Avance en el diagnóstico de enfermedades neurológicas : una señal de alerta temprana

Fil: Serra, Jorge A. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina.Fil: Domínguez, Raúl O. Universidad de Buenos Aires, Facultad de Medicina; Argentina.Fil: Lustig, Eugenia S. de. Universidad de Buenos Aires. Instituto Roffo; Argentina.Fil: Marschoff, Enrique R. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.A las graves consecuencias que ocasionan para las personas que las padecen, algunas enfermedades\nneurológicas, como el mal de Alzheimer, presentan además otro inconveniente: su detección resulta\nmuy dificultosa y se basa fundamentalmente en la evaluación médica. Luego de años de trabajo, un\ngrupo multidisciplinario de investigadores de la UBA ha logrado un promisorio avance que permitiría\ndiagnosticar y diferenciar entre sí a este tipo de dolencias, a través de un análisis de sangre que\nmediría el estrés oxidativo de los posibles afectados

The global EPTO database: Worldwide occurrences of aquatic insects

Motivation: Aquatic insects comprise 64% of freshwater animal diversity and are widely used as bioindicators to assess water quality impairment and freshwater ecosystem health, as well as to test ecological hypotheses. Despite their importance, a comprehensive, global database of aquatic insect occurrences for mapping freshwater biodiversity in macroecological studies and applied freshwater research is missing. We aim to fill this gap and present the Global EPTO Database, which includes worldwide geo-referenced aquatic insect occurrence records for four major taxa groups: Ephemeroptera, Plecoptera, Trichoptera and Odonata (EPTO). Main type of variables contained: A total of 8,368,467 occurrence records globally, of which 8,319,689 (99%) are publicly available. The records are attributed to the corresponding drainage basin and sub-catchment based on the Hydrography90m dataset and are accompanied by the elevation value, the freshwater ecoregion and the protection status of their location. Spatial location and grain: The database covers the global extent, with 86% of the observation records having coordinates with at least four decimal digits (11.1 m precision at the equator) in the World Geodetic System 1984 (WGS84) coordinate reference system. Time period and grain: Sampling years span from 1951 to 2021. Ninety-nine percent of the records have information on the year of the observation, 95% on the year and month, while 94% have a complete date. In the case of seven sub-datasets, exact dates can be retrieved upon communication with the data contributors.Major taxa and level of measurement: Ephemeroptera, Plecoptera, Trichoptera and Odonata, standardized at the genus taxonomic level. We provide species names for 7,727,980 (93%) records without further taxonomic verification. Software format: The entire tab-separated value (.csv) database can be downloaded and visualized at https://glowa bio.org/proje ct/epto_datab ase/. Fifty individual datasets are also available at https://fred.igb-berlin. de, while six datasets have restricted access. For the latter, we share metadata and the contact details of the authors

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Global urban environmental change drives adaptation in white clover

Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural clines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale

Systemic oxidative stress associated with the neurological diseases of aging

Markers of oxidative stress were measured in blood samples of 338 subjects (965 observations): Alzheimer´s, vascular dementia, diabetes (type II) superimposed to dementias, Parkinson´s disease and controls. Patients showed increased thiobarbituric acid reactive substances (+21%; P < 0.05), copper-zinc superoxide dismutase (+64%; P < 0.001) and decreased antioxidant capacity (-28%; P < 0.001); pairs of variables resulted linearly related across groups (P < 0.001). Catalase and glutathione peroxidase, involved in discrimination between diseases, resulted non-significant. When diabetes is superimposed with dementias, changes resulted less marked but significant. Also, superoxide dismutase resulted not linearly correlated with any other variable or age-related (pure Alzheimer´s peaks at 70 years, P < 0.001). Systemic oxidative stress was significantly associated (P 0.001) with all diseases indicating a disbalance in peripheral/adaptive responses to oxidative disorders through different free radical metabolic pathways. While other changes-methionine cycle, insulin correlation-are also associated with dementias, the responses presented here show a simple linear relation between prooxidants and antioxidant defenses.Fil: Serra, Jorge Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Programa de Radicales Libres; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Enzimología, Estrés Oxidativo y Metabolismo; ArgentinaFil: Domínguez, Raúl O.. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Fundación Argentina Contra las Enfermedades Neurológicas del Envejecimiento; ArgentinaFil: Marschoff, Enrique Ricardo. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Ciencias Biológicas; ArgentinaFil: Guareschi, Eduardo M.. Laboratorio de Investigaciones Clínicas; ArgentinaFil: Famulari, Arturo L.. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto Alberto C. Taquini de Investigaciones En Medicina Traslacional. - Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiologicas "prof. Dr. Alberto C. Taquini". Instituto Alberto C. Taquini de Investigaciones En Medicina Traslacional.; Argentina. Fundación Argentina Contra las Enfermedades Neurológicas del Envejecimiento; ArgentinaFil: Boveris, Alberto Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Programa de Radicales Libres; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Enzimología, Estrés Oxidativo y Metabolismo; Argentin

Neurological disorders in an elderly cohort that experienced past stressful events: a retrospective-prospective study

Background: Psychological stress may be a risk factor for dementia, but the association between exposure to stressful life events and the development of cognitive dysfunction has not been conclusively demonstrated. We hypothesize that if a stressful event has an impact on the sub-jects, its effects would be different in the three diseases. Objective: This study aims to assess the effects of stressful events in senior patients who later de-veloped ischemic stroke, Alzheimer's, or Parkinson's disease. Material and Methods: Together with demographic variables (age, sex, race, socioeconomic and cultural levels), five types of past stressful events, such as death or serious illness of close relatives, job dismissal, change of financial status, retirement, and change of residence, were recorded in 1024 patients with Alzheimer's disease, Parkinson's disease, and ischemic stroke. Time-to-diagnosis (months from the event to the first symptoms: retrospective study) and evolution time (years of follow-up of each patient: prospective study) were recorded. The variance and non-parametric methods were analyzed to the variables time-to-diagnosis and evolution time to analyze differences between these diseases. Results: The demographic variables, such as age, sex, race, economic and cultural levels, were found to be statistically non-significant; differences in the economic level were significant (PParkinson’s disease >Stroke), and minor differences (P<0.05) in evolution time. Conclusion: Differences in time-to-diagnosis between the diseases indicate that the stressful effect of having experienced the death or serious illness of a close relative has an impact on their emer-gence. The measurement of time-to-diagnosis and evolution time proves useful in detecting differences between diseases.Fil: Domínguez, Raúl O.. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Marschoff, Enrique Ricardo. Ministerio de Relaciones Exteriores, Comercio Interno y Culto. Dirección Nacional del Antártico. Instituto Antártico Argentino; ArgentinaFil: Oudkerk, Liliana M.. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: de la Ossa Angulo, Luis E.. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Villamizar Pérez, Susana. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Bianchi, Graciela A.. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Repetto, Marisa Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; ArgentinaFil: Serra, Jorge Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; Argentin

In Vitro and In Vivo Genetic Disease Modeling via NHEJ-Precise Deletions Using CRISPR-Cas9

The development of advanced gene and cell therapies for the treatment of genetic diseases requires reliable animal and cellular models to test their efficacy. Moreover, the availability of the target human primary cells of these therapies is reduced in many diseases. The development of endonucleases that can cut into specific sites of the cell genome, as well as the repair of the generated break by non-homologous end-joining, results in a variety of outcomes, insertions, deletions, and inversions that can induce the disruption of any specific gene. Among the many methods that have been developed for gene editing, CRISPR-Cas9 technology has become one of the most widely used endonuclease tools due to its easy design and its low cost. It has also been reported that the use of two guides, instead of just the one required, reduces the outcomes of non-homologous end joining mainly to the precise genomic sequences between the cutting sites of the guides used. We have explored this strategy to generate useful cellular and animal models. Different distances between the two guides have been tested (from 8 to 500 bp apart), and using the optimal range of 30–60 bp we have obtained a human primary cellular model of a genetic disease, pyruvate kinase deficiency, where the availability of the target cells is limited. We have also generated an in vivo model of glycolate oxidase (GO) deficiency, which is an enzyme involved in the glyoxylate metabolism following the same strategy. We demonstrate that the use of two-guide CRISPR-Cas9-induced non-homologous end joining is a feasible and useful tool for disease modeling, and it is most relevant to those diseases in which it is difficult to get the cells that will be genetically manipulated

In Vitro and In Vivo Genetic Disease Modeling via NHEJ-Precise Deletions Using CRISPR-Cas9

The development of advanced gene and cell therapies for the treatment of genetic diseases requires reliable animal and cellular models to test their efficacy. Moreover, the availability of the target human primary cells of these therapies is reduced in many diseases. The development of endonucleases that can cut into specific sites of the cell genome, as well as the repair of the generated break by non-homologous end-joining, results in a variety of outcomes, insertions, deletions, and inversions that can induce the disruption of any specific gene. Among the many methods that have been developed for gene editing, CRISPR-Cas9 technology has become one of the most widely used endonuclease tools due to its easy design and its low cost. It has also been reported that the use of two guides, instead of just the one required, reduces the outcomes of non-homologous end joining mainly to the precise genomic sequences between the cutting sites of the guides used. We have explored this strategy to generate useful cellular and animal models. Different distances between the two guides have been tested (from 8 to 500 bp apart), and using the optimal range of 30–60 bp we have obtained a human primary cellular model of a genetic disease, pyruvate kinase deficiency, where the availability of the target cells is limited. We have also generated an in vivo model of glycolate oxidase (GO) deficiency, which is an enzyme involved in the glyoxylate metabolism following the same strategy. We demonstrate that the use of two-guide CRISPR-Cas9-induced non-homologous end joining is a feasible and useful tool for disease modeling, and it is most relevant to those diseases in which it is difficult to get the cells that will be genetically manipulated