Status report of a systematic investigation on low-dose ionizing radiation effects in mammalian cells

In the last 15 years a growing interest in the biological effects induced by low doses of ionizing radiation has arisen in the scientific community, due to an increasing number of experimental evidences showing a plethora of non-linear effects occurring after low-dose irradiations. In particular, hyper-radiosensitivity and induced radioresistance (HRS/IRR) have been reported after exposure to low- and high-LET radiation, in human (normal and tumoural) and other mammalian cells in vitro. In this framework, Chinese hamster V79 cells, human primary fibroblasts (HFFF2) and murine embryonic fibroblasts (MEFs) were irradiated with broadbeams of protons in the dose range 0.1–5.0Gy and at 1 Gy/min dose-rate. Cellular response has been evaluated in terms of cell survival, micronuclei induction, chromosomal aberrations and telomere length alterations. For comparison purpose, the same end-points were studied after X/γ-rays irradiation

Statistical distribution of quantum entanglement for a random bipartite state

We compute analytically the statistics of the Renyi and von Neumann entropies (standard measures of entanglement), for a random pure state in a large bipartite quantum system. The full probability distribution is computed by first mapping the problem to a random matrix model and then using a Coulomb gas method. We identify three different regimes in the entropy distribution, which correspond to two phase transitions in the associated Coulomb gas. The two critical points correspond to sudden changes in the shape of the Coulomb charge density: the appearance of an integrable singularity at the origin for the first critical point, and the detachement of the rightmost charge (largest eigenvalue) from the sea of the other charges at the second critical point. Analytical results are verified by Monte Carlo numerical simulations. A short account of some of these results appeared recently in Phys. Rev. Lett. {\bf 104}, 110501 (2010).Comment: 7 figure

Cannabidiol skews biased agonism at cannabinoid CB1 and CB2 receptors with smaller effect in CB1-CB2 heteroreceptor complexes

Currently, biased agonism is at the center stage of drug development approaches. We analyzed effects of a battery of cannabinoids plus/minus cannabidiol (CBD) in four functional parameters (cAMP levels, phosphorylation of extracellular signal–regulated kinases (ERK1/2), β-arrestin recruitment and label-free/DMR) in HEK-293T cells expressing cannabinoid receptors, CB or CB, or CB-CB heteroreceptor complexes. In all cases two natural agonists plus two selective synthetic agonists were used. Furthermore, the effect of cannabidiol, at a dose (100 nM) that does not allow significant binding to the orthosteric center of either receptor, was measured. From the huge amount of generated data, we would like to highlight that the two psychotropic molecules (Δ-tetrahydrocannabinol/THC and CP-55940) showed similar bias in CBR and that the bias of THC was particularly relevant toward MAPK pathway. Furthermore, THC did not activate the G protein coupled to CBR. Interestingly, the biased agonism was reduced when assays were performed in cells expressing the two receptors, thus suggesting that the heteromer allows less functional selectivity. In terms of cannabidiol action, the phytocannabinoid altered the functional responses, likely by allosteric means, and modified potency, agonist IC/EC values and biased agonism in qualitative and/or quantitative different ways depending on the agonist. The effect of cannabidiol on anandamide actions on both cannabinoid receptors was particularly noteworthy as was significantly different from that of other compounds. Results are a compendium of data on biased agonism on cannabinoid receptors in the absence and presence of cannabidiol. In addition, for the first time, GPCR biased agonism is characterized in an heteromeric context.This work was partially supported by grants from the Spanish Ministry of Economy and Competitiveness (Ref. no. BFU2015-64405-R and SAF2017-84117-R; they may include FEDER funds) and by grant 201413-30 from: Fundació la Marató de TV3Peer Reviewe

The Deubiquitinating Enzyme Ataxin-3 Regulates Ciliogenesis and Phagocytosis in the Retina

Expansion of a CAG repeat in ATXN3 causes the dominant polyglutamine disease spinocerebellar ataxia type 3 (SCA3), yet the physiological role of ATXN3 remains unclear. Here, we focus on unveiling the function of Ataxin-3 (ATXN3) in the retina, a neurological organ amenable to morphological and physiological studies. Depletion of Atxn3 in zebrafish and mice causes morphological and functional retinal alterations and, more precisely, photoreceptor cilium and outer segment elongation, cone opsin mislocalization, and cone hyperexcitation. ATXN3 localizes at the basal body and axoneme of the cilium, supporting its role in regulating ciliary length. Abrogation of Atxn3 expression causes decreased levels of the regulatory protein KEAP1 in the retina and delayed phagosome maturation in the retinal pigment epithelium. We propose that ATXN3 regulates two relevant biological processes in the retina, namely, ciliogenesis and phagocytosis, by modulating microtubule polymerization and microtubule-dependent retrograde transport, thus positing ATXN3 as a causative or modifier gene in retinal/macular dystrophies

Semillas en el tiempo : el latinoamericanismo filosófico contemporáneo

Los trabajos que conforman este Iibro giran en torno a un eje: los filósofos latinoamericanistas contemporáneos, desde 1950 en adelante. Todos ellos pensadores que han reflexionado desde adentro, desde el continente acerca de la identidad cultural y social de América Latina: ¿qué es América, qué es ser americano, cuál es su historia, cuáles son sus contribuciones, qué problemas se derivan de sus relaciones con el Occidente, qué problemas del pasado inciden en su presente, de qué modo debe asumir ese pasado, qué conflictos se desprenden de su estructura de clases? Éstas son algunas de las preguntas que vertebran el nuevo movimiento, que se cuestiona fuertemente la identidad latinoamericana. La relevancia especial de "Semillas en el tiempo" reside en que los autores de los estudios son destacados especialistas en la materia, tanto por sus conocimientos acerca de la Filosofía, como por su dedicación al estudio de la problemática latinoamericana

Spanish Consensus Document on the Treatment Algorithm for Rosacea

Recent scientific evidence and the incorporation of new drugs into the therapeutic arsenal against rosacea have made it necessary to review and update treatment criteria and strategies. To this end, a panel of 15 dermatologists, all experts in rosacea, was formed to share experiences and discuss treatment options, response criteria, and changes to treatment. Based on a critical review of the literature and a discussion of the routine practices of Spanish dermatologists, the panel proposed and debated different options, with consideration of the experience of professionals and the preferences of patients or equality criteria. Following validation of the proposals, the final recommendations were formulated and, together with the evidence from the main international guidelines and studies, used to produce this consensus document. The goal of this consensus document is to provide dermatologists with practical recommendations for the management of rosacea. Las últimas evidencias científicas y la incorporación de nuevos fármacos al arsenal terapéutico de la rosácea hacen necesario revisar y actualizar los criterios y estrategias de tratamiento. Con este fin, un grupo de 15 dermatólogos expertos en esta enfermedad aportaron y discutieron acerca de las diferentes terapias y los criterios de respuesta y cambio de tratamiento. Partiendo de la revisión crítica de la bibliografía y de la exposición de los hábitos de los dermatólogos españoles en su práctica clínica, se formularon distintas propuestas que fueron debatidas teniendo en consideración tanto la experiencia profesional como las preferencias de los pacientes o los criterios de equidad. Una vez validadas las propuestas, se formularon las recomendaciones finales que, junto con la evidencia aportada por las principales guías y estudios internacionales, dieron lugar al presente documento. El objetivo de este consenso es ofrecer al dermatólogo un enfoque práctico para abordar la rosácea

Subjects With Diabetes Mellitus Are at Increased Risk for Developing Tuberculosis : A Cohort Study in an Inner-City District of Barcelona (Spain)

Altres ajuts: Spanish Ministry of Economy and the Institut Universitari per a la Recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (Catalan Health Institute, PREDOC_ECO-19/2).Background: Tuberculosis is the leading cause of mortality from lung infectious disease worldwide in recent years, and its incidence has re-emerged in large cities in low-incidence countries due to migration and socioeconomic deprivation causes. Diabetes mellitus and tuberculosis are syndemic diseases, with diabetes being considered a risk factor for developing tuberculosis. Objective: To investigate whether diabetic patients were at increased risk of tuberculosis living in an inner-district of a large city of northeastern Spain. Methods: Observational matched retrospective cohort study based on clinical records from the population of the lowest socioeconomic status in Barcelona (Ciutat Vella district). A cohort including patients with type 1 and type 2 diabetes mellitus in 2007 and new cases until 2016 (8004 subjects), matched 1:1 by sex and age with a non-diabetic cohort. Follow-up period was until December 31st 2018. We evaluated the risk of developing tuberculosis in diabetic patients compared to non-diabetic patients during the follow up period. We used time-to-event analysis to estimate the incidence of tuberculosis, and competing risks regression by clusters and conditional Cox regression models to calculate the hazard ratio (HR) and its 95% confidence intervals (CI). Results: Among the 16,008 included subjects, the median follow-up was 8.7 years. The mean age was 57.7 years; 61.2% men and 38.8% women in both groups. The incidence of tuberculosis was 69.9 per 100,000 person-years in diabetic patients, and 40.9 per 100,000 person-years in non-diabetic patients (HR = 1.90; CI: 1.18-3.07). After adjustment for the country of origin, chronic kidney disease, number of medical appointments, BMI, alcoholism and smoking, the risk remained higher in diabetic patients (1.66: CI 0.99-2.77). Additionally, subjects from Hindustan or with a history of alcohol abuse also showed a higher risk of developing tuberculosis (HR = 3.51; CI:1.87-6.57, and HR = 2.73; CI:1.22-6.12 respectively). Conclusion: People with diabetes mellitus were at higher risk of developing tuberculosis in a large cohort recruited in an inner-city district with a high incidence for this outcome, and low socioeconomic conditions and high proportion of migrants. This risk was higher among Hindustan born and alcohol abusers

Nonspecific synaptic plasticity improves the recognition of sparse patterns degraded by local noise

Safaryan, K. et al. Nonspecific synaptic plasticity improves the recognition of sparse patterns degraded by local noise. Sci. Rep. 7, 46550; doi: 10.1038/srep46550 (2017). This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ © The Author(s) 2017.Many forms of synaptic plasticity require the local production of volatile or rapidly diffusing substances such as nitric oxide. The nonspecific plasticity these neuromodulators may induce at neighboring non-active synapses is thought to be detrimental for the specificity of memory storage. We show here that memory retrieval may benefit from this non-specific plasticity when the applied sparse binary input patterns are degraded by local noise. Simulations of a biophysically realistic model of a cerebellar Purkinje cell in a pattern recognition task show that, in the absence of noise, leakage of plasticity to adjacent synapses degrades the recognition of sparse static patterns. However, above a local noise level of 20 %, the model with nonspecific plasticity outperforms the standard, specific model. The gain in performance is greatest when the spatial distribution of noise in the input matches the range of diffusion-induced plasticity. Hence non-specific plasticity may offer a benefit in noisy environments or when the pressure to generalize is strong.Peer reviewe

Crises and collective socio-economic phenomena: simple models and challenges

Financial and economic history is strewn with bubbles and crashes, booms and busts, crises and upheavals of all sorts. Understanding the origin of these events is arguably one of the most important problems in economic theory. In this paper, we review recent efforts to include heterogeneities and interactions in models of decision. We argue that the Random Field Ising model (RFIM) indeed provides a unifying framework to account for many collective socio-economic phenomena that lead to sudden ruptures and crises. We discuss different models that can capture potentially destabilising self-referential feedback loops, induced either by herding, i.e. reference to peers, or trending, i.e. reference to the past, and account for some of the phenomenology missing in the standard models. We discuss some empirically testable predictions of these models, for example robust signatures of RFIM-like herding effects, or the logarithmic decay of spatial correlations of voting patterns. One of the most striking result, inspired by statistical physics methods, is that Adam Smith's invisible hand can badly fail at solving simple coordination problems. We also insist on the issue of time-scales, that can be extremely long in some cases, and prevent socially optimal equilibria to be reached. As a theoretical challenge, the study of so-called "detailed-balance" violating decision rules is needed to decide whether conclusions based on current models (that all assume detailed-balance) are indeed robust and generic.Comment: Review paper accepted for a special issue of J Stat Phys; several minor improvements along reviewers' comment