA restriction fragment length polymorphism (rs1800497) has previously been shown to affect striatal dopamine metabolism. In this study we investigated a potential effect of this genetic variation on motivated action/inhibition learning. Two independent cohorts consisting of 87 and 95 healthy participants, respectively, were tested using the previously described valenced go/no-go learning paradigm in which participants learned the reward-associated no-go condition significantly worse than all other conditions. This effect was modulated by the TaqIA polymorphism, with carriers of the A1 allele showing a diminished learning-related performance enhancement in the rewarded no-go condition compared to the A2 homozygotes. This result highlights a modulatory role for genetic variability of the dopaminergic system in individual learning differences of action-valence interaction

Green functions for generalized point interactions in 1D: A scattering approach

Recently, general point interactions in one dimension has been used to model a large number of different phenomena in quantum mechanics. Such potentials, however, requires some sort of regularization to lead to meaningful results. The usual ways to do so rely on technicalities which may hide important physical aspects of the problem. In this work we present a new method to calculate the exact Green functions for general point interactions in 1D. Our approach differs from previous ones because it is based only on physical quantities, namely, the scattering coefficients, $R$ and $T$, to construct $G$. Renormalization or particular mathematical prescriptions are not invoked. The simple formulation of the method makes it easy to extend to more general contexts, such as for lattices of $N$ general point interactions; on a line; on a half-line; under periodic boundary conditions; and confined in a box.Comment: Revtex, 9 pages, 3 EPS figures. To be published in PR

NEMF mutations that impair ribosome-associated quality control are associated with neuromuscular disease

A hallmark of neurodegeneration is defective protein quality control. The E3 ligase Listerin (LTN1/Ltn1) acts in a specialized protein quality control pathway—Ribosome-associated Quality Control (RQC)—by mediating proteolytic targeting of incomplete polypeptides produced by ribosome stalling, and Ltn1 mutation leads to neurodegeneration in mice. Whether neurodegeneration results from defective RQC and whether defective RQC contributes to human disease have remained unknown. Here we show that three independently-generated mouse models with mutations in a different component of the RQC complex, NEMF/Rqc2, develop progressive motor neuron degeneration. Equivalent mutations in yeast Rqc2 selectively interfere with its ability to modify aberrant translation products with C-terminal tails which assist with RQC-mediated protein degradation, suggesting a pathomechanism. Finally, we identify NEMF mutations expected to interfere with function in patients from seven families presenting juvenile neuromuscular disease. These uncover NEMF’s role in translational homeostasis in the nervous system and implicate RQC dysfunction in causing neurodegeneration

Evaluación del riesgo de inundación a múltiples componentes en la costa del Maresme

The coast is one of the areas most affected by natural hazards, with floods being the most frequent and significant of these in terms of their induced impacts, so any management scheme requires their evaluation. In coastal areas, flooding is a hazard associated with different processes acting at different scales: coastal storms, flash floods and sea level rise (SLR). To address the problem as a whole, this study presents a methodology to undertake a preliminary integrated risk assessment of the magnitude of each flood component, taking into account their scope (extension of the affected area) and their temporal scale. The risk is quantified using specific indicators to assess the hazard magnitude (for each component) and the consequences. This allows for a robust comparison of the spatial risk distribution along the coast in order to identify both the most at-risk areas and the most influential risk components. This methodology is applied to a stretch of coastline (Maresme, Catalonia) representative of the Spanish Mediterranean coast. The results obtained characterise this coastline as an area with a relatively low overall risk, although some hotspots are identified as having high-risk values. Resumen: La costa es una de las zonas más sometidas a riesgos naturales, siendo la inundación uno de los más frecuentes e importantes en términos de daños inducidos, por lo que cualquier esquema de gestión requiere evaluación. La inundación en zonas costeras es una amenaza natural asociada a diferentes procesos que actúan a distintas escalas: tormentas costeras, riadas y subida del nivel del mar (SNM). Para abarcar la totalidad del problema, este trabajo propone una metodología para la evaluación preliminar del riesgo integrado de inundación costera a una escala regional que permite evaluar la magnitud de cada componente teniendo en cuenta su alcance (extensión de la zona afectada) y su escala temporal. El riesgo se cuantifica en función de unos indicadores específicos que valoran la magnitud de la amenaza para cada componente y las consecuencias. Esto permite comparar robustamente la distribución espacial del riesgo a lo largo de la costa, para identificar tanto zonas de mayor riesgo como las componentes que más contribuyen al mismo. Aplicamos esta metodología a un tramo de costa característica del Mediterráneo español (Maresme, Cataluña). Los resultados permiten caracterizar esta costa como un área con un riesgo global relativamente bajo, pero algunos puntos singulares con riesgo alto