Loss of canonical Wnt signaling is involved in the pathogenesis of Alzheimer's disease

Alzheimer's disease (AD) is the most common form of dementia in the older population, however, the precise cause of the disease is unknown. The neuropathology is characterized by the presence of aggregates formed by amyloid-β (Aβ) peptide and phosphorylated tau; which is accompanied by progressive impairment of memory. Diverse signaling pathways are linked to AD, and among these the Wnt signaling pathway is becoming increasingly relevant, since it plays essential roles in the adult brain. Initially, Wnt signaling activation was proposed as a neuroprotective mechanism against Aβ toxicity. Later, it was reported that it participates in tau phosphorylation and processes of learning and memory. Interestingly, in the last years we demonstrated that Wnt signaling is fundamental in amyloid precursor protein (APP) processing and that Wnt dysfunction results in Aβ production and aggregation in vitro. Recent in vivo studies reported that loss of canonical Wnt signaling exacerbates amyloid deposition in a transgenic (Tg) mouse model of AD. Finally, we showed that inhibition of Wnt signaling in a Tg mouse previously at the appearance of AD signs, resulted in memory loss, tau phosphorylation and Aβ formation and aggregation; indicating that Wnt dysfunction accelerated the onset of AD. More importantly, Wnt signaling loss promoted cognitive impairment, tau phosphorylation and Aβ1–42 production in the hippocampus of wild-type (WT) mice, contributing to the development of an Alzheimer's-like neurophatology. Therefore, in this review we highlight the importance of Wnt/β-catenin signaling dysfunction in the onset of AD and propose that the loss of canonical Wnt signaling is a triggering factor of AD

Draft Genome Sequence of a Multi-Metal Resistant Bacterium Pseudomonas putida ATH-43 Isolated from Greenwich Island, Antarctica

Indexación: Web of Science; Scopus.In this report we present the first draft genome sequence of a P. putida strain isolated from the Antarctic continent. The shotgun sequencing strategy, assembly, and subsequent annotation showed that the ATH-43 strain possesses a wide spectrum of genetic determinants involved in heavy metal and antibiotic resistance, apparently to cope with extreme oxidative stress conditions. P. putida ATH-43 genome now forms part of the 65 genomes of this species registered at the NCBI database (September, 2016) and it is highly related with the endophytic strain P. putida W619, which is also resistant to several heavy metals. Further characterization of multi-metal resistant psychrotrophic bacteria such as P. putida ATH-43 will be promising to develop novel strategies for heavy metal bioremediation in low temperature environments. All genome data has been submitted to NCBI.http://journal.frontiersin.org/article/10.3389/fmicb.2016.01777/ful

Aproximación a la construcción del concepto de multiplicación en el marco del estudio de clases

Este artículo da cuenta de una investigación que se centró en dos aspectos confluyentes: el mejoramiento de la enseñanza del concepto de multiplicación, que los alumnos evidencian haber aprendido de modo inadecuado e incompleto, y el desarrollo profesional de profesores de educación básica de establecimientos de dependencia municipal. La investigación acción buscaba favorecer el desarrollo de las capacidades de los profesores para elaborar e implementar una propuesta de enseñanza efectiva del concepto de multiplicación en el marco de Estudio de Clases. El estudio se sustentó en los fundamentos teóricos de la Teoría de la Transposición Didáctica y el Estudio de Clases. Los resultados reportados muestran progresos de los profesores en la profundización en el concepto de multiplicación y en el mejoramiento de las capacidades de enseñanza para la construcción del concepto de multiplicación en los alumnos

Long-term social isolation stress exacerbates sex-specific neurodegeneration markers in a natural model of Alzheimer’s disease

Social interactions have a significant impact on health in humans and animal models. Social isolation initiates a cascade of stress-related physiological disorders and stands as a significant risk factor for a wide spectrum of morbidity and mortality. Indeed, social isolation stress (SIS) is indicative of cognitive decline and risk to neurodegenerative conditions, including Alzheimer’s disease (AD). This study aimed to evaluate the impact of chronic, long-term SIS on the propensity to develop hallmarks of AD in young degus (Octodon degus), a long-lived animal model that mimics sporadic AD naturally. We examined inflammatory factors, bioenergetic status, reactive oxygen species (ROS), oxidative stress, antioxidants, abnormal proteins, tau protein, and amyloid-β (Aβ) levels in the hippocampus of female and male degus that were socially isolated from post-natal and post-weaning until adulthood. Additionally, we explored the effect of re-socialization following chronic isolation on these protein profiles. Our results showed that SIS promotes a pro-inflammatory scenario more severe in males, a response that was partially mitigated by a period of re-socialization. In addition, ATP levels, ROS, and markers of oxidative stress are severely affected in female degus, where a period of re-socialization fails to restore them as it does in males. In females, these effects might be linked to antioxidant enzymes like catalase, which experience a decline across all SIS treatments without recovery during re-socialization. Although in males, a previous enzyme in antioxidant pathway diminishes in all treatments, catalase rebounds during re-socialization. Notably, males have less mature neurons after chronic isolation, whereas phosphorylated tau and all detectable forms of Aβ increased in both sexes, persisting even post re-socialization. Collectively, these findings suggest that long-term SIS may render males more susceptible to inflammatory states, while females are predisposed to oxidative states. In both scenarios, the accumulation of tau and Aβ proteins increase the individual susceptibility to early-onset neurodegenerative conditions such as AD

Nitrogen-carbon graphite-like semiconductor synthesized from uric acid

A new carbon-nitrogen organic semiconductor has been synthesized by pyrolysis of uric acid. This layered carbon-nitrogen material contains imidazole-, pyridine (naphthyridine)- and graphitic-like nitrogen, as evinced by infrared and X-ray photoelectron spectroscopies. Quantum chemistry calculations support that it would consist of a 2D polymeric material held together by hydrogen bonds. Layers are stacked with an interplanar distance between 3.30 and 3.36 Å, as in graphite and coke. Terahertz spectroscopy shows a behavior similar to that of amorphous carbons, such as coke, with non-interacting layers. This material features substantial differences from polymeric carbon nitride, with some characteristics closer to those of nitrogen-doped graphene, in spite of its higher nitrogen content. The direct optical band gap, dependent on the polycondensation temperature, ranges from 2.10 to 2.32 eV. Although in general the degree of crystallinity is low, in the material synthesized at 600 °C some spots with a certain degree of crystallinity can be found

Postsynaptic dysfunction is associated with spatial and object recognition memory loss in a natural model of Alzheimer's disease

Alzheimer’s disease (AD) is an age-related neurodegenerative disorder associated with progressive memory loss, severe dementia, and hallmark neuropathological markers, such as deposition of amyloid-β (Aβ) peptides in senile plaques and accumulation of hyperphosphorylated tau proteins in neurofibrillary tangles. Recent evidence obtained from transgenic mouse models suggests that soluble, nonfibrillar Aβ oligomers may induce synaptic failure early in AD. Despite their undoubted value, these transgenic models rely on genetic manipulations that represent the inherited and familial, but not the most abundant, sporadic form of AD. A nontransgenic animal model that still develops hallmarks of AD would be an important step toward understanding how sporadic AD is initiated. Here we show that starting between 12 and 36 mo of age, the rodent Octodon degus naturally develops neuropathological signs of AD, such as accumulation of Aβ oligomers and phosphorylated tau proteins. Moreover, age-related changes in Aβ oligomers and tau phosphorylation levels are correlated with decreases in spatial and object recognition memory, postsynaptic function, and synaptic plasticity. These findings validate O. degus as a suitable natural model for studying how sporadic AD may be initiated

Optimization of Control Strategies for Non-Domiciliated Triatoma dimidiata, Chagas Disease Vector in the Yucatán Peninsula, Mexico

Chagas disease is the most important vector-borne disease in Latin America. Residual insecticide spraying has been used successfully for the elimination of domestic vectors in many regions. However, some vectors of non-domestic origin are able to invade houses, and they are now a key challenge for further disease control. We developed a mathematical model to predict the temporal variations in abundance of non-domiciliated vectors inside houses, based on triatomine demographic parameters. The reliability of the predictions was demonstrated by comparing these with different sets of insect collection data from the Yucatan peninsula, Mexico. We then simulated vector control strategies based on insecticide spraying, insect, screens and bednets to evaluate their efficacy at reducing triatomine abundance in the houses. An optimum reduction in bug abundance by at least 80% could be obtained by insecticide application only when doses of at least 50 mg/m2 were applied every year within a two-month period matching the house invasion season by bugs. Alternatively, the use of insect screens consistently reduced bug abundance in the houses and offers a sustainable alternative. Such screens may be part of novel interventions for the integrated control of various vector-borne diseases

The improbable transmission of Trypanosoma cruzi to human: the missing link in the dynamics and control of Chagas disease

Chagas disease has a major impact on human health in Latin America and is becoming of global concern due to international migrations. Trypanosoma cruzi, the etiological agent of the disease, is one of the rare human parasites transmitted by the feces of its vector, as it is unable to reach the salivary gland of the insect. This stercorarian transmission is notoriously poorly understood, despite its crucial role in the ecology and evolution of the pathogen and the disease. The objective of this study was to quantify the probability of T. cruzi vectorial transmission to humans, and to use such an estimate to predict human prevalence from entomological data. We developed several models of T. cruzi transmission to estimate the probability of transmission from vector to host. Using datasets from the literature, we estimated the probability of transmission per contact with an infected triatomine to be 5.8x10(-4) (95%CI: [2.6; 11.0] x 10(-4)). This estimate was consistent across triatomine species, robust to variations in other parameters, and corresponded to 900-4,000 contacts per case. Our models subsequently allowed predicting human prevalence from vector abundance and infection rate in 7/10 independent datasets covering various triatomine species and epidemiological situations. This low probability of T. cruzi transmission reflected well the complex and unlikely mechanism of transmission via insect feces, and allowed predicting human prevalence from basic entomological data. Although a proof of principle study would now be valuable to validate our models' predictive ability in an even broader range of entomological and ecological settings, our quantitative estimate could allow switching the evaluation of disease risk and vector control program from purely entomological indexes to parasitological measures, as commonly done for other major vector borne diseases. This might lead to different quantitative perspectives as these indexes are well known not to be proportional one to another

Search for chargino-neutralino production with mass splittings near the electroweak scale in three-lepton final states in √s=13 TeV pp collisions with the ATLAS detector

A search for supersymmetry through the pair production of electroweakinos with mass splittings near the electroweak scale and decaying via on-shell W and Z bosons is presented for a three-lepton final state. The analyzed proton-proton collision data taken at a center-of-mass energy of √s=13  TeV were collected between 2015 and 2018 by the ATLAS experiment at the Large Hadron Collider, corresponding to an integrated luminosity of 139  fb−1. A search, emulating the recursive jigsaw reconstruction technique with easily reproducible laboratory-frame variables, is performed. The two excesses observed in the 2015–2016 data recursive jigsaw analysis in the low-mass three-lepton phase space are reproduced. Results with the full data set are in agreement with the Standard Model expectations. They are interpreted to set exclusion limits at the 95% confidence level on simplified models of chargino-neutralino pair production for masses up to 345 GeV

Eco-bio-social determinants for house infestation by non-domiciliated Triatoma dimidiata in the Yucatan peninsula, Mexico

Background Chagas disease is a vector-borne disease of major importance in the Americas. Disease prevention is mostly limited to vector control. Integrated interventions targeting ecological, biological and social determinants of vector-borne diseases are increasingly used for improved control. Methodology/principal findings We investigated key factors associated with transient house infestation by T. dimidiata in rural villages in Yucatan, Mexico, using a mixed modeling approach based on initial null-hypothesis testing followed by multimodel inference and averaging on data from 308 houses from three villages. We found that the presence of dogs, chickens and potential refuges, such as rock piles, in the peridomicile as well as the proximity of houses to vegetation at the periphery of the village and to public light sources are major risk factors for infestation. These factors explain most of the intra-village variations in infestation. Conclusions/significance These results underline a process of infestation distinct from that of domiciliated triatomines and may be used for risk stratification of houses for both vector surveillance and control. Combined integrated vector interventions, informed by an Ecohealth perspective, should aim at targeting several of these factors to effectively reduce infestation and provide sustainable vector control