Developmental and interspecies comparison of morphology and plasticity in neuronal circuits involved in olfactory information processing

The anterior piriform cortex (aPCx) is a three layered paleocortex receiving afferent inputs from the olfactory bulb as well as local and long-range associational inputs. Neurons in layer 2 are segregated into layer 2A and layer 2B according to their position, morphology and implementation in the sensory and associative circuits. The dendritic architecture of these neurons is determined during postnatal development and plays an important role for the functionality and circuit integration of the two cell types. Here, confocal imaging, electrophysiology, morphometry and Ca2+ imaging, were combined in order to study the development of the dendritic arborizations for both subtypes of layer 2 neurons. Three different growth phases were identified: branch complexity determination, branch elongation and pruning, occurring at different time windows during development. Layer 2A and layer 2B neurons showed morphological differences between their apical and basal dendrites from the very first postnatal days; as well as phase-specific differences during development associated to differences in circuit implementation. During the first postnatal week, early spontaneous network activity in layer 2 of the aPCx displayed differences between layer 2A and layer 2B neurons in their functional connectivity, reflected in the morphological dissimilarities between their basal dendritic trees during the period of branch complexity determination. Additionally, strong differences in growth phase three were observed. Pruning was exclusive for layer 2B neurons and selective for apical dendrites receiving layer 1A sensory inputs. These differences between layer 2A and layer 2B cells in their morphological and functional development exhibit the close association between circuit specificity and neuronal development. Finally, synaptic plasticity in the mossy fiber (MF) pathway of the hippocampus in shrews was investigated and compared to mice. Although hippocampal structure in shrews is preserved, short and long-term plasticity at the MF synapsis was lower compared to mice, suggesting different involvement of these synapses in the behavioral outcome of different species.Der Cortex piriformis anterior (aPCx auf Englisch) ist ein dreischichtiger Paläokortex, der sensorische afferente Eingänge aus dem Riechkolben sowie intracerebrale assoziative Eingänge empfängt. Die Neuronen in Schicht 2 werden nach ihrer Position, Morphologie und Einbindung in die sensorischen und rekurrenten Netzwerke in die Schichten 2A und 2B unterteilt. Die dendritische Architektur dieser Neurone wird während der postnatalen Entwicklung festgelegt und spielt eine wichtige Rolle für die Funktionalität und Netzwerkintegration der beiden Zelltypen. Hier wurden konfokales Imaging, Elektrophysiologie, Morphometrie und Kalzium-Imaging kombiniert, um die Entwicklung der Dendritenbäume für beide Subtypen von Schicht-2-Neuronen zu untersuchen. Es wurden drei verschiedene Wachstumsphasen identifiziert: Bestimmung der Komplexität der Verzweigung, Verlängerung der Verzweigung und strukturelle Vereinfachung, die in verschiedenen Zeitfenstern während der Entwicklung auftreten. Neurone der Schicht 2A und der Schicht 2B zeigten bereits in den ersten postnatalen Tagen morphologische Unterschiede zwischen ihren apikalen und basalen Dendriten sowie phasenspezifische Unterschiede während der Entwicklung, die mit Unterschieden in der Netzwerkimplementierung verbunden sind. Während der ersten postnatalen Woche zeigte die frühe spontane Netzwerkaktivität in Schicht 2 des aPCx Unterschiede in der funktionellen Konnektivität zwischen Neuronen der Schicht 2A und Schicht 2B, die sich in den morphologischen Unterschieden zwischen ihren basalen Dendritenbäumen während der Bestimmung der Verzweigungskomplexität widerspiegelten. Außerdem wurden starke Unterschiede in der dritten Wachstumsphase beobachtet. Die strukturelle Vereinfachung fand ausschließlich bei Neuronen der Schicht 2B statt und war selektiv für apikale Dendriten, die sensorische Inputs der Schicht 1A erhielten. Diese Unterschiede zwischen Zellen der Schicht 2A und der Schicht 2B in ihrer morphologischen und funktionellen Entwicklung zeigen den engen Zusammenhang zwischen Netzwerkspezifität und neuronaler Entwicklung. Schließlich wurde die synaptische Plastizität des Moosfaser (MF)-Trakts des Hippocampus bei Spitzmäusen untersucht und mit der von Mäusen verglichen. Obwohl die Struktur des Hippocampus bei Spitzmäusen erhalten ist, war die Kurz- und Langzeitplastizität an den MF-Synapsen im Vergleich zu Mäusen geringer, was auf eine unterschiedliche Beteiligung dieser Synapsen an spezifisch adaptierte Verhaltensweisen der beiden Spezies hindeutet

Análisis del Cumplimiento Al Plan de Gestión Integral de Residuos Sólidos en el Municipio de Madrid Cundinamarca entre el Año 2017-2019

El manejo de los residuos sólidos en las sociedades contemporáneas se ha vuelto una problemática común a todos, en donde manejar los residuos generados por la humanidad se ha vuelto una obligación que nace desde el seno de los hogares y debe ser regulado y controlado por los Estados actuales. En el año 2015 al evaluar los Objetivos del Milenio se establecieron los Objetivos de Desarrollo Sostenible que permiten convertir el planeta en un lugar habitable y sostenible para todos quienes habitamos en él, los ODS obliga a los Estados a legislar de forma que los residuos que los ciudadanos generamos sean separados en aprovechable y no aprovechables. Es debido a lo anterior que en el último decenio el congreso colombiano legislo sobre la disposición final de residuos sólidos y la creación de los Planes de gestión Integral de Residuos Sólidos.Solid waste management in contemporary societies has become a common problem for all, where managing waste generated by humanity has become an obligation that arises from within households and must be regulated and controlled by the States. current. In 2015, when evaluating the Millennium Goals, the Sustainable Development Goals were established that allow the planet to become a livable and sustainable place for all of us who inhabit it, the SDGs compel States to legislate in such a way that the waste that the citizens we generate are separated into usable and unusable. It is due to the foregoing that in the last decade the Colombian Congress legislated on the final disposal of solid waste and the creation of Comprehensive Solid Waste Management Plans

SamuROI, a Python-Based Software Tool for Visualization and Analysis of Dynamic Time Series Imaging at Multiple Spatial Scales

The measurement of activity in vivo and in vitro has shifted from electrical to optical methods. While the indicators for imaging activity have improved significantly over the last decade, tools for analysing optical data have not kept pace. Most available analysis tools are limited in their flexibility and applicability to datasets obtained at different spatial scales. Here, we present SamuROI (Structured analysis of multiple user-defined ROIs), an open source Python-based analysis environment for imaging data. SamuROI simplifies exploratory analysis and visualization of image series of fluorescence changes in complex structures over time and is readily applicable at different spatial scales. In this paper, we show the utility of SamuROI in Ca2+-imaging based applications at three spatial scales: the micro-scale (i.e., sub-cellular compartments including cell bodies, dendrites and spines); the meso-scale, (i.e., whole cell and population imaging with single-cell resolution); and the macro-scale (i.e., imaging of changes in bulk fluorescence in large brain areas, without cellular resolution). The software described here provides a graphical user interface for intuitive data exploration and region of interest (ROI) management that can be used interactively within Jupyter Notebook: a publicly available interactive Python platform that allows simple integration of our software with existing tools for automated ROI generation and post-processing, as well as custom analysis pipelines. SamuROI software, source code and installation instructions are publicly available on GitHub and documentation is available online. SamuROI reduces the energy barrier for manual exploration and semi-automated analysis of spatially complex Ca2+ imaging datasets, particularly when these have been acquired at different spatial scales.Peer Reviewe

CATEGORIAS ESENCIALES PARA COMPRENDER LA EXISTENCIA DEL SER HUMANO Y SUS TRANSFORMACIONES EN LA PSICOLOGIA HUMANISTA EXISTENCIAL

The current article appears as an intent to buildup a conceptual, punctual, and deep reflectionin the exercise of an enlightening thought aboutthe human being and his transformations, whatthe Humanistic-Existential psychology considersto be the principles to understand existence;four essential categories are approached beingthe capital elements for the research in theContemporary Transformations group

Socialización

La salud pública es sumamente importante ya que esta se puede definir como un conjunto de políticas orientadas a promover y mantener la salud de la población. La importancia de la salud pública radica principalmente en que nuestra salud está a cargo del estado, y esto trae como consecuencia que nos garantice el acceso al sistema sanitario como también a sus diferentes programas de prevención y curación con el fin de tener una mejora en la calidad de vida.Public health is extremely important since it can be defined as a set of policies aimed at promoting and maintaining the health of the population. The importance of public health lies mainly in the fact that our health is in charge of the state, and this results in that it guarantees us access to the health system as well as its different prevention and cure programs in order to have an improvement in the quality of life

Branch point strength controls species-specific CAMK2B alternative splicing and regulates LTP

Regulation and functionality of species-specific alternative splicing has remained enigmatic to the present date. Calcium/calmodulin-dependent protein kinase IIβ (CaMKIIβ) is expressed in several splice variants and plays a key role in learning and memory. Here, we identify and characterize several primate-specific CAMK2B splice isoforms, which show altered kinetic properties and changes in substrate specificity. Furthermore, we demonstrate that primate-specific CAMK2B alternative splicing is achieved through branch point weakening during evolution. We show that reducing branch point and splice site strengths during evolution globally renders constitutive exons alternative, thus providing novel mechanistic insight into cis-directed species-specific alternative splicing regulation. Using CRISPR/Cas9, we introduce a weaker, human branch point sequence into the mouse genome, resulting in strongly altered Camk2b splicing in the brains of mutant mice. We observe a strong impairment of long-term potentiation in CA3-CA1 synapses of mutant mice, thus connecting branch point–controlled CAMK2B alternative splicing with a fundamental function in learning and memory

The MAPT H1 Haplotype Is a Risk Factor for Alzheimer's Disease in APOE E4 Non-carriers

An ancestral inversion of 900 kb on chromosome 17q21, which includes the microtubule-associated protein tau (MAPT) gene, defines two haplotype clades in Caucasians (H1 and H2). The H1 haplotype has been linked inconsistently with AD. In a previous study, we showed that an SNP tagging this haplotype (rs1800547) was associated with AD risk in a large population from the Dementia Genetics Spanish Consortium (DEGESCO) including 4435 cases and 6147 controls. The association was mainly driven by individuals that were non-carriers of the APOE ?4 allele. Our aim was to replicate our previous findings in an independent sample of 4124 AD cases and 3290 controls from Spain (GR@ACE project) and to analyze the effect of the H1 sub-haplotype structure on the risk of AD. The H1 haplotype was associated with AD risk (OR = 1.12; p = 0.0025). Stratification analysis showed that this association was mainly driven by the APOE ?4 non-carriers (OR = 1.15; p = 0.0022). Pooled analysis of both Spanish datasets (n = 17,996) showed that the highest AD risk related to the MAPT H1/H2 haplotype was in those individuals that were the oldest [third tertile (>77 years)] and did not carry APOE ?4 allele (p = 0.001). We did not find a significant association between H1 sub-haplotypes and AD. H1c was nominally associated but lost statistical significance after adjusting by population sub-structure. Our results are consistent with the hypothesis that genetic variants linked to the MAPT H1/H2 are tracking a genuine risk allele for AD. The fact that this association is stronger in APOE ?4 non-carriers partially explains previous controversial results and might be related to a slower alternative causal pathway less dependent on brain amyloid load.ACKNOWLEDGMENTS: The Genome Research at Fundacio ACE/Dementia Genetics Spanish Consortium (GR@ACE/DEGESCO) would like to thank patients and controls who participated in this project. GR@ACE/DEGESCO GWAS program was funded by Grifols SA, Fundacion Bancaria “La Caixa,” and Fundació ACE, Institut Català de Neurociències Aplicades. PS-J and AR have also received support by grant PI16/01861. Accion Estrategica en Salud integrated in the Spanish National ICDCi Plan and financed by Instituto de Salud Carlos III (ISCIII) – Subdireccion General de Evaluacion and the Fondo Europeo de Desarrollo Regional (FEDER – “Una Manera de Hacer Europa”). PS-J was supported by IDIVAL, Instituto de Salud Carlos III [Fondo de Investigacion Sanitario, PI08/0139, PI12/02288, PI16/01652, JPND (DEMTEST PI11/03028)], and the CIBERNED program. We thank Biobanco Valdecilla for their support. LM was supported by Consejería de Salud de la Junta de Andalucía (Grant PI-0001/2017). DEGESCO was also sponsored by the Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED, Spain). Control samples and data from patients included in this study were provided in part by the National DNA Bank Carlos III (www.bancoadn.org, University of Salamanca, Spain) and Hospital Universitario Virgen de Valme (Sevilla, Spain) and they were processed following standard operating procedures with the appropriate approval of the Ethical and Scientific Committee. The genotyping service to generate GR@ACE/DEGESCO GWAS data was carried out at CEGEN-PRB3-ISCIII; it was supported by grant PT17/0019, of the PE ICDCi 2013–2016, funded by ISCIII and ERDF. GR@ACE/DEGESCO consortia would also like to thank to all researchers contributing to this project

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Burden of injury along the development spectrum : associations between the Socio-demographic Index and disability-adjusted life year estimates from the Global Burden of Disease Study 2017

Background The epidemiological transition of non-communicable diseases replacing infectious diseases as the main contributors to disease burden has been well documented in global health literature. Less focus, however, has been given to the relationship between sociodemographic changes and injury. The aim of this study was to examine the association between disability-adjusted life years (DALYs) from injury for 195 countries and territories at different levels along the development spectrum between 1990 and 2017 based on the Global Burden of Disease (GBD) 2017 estimates. Methods Injury mortality was estimated using the GBD mortality database, corrections for garbage coding and CODEm-the cause of death ensemble modelling tool. Morbidity estimation was based on surveys and inpatient and outpatient data sets for 30 cause-of-injury with 47 nature-of-injury categories each. The Socio-demographic Index (SDI) is a composite indicator that includes lagged income per capita, average educational attainment over age 15 years and total fertility rate. Results For many causes of injury, age-standardised DALY rates declined with increasing SDI, although road injury, interpersonal violence and self-harm did not follow this pattern. Particularly for self-harm opposing patterns were observed in regions with similar SDI levels. For road injuries, this effect was less pronounced. Conclusions The overall global pattern is that of declining injury burden with increasing SDI. However, not all injuries follow this pattern, which suggests multiple underlying mechanisms influencing injury DALYs. There is a need for a detailed understanding of these patterns to help to inform national and global efforts to address injury-related health outcomes across the development spectrum.Peer reviewe

Estimating global injuries morbidity and mortality : methods and data used in the Global Burden of Disease 2017 study

Background: While there is a long history of measuring death and disability from injuries, modern research methods must account for the wide spectrum of disability that can occur in an injury, and must provide estimates with sufficient demographic, geographical and temporal detail to be useful for policy makers. The Global Burden of Disease (GBD) 2017 study used methods to provide highly detailed estimates of global injury burden that meet these criteria. Methods: In this study, we report and discuss the methods used in GBD 2017 for injury morbidity and mortality burden estimation. In summary, these methods included estimating cause-specific mortality for every cause of injury, and then estimating incidence for every cause of injury. Non-fatal disability for each cause is then calculated based on the probabilities of suffering from different types of bodily injury experienced. Results: GBD 2017 produced morbidity and mortality estimates for 38 causes of injury. Estimates were produced in terms of incidence, prevalence, years lived with disability, cause-specific mortality, years of life lost and disability-adjusted life-years for a 28-year period for 22 age groups, 195 countries and both sexes. Conclusions: GBD 2017 demonstrated a complex and sophisticated series of analytical steps using the largest known database of morbidity and mortality data on injuries. GBD 2017 results should be used to help inform injury prevention policy making and resource allocation. We also identify important avenues for improving injury burden estimation in the future