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1.
Cell Calcium ; 86: 102127, 2020 03.
Article in English | MEDLINE | ID: mdl-31954928

ABSTRACT

Mitochondrial free calcium is critically linked to the regulation of cellular metabolism. Free ionic calcium concentration within these organelles is determined by the interplay between two processes: exchange across the mitochondrial inner membrane and calcium-buffering within the matrix. During stimulated calcium uptake, calcium is primarily buffered by orthophosphate, preventing calcium toxicity while allowing for well-regulated yet elevated calcium loads. However, if limited to orthophosphates only, this buffering system is expected to lead to the irreversible formation of insoluble precipitates, which are not observed in living cells, under physiological conditions. Here, we demonstrate that the regulation of free mitochondrial calcium requires the presence of free inorganic polyphosphate (polyP) within the organelle. We found that the overexpression of a mitochondrial-targeted enzyme hydrolyzing polyP leads to the loss of the cellular ability to maintain elevated calcium concentrations within the organelle, following stimulated cytoplasmic signal. We hypothesize that the presence of polyP prevents the formation of calcium-phosphate insoluble clusters, allowing for the maintenance of elevated free calcium levels, during stimulated calcium uptake.


Subject(s)
Calcium/metabolism , Mitochondria/metabolism , Polyphosphates/pharmacology , Adenosine Triphosphate/pharmacology , Benzoates/metabolism , Bridged Bicyclo Compounds/metabolism , Calcium Signaling/drug effects , Cell Membrane Permeability/drug effects , Cycloheptanes/metabolism , HEK293 Cells , Humans , Membrane Potential, Mitochondrial/drug effects , Mitochondria/drug effects , Models, Biological , Ruthenium Red/metabolism , Sesquiterpenes/metabolism
3.
Elife ; 62017 12 19.
Article in English | MEDLINE | ID: mdl-29256863

ABSTRACT

Pyramidal cells and interneurons expressing parvalbumin (PV), somatostatin (SST), and vasoactive intestinal peptide (VIP) show cell-type-specific connectivity patterns leading to a canonical microcircuit across cortex. Experiments recording from this circuit often report counterintuitive and seemingly contradictory findings. For example, the response of SST cells in mouse V1 to top-down behavioral modulation can change its sign when the visual input changes, a phenomenon that we call response reversal. We developed a theoretical framework to explain these seemingly contradictory effects as emerging phenomena in circuits with two key features: interactions between multiple neural populations and a nonlinear neuronal input-output relationship. Furthermore, we built a cortical circuit model which reproduces counterintuitive dynamics observed in mouse V1. Our analytical calculations pinpoint connection properties critical to response reversal, and predict additional novel types of complex dynamics that could be tested in future experiments.


Subject(s)
Cerebral Cortex/cytology , Cerebral Cortex/physiology , Interneurons/physiology , Nerve Net/physiology , Pyramidal Cells/physiology , Animals , Mice , Models, Neurological
4.
Cell ; 171(2): 456-469.e22, 2017 Oct 05.
Article in English | MEDLINE | ID: mdl-28985566

ABSTRACT

The stereotyped features of neuronal circuits are those most likely to explain the remarkable capacity of the brain to process information and govern behaviors, yet it has not been possible to comprehensively quantify neuronal distributions across animals or genders due to the size and complexity of the mammalian brain. Here we apply our quantitative brain-wide (qBrain) mapping platform to document the stereotyped distributions of mainly inhibitory cell types. We discover an unexpected cortical organizing principle: sensory-motor areas are dominated by output-modulating parvalbumin-positive interneurons, whereas association, including frontal, areas are dominated by input-modulating somatostatin-positive interneurons. Furthermore, we identify local cell type distributions with more cells in the female brain in 10 out of 11 sexually dimorphic subcortical areas, in contrast to the overall larger brains in males. The qBrain resource can be further mined to link stereotyped aspects of neuronal distributions to known and unknown functions of diverse brain regions.


Subject(s)
Brain Mapping , Brain/physiology , Sex Characteristics , Animals , Brain/cytology , Female , Humans , Interneurons/cytology , Male , Mammals/physiology
5.
Arch. bronconeumol. (Ed. impr.) ; 50(9): 404-406, sept. 2014. tab, graf
Article in Spanish | IBECS | ID: ibc-128475

ABSTRACT

Se realiza un análisis retrospectivo de las características de los pacientes con derrame pleural secundario a Streptococcus milleri diagnosticados en nuestro hospital entre enero de 2011 y marzo 2013. Se diagnosticaron 7 pacientes con una edad media de 60 años, el 57% con hábito enólico importante y el 43% fumadores. Los factores asociados más frecuentemente fueron el alcoholismo, la existencia de neumonía previa y diabetes mellitus. En 2 pacientes se identificaron otros gérmenes, como Enterobacter aerogenes, Bacteroides capillosus y Prevotella intermedia. La duración media del tratamiento antibiótico fue de 28 días. En 6 casos (86%) se realizó drenaje pleural con tubo de tórax, y un paciente precisó cirugía por evolución tórpida. La duración media de la hospitalización fue de 30 días, con evolución satisfactoria en todos los casos, aunque con alteración funcional restrictiva residual


In this study we analyzed the characteristics of patients with pleural effusion secondary to Streptococcus milleri studied retrospectively between January and March 2013 and found seven patients with a mean age of 60 years; 43% of them were smokers and 57% with a drinking habit. The most common associated factors were alcoholism, previous pneumonia and diabetes. Other bacteria were identified as Enterobacter aerogenes, Bacteroides and Prevotella intermedia capillosus in two patients. The mean duration of antibiotic therapy was 28 days; six patients underwent pleural drainage by chest tube and one patient needed surgery due to poor clinical progress. The mean duration of hospitalization was 30 days with satisfactory outcome in all cases, despite some changes in residual function


Subject(s)
Humans , Male , Female , Middle Aged , Pleural Effusion/diagnosis , Pleural Effusion/therapy , Empyema/complications , Empyema/diagnosis , Bacteroides/isolation & purification , Bacteroides Infections/complications , Retrospective Studies , Risk Factors , Streptococcus milleri Group/isolation & purification , Enterobacter aerogenes/isolation & purification , Empyema, Pleural/complications , Empyema, Pleural/diagnosis , Endoscopy/methods , Amoxicillin-Potassium Clavulanate Combination/therapeutic use
6.
Article in English | MEDLINE | ID: mdl-24229242

ABSTRACT

Characterizing the influence of network properties on the global emerging behavior of interacting elements constitutes a central question in many areas, from physical to social sciences. In this article we study a primary model of disordered neuronal networks with excitatory-inhibitory structure and balance constraints. We show how the interplay between structure and disorder in the connectivity leads to a universal transition from trivial to synchronized stationary or periodic states. This transition cannot be explained only through the analysis of the spectral density of the connectivity matrix. We provide a low-dimensional approximation that shows the role of both the structure and disorder in the dynamics.

7.
Chaos ; 23(4): 043134, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24387573

ABSTRACT

In this article, we consider a model of dynamical agents coupled through a random connectivity matrix, as introduced by Sompolinsky et al. [Phys. Rev. Lett. 61(3), 259-262 (1988)] in the context of random neural networks. When system size is infinite, it is known that increasing the disorder parameter induces a phase transition leading to chaotic dynamics. We observe and investigate here a novel phenomenon in the sub-critical regime for finite size systems: the probability of observing complex dynamics is maximal for an intermediate system size when the disorder is close enough to criticality. We give a more general explanation of this type of system size resonance in the framework of extreme values theory for eigenvalues of random matrices.


Subject(s)
Models, Neurological , Neural Networks, Computer
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