Increased Confinement and Polydispersity of STIM1 and Orai1 after Ca2+ Store Depletion.

STIM1 (a Ca2+ sensor in the endoplasmic reticulum (ER) membrane) and Orai1 (a pore-forming subunit of the Ca2+-release-activated calcium channel in the plasma membrane) diffuse in the ER membrane and plasma membrane, respectively. Upon depletion of Ca2+ stores in the ER, STIM1 translocates to the ER-plasma membrane junction and binds Orai1 to trigger store-operated Ca2+ entry. However, the motion of STIM1 and Orai1 during this process and its roles to Ca2+ entry is poorly understood. Here, we report real-time tracking of single STIM1 and Orai1 particles in the ER membrane and plasma membrane in living cells before and after Ca2+ store depletion. We found that the motion of single STIM1 and Orai1 particles exhibits anomalous diffusion both before and after store depletion, and their mobility-measured by the radius of gyration of the trajectories, mean-square displacement, and generalized diffusion coefficient-decreases drastically after store depletion. We also found that the measured displacement distribution is non-Gaussian, and the non-Gaussian parameter drastically increases after store depletion. Detailed analyses and simulations revealed that single STIM1 and Orai1 particles are confined in the compartmentalized membrane both before and after store depletion, and the changes in the motion after store depletion are explained by increased confinement and polydispersity of STIM1-Orai1 complexes formed at the ER-plasma membrane junctions. Further simulations showed that this increase in the confinement and polydispersity after store depletion localizes a rapid increase of Ca2+ influx, which can facilitate the rapid activation of local Ca2+ signaling pathways and the efficient replenishing of Ca2+ store in the ER in store-operated Ca2+ entry.

Balance of microtubule stiffness and cortical tension determines the size of blood cells with marginal band across species.

The fast bloodstream of animals is associated with large shear stresses. To withstand these conditions, blood cells have evolved a special morphology and a specific internal architecture to maintain their integrity over several weeks. For instance, nonmammalian red blood cells, mammalian erythroblasts, and platelets have a peripheral ring of microtubules, called the marginal band, that flattens the overall cell morphology by pushing on the cell cortex. In this work, we model how the shape of these cells stems from the balance between marginal band rigidity and cortical tension. We predict that the diameter of the cell scales with the total microtubule polymer and verify the predicted law across a wide range of species. Our analysis also shows that the combination of the marginal band rigidity and cortical tension increases the ability of the cell to withstand forces without deformation. Finally, we model the marginal band coiling that occurs during the disk-to-sphere transition observed, for instance, at the onset of blood platelet activation. We show that when cortical tension increases faster than cross-linkers can unbind, the marginal band will coil, whereas if the tension increases more slowly, the marginal band may shorten as microtubules slide relative to each other.

Real-time subpixel-accuracy tracking of single mitochondria in neurons reveals heterogeneous mitochondrial motion.

Mitochondria are essential for cellular survival and function. In neurons, mitochondria are transported to various subcellular regions as needed. Thus, defects in the axonal transport of mitochondria are related to the pathogenesis of neurodegenerative diseases, and the movement of mitochondria has been the subject of intense research. However, the inability to accurately track mitochondria with subpixel accuracy has hindered this research. Here, we report an automated method for tracking mitochondria based on the center of fluorescence. This tracking method, which is accurate to approximately one-tenth of a pixel, uses the centroid of an individual mitochondrion and provides information regarding the distance traveled between consecutive imaging frames, instantaneous speed, net distance traveled, and average speed. Importantly, this new tracking method enables researchers to observe both directed motion and undirected movement (i.e., in which the mitochondrion moves randomly within a small region, following a sub-diffusive motion). This method significantly improves our ability to analyze the movement of mitochondria and sheds light on the dynamic features of mitochondrial movement.

Self-organization of plasticity and specialization in a primitively social insect.

Biological systems have the capacity to not only build and robustly maintain complex structures but also to rapidly break up and rebuild such structures. Here, using primitive societies of Polistes wasps, we show that both robust specialization and rapid plasticity are emergent properties of multi-scale dynamics. We combine theory with experiments that, after perturbing the social structure by removing the queen, correlate time-resolved multi-omics with video recordings. We show that the queen-worker dimorphism relies on the balance between the development of a molecular queen phenotype in all insects and colony-scale inhibition of this phenotype via asymmetric interactions. This allows Polistes to be stable against intrinsic perturbations of molecular states while reacting plastically to extrinsic cues affecting the whole society. Long-term stability of the social structure is reinforced by dynamic DNA methylation. Our study provides a general principle of how both specialization and plasticity can be achieved in biological systems. A record of this paper's transparent peer review process is included in the supplemental information.

Hemorragia supratentorial espontánea: un modelo matemático predictivo de mortalidad / Spontaneus supratentorial hemorrhage: a mathematical model to predict mortality

Plantear un modelo matemático predictivo de mortalidad para la hemorragia supratentorial espontánea. Material y métodos: Se efectuó un estudio prospectivo en las unidades de Terapia Intensiva del Hospital General Manuel Belgrano y el Policlínico Central de la Unión Obrera Metalúrgica (Buenos Aires, Argentina). Se evaluó la localización de la hemorragia, el volumen del hematoma (V), la presencia de volcado ventricular (VV) y la desviación de la línea media (DLM). Resultados: El análisis mostró que el volumen del hematoma, la desviación de la línea media y la presencia de volcado ventricular se comportaron como factores predictivos independientes de mortalidad. Por el método de regresión logística múltiple se demuestra que el volcado ventricular incrementa el riesgo de mortalidad en 3.1 veces. Por cada centímetro cúbico de aumento del volumen del hematoma se incrementa la mortalidad un 6.2%, y por cada milímetro de desviación de la línea media la probabilidad de mortalidad se incrementa en 32.8%. Este modelo demuestra tener una sensibilidad del 79.8% y una especificidad del 95.2%. El rango de clasificación correcta es del 89%. El logit del modelo fue: -4.948 + 1.415 (VV) + 0.06 (V) + 0.248 (DLM). Conclusiones: En la población en estudio fue posible plantear un modelo matemático de probabilidad con alta sensibilidad y especificidad...

Método de recolección de datos de enfermos coronarios para base de datos y análisis por computación / Method of gathering of data of sick coronary for data base and computation analysis

Se desarrolló un sistema de computación que permite la recolección, tabulación y codificación de datos de enfermos coronarios. Este método permite el análisis, por programas estándar de base de datos, como también por planillas de cálculo electrónico disponibles para la mayoría de las computadoras en el mercado