Different outcome of sarcoglycan missense mutation between human and mouse

Sarcoglycanopathies are rare autosomic limb girdle muscular dystrophies caused by mutations in one of the genes coding for sarcoglycan (α, β, δ, and γ-sarcoglycans). Sarcoglycans form a complex, which is an important part of the dystrophin-associated glycoprotein complex that protects sarcolemma against muscle contraction-induced damages. Absence of one of the sarcoglycan at the plasma membrane induces the disappearance of the whole complex and perturbs muscle fiber membrane integrity. We previously demonstrated that point mutations in the human sarcoglycan genes affects the folding of the corresponding protein, which is then retained in the endoplasmic reticulum by the protein quality control and prematurely degraded by the proteasome. Interestingly, modulation of the quality control using pharmacological compounds allowed the rescue of the membrane localization of the mutated sarcoglycan. Two previously generated mouse models, knock-in for the most common sarcoglycan mutant, R77C α-sarcoglycan, failed in reproducing the dystrophic phenotype observed in human patients. Based on these results and the need to test therapies for these fatal diseases, we decided to generate a new knock-in mouse model carrying the missense mutation T151R in the β-sarcoglycan gene since this is the second sarcoglycan protein with the most frequently reported missense mutations. Muscle analysis, performed at the age of 4 and 9-months, showed the presence of the mutated β-sarcoglycan protein and of the other components of the dystrophin-associated glycoprotein complex at the muscle membrane. In addition, these mice did not develop a dystrophic phenotype, even at a late stage or in condition of stress-inducing exercise. We can speculate that the absence of phenotype in mouse may be due to a higher tolerance of the endoplasmic reticulum quality control for amino-acid changes in mice compared to human

El sistema de recursos en el Proyecto del nuevo Código procesal civil brasileño

[Resumen:] En Brasil se discute la publicación de un nuevo Código Procesal Civil desde hace cinco años, y actualmente se encuentra en la fase final de promulgación de la nueva Ley. El presente artículo analiza las principales propuestas de modificación legislativa, del Derecho positivo vigente, en relación a los recursos civiles. El sistema de recursos brasileño es bastante complejo y con innumerables mecanismos especies de recursos, teniendo un importantísimo impacto en el orden civil. El análisis de las modificaciones está hecha desde una perspectiva analítico-crítica, en la cual los autores se sitúan hacia las posiciones y elecciones realizadas en el Poryecto de Nuevo Código Procesal Civil[AbsracCt:] For about five years, Brazil has been discussing a new Civil Procedure Code, which finds itself on the verge of becoming a reality, as it is, at the moment, at its original “house”, the Senate, for final debates and following proclamation. The present article is a study of the main propositions on the appeal system. The brazilian appeal system is rather complex, with numerous and different kinds of appeals, which has a great impact on civil jurisdiction. The study brings a critical and analytical perspective of the main proposed amendments, changes and choices made in the Draft of the Civil Procedure Code.

Does haemosporidian infection affect hematological and biochemical profiles of the endangered Black-fronted piping-guan (Aburria jacutinga)?

Infectious diseases can cause deleterious effects on bird species, leading to population decline and extinction. Haemosporidia can be recognized by their negative effects on host fitness, including reproductive success and immune responses. In captivity, outbreaks of haemosporidian infection have been observed in birds in zoos and aviaries. The endemic Brazilian Atlantic rainforest species Aburria jacutinga is one of the most endangered species in the Cracidae family, and wild populations of this species are currently found mainly in conservation areas in only two Brazilian states. In this study, we aimed to evaluate the effects of avian haemosporidia on hematological and biochemical parameters in two captive populations of A. jacutinga. Forty-two animals were assessed, and the haemosporidian prevalence was similar for males and females. The occurrence of haemosporidian infection in captive A. jacutinga observed in this study was similar to results found in other captive and wild birds in Brazil. We found three different lineages of haemosporidia. Two lineages were identified as Plasmodium sp., one of which was previously detected in Europe and Asia, and the other is a new lineage closely related to P. gallinaceum. A new third lineage was identified as Haemoproteus sp. We found no significant differences in hematological and biochemical values between infected and non-infected birds, and the haemosporidian lineage did not seem to have an impact on the clinical and physiological parameters of A. jacutinga. This is the first report on an evaluation of natural haemosporidian infections diagnosed by microscopic and molecular methods in A. jacutinga by hematology, blood biochemistry, and serum protein values. Determining physiological parameters, occurrence and an estimation of the impact of haemosporidia in endangered avian species may contribute to the management of species rehabilitation and conservation

High-precision measurement of the hypertriton lifetime and Λ-separation energy exploiting ML algorithms with ALICE at the LHC.

L'abstract è presente nell'allegato / the abstract is in the attachmen

Recursos alimentares e dieta de uma comunidade de psitacídeos em uma mata ciliar no Pantanal Sul (Brasil)

Psitacídeos neotropicais usualmente exploram o dossel das florestas em busca de alimentos como néctar, flores, folhas, polpa e sementes de frutos. Como essas aves não estabelecem territórios, movimentam-se através de mosaicos de vegetação no sentido de utilizar recursos alimentares, produzidos massivamente, à medida que se tornam disponíveis. Neste estudo, nós examinamos a utilização de uma mata ciliar, no Pantanal Sul (Brasil), por uma comunidade de psitacídeos, constituída por um gradiente de formas que incluiu desde o pequeno Brotogeris chiriri até a grande Ara chloroptera. Os recursos vegetais, importantes para os psitacídeos, foram produzidos massivamente durante a estação chuvosa (frutos carnosos), subseqüentemente durante as cheias anuais (também frutos carnosos) e, finalmente, na estação seca (flores). Tanto as pequenas quanto as grandes espécies consumiram tais frutos, no entanto os periquitos utilizaram predominantemente a polpa, enquanto as espécies maiores consumiram em proporções similares a polpa e as sementes. Durante a estação seca os periquitos utilizaram extraordinariamente néctar das flores, sobretudo produzido por Inga vera, que anualmente floresceu massivamente ao final da estação seca, período mais rigoroso do ano. Dentre as espécies maiores, apenas Propyrrhura auricollis utilizou substancialmente néctar. A intensa produção de frutos, tipicamente dispersos por peixes ou pela água durante a cheia anual, foi amplamente utilizada pelos psitacídeos. Portanto, ao contrário dos padrões de frutificação da maioria das matas secas neotropicais, a ocorrência de um pico de frutificação durante as cheias emerge como um evento marcante de disponibilidade de frutos, num período (transição da estação úmida para a seca) em que tipicamente tendem a declinar. Nesse sentido, a peculiar produção massiva de flores e frutos, nessa mata ciliar, potencialmente contribui para manutenção das grandes populações de psitacídeos, ainda presentes, no Pantanal Sul.ABSTRACT - Neotropical parrots usually forage in forest canopies for nectar, flowers, leaves, fruit pulp, and seeds. As they have no all-purpose territories, these birds usually exploit vegetation mosaics in order to use plentiful resources as they become available. In this study we examine the use of a gallery forest in the southern Pantanal (Brazil) by a diverse parrot community that ranged from Brotogeris chiriri (a small species) to Ara chloroptera (a large one). Plant food resources principally used by parrots were abundantly available during the rainy season (fleshy fruits), the annual floods (fleshy fruits), and the dry season (flowers). While both smaller and larger species foraged on fruits, parakeets largely consumed the pulp, while larger parrot species used pulp and seeds. In the dry season parakeets foraged extensively on nectar, especially Inga vera nectar that was abundantly available during the last two months of the dry season, the harshest period of the year. Among larger parrots, only Propyrrhura auricollis frequently harvested nectar. Fruits maturing during floods, despite being fish- or water- dispersed were extensively used by the parrots. Hence, unlike what happens in most other Neotropical dry forests, occurrence of a fruiting peak during the annual flooding, which occurs in the transition from the wet to the dry season, constitutes an extra and significant episode of food availability, since in this period, fruit production normally declines. Therefore, the unique and abundant availability of flowers and fruits in this gallery forest may account for the presence of large parrot populations in the southern Pantanal

SLEEP-LIKE CORTICAL BISTABILITY IN VEGETATIVE STATE PATIENTS

The human brain is able to generate a wide repertoire of behavioral and psychological phenomena spanning from simple motor acts to cognition, from unimodal sensory perceptions to conscious experience. All these abilities are based on two key parameters of cortico-thalamic circuits functioning: the reactivity to a direct, local stimulation (cortical excitability) and the ability to causally interact (cortical effective connectivity). Indeed, alterations of these parameters have been suggested to underlie neurologic and psychiatric conditions. Over the last ten years, high-density electroencephalography combined with transcranial magnetic stimulation (TMS/hd-EEG) has been used to non-invasively probe cortical excitability and connectivity and to track over time pathological alterations, plastic changes and therapy-induced modifications in cortical circuits. A recently proposed theory suggests that consciousness depends on the brain\u2019s ability to engage in complex activity patterns that are, at once, distributed among interacting cortical areas (integrated) and differentiated in space and time (information-rich). In a recent series of experiments the electroencephalographic TMS-evoked brain response was recorded in healthy subjects during wakefulness, non-rapid eyes movement sleep (NREM), under pharmacological conditions (anesthesia), and pathological conditions (severely brain-injured, vegetative state patients). Indeed, TMS/hd-EEG measurements showed that during wakefulness the brain is able to sustain long-range specific patterns of activation, while when consciousness fades in NREM sleep, anesthesia and vegetative state, the thalamo-cortical system produces either a local or a global slow wave which underlies respectively a loss of differentiation or integration. We hypothesize that, like spontaneous sleep slow waves, the slow waves triggered by TMS are due to bistability between periods of neuronal activity (up-state) and silence (down-state) in cortical networks. Thalamo-cortical bistability could impair the ability of thalamo-cortical circuits to sustain long-range, differentiated patterns of activation, a key theoretical requisite for consciousness. Animal studies show that the extracellular signature of the down-state is a transient suppression of high frequency (>20Hz) power in the local field potential (LFP). More recently, intracranial recordings during NREM sleep in humans have shown that a intracranial stimulations induce a widespread suppression of high frequencies (i.e. cortical down-states) that impair the ability of thalamo-cortical circuits to engage in causal interactions. In the present thesis we use a TMS/hd-EEG approach in patients affected by disorders of consciousness such as vegetative state (VS) and minimally conscious state (MCS) to investigate whether bistability could underlie also pathological loss of consciousness. To verify this hypothesis, we recorded TMS-evoked potentials (TEPs) in awake VS and MCS patients as well as in healthy controls (HC) during wakefulness and NREM sleep. TEPs were analyzed by means of time-frequency analyses (power and phase-locking factor - PLF). We observed that TEPs recorded in VS patients were characterized by a large positive-negative deflection, closely resembling the one recorded in HC during NREM sleep. This sleep-like slow-wave was associated with a significant suppression of power in the high frequency band (>20 Hz) together with an early drop of PLF. Interestingly, in VS patients the power suppression slowly recovered to the baseline whereas in the NREM sleep of HC it was replaced by a late increase of power. Finally, the recovery of consciousness assessed in two patients evaluated longitudinally was paralleled by the resurgence of TEPs high frequency oscillations and by an increase of PLF duration. These results suggest that the slow waves evoked by TMS in VS patients possibly reflect a condition of cortical bistability that prevents the entrainment of thalamocortical modules in effective interactions and, hence, the emergence of consciousness. Intriguingly, the resumption of TEPs high frequency oscillations and a longer duration of phase-locked components (PLF) seem to be associated with the recovery of consciousness. Since bistability is, in principle, reversible and its mechanisms are well understood at the cellular and network level, it may represent a suitable target for novel therapeutic approaches in patients in whom consciousness is impaired, in spite of preserved cortical activity

O LIVRO DIDÁTICO E A FORMAÇÃO DO LEITOR

Saber ler, hoje, no mais privilgio de ningum, mas direito de todos e a escola, como instituio encarregada de dar essa formao s pessoas, tem procurado desempenhar sua tarefa da maneira mais eficiente possvel. A mudana do conceito de indivduo alfabetizado para letrado exige das escolas um novo olhar sobre o cidado que est sendo formado, porque ele no poder ser mais um ledor, mas algum capaz de interagir no meio em que vive de maneira eficiente. Quando se realizam testes para avaliao da competncia leitora dos alunos, o resultado tem sido, a maioria das vezes, um fracasso. Sabendo-se que o livro didtico muitas vezes utilizado como material bsico de leitura, atravs deste trabalho pretende-se lanar um olhar sobre o livro didtico de Portugus utilizado em escolas de ensino mdio de Cianorte

Galeazzo Alessi e il Libro dei Misteri (1565-1572). Un architetto e il progetto per una Nuova Gerusalemme sul Sacro Monte di Varallo.

L'abstract è presente nell'allegato / the abstract is in the attachmen

A modelagem matemática como recurso didático em projetos interdisciplinares

Este estudo examina o envolvimento e acompanhamento de um grupo de alunos de Cálculo na realização de um projeto interdisciplinar, que utiliza a Modelagem Matemática como recurso didático. O relato da experiência e a avaliação dos resultados mostrou ganhos no processo de ensino e aprendizagem da disciplina, oportunidades de aplicação e reflexão sobre situações reais e proporcionou novos questionamentos e redirecionamentos ao professor-orientador