Phytocannabinoids as potential tools for ameliorating Rett Syndrome-like phenotype in Mecp2-null mice.

Rett syndrome (RTT) is an X-linked neurodevelopmental disorder with a prevalence rate of 1 in 10,000 females. RTT patients have apparently normal perinatal development until about 6-18 months of age, after which they undergo a period of rapid regression, characterized by the appearance of autistic features, stereotypic hand movements and loss of language. RTT girls also have seizures during childhood, breathing arrhythmias, develop scoliosis and lose mobility between ages 1 and 4 years. Recently, there has been growing interest in the therapeutic potential of phytocannabinoids in the context of neurological diseases. Interestingly, several preclinical and clinical data support the ability of some phytocannabinoids to modulate cognitive and motor functions, mood and neuronal excitability, all of which are altered in RTT. Despite this evidence, so far no studies have addressed the potential therapeutic application of phytocannabinoids in RTT. Based on these premises, the aim of this project was to evaluate the ability of chronic administration of the phytocannabinoids, cannabidivarin (CBDV) and cannabidiolic acid (CBDA), to affect neurological and motor defects as well as cognitive deficits in a mouse model of RTT, namely Mecp2 knockout (KO) mice. To this aim, Mepc2 KO mice were treated daily with CBDV (or relative vehicle) at the doses of 0.2, 2, 20 or 200 mg/kg or CBDA (or relative vehicle) at the dose of 2 and 20 mg/kg from postnatal day (PND) 28 to 66. During the whole treatment schedule, motor and neurological signs were scored while short- and long-term memory deficits were evaluated at PND 41, 56 and 66. 24 hours after the last injection, brain tissues were collected to investigate the presence of alterations on neurotrophic factors (BDNF and IGF-1), inflammatory markers (CD11b, GFAP and TNF\u3b1) as well as components of the endocannabinoid system. The present findings provide for the first time direct evidence that CBDV and CBDA improve motor and neurological signs as well as cognitive deficits in Mecp2 KO mice. In particular, CBDV administration delays the appearance neurological and motor signs in Mecp2 KO mice in a time window between 5 and 7 weeks of age. Conversely, CBDA administration ameliorates motor signs only at later stages of the disease progression, i.e. 8 and 9 weeks of age. Remarkably, both phytocannabinoids exert a complete and enduring beneficial effect towards short- and long-term memory deficits in Mecp2 KO animals. At the biochemical level, chronic treatments with CBDV and CBDA enhance the expression of both BDNF and IGF-1 and reduce microglia activation in the brain of Mecp2 KO mice. Moreover, Mecp2 deletion results in alterations in the endocannabinoid system that could likely sustain RTT-like phenotype, and chronic CBDV treatment further modulates them. Although further studies are needed to directly assess the mechanism(s) through which CBDV and CBDA can improve RTT-like phenotype in Mecp2 KO mice, overall these findings suggest for the first time a potential therapeutic application of the phytocannabinoids CBDV and CBDA in the context of RTT

Phytocannabinoids as potential tools for ameliorating Rett Syndrome-like phenotype in Mecp2-null mice.

Rett syndrome (RTT) is an X-linked neurodevelopmental disorder with a prevalence rate of 1 in 10,000 females. RTT patients have apparently normal perinatal development until about 6-18 months of age, after which they undergo a period of rapid regression, characterized by the appearance of autistic features, stereotypic hand movements and loss of language. RTT girls also have seizures during childhood, breathing arrhythmias, develop scoliosis and lose mobility between ages 1 and 4 years. Recently, there has been growing interest in the therapeutic potential of phytocannabinoids in the context of neurological diseases. Interestingly, several preclinical and clinical data support the ability of some phytocannabinoids to modulate cognitive and motor functions, mood and neuronal excitability, all of which are altered in RTT. Despite this evidence, so far no studies have addressed the potential therapeutic application of phytocannabinoids in RTT. Based on these premises, the aim of this project was to evaluate the ability of chronic administration of the phytocannabinoids, cannabidivarin (CBDV) and cannabidiolic acid (CBDA), to affect neurological and motor defects as well as cognitive deficits in a mouse model of RTT, namely Mecp2 knockout (KO) mice. To this aim, Mepc2 KO mice were treated daily with CBDV (or relative vehicle) at the doses of 0.2, 2, 20 or 200 mg/kg or CBDA (or relative vehicle) at the dose of 2 and 20 mg/kg from postnatal day (PND) 28 to 66. During the whole treatment schedule, motor and neurological signs were scored while short- and long-term memory deficits were evaluated at PND 41, 56 and 66. 24 hours after the last injection, brain tissues were collected to investigate the presence of alterations on neurotrophic factors (BDNF and IGF-1), inflammatory markers (CD11b, GFAP and TNFα) as well as components of the endocannabinoid system. The present findings provide for the first time direct evidence that CBDV and CBDA improve motor and neurological signs as well as cognitive deficits in Mecp2 KO mice. In particular, CBDV administration delays the appearance neurological and motor signs in Mecp2 KO mice in a time window between 5 and 7 weeks of age. Conversely, CBDA administration ameliorates motor signs only at later stages of the disease progression, i.e. 8 and 9 weeks of age. Remarkably, both phytocannabinoids exert a complete and enduring beneficial effect towards short- and long-term memory deficits in Mecp2 KO animals. At the biochemical level, chronic treatments with CBDV and CBDA enhance the expression of both BDNF and IGF-1 and reduce microglia activation in the brain of Mecp2 KO mice. Moreover, Mecp2 deletion results in alterations in the endocannabinoid system that could likely sustain RTT-like phenotype, and chronic CBDV treatment further modulates them. Although further studies are needed to directly assess the mechanism(s) through which CBDV and CBDA can improve RTT-like phenotype in Mecp2 KO mice, overall these findings suggest for the first time a potential therapeutic application of the phytocannabinoids CBDV and CBDA in the context of RTT

GPS/INS integration for pedestrian navigation

This research has been sponsored by the Centre Suisse d'Electronique et de Microtechnique (CSEM) in Neuchâtel, Switzerland. It introduces a system and the algorithms for Pedestrian Navigation using a combination of sensors. The main objective is to localise a pedestrian anywhere and at any moment. The equipments utilised to fulfill this requirement are a Global Navigation Satellite System (GNSS) receiver and inertial sensors, which are attached to the person and as such need to be portable. An overview of Pedestrian Navigation constitutes the first part of the document. This new domain is examined from four different views: applications, tools (or sensors), architecture of the system and finally environment in which the pedestrian is travelling. As part of this process, the "state of the art" situation is presented. The approach followed in order to aid pedestrian to navigate is based on the Dead Reckoning technique coupled with GNSS. Consequently, the resolution of the travelled "distance" is separated from the resolution of the orientation of the walk. For the computation of the distance, a new technique based upon accelerometers and GNSS has been developed and demonstrated. The accelerometers are not used as a classical pedometer (counter of the number of steps) and the technique is not based on the double integration to obtain successively speed and distance. Instead, signal processing allows, considering individual parameters, the walking speed to be obtained directly from the signal of the accelerometers. This process, as well as the manner to determine the individual parameters, is presented in detail. The development of the algorithms is based on research performed in both the navigation and the medical domains (mainly in physiology). The computation of the orientation is more classical. It is based on the measurements made by a gyroscope and a GNSS receiver. The particularity of this study is the use of a single gyroscope to determine the orientation of the walk instead of three for the classical technique of inertial navigation. The influence of body movement on the gyroscope output has been deeply examined to determine the most appropriate way to process the signal of the gyroscope. The feasibility of the use of a single gyro, in the context of pedestrian navigation, is demonstrated. The potential added value for introducing a magnetic compass in the system is also evaluated. Finally a centralised Kalman filter has been designed and tested to merge all the sensors outputs, to combine the distance and the orientation, to integrate the Dead Reckoning solution and the GNSS solutions and to estimate all the parameters in a close to real-time process. The efficiency of this filter is demonstrated through different tests

Dos Enfoques para Mejorar la Navegación Pedestre por GPS

El presente artículo presenta la calibración de los diferentes modelos utilizados para la navegación pedestre. La información sobre distancias recorridas y elazimut detectado por sensores inerciales es combinada con observaciones de GPSutilizando filtrado de Kalman. Todos los modelos utilizan posiciones de GPS sincorrecciones diferenciales para calibrar los errores sistemáticos presentes en sensores inerciales.Han sido desarrollados diferentes prototipos que integran compases: c.agnéticosdigitales o giroscopios, acelerómetros tri- o bi-axiales, un altímetro y un receptorGPS de monofrecuencia.Los resultados demuestran que un sistema integrado, comparado al uso de unreceptor GPS solo, mejora la fiabilidad y precisión de la trayectoria. Una precisiónabsoluta de menos de 5 metros se logra y se mantiene incluso bajo el modo DecidReckoning (DR.) (cálculo estimado), por ejemplo cuando ninguna señal de satéliteestá disponible. Aprovechando la fuerte correlación entre épocas, no es necesarioel uso de correcciones de DGPS para calibrar los modelos de DR.Lo numerosos desafíos de este campo de investigación se desarrollan en estemomento en el Instituto de Geomática (IGEO-TOPO) del Swiss Federal Instituteof Technology (EPFL) en estrecha colaboración con el Swiss Center for Electronicsand Microtechnology (CSEM) como también con Leica Geosystems AG

The Genome of the Blind Soil-Dwelling and Ancestrally Wingless Dipluran Campodea augens: A Key Reference Hexapod for Studying the Emergence of Insect Innovations.

The dipluran two-pronged bristletail Campodea augens is a blind ancestrally wingless hexapod with the remarkable capacity to regenerate lost body appendages such as its long antennae. As sister group to Insecta (sensu stricto), Diplura are key to understanding the early evolution of hexapods and the origin and evolution of insects. Here we report the 1.2-Gb draft genome of C. augens and results from comparative genomic analyses with other arthropods. In C. augens, we uncovered the largest chemosensory gene repertoire of ionotropic receptors in the animal kingdom, a massive expansion that might compensate for the loss of vision. We found a paucity of photoreceptor genes mirroring at the genomic level the secondary loss of an ancestral external photoreceptor organ. Expansions of detoxification and carbohydrate metabolism gene families might reflect adaptations for foraging behavior, and duplicated apoptotic genes might underlie its high regenerative potential. The C. augens genome represents one of the key references for studying the emergence of genomic innovations in insects, the most diverse animal group, and opens up novel opportunities to study the under-explored biology of diplurans

Dinâmica e simulação computacional do COVID-19 no Paraguai em fevereiro de 2021

The 2019 coronavirus disease is a worldwide concern, its spread is related to the characteristics of the virus and the taking of government, public health and social habits. Using mathematical and computational tools help to have an overview of the current situation and a future of this problem. In order to reflect behavior of this disease through simulation with system dynamics and evaluating the number of active infections, deaths and recoveries in Paraguay in the month of February 2021, the Vensim software was released by applying a modification of the basic model of epidemiology of Kermack and McKendrick who consider the population of susceptible, processed and recovered. The simulation of this dynamic has presented differences of 758 active cases, 216 deaths and 37009 recovered with respect to what was reported, with active cases being the most important approximation of the study.La enfermedad por coronavirus del 2019 es una preocupación a nivel mundial, su propagación está relacionada a características propias del virus y a la toma de acciones gubernamentales, de salud pública y hábitos sociales. Utilizar herramientas matemáticas y computacionales ayuda a tener un panorama de la situación actual y a futuro de esta problemática. Con el objetivo de reflejar el comportamiento de esta enfermedad mediante simulación con dinámica de sistemas y evaluar la cantidad de contagios activos, muertes y recuperados en Paraguay en el mes de febrero del 2021 se utilizó el software Vensim aplicando una modificación del modelo básico de epidemiología de Kermack y McKendrick que considera a la población de susceptibles, infectados y recuperados. La simulación de esta dinámica ha presentado diferencias de 758 casos activos, 216 muertes y 37009 recuperados respecto a lo reportado, siendo los casos activos la aproximación más importante del estudio.A doença do coronavírus 2019 é uma preocupação mundial, sua disseminação está relacionada às características do vírus e à toma de ações governamentais, de saúde pública e hábitos sociais. O uso de ferramentas matemáticas e computacionais ajudam a ter uma visão geral da situação atual e futura deste problema. Para refletir o comportamento desta doença através de simulação com dinâmica de sistemas e avaliar o número de infecções ativas, óbitos e recuperações no Paraguai no mês de fevereiro de 2021, foi utilizado o software Vensim, aplicando uma modificação do modelo básico de epidemiologia de Kermack e McKendrick que considera a população de suscetíveis, infectados e recuperados. A simulação dessa dinâmica apresentou diferenças de 758 casos ativos, 216 óbitos e 37.009 recuperados em relação ao informado, sendo os casos ativos a aproximação mais importante do estudo