Ontogeny of ATP hydrolysis and isoform expression of the Plasma Membrane Ca2+-ATPase in mouse brain.

Background: Plasma membrane Ca2+-ATPases (PMCAs) are high affinity Ca2+ transporters actively involved in intracellular Ca2+ homeostasis. Considering the critical role of Ca2+ signalling in neuronal development and plasticity, we have analyzed PMCA-mediated Ca2+-ATPase activity and PMCA-isoform content in membranes from mouse cortex, hippocampus and cerebellum during postnatal development. Results: PMCA activity was detected from birth, with a faster evolution in cortex than in hippocampus and cerebellum. Western blots revealed the presence of the four isoforms in all regions, with similar increase in their expression patterns as those seen for the activity profile. Immunohistochemistry assays in cortex and hippocampus showed co-expression of all isoforms in the neuropil associated with synapses and in the plasma membrane of pyramidal cells soma, while cerebellum showed a more isoform-specific distribution pattern in Purkinje cells. Conclusion: These results show an upregulation of PMCA activity and PMCA isoforms expression during brain development in mouse, with specific localizations mainly in cerebellum. Overall, our findings support a close relationship between the ontogeny of PMCA isoforms and specific requirements of Ca2+ during development of different brain areas.post-print2271 K

Inhibition of PMCA activity by tau as a function of aging and Alzheimer's neuropathology

© 2015 Elsevier B.V.. Ca2+-ATPases are plasma membrane and intracellular membrane transporters that use the energy of ATP hydrolysis to pump cytosolic Ca2+ out of the cell (PMCA) or into internal stores. These pumps are the main high-affinity Ca2+ systems involved in the maintenance of intracellular free Ca2+ at the properly low level in eukaryotic cells. The failure of neurons to keep optimal intracellular Ca2+ concentrations is a common feature of neurodegeneration by aging and aging-linked neuropathologies, such as Alzheimer's disease (AD). This disease is characterized by the accumulation of β-amyloid senile plaques and neurofibrillary tangles of tau, a protein that plays a key role in axonal transport. Here we show a novel inhibition of PMCA activity by tau which is concentration-dependent. The extent of inhibition significantly decreases with aging in mice and control human brain membranes, but inhibition profiles were similar in AD-affected brain membrane preparations, independently of age. No significant changes in PMCA expression and localization with aging or neuropathology were found. These results point out a link between Ca2+-transporters, aging and neurodegeneration mediated by tau protein.Ministerio de Economía y Competitividad and Fundación Marcelino Botín (to A.M.M.); Junta de Extremadura and FEDERPeer Reviewe

Developmental distribution of plasma membrane Ca2+-ATPase isoforms in chick cerebellum.

The plasma membrane Ca2+-ATPase (PMCA) is highly expressed in the nervous system, but little information is available about its implication in neuronal development. We have analyzed the expression and localization of different isoforms of PMCA in membrane vesicles and sections of chick cerebellum from embryonic day 10 to hatching. We found that the relative amount of each PMCA isoform and their spatiotemporal distribution in the cerebellum are directly linked to precise cellular types during the cerebellar maturation, even in a non-neural tissue as choroid plexus. Purkinje cells contain the highest diversity of PMCA isoforms of the cerebellar cortex since the moment of its morphogenesis. From embryonic day 15, the PMCA2 was highly expressed in the whole Purkinje cell, while PMCAs 1 and 3 had a more restricted distribution in the soma and dendritic branches, and these distributions were evolving according with cell maturation. Other cellular types seem to contain a specific combination of isoforms, but with a well-defined distribution pattern at late moments of development. Thus, PMCAs 1 and 3 were located in the soma of molecular layer interneurons, and only the PMCA2 was observed in granule cells at hatching. Furthermore, PMCA isoforms are also expressed in cellular compartments characterized by a high amount of synapses, suggesting a key role of these proteins in synaptogenesis and in the maturation of neuronal electrophysiological properties.post-print1698 K

Estudio de transmisión intergeneracional del apego entre padres, madres y sus hijos adultos jóvenes en una muestra de familias de la región del Maule

71 p.El objetivo principal de la investigación es determinar la presencia de transmisión intergeneracional de dimensiones de apego, entendida como la asociación entre los estilos de apego de progenitores (padre-madre) y sus hijos e hijas adultos jóvenes. La muestra está compuesta por 185 familias de la Región del Maule.Los participantes respondieron, a modo de auto-reporte, el Cartes Modeles Internes of Relation (CAMIR), instrumento que mide las representaciones de apego. Además, se aplicó una encuesta sociodemográfica obteniendo los siguientes datos: edad, sexo, nivel socioeconómico y relaciones de pareja actuales. Para cumplir con el objetivo de este estudio, se determinó la relación entre las los estilos de apego de madres, madres e hijos, en las dimensiones de apego seguro y apego inseguro (evitativo y preocupado). Los resultados obtenidos arrojaron que, en la díada padre-hijo no existe asociación entre la dimensión de apego seguro, pero sí una relación positiva específica en las dimensiones de apego preocupado y evitativo de padres e hijos. En cuanto a la díada madre-hijo los resultados arrojan una correlación positiva significativa entre la dimensión de apego seguro y evitativo de madres e hijos. En conclusión, se evidencia transmisión intergeneracional en las díadas padre-hijo en las dimensiones de apego inseguro (preocupado y evitativo), no así en la dimensión de apego seguro. En cuanto a las díadas madres-hijos, existe transmisión en las dimensiones de apego seguro y evitativo, no así, en la dimensión de apego preocupado. Tras lo anterior, se sugiere que la transmisión del apego es producto de la combinación de las dimensiones de apego de ambos padres. Específicamente, la dimensión de apego seguro es asociada a la transmisión por parte de la madre y la inseguridad por parte de los padres. Además, la evitación estaría influenciada por ambos progenitores.Palabras claves: Transmisión intergeneracional del apego, Apego adulto, Estilos de Apeg

3-Methylcrotonyl-CoA carboxylase deficiency detected by tandem mass spectrometry in mexican population.

Tandem mass spectrometry (MS/MS) was introduced to expand newborn screening in Nuevo Leon, Mexico. This has permitted an increase in the diagnosis of many metabolic disorders including isolated 3 methylcrotonyl CoA carboxylase deficiency (3 MCC). Detection of an elevation of C5OH by MS/MS is associated with leucine catabolism disorders; false positive results are related with maternal transfer or immaturity of the enzymatic systems. The confirmatory diagnosis is based on organic acids test in urine and decreased enzyme activity in fibroblasts. We report three cases of abnormal C5OH in among 42 264 newborns (1:14000).1 The diagnosis was confirmed in only one child (~1:40 000). The incidence of 3 MCC deficiency in our state is similar to that of other populations. This is the first report about the incidence of this disorder in newborns in a Mexican population

Microglia and Microglia-Like Cells: Similar but Different

We want to thank all people for fighting in the front line of the COVID-19 pandemic, during which most parts of this article was written. We also acknowledge the task of the reviewers who contributed to improve the quality of this article.Microglia are the tissue-resident macrophages of the central nervous parenchyma. In mammals, microglia are thought to originate from yolk sac precursors and posteriorly maintained through the entire life of the organism. However, the contribution of microglial cells from other sources should also be considered. In addition to “true” or “bonafide” microglia, which are of embryonic origin, the so-called “microglia-like cells” are hematopoietic cells of bone marrow origin that can engraft the mature brain mainly under pathological conditions. These cells implement great parts of the microglial immune phenotype, but they do not completely adopt the “true microglia” features. Because of their pronounced similarity, true microglia and microglia-like cells are usually considered together as one population. In this review, we discuss the origin and development of these two distinct cell types and their differences. We will also review the factors determining the appearance and presence of microglia-like cells, which can vary among species. This knowledge might contribute to the development of therapeutic strategies aiming at microglial cells for the treatment of diseases in which they are involved, for example neurodegenerative disorders like Alzheimer’s and Parkinson’s diseases.University of Granada, Spain, and FEDER-Junta de Andalucía, Spain (grant number A1-CTS-324- UGR18

Bancos de sangre y SIDA

En los 10 años transcurridos desde la investigación del virus del sida, epidemia ha afectado a todos los sectores de la sociedad y a todas las instituciones: familia, empresa, gobierno, ejército y comunidad en general. También ha influido profundamente en la práctica científica, médica y asistencial en el mundo entero. El SIDA ha dejado al descubierto la vulnerabilidad de la condición humana

Follow-Up Biomarkers in the Evolution of Prostate Cancer, Levels of S100A4 as a Detector in Plasma

The management and screening of prostate cancer (PC) is still the main problem in clinical practice. In this study, we investigated the role of aggressiveness genetic markers for PC stratification. We analyzed 201 plasma samples from PC patients and controls by digital PCR. For selection and validation, 26 formalin-fixed paraffin-embedded tissues, 12 fresh tissues, and 24 plasma samples were characterized by RNA-Seq, immunochemistry, immunofluorescence, Western blot, and extracellular-vesicles analyses. We identified three novel non-invasive biomarkers; all with an increased expression pattern in patients (PCA3: p = 0.002, S100A4: p <= 0.0001 and MRC2: p = 0.005). S100A4 presents the most informative AUC (area under the curve) (0.735). Combination of S100A4, MRC2, and PCA3 increases the discriminatory power between patients and controls and between different more and less aggressive stages (AUC = 0.761, p <= 0.0001). However, although a sensitivity of 97.47% in PCA3 and a specificity of 90.32% in S100A4 was reached, the detection signal level could be variable in some analyses owing to tumor heterogeneity. This is the first time that the role of S100A4 and MRC2 has been described in PC aggressiveness. Moreover, the combination of S100A4, MRC2, and PCA3 has never been described as a non-invasive biomarker for PC screening and aggressiveness.Ministry of Health, Andalusia Government Leonardo de la Pena 2020 research grant - Urology Research Foundation (FIU) PI-0319-201

Switching Roles: Beneficial Effects of Adipose Tissue-Derived Mesenchymal Stem Cells on Microglia and Their Implication in Neurodegenerative Diseases

This research was funded by the Andalusian Government, Spain (grant no. P20-01255 to M.D. and FEDER program grant no. A1-CTS-324-UGR18 to M.R.S.) and by the Spanish Ministry for Economy and Competition, Spain (grant no. SAF2017-85602-R and PID2020-119638RB-I00, both to E.G.-R.). A.I.S.-C. was the awardee of a Research Starting Fellowship for master´s students at the University of Granada, Spain. The APC was funded by MDPI.Neurological disorders, including neurodegenerative diseases, are often characterized by neuroinflammation, which is largely driven by microglia, the resident immune cells of the central nervous system (CNS). Under these conditions, microglia are able to secrete neurotoxic substances, provoking neuronal cell death. However, microglia in the healthy brain carry out CNS-supporting functions. This is due to the ability of microglia to acquire different phenotypes that can play a neuroprotective role under physiological conditions or a pro-inflammatory, damaging one during disease. Therefore, therapeutic strategies focus on the downregulation of these neuroinflammatory processes and try to re-activate the neuroprotective features of microglia. Mesenchymal stem cells (MSC) of different origins have been shown to exert such effects, due to their immunomodulatory properties. In recent years, MSC derived from adipose tissue have been made the center of attention because of their easy availability and extraction methods. These cells induce a neuroprotective phenotype in microglia and downregulate neuroinflammation, resulting in an improvement of clinical symptoms in a variety of animal models for neurological pathologies, e.g., Alzheimer’s disease, traumatic brain injury and ischemic stroke. In this review, we will discuss the application of adipose tissue-derived MSC and their conditioned medium, including extracellular vesicles, in neurological disorders, their beneficial effect on microglia and the signaling pathways involved.Andalusian Government, Spain P20-01255FEDER program grant no. A1-CTS-324-UGR18Spanish Ministry for Economy and Competition, Spain (grant no. SAF2017-85602-R and PID2020-119638RB-I00)Research Starting Fellowship for master´s students at the University of Granada, SpainMDP