Emergent bursting and synchrony in computer simulations of neuronal cultures

Experimental studies of neuronal cultures have revealed a wide variety of spiking network activity ranging from sparse, asynchronous firing to distinct, network-wide synchronous bursting. However, the functional mechanisms driving these observed firing patterns are not well understood. In this work, we develop an in silico network of cortical neurons based on known features of similar in vitro networks. The activity from these simulations is found to closely mimic experimental data. Furthermore, the strength or degree of network bursting is found to depend on a few parameters: the density of the culture, the type of synaptic connections, and the ratio of excitatory to inhibitory connections. Network bursting gradually becomes more prominent as either the density, the fraction of long range connections, or the fraction of excitatory neurons is increased. Interestingly, biologically prevalent values of parameters result in networks that are at the transition between strong bursting and sparse firing. Using principal components analysis, we show that a large fraction of the variance in firing rates is captured by the first component for bursting networks. These results have implications for understanding how information is encoded at the population level as well as for why certain network parameters are ubiquitous in cortical tissue

A phase 3 multicenter, prospective, open-label efficacy and safety study of immune globulin (human) 10% caprylate/chromatography purified in patients with myasthenia gravis exacerbations

Background: Myasthenia gravis (MG) is an autoimmune disorder affecting neuromuscular transmission. Exacerbations may involve increasing bulbar weakness and/or sudden respiratory failure, both of which can be critically disabling. Management of MG exacerbations includes plasma exchange and intravenous immunoglobulin (IVIG); they are equally effective, but patients experience fewer side effects with IVIG. The objective of this study was to assess the efficacy and safety of immune globulin caprylate/chromatography purified (IGIV-C) in subjects with MG exacerbations. Methods: This prospective, open-label, non-controlled 28-day clinical trial was conducted in adults with MG Foundation of America class IVb or V status. Subjects received IGIV-C 2 g/kg over 2 consecutive days (1 g/kg/day) and were assessed for efficacy/safety on Days 7, 14, 21, and 28. The primary efficacy endpoint was the change from Baseline in quantitative MG (QMG) score to Day 14. Secondary endpoints of clinical response, Baseline to Day 14, included at least a 3-point decrease in QMG and MG Composite and a 2-point decrease in MG-activities of daily living (MG-ADL). Results: Forty-nine subjects enrolled. The change in QMG score at Day 14 was significant (p < 0.001) in the Evaluable (-6.4, n = 43) and Safety (-6.7, n = 49) populations. Among evaluable subjects, Day 14 response rates were 77, 86, and 88% for QMG, MG Composite, and MG-ADL, respectively. IGIV-C showed good tolerability with no serious adverse events. Conclusions: The results of this study show that IGIV-C was effective, safe, and well tolerated in the treatment of MG exacerbations

Psychophysical Olfactory Tests and Detection of COVID-19 in Patients With Sudden Onset Olfactory Dysfunction: A Prospective Study

Objective: To investigate the coronavirus disease 2019 (COVID-19) status of patients with initial sudden olfactory anosmia (ISOA) through nasopharyngeal swabs for reverse transcription–polymerase chain reaction (RT-PCR) analysis and to explore their olfactory dysfunctions with psychophysical olfactory evaluation. Methods: A total of 78 ISOA patients were recruited from April 6, 2020, to April 10, 2020, through a public call of University of Mons (Mons, Belgium). Patients benefited from nasopharyngeal swabs and fulfilled the patient-reported outcome questionnaire. Among them, 46 patients performed psychophysical olfactory evaluation using olfactory identification testing. Based on the duration of the ISOA, 2 groups of patients were compared: patients with olfactory dysfunction duration ≤12 days (group 1) and those with duration >12 days (group 2). Results: In group 1, 42 patients (87.5%) had a positive viral load determined by RT-PCR and 6 patients (12.5%) were negative. In group 2, 7 patients (23%) had a positive viral load and 23 patients (77%) were negative. The psychophysical olfactory evaluation reported that anosmia and hyposmia occurred in 24 (52%) and 11 (24%) patients, respectively. Eleven patients were normosmic. The viral load was significantly higher in patients of group 1 compared with those of group 2. Conclusions: Coronavirus disease 2019 was detected in a high proportion of ISOA patients, especially over the first 12 days of olfactory dysfunction. Anosmia is an important symptom to consider in the detection of COVID-19 infection

Biotransformation of β-Hydroxypyruvate and Glycolaldehyde to L-Erythrulose by Pichia pastoris strain GS115 overexpressing native Transketolase

Transketolase is a proven biocatalytic tool for asymmetric carbon-carbon bond formation, both as a purified enzyme and within bacterial whole-cell biocatalysts. The performance of Pichia pastoris as a host for transketolase whole-cell biocatalysis was investigated using a transketolase-overexpressing strain to catalyse formation of L-erythrulose from β- hydroxypyruvic acid and glycolaldehyde substrates. Pichia pastoris transketolase coding sequence from the locus PAS_chr1-4_0150 was subcloned downstream of the methanolinducible AOX1 promoter in a plasmid for transformation of strain GS115, generating strain TK150. Whole and disrupted TK150 cells from shake flasks achieved 62% and 65% conversion, respectively, under optimal pH and methanol induction conditions. In a 300µL reaction, TK150 samples from a 1L fed-batch fermentation achieved a maximum Lerythrulose space time yield (STY) of 46.58 g L -1 hr-1, specific activity of 155 U gCDW -1 , product yield on substrate (Yp/s) of 0.52 mol mol-1 and product yield on catalyst (Yp/x) of 2.23g gCDW -1. We have successfully exploited the rapid growth and high biomass characteristics of Pichia pastoris in whole cell biocatalysis. At high cell density, the engineered TK150 Pichia pastoris strain tolerated high concentrations of substrate and product to achieve high STY of the chiral sugar L-erythrulose

La extensión universitaria como espacio dialógico de construcción y problematización de saberes y prácticas.

En los últimos cinco años, hemos ido construyendo la idea de acercar las cátedras Problemática Educativa y Política Educativa perteneciente a los Profesorados y a la Licenciatura en Psicopedagogía de la UNPA a la comunidad, haciendo extensivos ciertos contenidos y problemáticas trabajados a distintos actores e instituciones sociales. Intentaremos dar cuenta del recorrido trazado por los equipos de cátedra en estos últimos años, trayectoria que implica un posicionamiento político e ideológico respecto de la educación en general y de la función de la Universidad en particular, tomando cuerpo en un Programa de Extensión de formación e intervención desde una perspectiva crítica, donde se articulan la formación de grado, la extensión y la investigación participativa. Dicho programa implica un gran desafío teórico metodológico dado que -como intentaremos desarrollar- significa rupturas, quiebres en prácticas académicas establecidas, arraigadas en la tradición universitaria y en nuestras propias biografías personales y profesionales. Desde los aportes de las teorías críticas, y fundamentalmente al trabajar la obra de Paulo Freire se decide llevar adelante una serie de acciones de extensión entendida como coproducción, proponiendo experiencias pensadas como acontecimientos, concretadas en jornadas y talleres de educación popular, abiertos a toda la comunidad y otras sólo a los docentes de nuestro sistema educativo provincial, posibilitando diferentes intercambios con los actores sociales participantes. El análisis realizado sobre los emergentes recabados en estos encuentros, la participación en este proceso de reflexión de algunos de los protagonistas externos a la universidad, no sólo posibilita el enriquecimiento teórico-metodológico al interior de las cátedras, sino que permite la reformulación de problemas y desafíos, en base a un diagnóstico más aproximado de las condiciones simbólicas y socio-afectivas de los diferentes colectivos con los que interactuamos, en beneficio de proyectar futuras acciones para alcanzar algunos resultados superadores de la situación inicial. Estas experiencias generaron la necesidad de profundizar los alcances de los resultados obtenidos, a la vez que abrieron nuevos interrogantes y desafíos que dieron origen a un proyecto de investigación participativa: “La educación popular, una alternativa pedagógico-política en los actuales escenarios. Posibles articulaciones con el sistema educativo formal”, integrado por este equipo de trabajo, docentes del sistema educativo provincial y estudiantes. La investigación así concebida irá complejizando teórica y metodológicamente las prácticas llevadas adelante en las acciones de extensión y en los desarrollos de la formación de grado, a la vez que en un proceso espiralado, se retroalimentará en el ejercicio de una praxis crítica

Biallelic JAK1 mutations in immunodeficient patient with mycobacterial infection

Mutations in genes encoding components of the immune system cause primary immunodeficiencies. Here, we study a patient with recurrent atypical mycobacterial infection and early-onset metastatic bladder carcinoma. Exome sequencing identified two homozygous missense germline mutations, P733L and P832S, in the JAK1 protein that mediates signalling from multiple cytokine receptors. Cells from this patient exhibit reduced JAK1 and STAT phosphorylation following cytokine stimulations, reduced induction of expression of interferon-regulated genes and dysregulated cytokine production; which are indicative of signalling defects in multiple immune response pathways including Interferon-γ production. Reconstitution experiments in the JAK1-deficient cells demonstrate that the impaired JAK1 function is mainly attributable to the effect of the P733L mutation. Further analyses of the mutant protein reveal a phosphorylation-independent role of JAK1 in signal transduction. These findings clarify JAK1 signalling mechanisms and demonstrate a critical function of JAK1 in protection against mycobacterial infection and possibly the immunological surveillance of cancer.Wellcome Trust (095198/Z/10/Z and 090233/Z/09/Z); Higher Education Funding Council for England; Great Ormond Street Hospital Children’s Charity; National Institute for Health Research (NIHR); Great Ormond Street Hospital Biomedical Research Centre; NIHR Cambridge Biomedical Research Centre; Alfonso Martin Escudero Foundatio

Brazilian spring wheat germplasm as source of genetic variability.

As part of a Canada-Brazil germplasm exchange, 106 modern and ancient Brazilian spring wheat cultivars have been genotyped and phenotypically evaluated in Canada since 201