Molecular targets of atypical antipsychotics: From mechanism of action to clinical differences

The introduction of atypical antipsychotics (AAPs) since the discovery of its prototypical drug clozapine has been a revolutionary pharmacological step for treating psychotic patients as these allow a significant recovery not only in terms of hospitalization and reduction in symptoms severity, but also in terms of safety, socialization and better rehabilitation in the society. Regarding the mechanism of action, AAPs are weak D2 receptor antagonists and they act beyond D2 antagonism, involving other receptor targets which regulate dopamine and other neurotransmitters. Consequently, AAPs present a significant reduction of deleterious side effects like parkinsonism, hyperprolactinemia, apathy and anhedonia, which are all linked to the strong blockade of D2 receptors. This review revisits previous and current findings within the class of AAPs and highlights the differences in terms of receptor properties and clinical activities among them. Furthermore, we propose a continuum spectrum of “atypia” that begins with risperidone (the least atypical) to clozapine (the most atypical), while all the other AAPs fall within the extremes of this spectrum. Clozapine is still considered the gold standard in refractory schizophrenia and in psychoses present in Parkinson's disease, though it has been associated with adverse effects like agranulocytosis (0.7%) and weight gain, pushing the scientific community to find new drugs as effective as clozapine, but devoid of its side effects. To achieve this, it is therefore imperative to characterize and compare in depth the very complex molecular profile of AAPs. We also introduce relatively new concepts like biased agonism, receptor dimerization and neurogenesis to identify better the old and new hallmarks of “atypia”. Finally, a detailed confrontation of clinical differences among the AAPs is presented, especially in relation to their molecular targets, and new means like therapeutic drug monitoring are also proposed to improve the effectiveness of AAPs in clinical practice.Fondazione ARPA (2016_2), a non-profitorganization founded in 1992 (http://www.fondazionearpa.it) and byProgetti di Ricerca di Ateneo (PRA 2015_008

Expected Performance of the ATLAS Experiment - Detector, Trigger and Physics

A detailed study is presented of the expected performance of the ATLAS detector. The reconstruction of tracks, leptons, photons, missing energy and jets is investigated, together with the performance of b-tagging and the trigger. The physics potential for a variety of interesting physics processes, within the Standard Model and beyond, is examined. The study comprises a series of notes based on simulations of the detector and physics processes, with particular emphasis given to the data expected from the first years of operation of the LHC at CERN

Role of the Lateral Paragigantocellular Nucleus in the Network of Paradoxical (REM) Sleep: An Electrophysiological and Anatomical Study in the Rat

The lateral paragigantocellular nucleus (LPGi) is located in the ventrolateral medulla and is known as a sympathoexcitatory area involved in the control of blood pressure. In recent experiments, we showed that the LPGi contains a large number of neurons activated during PS hypersomnia following a selective deprivation. Among these neurons, more than two-thirds are GABAergic and more than one fourth send efferent fibers to the wake-active locus coeruleus nucleus. To get more insight into the role of the LPGi in PS regulation, we combined an electrophysiological and anatomical approach in the rat, using extracellular recordings in the head-restrained model and injections of tracers followed by the immunohistochemical detection of Fos in control, PS-deprived and PS-recovery animals. With the head-restrained preparation, we showed that the LPGi contains neurons specifically active during PS (PS-On neurons), neurons inactive during PS (PS-Off neurons) and neurons indifferent to the sleep-waking cycle. After injection of CTb in the facial nucleus, the neurons of which are hyperpolarized during PS, the largest population of Fos/CTb neurons visualized in the medulla in the PS-recovery condition was observed in the LPGi. After injection of CTb in the LPGi itself and PS-recovery, the nucleus containing the highest number of Fos/CTb neurons, moreover bilaterally, was the sublaterodorsal nucleus (SLD). The SLD is known as the pontine executive PS area and triggers PS through glutamatergic neurons. We propose that, during PS, the LPGi is strongly excited by the SLD and hyperpolarizes the motoneurons of the facial nucleus in addition to local and locus coeruleus PS-Off neurons, and by this means contributes to PS genesis

Drons col·laboratius

La robòtica col·laborativa és senzillament robots dissenyats per dur a terme treballs de col·laboració amb els humans. Els robots col·laboratius o cobots són cada cop més utilitzats a les indústries. La robòtica col·laborativa és un dels àmbits d'actualitat en aquests moments. Però també és un dels més interessants en més d'un sentit. Com es comuniquen dos drons autònoms que col·laboren per fer una tasca? Com són aquests missatges que s'envien? Que poden fer que no podrien fer sols? Aquestes són algunes de les preguntes que ens volem respondre en aquest projecte. En aquest treball es presenta un disseny i implementació de dos drons terrestres que es comuniquen per col·laborar entre ells per resoldre una tasca.Collaborative robotics is simply robots designed to perform collaborative work with humans. Collaborative robots or cobots are increasingly used in industries. Collaborative robotics is one of the current topics now. But it is also one of the most interesting in more ways than one. How do two autonomous drones that collaborate to perform a task communicate? How are these messages sent? What can they do that they could not do alone? These are some of the questions we want to answer in this project. This work presents a design and implementation of two ground drones that communicate to collaborate with each other to solve a task.La robótica colaborativa es sencillamente robots diseñados para llevar a cabo trabajos de colaboración con los humanos. Los robots colaborativos o cobots son cada vez más utilizados en las industrias. La robótica colaborativa es uno de los ámbitos de actualidad. Pero también es uno de los más interesantes en más de un sentido. ¿Cómo se comunican drones autónomos que colaboran para hacer una tarea? ¿Cómo son estos mensajes que es envían? ¿Qué pueden hacer que no lo podrían hacer solos? Estas son algunas de las preguntas que queremos responder con este proyecto. En este trabajo se presenta un diseño e implementación de dos drones terrestres que se comunican para colaborar entre ellos para resolver una tarea

Growth and Survival of Western Red-Cedar Seedlings in Forest Park

In 2005, western red-cedar (Thuja plicata) seedlings were planted in Forest Park in Portland, Oregon to ascertain whether mammalian predation had a role in low seedling recruitment in the park. Nine study sites, three in each section (city, middle, and far) of the park were located along an urban-rural land use gradient. At each site, 27 seedlings were planted. Each tree was randomly assigned to one of three groups: deer exclusion, rodent exclusion, or control. Each was measured prior to installation of exclusion devices (March 2005). Tree height, width, basal diameter, percent of branches grazed and mortality rate has been measured annually. All trees were remeasured in the summer of 2015. Trees grew better in the far section of the park in terms of increased height and basal area. Grazing was highest in the middle and far sections. Tree mortality was lowest in the far section and highest in the city. Our findings suggest factors related to urbanization are impacting seedling survival in Forest Park

Developing Genetic Resources in the Threatened Whitebark Pine

Whitebark pine (Pinus albicaulis) is an alpine species that is being decimated by white pine blister rust, a fungal pathogen. Outside efforts to screen for rust-resistant individuals are proceeding without input on where genetic diversity exists. We are building a set of genetic tools that will allow us to screen for rangewide genetic diversity to pinpoint populations that have been undersampled in rust-resistant screens. The markers we are developing, termed microsatellites, are short repeating DNA sequences that work much like a fingerprint. The development of microsatellite markers can be used to determine population structure, connectivity, heterozygosity, and parentage. As a genetic tool, these markers could aid in the conservation of the threatened whitebark pine (Pinus albicaulis). We need a set of 10-15 microsatellites to ensure maximum discriminating power amongst individuals and populations. Putative microsatellite regions were identified by enriching genomic libraries for dinucleotide microsatellites and then sequencing on the Illumina GA2. Potential microsatellite primers were screened across a set of exemplars; gel electrophoresis and capillary electrophoresis were used to identify heterozygosity and polymorphism. To date we have screened nearly 200 candidates, and we have identified seven microsatellites, with an additional three loci of interest

Women with Words

This article is a short biography of journalist Gloria Campos, based on an oral history discussing her childhood, education, and career