The modular systems biology approach to investigate the control of apoptosis in Alzheimer's disease neurodegeneration

Apoptosis is a programmed cell death that plays a critical role during the development of the nervous system and in many chronic neurodegenerative diseases, including Alzheimer's disease (AD). This pathology, characterized by a progressive degeneration of cholinergic function resulting in a remarkable cognitive decline, is the most common form of dementia with high social and economic impact. Current therapies of AD are only symptomatic, therefore the need to elucidate the mechanisms underlying the onset and progression of the disease is surely needed in order to develop effective pharmacological therapies. Because of its pivotal role in neuronal cell death, apoptosis has been considered one of the most appealing therapeutic targets, however, due to the complexity of the molecular mechanisms involving the various triggering events and the many signaling cascades leading to cell death, a comprehensive understanding of this process is still lacking. Modular systems biology is a very effective strategy in organizing information about complex biological processes and deriving modular and mathematical models that greatly simplify the identification of key steps of a given process. This review aims at describing the main steps underlying the strategy of modular systems biology and briefly summarizes how this approach has been successfully applied for cell cycle studies. Moreover, after giving an overview of the many molecular mechanisms underlying apoptosis in AD, we present both a modular and a molecular model of neuronal apoptosis that suggest new insights on neuroprotection for this disease

Tectonic Setting of the Tordillo Formation in the Aconcagua Fold-and-Thrust Belt

At the northwestern Mendoza province, the Mesozoic infill of the Neuquén Basin is tectonically repeated in the Aconcagua fold-and-thrust belt. Particularly, the Tordillo Formation (commonly associated with the Kimmeridgian) represents a local low stand period of sea level, with mainly alluvial and fluvial sediments. Toward the western sector of the belt, it interfingers with volcanic and volcaniclastic materials and presents a marked increase in the thickness. This unit was studied in two localities at the Blanco River valley, at the undeformed sector and over the second thrust that produces a second repetition of the Upper Jurassic and Lower Cretaceous sequences in the Aconcagua fold-and-thrust belt. This transect exposes facies variations and a significant increase in thickness to the west. Additionally, provenance analysis and paleocurrent directions indicate that the sediment supply was located to the E-SE, and that the underlying units were exhumed at the time of deposition of the Late Jurassic red beds. A consistent thickness increment of the Upper Jurassic deposits to the west through the Aconcagua fold-and-thrust belt suggests that sedimentation was controlled by NNW-directed structures. This is also supported by facies analyses that demonstrate high topographic breaks affecting a smooth westdipping fluvial ramp toward the volcanic arc. These features support an extensional setting for the deposition of the Tordillo Formation at the latitudes of the Aconcagua fold-and-thrust belt, as other authors have proposed for the Malargüe fold-and-thrust belt to the south. Plate tectonic reconstructions suggest trench rollback during this time previous to the westward migration of the South American plate, which is consistent with the back-arc extension proposed in the previous works.Fil: Acevedo, Eliana Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Estudios Andinos "Don Pablo Groeber". Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Estudios Andinos "Don Pablo Groeber"; ArgentinaFil: Rosselot, Eduardo Agustín. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Estudios Andinos "Don Pablo Groeber". Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Estudios Andinos "Don Pablo Groeber"; ArgentinaFil: Martos, Federico Exequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Estudios Andinos "Don Pablo Groeber". Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Estudios Andinos "Don Pablo Groeber"; ArgentinaFil: Fennell, Lucas Martín. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Estudios Andinos "Don Pablo Groeber". Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Estudios Andinos "Don Pablo Groeber"; ArgentinaFil: Naipauer, Maximiliano. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Geocronología y Geología Isotópica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Geocronología y Geología Isotópica; ArgentinaFil: Folguera Telichevsky, Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Estudios Andinos "Don Pablo Groeber". Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Estudios Andinos "Don Pablo Groeber"; Argentin

C-cell hyperplasia, pheochromocytoma and sympathoadrenal malformation in a mouse model of multiple endocrine neoplasia type 2B

Dominantly inherited multiple endocrine neoplasia type 2B (MEN2B) is characterized by tumors of the thyroid C-cells and adrenal chromaffin cells, together with ganglioneuromas of the gastrointestinal tract and other developmental abnormalities. Most cases are caused by substitution of threonine for Met918 in the RET receptor tyrosine kinase, which is believed to convert the RET gene to an oncogene by altering the enzyme's substrate specificity. We report the production of a mouse model of MEN2B by introduction of the corresponding mutation into the ret gene. Mutant mice displayed C-cell hyperplasia and chromaffin cell hyperplasia progressing to pheochromocytoma. Homozygotes did not develop gastrointestinal ganglioneuromas, but displayed ganglioneuromas of the adrenal medulla, enlargement of the associated sympathetic ganglia and a male reproductive defect. Surprisingly, homozygotes did not display any developmental defects attributable to a loss-of-function mutation. Thus, while our results support the conclusion that the Met918Thr substitution is responsible for MEN2B, they suggest that the substrate specificity of the RET kinase does not interfere with its normal role in the development of the kidneys and enteric nervous system

Vis-NIR-SWIR remote sensing products as new soil data for digital soil mapping

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