Economic globalization and decentralization: A centrifugal or centripetal relationship?

One of the most significant economic trends in the last decades has been the integration of countries in international markets. What have been the consequences of global economic integration upon the territorial organization of the states? Has it contributed to centralize powers or to further decentralization? The literature so far has provided inconclusive evidence. In this article we shed new light on the relationship between economic globalization and territorial politics by using a varied source of data such as the Regional Authority Index, and the KOF indices of globalization for the period 1970-2010. Results show that economic globalization is positively associated to decentralization, particularly in those countries with more regionalist parties and where levels of inequality are lower

SEMCAL, S.A. : plan estratégico de marketing (2015-2020)

El presente trabajo tiene la finalidad de incrementar el nivel de notoriedad de la empresa familiar SEMCAL, S.A., dedicada al sector del vending, a través de la elección de varias estrategias que supondrán un aumento en las ventas y una mejora en el servicio. Para ello, se ofrece una propuesta de acción a cinco años donde se procederá a implantar nuevas medidas que permitirán a la empresa entrar en nuevos mercados, introducir nuevos productos e incluir nuevas formas de ofrecerles en sus máquinas expendedoras. Su larga trayectoria en el sector, permite a la empresa tener un amplio conocimiento tanto de su entorno como de sus competidores, lo que convierte a su experiencia en una ventaja que le permitirá avanzar hacia los objetivos marcados hasta 2020.The present work aims to increase the level of notoriety of SEMCAL, S.A., a family-owned company engaged in the vending sector, through the choice of several strategies that will increase the sales and improve the service. For this purpose, an action plan proposal is offered over five years to implement new measures which will allow the company to enter new markets, introduce new products and include new ways to offer them in their vending machines. Its long history in the industry allows the company to have a broad knowledge of both their environment and their competitors, turning that experience into an advantage that will lead the company to accomplish its objectives by 2020

Neuronal p38α mediates synaptic and cognitive dysfunction in an Alzheimer’s mouse model by controlling β-amyloid production.

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by a severe and progressive neuronal loss leading to cognitive dysfunctions. Previous reports, based on the use of chemical inhibitors, have connected the stress kinase p38α to neuroinflammation, neuronal death and synaptic dysfunction. To explore the specific role of neuronal p38α signalling in the appearance of pathological symptoms, we have generated mice that combine expression of the 5XFAD transgenes to induce AD symptoms with the downregulation of p38α only in neurons (5XFAD/p38α∆-N). We found that the neuronal-specific deletion of p38α improves the memory loss and long-term potentiation impairment induced by 5XFAD transgenes. Furthermore, 5XFAD/p38α∆-N mice display reduced amyloid-β accumulation, improved neurogenesis, and important changes in brain cytokine expression compared with 5XFAD mice. Our results implicate neuronal p38α signalling in the synaptic plasticity dysfunction and memory impairment observed in 5XFAD mice, by regulating both amyloid-β deposition in the brain and the relay of this accumulation to mount an inflammatory response, which leads to the cognitive deficits.post-print1848 K

Astrocytic p38α MAPK drives NMDA receptor-dependent long-term depression and modulates long-term memory.

NMDA receptor-dependent long-term depression (LTD) in the hippocampus is a well-known form of synaptic plasticity that has been linked to different cognitive functions. The core mechanism for this form of plasticity is thought to be entirely neuronal. However, we now demonstrate that astrocytic activity drives LTD at CA3-CA1 synapses. We have found that LTD induction enhances astrocyte-to-neuron communication mediated by glutamate, and that Ca2+ signaling and SNARE-dependent vesicular release from the astrocyte are required for LTD expression. In addition, using optogenetic techniques, we show that low-frequency astrocytic activation, in the absence of presynaptic activity, is sufficient to induce postsynaptic AMPA receptor removal and LTD expression. Using cell-type-specific gene deletion, we show that astrocytic p38α MAPK is required for the increased astrocytic glutamate release and astrocyte-to-neuron communication during low-frequency stimulation. Accordingly, removal of astrocytic (but not neuronal) p38α abolishes LTD expression. Finally, this mechanism modulates long-term memory in vivo.post-print5316 K

Neuronal p38α mediates age‐associated neural stem cell exhaustion and cognitive decline

[EN] Neuronal activity regulates cognition and neural stem cell (NSC) function. The molecular pathways limiting neuronal activity during aging remain largely unknown. In this work, we show that p38MAPK activity increases in neurons with age. By using mice expressing p38α-lox and CamkII-Cre alleles (p38α∆-N), we demonstrate that genetic deletion of p38α in neurons suffices to reduce age-associated elevation of p38MAPK activity, neuronal loss and cognitive decline. Moreover, aged p38α∆-N mice present elevated numbers of NSCs in the hippocampus and the subventricular zone. These results reveal novel roles for neuronal p38MAPK in age-associated NSC exhaustion and cognitive decline

Predictive Power of the "Trigger Tool" for the detection of adverse events in general surgery: a multicenter observational validation study

Background In spite of the global implementation of standardized surgical safety checklists and evidence-based practices, general surgery remains associated with a high residual risk of preventable perioperative complications and adverse events. This study was designed to validate the hypothesis that a new “Trigger Tool” represents a sensitive predictor of adverse events in general surgery. Methods An observational multicenter validation study was performed among 31 hospitals in Spain. The previously described “Trigger Tool” based on 40 specific triggers was applied to validate the predictive power of predicting adverse events in the perioperative care of surgical patients. A prediction model was used by means of a binary logistic regression analysis. Results The prevalence of adverse events among a total of 1,132 surgical cases included in this study was 31.53%. The “Trigger Tool” had a sensitivity and specificity of 86.27% and 79.55% respectively for predicting these adverse events. A total of 12 selected triggers of overall 40 triggers were identified for optimizing the predictive power of the “Trigger Tool”. Conclusions The “Trigger Tool” has a high predictive capacity for predicting adverse events in surgical procedures. We recommend a revision of the original 40 triggers to 12 selected triggers to optimize the predictive power of this tool, which will have to be validated in future studies

The stress-activated protein kinases p38α/β and JNK1/2 cooperate with Chk1 to inhibit mitotic entry upon DNA replication arrest

Accurate DNA replication is crucial for the maintenance of genome integrity. To this aim, cells have evolved complex surveillance mechanisms to prevent mitotic entry in the presence of partially replicated DNA. ATR and Chk1 are key elements in the signal transduction pathways of DNA replication checkpoint; however, other kinases also make significant contributions. We show here that the stress kinases p38 and JNK are activated when DNA replication is blocked, and that their activity allows S/M, but not G₂/M, checkpoint maintenance when Chk1 is inhibited. Activation of both kinases by DNA replication inhibition is not mediated by the caffeine-sensitive kinases ATR or ATM. Phosphorylation of MKK3/6 and MKK4, p38 and JNK upstream kinases was also observed upon DNA replication inhibition. Using a genetic approach, we dissected the p38 pathway and showed that both p38α and p38β isoforms collaborate to inhibit mitotic entry. We further defined MKK3/6 and MK2/3 as the key upstream and downstream elements in the p38 signaling cascade after replication arrest. Accordingly, we found that the stress signaling pathways collaborate with Chk1 to keep cyclin B1/Cdk1 complexes inactive when DNA replication is inhibited, there by preventing cell cycle progression when DNA replication is stalled. Our results show a complex response to replication stress, where multiple pathways are activated and fulfill overlapping roles to prevent mitotic entry with unreplicated DNA

Mucus-Activatable Shiga Toxin Genotype stx2d in Escherichia coli O157:H7

We identified the mucus-activatable Shiga toxin genotype stx2d in the most common hemolytic uremic syndrome–associated Escherichia coli serotype, O157:H7. stx2d was detected in a strain isolated from a 2-year-old boy with bloody diarrhea in Spain, and whole-genome sequencing was used to confirm and fully characterize the strain

Understanding brain function in vascular cognitive impairment and dementia with EEG and MEG: A systematic review

Vascular Cognitive Impairment (VCI) is the second most prevalent dementia after Alzheimer’s Disease (AD), and cerebrovascular disease (CBVD) is a major comorbid contributor to the progression of most neurodegenerative diseases. Early differentiation of cognitive impairment is critical given both the high prevalence of CBVD, and that its risk factors are modifiable. The ability for electroencephalogram (EEG) and magnetoencephalogram (MEG) to detect changes in brain functioning for other dementias suggests that they may also be promising biomarkers for early VCI. The present systematic review aims to summarize the literature regarding electrophysiological patterns of mild and major VCI. Despite considerable heterogeneity in clinical definition and electrophysiological methodology, common patterns exist when comparing patients with VCI to healthy controls (HC) and patients with AD, though there is a low specificity when comparing between VCI subgroups. Similar to other dementias, slowed frequency patterns and disrupted inter- and intra-hemispheric connectivity are repeatedly reported for VCI patients, as well as longer latencies and smaller amplitudes in evoked responses. Further study is needed to fully establish MEG and EEG as clinically useful biomarkers, including a clear definition of VCI and standardized methodology, allowing for comparison across groups and consolidation of multicenter efforts

Oxidative stress is a central target for physical exercise neuroprotection against pathological brain aging

Physical exercise is suggested for preventing or delaying senescence and Alzheimer’s disease (AD). We have examined its therapeutic value in the advanced stage of AD-like pathology in 3xTg-AD female mice through voluntary wheel running from 12 to 15 months of age. Mice submitted to exercise showed improved body fitness, immunorejuvenation, improvement of behavior and cognition, and reduced amyloid and tau pathology. Brain tissue analysis of aged 3xTg-AD mice showed high levels of oxidative damage. However, this damage was decreased by physical exercise through regulation of redox homeostasis. Network analyses showed that oxidative stress was a central event, which correlated with AD-like pathology and the AD-related behaviors of anxiety, apathy, and cognitive loss. This study corroborates the importance of redox mechanisms in the neuroprotective effect of physical exercise, and supports the theory of the crucial role of oxidative stress in the switch from normal brain aging to pathological aging and AD.Postprint (author’s final draft