A process-specific approach in the study of normal aging deficits in cognitive control: What deteriorates with age?

Bearing in mind that cognitive control is a complex function that includes several processes, it is not clear exactly which ones deteriorate with age. In fact, controversial results have been found. For example, some studies indicate that age-related deficits are observed in proactive and not in reactive control, others show that it is reactive control that is impaired and not proactive control, and some studies find no deficits at all (e.g., Kopp, Lange, Howe, & Wessel, 2014; Xiang et al., 2016). One possible reason is that the contribution of different processes to the deterioration of cognitive control was investigated separately, i.e., without testing all processes within the same paradigm. Therefore, the main goal of the present experiment was to study the impact of normal aging on several processes related to cognitive control within the same task, which included both Simon and Spatial Stroop trials. The study focused on the following processes: generation of conflict measured by automatic response capture (i.e., stronger task-irrelevant information processing compared to task-relevant information processing); conflict detection; and control implementation (which can be reactive control, both within trials and across trials, and proactive control, as a task-set strategy). The results showed larger automatic response capture for older adults when facing a stimulus-response conflict (Simon) but not a stimulus-stimulus conflict (Spatial Stroop). Similarly, older adults also showed larger detection effects for both conflicts. However, regarding control implementation, they only showed difficulties in inhibiting the early automatic response capture (within-trial reactive control) but not reactive control across trials or proactive control. In conclusion, it seems that older adults are more affected by the presence of task-irrelevant information, especially when it comes to resolving stimulus-response conflict. However, they showed no impairments in their ability to implement cognitive control both across trials and as a task-set strategy

Comparing neural substrates of emotional vs. non-emotional conflict modulation by global control context

The efficiency with which the brain resolves conflict in information processing is determined by contextual factors that modulate internal control states, such as the recent (local) and longer-term (global) occurrence of conflict. Local “control context” effects can be observed in trial-by-trial adjustments to conflict (congruency sequence effects: less interference following incongruent trials), whereas global control context effects are reflected in adjustments to the frequency of conflict encountered over longer sequences of trials (“proportion congruent effects”: less interference when incongruent trials are frequent). Previous neuroimaging and lesion studies suggest that the modulation of conflict-control processes by local control context relies on partly dissociable neural circuits for cognitive (non-emotional) vs. emotional conflicts. By contrast, emotional and non-emotional conflict-control processes have not been contrasted with respect to their modulation by global control context. We addressed this aim in a functional magnetic resonance imaging (fMRI) study that varied the proportion of congruent trials in emotional vs. non-emotional conflict tasks across blocks. We observed domain-general conflict-related signals in the dorsal anterior cingulate cortex (dACC) and pre-supplementary motor area and, more importantly, task-domain also interacted with global control context effects: specifically, the dorsal striatum and anterior insula tracked control-modulated conflict effects exclusively in the emotional domain. These results suggest that, similar to the neural mechanisms of local control context effects, there are both overlapping as well as distinct neural substrates involved in the modulation of emotional and non-emotional conflict-control by global control context.This work was supported by NIMH grant 5R01MH087610 (Tobias Egner), a research position grant (FPU grant; AP2008-04006) (Maryem Torres-Quesada), and Spain's Ministerio de Ciencia y Tecnología (PSI2008-04223PSIC, PSI2012-34158, and CONSOLIDER-INGENIO2010 CS)

A Spectroscopic study of colchicine in the solid state and in solution by multinuclear magnetic resonance and vibrational circular dichroism

Although almost 200-years-old, several unknown aspects remain to be explored of colchicine, the unique available drug for acute flares of gout. In this article, we report density-functional theory (DFT) studies of geometry, energy, and NMR; 1H-, 13C-, and 15N-NMR chemical shifts and some spin-spin coupling constants, including the complete analysis of the saturated part (ring B); the assignment of both enantiomers by NMR using a chiral solvating agent; solid-state NMR experiments of the different forms of natural and racemic colchicine, and IR and vibrational circular dichroism (VCD) studies of these same forms. Copyright © 2014 Verlag Helvetica Chimica Acta AG, Zürich.Peer Reviewe

Counterregulation of cAMP-directed kinase activities controls ciliogenesis

The primary cilium emanates from the cell surface of growth-arrested cells and plays a central role in vertebrate development and tissue homeostasis. The mechanisms that control ciliogenesis have been extensively explored. However, the intersection between GPCR signaling and the ubiquitin pathway in the control of cilium stability is unknown. Here, we observe that cAMP elevation promotes cilia resorption. At centriolar satellites, we identify a multimeric complex nucleated by PCM1 that includes two kinases, NEK10 and PKA, and the E3 ubiquitin ligase CHIP. We show that NEK10 is essential for ciliogenesis in mammals and for the development of medaka fish. PKA phosphorylation primes NEK10 for CHIP-mediated ubiquitination and proteolysis resulting in cilia resorption. Dearangement of this control mechanism occurs in proliferative and genetic disorders. These findings unveil a pericentriolar kinase signalosome that efficiently links the cAMP cascade with the ubiquitin-proteasome system, controlling essential aspects of ciliogenesis

Los gasterópodos terrestres del Cuaternario Superior de Gran Canaria (Islas Canarias)- Land gastropods of the Upper Quaternary in Gran Canaria (Canary Islands)

Hemos estudiado la estratigrafía, cronología y paleontología de ocho depósitos sedimentarios (siete paleodunas y un derrubio de ladera) del Pleistoceno Superior de la isla de Gran Canaria (Islas Canarias). Las paleodunas se caracterizan por una alternancia de dunas y paleosuelos, que varía entre un ciclo en la Playa de Jinámar, y once en el Lazareto (Gando). La cronología de estos depósitos, obtenida por racemización de aminoácidos sobre ejemplares del género Theba y calibrada con 14C, muestra una edad entre 44,4 Ka a 22,2 Ka. La aminoestratigrafía ha permitido asignar estos depósitos a cuatro aminozonas (AM2 a AM5) de las registradas por Ortiz et al. (2006). Las asociaciones fósiles de gasterópodos terrestres están representadas por 20 especies pertenecientes a 8 familias, con un grado de endemismo del 95%. Los cambios faunísticos detectados, con respecto a la actualidad, se refieren a la extinción del 25 % de las especies del Pleistoceno Superior, y a la disminución de la extensión geográfica de algunas especies como Theba arinagae y T. aff. grasseti. - A stratigraphic, chronological and paleontological study of eight sedimentary deposits (seven palaeodunes and a colluvial slide) in the Upper Pleistocene of Gran Canaria (Canary Islands) has been undertaken. The palaeodunes are characterized by dune-palaeosoil alternation, from an only cycle in Playa de Jinámar to eleven in Lazareto (Gando). The chronology of these deposits, obtained by amino acid racemisation and 14C datations in Theba genus samples, displays an age between 44,4 Ka and 22,2 Ka. The aminostratigraphy study appoints to these sediments belong to four amino zones (AM2 to AM5) reported by Ortiz et al. (2006). The land snail fossil assemblages are represented by 20 species belonging to eight families, with an endemic degree around 95%. The detected fossil fauna changes with regard to present fauna reveal an Upper Pleistocene species extinction at about 25% and geographic extension decreasing of some species as Theba arinagae and T. aff. grasset

Synthesis and screening of 6‐alkoxy purine analogs as cell type‐selective apoptotic inducers in Jurkat cells

Ministerio de Ciencia e Innovacion, Grant/Award Number: RTC-2017-6620; Ministerio de Educacion, Cultura y Deporte, Grant/Award Number: FPU 14/00818Purines are ubiquitous structures in cell biology involved in a multitude of cellular processes, because of which substituted purines and analogs are considered excellent scaffolds in drug design. In this study, we explored the key structural features of a purine‐based proapoptotic hit, 8‐tert‐butyl‐9‐phenyl‐6‐benzyloxy‐9Hpurine (1), by setting up a library of 6‐alkoxy purines with the aim of elucidating the structural requirements that govern its biological activity and to study the cell selectivity of this chemotype. This was done by a phenotypic screening approach based on cell cycle analysis of a panel of six human cancer cell lines, including T cell leukemia Jurkat cells. From this study, two derivatives (12 and 13) were identified as Jurkat‐selective proapoptotic compounds, displaying superior potency and cell selectivity than hit 1.Instituto de Salud Carlos III Spanish Government European Commission RTC-2017-6620Ministerio de Educacion, Cultura y Deporte FPU 14/0081

Pattern and process in Amazon tree turnover, 1976-2001

Previous work has shown that tree turnover, tree biomass and large liana densities have increased in mature tropical forest plots in the late twentieth century. These results point to a concerted shift in forest ecological processes that may already be having significant impacts on terrestrial carbon stocks, fluxes and biodiversity. However, the findings have proved controversial, partly because a rather limited number of permanent plots have been monitored for rather short periods. The aim of this paper is to characterize regional-scale patterns of 'tree turnover' (the rate with which trees die and recruit into a population) by using improved datasets now available for Amazonia that span the past 25 years. Specifically, we assess whether concerted changes in turnover are occurring, and if so whether they are general throughout the Amazon or restricted to one region or environmental zone. In addition, we ask whether they are driven by changes in recruitment, mortality or both. We find that: (i) trees 10 cm or more in diameter recruit and die twice as fast on the richer soils of southern and western Amazonia than on the poorer soils of eastern and central Amazonia; (ii) turnover rates have increased throughout Amazonia over the past two decades; (iii) mortality and recruitment rates have both increased significantly in every region and environmental zone, with the exception of mortality in eastern Amazonia; (iv) recruitment rates have consistently exceeded mortality rates; (v) absolute increases in recruitment and mortality rates are greatest in western Amazonian sites; and (vi) mortality appears to be lagging recruitment at regional scales. These spatial patterns and temporal trends are not caused by obvious artefacts in the data or the analyses. The trends cannot be directly driven by a mortality driver (such as increased drought or fragmentation-related death) because the biomass in these forests has simultaneously increased. Our findings therefore indicate that long-acting and widespread environmental changes are stimulating the growth and productivity of Amazon forests

Valuation of ecosystem services on Llancanello wetlands, Malargüe, Argentina

Cada vez más los ecosistemas están cediendo espacios para el avance de la frontera agropecuaria. En ausencia de conocimientos y políticas adecuadas, se han generado pérdidas severas en la capacidad de los ecosistemas para sostener la productividad de los suelos, proveer agua limpia, controlar los caudales de ríos e inundaciones, o para regular la composición de la atmósfera y el clima (entre otros beneficios). El progresivo reconocimiento científico y la concientización sobre los servicios ecosistémicos han vuelto inadmisible el reemplazo indiscriminado de bosques, pastizales y humedales para su aprovechamiento productivo sin una adecuada evaluación de los efectos colaterales o externalidades que los acompañan. Los servicios ecosistémicos se pueden definir como todos aquellos beneficios que la sociedad obtiene de los ecosistemas (de provisión, de regulación, bienes tangibles, recursos naturales, beneficios culturales, estéticos y educacionales); un concepto cada vez más aplicado a la conservación del medio ambiente, el bienestar humano y la implicación de las intervenciones antropogénicas en el medio natural, según lo establecido por la Evaluación de los Ecosistemas del Milenio, (MEA 2005). El Área Natural Protegida «Humedal Llancanello», ubicada en el departamento de Malargüe, es reconocido como humedal de importancia internacional por la gran cantidad de aves acuáticas que alberga (flamencos, cisnes, garzas, patos entre los más abundantes). Este lugar de gran belleza escénica, patrimonio turístico y de biodiversidad de los mendocinos es afectado por diversas problemáticas. La pérdida y fragmentación de hábitats puede poner en riesgo severo la supervivencia de muchas especies aviares migratorias y en muchos casos predisponer a su extinción. La disminución del uso recreativo y turístico de la reserva y los impactos ambientales que pueden ejercer la explotación petrolera, minera y agropecuaria, hacen este sitio altamente vulnerable para su conservación. Es importante la necesidad de desarrollar herramientas y propuestas que puedan ser utilizadas por los tenedores de tierras, gestores políticos y empresas involucradas para garantizar un uso sostenible de los servicios ecosistémicos que este sitio ofrece

Sex and gender differences in acute stroke care: metrics, access to treatment and outcome. A territorial analysis of the Stroke Code System of Catalonia

Introduction: Previous studies have reported differences in the management and outcome of women stroke patients in comparison with men. We aim to analyze sex and gender differences in the medical assistance, access to treatment and outcome of acute stroke patients in Catalonia. Patients and methods: Data were obtained from a prospective population-based registry of stroke code activations in Catalonia (CICAT) from January/2016 to December/2019. The registry includes demographic data, stroke severity, stroke subtype, reperfusion therapy, and time workflow. Centralized clinical outcome at 90 days was assessed in patients receiving reperfusion therapy. Results: A total of 23,371 stroke code activations were registered (54% men, 46% women). No differences in prehospital time metrics were observed. Women more frequently had a final diagnosis of stroke mimic, were older and had a previous worse functional situation. Among ischemic stroke patients, women had higher stroke severity and more frequently presented proximal large vessel occlusion. Women received more frequently reperfusion therapy (48.2% vs 43.1%, p < 0.001). Women tended to present a worse outcome at 90 days, especially for the group receiving only IVT (good outcome 56.7% vs 63.8%; p < 0.001), but not for the group of patients treated with IVT + MT or MT alone, although sex was not independently associated with clinical outcome in logistic regression analysis (OR 1.07; 95% CI, 0.94–1.23; p = 0.27) nor in the analysis after matching using the propensity score (OR 1.09; 95% CI, 0.97–1.22). Discussion and conclusion: We found some differences by sex in that acute stroke was more frequent in older women and the stroke severity was higher. We found no differences in medical assistance times, access to reperfusion treatment and early complications. Worse clinical outcome at 90 days in women was conditioned by stroke severity and older age, but not by sex itself