Microglial memory of early life stress and inflammation: Susceptibility to neurodegeneration in adulthood

We review evidence supporting the role of early life programming in the susceptibility for adult neurodegenerative diseases while highlighting questions and proposing avenues for future research to advance our understanding of this fundamental process. The key elements of this phenomenon are chronic stress, neuroinflammation triggering microglial polarization, microglial memory and their connection to neurodegeneration. We review the mediating mechanisms which may function as early biomarkers of increased susceptibility for neurodegeneration. Can we devise novel early life modifying interventions to steer developmental trajectories to their optimum?.Fil: Desplats, Paula. University of California; Estados UnidosFil: Gutierrez, Ashley M.. University of California; Estados UnidosFil: Antonelli, Marta Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Frasch, Martin G.. University of Washington; Estados Unido

Transcriptional activation of the proapoptotic bik gene by E2F proteins in cancer cells

AbstractBH3-only proteins are required for execution of apoptotic cell death. We have found that one of these proteins, Bik, is strongly induced in cancer cells treated with chemotherapeutic agents. Furthermore, we showed that chemotherapy-induced expression of bik is independent of p53. Consistent with its pro-apoptotic activity, blockade of bik expression reduces the adriamycin-mediated apoptotic cell death. We also found that the bik gene is transcriptionally activated by E2F proteins. Consistently, adriamycin induces the E2F-bik pathway. In addition, E2Fs transactivate bik by a p53-independent mechanism. Thus, our data indicate that transcriptional regulation of bik contributes to the efficient apoptotic response to chemotherapeutic agents

Architecture of an object-oriented modeling framework for human occupation

The limitations of the actual theoretical structure of occupational science are discussed emphasizing on its implications when dealing with the stability and sustainability of social systems. By using a literature review focused on the time evolution and disciplinary distribution of the scientific production about human occupation, it is verified the insufficient production leading to the development of models that facilitate quantitative reasoning to support decision making. As an alternative, the architecture of an object-oriented framework is proposed. The framework is presented by using an UML (Unified Modeling Language) class diagram of a generic occupational system, including the class model of each system’s component: attributes and behaviors. Finally, guidelines are given for the use of the models produced with the framework in simulating diverse occupation systems scenarios

The mesh is a network of microtubule connectors that stabilizes individual kinetochore fibers of the mitotic spindle

Kinetochore fibers (K-fibers) of the mitotic spindle are force-generating units that power chromosome movement during mitosis. K-fibers are composed of many microtubules that are held together throughout their length. Here we show, using 3D electron microscopy, that K-fiber microtubules are connected by a network of microtubule connectors. We term this network 'the mesh'. The K-fiber mesh is made of linked multipolar connectors. Each connector has up to four struts, so that a single connector can link up to four microtubules. Molecular manipulation of the mesh by overexpression of TACC3 causes disorganization of the K-fiber microtubules. Optimal stabilization of K-fibers by the mesh is required for normal progression through mitosis. We propose that the mesh stabilizes K-fibers by pulling MTs together and thereby maintaining the integrity of the fiber. Our work thus identifies the K-fiber meshwork of linked multipolar connectors as a key integrator and determinant of K-fiber structure and function

Molluscs collected with otter trawl in the northern Alboran Sea: main assemblages, spatial distribution and environmental linkage

Molluscan assemblages of circalittoral and bathyal soft bottoms of the northern Alboran Sea were studied using an experimental otter trawl. Samples of fauna were collected from 190 hauls during four MEDITS surveys carried out in spring between 2012 and 2015 at depths ranging from 30 to 800 m. Measurements of water column variables (temperature and salinity) and sediment samples were taken in the same locations where faunistic sampling was carried out. A total of 101 species grouped in 55 families were recorded. Cephalopods were the most abundant group, with Abralia veranyi dominating in abundance, Octopus vulgaris in biomass and Illex coindetii and Todarodes sagittatus being the most frequently collected species. Multivariate analyses carried out separately with abundance data of demersal species, benthic species, bivalves, gastropods and cephalopods as well as of all molluscs, generally resulted in three main molluscan assemblages corresponding to a shelf assemblage (30-200 m depth), an upper slope assemblage (201-350 m depth), and a middle slope assemblage (351-800 m depth). PERMANOVA test revealed that significant differences of different groups of molluscs in relation to depth were more acute than to geographical sectors of the Alboran Sea (eastern, central, eastern and insular sectors). Abundance, biomass and species richness decreased with depth with a clear dominance of cephalopods in the slope. Significant geographical differences were mainly detected for demersal and benthic species as well as for gastropods and cephalopods between the insular sector (Alboran Island) and the western and eastern continental sectors. Both depth and temperature were the most influencing variables in the different CCA analyses using datasets of molluscs with different life styles and from different classes, but sedimentological variables displayed a more acute significant relationship with the benthic molluscs than with the demersal ones

Evidence formulti-cycle sedimentation and provenance constraints from

Laser ablation ICP-MS U–Pb analyses were conducted on detrital zircons of Triassic sandstone and conglomerate from the Lusitanian basin in order to: i) document the age spectra of detrital zircon; ii) compare U–Pb detrital zircon ages with previous published data obtained from Upper Carboniferous, Ordovician, Cambrian and Ediacaran sedimentary rocks of the pre-Mesozoic basement of western Iberia; iii) discuss potential sources; and iv) test the hypothesis of sedimentary recycling. U–Pb dating of zircons established a maximum depositional age for this deposit as Permian (ca. 296Ma),which is about sixty million years older compared to the fossil content recognized in previous studies (Upper Triassic). The distribution of detrital zircon ages obtained points to common source areas: the Ossa–Morena and Central Iberian zones that outcrop in and close to the Porto–Tomar fault zone. The high degree of immaturity and evidence of little transport of the Triassic sediment suggests that granite may constitute primary crystalline sources. The Carboniferous age of ca. 330 Ma for the best estimate of crystallization for a granite pebble in a Triassic conglomerate and the Permian–Carboniferous ages (ca. 315Ma) found in detrital zircons provide evidence of the denudation of Variscan and Cimmerian granites during the infilling of continental rift basins in western Iberia. The zircon age spectra found in Triassic strata are also the result of recycling from the Upper Carboniferous Buçaco basin,which probably acted as an intermediate sediment repository.U–Pb data in this study suggest that the detritus from the Triassic sandstone and conglomerate of the Lusitanian basin is derived fromlocal source areas with features typical of Gondwana,with no sediment from external sources from Laurussia or southwestern Iberia

Ancient Origin and Gene Mosaicism of the Progenitor of Mycobacterium tuberculosis

The highly successful human pathogen Mycobacterium tuberculosis has an extremely low level of genetic variation, which suggests that the entire population resulted from clonal expansion following an evolutionary bottleneck around 35,000 y ago. Here, we show that this population constitutes just the visible tip of a much broader progenitor species, whose extant representatives are human isolates of tubercle bacilli from East Africa. In these isolates, we detected incongruence among gene phylogenies as well as mosaic gene sequences, whose individual elements are retrieved in classical M. tuberculosis. Therefore, despite its apparent homogeneity, the M. tuberculosis genome appears to be a composite assembly resulting from horizontal gene transfer events predating clonal expansion. The amount of synonymous nucleotide variation in housekeeping genes suggests that tubercle bacilli were contemporaneous with early hominids in East Africa, and have thus been coevolving with their human host much longer than previously thought. These results open novel perspectives for unraveling the molecular bases of M. tuberculosis evolutionary success

Sedimentary record of the amalgamation and break-up of Pangaea: U-Pb detrital zircon geochronology and provenance of Carboniferous-Triassic siliciclastic rocks (SW Iberia)

In SW Iberia there is a basal unconformity where Triassic sandstones overlie previously deformed Carboniferous turbidites. This important stratigraphic boundary records the transition from the final stages of Pangaea’s amalgamation to the initial stages of break-up. U-Pb dating of detrital zircon from Carboniferous greywackes of the South Portuguese Zone and Triassic sandstones of the Algarve and Alentejo basins was carried out to conduct a study of sedimentary provenance. The radiometric ages obtained by LA-ICP-MS show that most of the samples have common age spectra which are typical of North Gondwana sources: Archean and Paleoproterozoic ages characteristic of the West African craton, Neoproterozoic ages associated with Cadomian and Pan-African orogenies, and Cambrian ages related to the intra-continental rifting of North Gondwana. The only exception is a Visean immature greywacke that was probably derived from Devonian magmatic arcs related to the Variscan orogeny. Very rare pre-Devonian zircons indicate faint contributions from recycled sediments. In contrast the Serpukhovian to Moscovian greywackes are derived from felsic mature source rocks and include Proterozoic and Paleozoic detrital zircons suggesting recycling of an old basement. They also include Ordovician and Silurian detrital zircons, the ages of which have no correspondence in North Gondwana, and thus indicate an external source (Laurussia?). U-Pb ages younger than Ordovician are significant in the Triassic sandstone of the Alentejo basin and resemble the zircon populations of the Serpukhovian to Moscovian greywackes from the South Portuguese Zone. U-Pb ages younger than Neoproterozoic are poorly represented in the zircon population of the Triassic sandstone from the Algarve basin, which rests unconformably upon Moscovian turbidites, pointing to Upper Devonian quartzites of the South Portuguese Zone as probable sources, since they are dominated by Precambrian detrital zircons. These differences occurring in the Triassic basins suggest that detrital zircon populations could be derived from two independent sources and paleo-drainage systems due to complex crustal-block extension architecture

Predominance of Ancestral Lineages of Mycobacterium tuberculosis in India

Molecular epidemiologic findings suggest an ancient focus of TB