Membrane cholesterol interferes with tyrosine phosphorylation but facilitates the clustering and signal transduction of EGFR

Epidermal growth factor receptor (EGFR) activates major cell signaling pathways that regulate various cell responses. Its dimerization and clustering coupled with its lateral mobility are critical for EGFR function, but the contribution of the plasma membrane environment to EGFR function is unknown. Here we show, using single-molecule analysis, that EGFR mobility and clustering are altered by the depletion of cholesterol or sphingomyelin, major lipids of membrane subdomains, causing significant changes in EGFR signaling. When cholesterol was depleted, the subdomain boundary in EGFR diffusion disappeared, the fraction of EGFR pre-dimers was increased, and the ligand-induced phosphorylation of EGFR was enhanced. In addition, the depletion of either lipid prevented the formation of immobile clusters after EGF association and decreased the phosphorylation of downstream proteins. Our results revealed that cholesterol plays dichotomous roles in the signaling pathway of EGFR and that clustering in the membrane subdomains is critical for EGFR signal transduction.

¿Equivale una mejor visión a una mejor intubación? Artículo original: MazzinariG, Rovira L, Henao L, Ortega J, Casasempere A, Fernandez Y. Effect of Dynamic Versus Stylet-Guided Intubation on First-Attempt Success in Difficult Airways Undergoing Glidescope Laryngoscopy: A Randomized Controlled Trial. Anesthesia-Analgesia. June 2019.Volume 128.Number 6.

El fracaso de intubación en un paciente con Vía Aérea Difícil (VAD) todavía no es infrecuente, es por ello que la amplia utilización de dispositivos de rescate de la laringoscopia directa sigue en auge. Es en este ámbito donde cobran fuerza los videolaringoscopios, que ofrecen una laringoscopia indirecta a través de un montaje multivariado de lentes y ópticas. Los videolaringoscopios nos han aportado en la especialidad de Anestesiología una visión enormemente nítida en muchos casos de glotis prácticamente imposibles, mejorando por tanto el grado de visibilidad ( clasificado en la Escala de Cormack-Lehane), pero esta ventaja no siempre conduce a un aumento en la tasa de éxito de intubación traqueal, debido a que la adecuada inserción del tubo a través de las cuerdas vocales es un factor limitante. Por ello se precisa de guías que permitan dar al tubo endotraqueal una forma adecuada para una correcta intubación. En este estudio se pretende evaluar la tasa de éxito con un videolaringoscopio usando una guía tradicional preformada con cierto ángulo de movilidad anteroposterior vs guía flexible que permite movilidad anteroposterior y lateral como es un fibrobroncospio con la fibra óptica apagada. Los resultados muestran una mejor tasa éxito en la intubación en el primer intento y menor tasa de complicaciones en el manejo de las vías respiratorias. ABSTRACT Better vision makes better intubation? The failure of intubation in a patient with Difficult Airway (VAD) is not yet uncommon, which is why the wide use of rescue devices for direct laryngoscopy is still booming. It is in this area where videolaryngoscopy gain strength, offering indirect laryngoscopy through a multivariate assembly of lenses and optics. Videolaryngoscopy have given us in Anesthesiology an enormously clear vision in many cases of practically impossible glottis, thus improving the degree of visibility (classified in the Cormack-Lehane Scale), but this advantage does not always lead to an increase in the success rate of tracheal intubation, due to the proper insertion of the tube through the vocal cords is a limiting factor. Therefore, stylet-guides are required that need to give the endotracheal tube a suitable form for proper intubation. In this study, it is expected to evaluate the success rate with a videolaryngoscope using a traditional preformed stylet-guide with a certain angle of anteroposterior mobility vs. flexible guidance that allows anteroposterior and lateral mobility such as a fiberscope with the optical fiber turned off. The results experienced a better success rate in intubation on the first attempt and a lower rate of complications in airway management with glidescope+fiberscope.

β-Arrestin 2 and ERK1/2 Are Important Mediators Engaged in Close Cooperation between TRPV1 and µ-Opioid Receptors in the Plasma Membrane

The interactions between TRPV1 and µ-opioid receptors (MOR) have recently attracted much attention because these two receptors play important roles in pain pathways and can apparently modulate each other’s functioning. However, the knowledge about signaling interactions and crosstalk between these two receptors is still limited. In this study, we investigated the mutual interactions between MOR and TRPV1 shortly after their activation in HEK293 cells expressing these two receptors. After activation of one receptor we observed significant changes in the other receptor’s lateral mobility and vice versa. However, the changes in receptor movement within the plasma membrane were not connected with activation of the other receptor. We also observed that plasma membrane β-arrestin 2 levels were altered after treatment with agonists of both these receptors. Knockdown of β-arrestin 2 blocked all changes in the lateral mobility of both receptors. Furthermore, we found that β-arrestin 2 can play an important role in modulating the effectiveness of ERK1/2 phosphorylation after activation of MOR in the presence of TRPV1. These data suggest that β-arrestin 2 and ERK1/2 are important mediators between these two receptors and their signaling pathways. Collectively, MOR and TRPV1 can mutually affect each other’s behavior and β-arrestin 2 apparently plays a key role in the bidirectional crosstalk between these two receptors in the plasma membrane.

Using the portable luminescence reader to assess the historical lateral mobility of river channels: preliminary promising results

<p><strong>Timothée Jautzy<sup>1,2</sup>, </strong><strong>Dominik Brill<sup>3</sup>, </strong><strong>Laurent Schmitt<sup>1</sup>, </strong><strong>Gilles Rixhon<sup>4</sup></strong></p><p>Obtaining robust chronological data on landforms and their related deposits together with constraining rates of earth surface processes have constantly represented a major challenge in Quaternary science. In the fluvial context, Optically Stimulated Luminescence (OSL) is particularly well-established but still faces several limitations. It notably requires expensive and time-consuming sample processing and measurement, frequently resulting in a poor spatial and stratigraphical distribution of sampling which may negatively impact the chronological information. To overcome this main limitation, a Portable OSL reader (POSL) has been recently developed (Sanderson & Murphy, 2010). It consists in directly capturing a luminescence signal (counts per seconds) on unprepared sediment samples. This technique is quick and affordable but, unlike conventional OSL, is not able to yield numerical age estimates.</p><p>This contribution explores POSL capacities to provide useful relative age information on alluvial sediments from the last centuries. We study and compare 42 samples collected from three alluvial profiles located in the floodplain of a gravelly-sandy mid-sized river: the Bruche (i.e. a sub-tributary of the Upper Rhine, France). POSL stimulations, including both blue and infra-red signals, are performed in combination with grain size analysis. We observe (i) an overall increase of signal intensity with increasing depth, (ii) a very good match between blue and IR signals and (iii) no systematic correlation between signal intensity and grain size. Whilst this last point must still be confirmed (i.e. signal intensity does not primarily depend on grain size), our preliminary results positively suggest that POSL is a promising tool to provide a relative chronology for very young alluvial sediments. Furthermore, it may also provide information on geomorphic processes. These results will be combined soon to numerical dating (OSL and <sup>14</sup>C) and compared to outcomes of a planimetric analysis to thoroughly reconstruct the historical lateral mobility of the Bruche river.</p>

The engulfment receptor Draper organizes the postsynaptic spectrin cytoskeleton into corrals containing synaptic proteins and promotes synaptic renewal

SummaryThe spectrin cytoskeleton is required for development of the Drosophila neuromuscular junction (NMJ) but its role is unclear. Here we show that the muscle spectrin lattice functions to corral membrane-associated synaptic proteins and limit their lateral mobility. Drosophila adducin, Hts, is required for integrity of the spectrin cytoskeleton and disruption of Hts function results in failure of the corrals. The spectrin cytoskeleton is itself patterned at the muscle membrane by the engulfment receptor Draper (Drpr) through regulation of Hts. We find patches of membrane where the spectrin cytoskeleton is organized into bilaterally symmetric patterns, which coincide with a field of Drpr-dependent structures similar to phagocytic pseudopods. The bilaterally symmetric patterns are likely created by folds of the muscle membrane in the pseudopods. We present evidence that the folds trap nascent boutons of motor neurons, leading to boutons with a bilaterally symmetric organization of the postsynaptic membrane. Drpr thus acts as a sensor of synaptic damage that promotes synaptogenesis.

Lateral Moves, Promotions, and Task-Specific Human Capital: Theory and Evidence

This paper studies the link between lateral mobility and promotions. The first part of the paper extends the theoretical literature by incorporating lateral moves into a job assignment model with task-specific human capital accumulation. The model thus predicts that workers who are laterally moved in one period are more likely to be subsequently promoted and experience larger wage growth compared with workers who are not laterally moved. In addition, workers with very high levels of education are less likely to be laterally moved compared with workers with lower levels of education. We test the model’s predictions using a large employer–employee linked panel dataset on senior managers in a sample of large US firms during the period 1981 to 1985. Our findings support the theoretical predictions and show the importance of lateral mobility in wage and promotion dynamics. (JEL J31, M51)