Impairment of Adenosinergic System in Rett syndrome: Novel Therapeutic Target to Boost BDNF Signalling

Rett syndrome (RTT; OMIM#312750) is mainly caused by mutations in the X-linked MECP2 gene (methyl-CpG-binding protein 2 gene; OMIM*300005), which leads to impairments in the brain-derived neurotrophic factor (BDNF) signalling. The boost of BDNF mediated effects would be a significant breakthrough but it has been hampered by the difficulty to administer BDNF to the central nervous system. Adenosine, an endogenous neuromodulator, may accomplish that role since through A2AR it potentiates BDNF synaptic actions in healthy animals. We thus characterized several hallmarks of the adenosinergic and BDNF signalling in RTT and explored whether A2AR activation could boost BDNF actions. For this study, the RTT animal model, the Mecp2 knockout (Mecp2-/y) (B6.129P2 (C)-Mecp2tm1.1Bird/J) mouse was used. Whenever possible, parallel data was also obtained from post-mortem brain samples from one RTT patient. Ex vivo extracellular recordings of field excitatory post-synaptic potentials in CA1 hippocampal area were performed to evaluate synaptic transmission and long-term potentiation (LTP). RT-PCR was used to assess mRNA levels and Western Blot or radioligand binding assays were performed to evaluate protein levels. Changes in cortical and hippocampal adenosine content were assessed by liquid chromatography with diode array detection (LC/DAD). Hippocampal ex vivo experiments revealed that the facilitatory actions of BDNF upon LTP is absent in Mecp2-/y mice and that TrkB full-length (TrkB-FL) receptor levels are significantly decreased. Extracts of the hippocampus and cortex of Mecp2-/y mice revealed less adenosine amount as well as less A2AR protein levels when compared to WT littermates, which may partially explain the deficits in adenosinergic tonus in these animals. Remarkably, the lack of BDNF effect on hippocampal LTP in Mecp2-/y mice was overcome by selective activation of A2AR with CGS21680. Overall, in Mecp2-/y mice there is an impairment on adenosinergic system and BDNF signalling. These findings set the stage for adenosine-based pharmacological therapeutic strategies for RTT, highlighting A2AR as a therapeutic target in this devastating pathology.info:eu-repo/semantics/publishedVersio

Avaliação do comportamento ingestivo em búfalas lactantes suplementadas com ração à base de resíduos industriais: cupuaçu e murumuru.

Este trabalho tem por objetivo estudar a influência da suplementação com torta de cupuaçu (Theobroma grandiflorum) e torta de murumuru (Astrocaryum murumuru), no comportamento ingestivo de vacas em lactação búfalos sob pastejo rotacionado. A pesquisa utilizou 12 búfalas distribuídos em quadrado latino 3 x 3, com quatro repetições. Nós adquirimos o resíduo de murumuru e cupuaçu, a partir da indústria de cosméticos. O Comportamento alimentar de vacas pastando foi realizada a cada 21 dias. O trabalho concluiu que a inclusão de torta de cupuaçu ou torta de murumuru não altera o comportamento alimentar de búfalas em lactação em comparação com a suplementação de farinha de milho e soja

Produção de leite e consumo de concentrado em búfalas lactantes suplementadas com concentrado à base de torta de cupuaçu (Theobroma grandiflorum) e torta de murumuru (Astrocaryum murumuru).

O objetivo deste estudo foi avaliar a produção de leite e o consumo de concentrado em búfalas em lactação suplementadas com resíduos agro-industrial, torta de cupuaçu (Theobroma grandiflorum) e torta de murumuru (Astrocaryum murumuru). A quantidade de concentrado foi administrada com base na produção de leite individual. O delineamento experimental foi o quadrado latino 3 x 3, quatro quadrados, distribuídos de acordo com a data de parição das búfalas. O experimento durou 63 dias, com três períodos de 21 dias, com 10 dias de adaptação inicial e os últimos 11 dias para recolher os resultados. O consumo de suplemento e produção de leite foram avaliados nos últimos sete dias de cada período. Para a análise estatística foi utilizado o modelo misto (PROC MIXED) do SAS (SAS, 1999). Não houve diferença estatística para o consumo de concentrado e produção de leite. As tortas de cupuaçu e de murumuru podem ser usado como suplementação alimentar alternativa em búfalas em lactação, trazendo um desempenho semelhante ao concentrado à base de milho e soj

The cost of promiscuity: sexual transmission of Nosema microsporidian parasites in polyandrous honey bees

Multiple mating (and insemination) by females with different males, polyandry, is widespread across animals, due to material and/or genetic benefits for females. It reaches particularly high levels in some social insects, in which queens can produce significantly fitter colonies by being polyandrous. It is therefore a paradox that two thirds of eusocial hymenopteran insects appear to be exclusively monandrous, in spite of the fitness benefits that polyandry could provide. One possible cost of polyandry could be sexually transmitted parasites, but evidence for these in social insects is extremely limited. Here we show that two different species of Nosema microsporidian parasites can transmit sexually in the honey bee Apis mellifera. Honey bee males that are infected by the parasite have Nosema spores in their semen, and queens artificially inseminated with either Nosema spores or the semen of Nosema-infected males became infected by the parasite. The emergent and more virulent N. ceranae achieved much higher rates of infection following insemination than did N. apis. The results provide the first quantitative evidence of a sexually transmitted disease (STD) in social insects, indicating that STDs may represent a potential cost of polyandry in social insects

Restor(y)ing meaning: reading Manoel de Oliveira’s Non ou a Vã Glória de Mandar

Manoel de Oliveira’s Non ou a Vã Glória de Mandar (1990) is a landmark in Lusophone cinema’s revisitation of the history of Portuguese expansion and colonial conflicts. This article aims at analysing the film’s political import by extrapolating from Jacques Rancière’s meditation on the ‘aesthetic regime’ and from Manoel de Oliveira’s references to Derridean deconstruction. Non and Oliveira’s filming praxis both exceed and disrupt the filmmaker’s personal logocentric and teleological theories of history and cinema

Investigating the seismic response of URM walls with irregular opening layout through different modeling approaches

TThe façade and internal walls of unreinforced masonry (URM) buildings often present an irregular opening layout, due to architectural reasons or modifications to the structure, which make the expected seismic damage pattern less predictable a priori. Therefore, the discretization of the walls in structural components is not standardized, conversely to cases with a regular opening layout for which the available modeling methods are corroborated by seismic damage surveys reporting recurrent failure patterns. The structural component discretization is a relevant step for the code-conforming seismic assessment, typically based on comparing the internal forces and drifts of each component to strength criteria and drift thresholds. Therefore, the lack of well-established approaches can significantly influence the assessment. The issue is even more evident when the structural components must be identified a priori in the modeling stage, namely for equivalent frame models. The applicability of available methods for discretization of URM walls with irregular opening layout has been already investigated in literature, but a conclusive judgment requires further studies. In this context, this paper presents an overview of the preliminary results addressing the numerical modeling of this type of walls within the framework of the DPC-ReLUIS 2022-2024 project (Subtask 10.3), funded by the Italian Department of Civil Protection. The Subtask aims to propose consensus-based recommendations for researchers and practitioners which can contribute to harmonize the use of different modeling approaches. Seven research groups are involved in the research, adopting different modeling approaches and computer codes, but similar assumptions and the same analysis method (pushover) are used. The benchmark URM structure illustrated in the paper is a two-story wall from which four configurations with increasing irregularity of opening layout were derived. The results of four modeling approached are presented. Three of them reproduce the mechanical response of masonry at the material scale by means of FE models implemented in OpenSees, DIANA and Abaqus software, while the remaining approach describes the mechanical response of masonry at the macro-element scale in 3DMacro software. Results were compared in terms of capacity curves, predicted failure mechanisms and evolution of internal forces in piers. The adoption of consistent assumptions among the different approaches led to an overall agreement of predictions at both wall and pier scales, particularly in terms of damage pattern with higher concentration of damage at the ground story. Despite that, differences on the pushover curves have been highlighted. They are mainly due to some deviations of the internal forces in squat piers deriving from a complex load flow in these elements.DPC - Dipartimento della Protezione Civile, Presidenza del Consiglio dei Ministri(LA/P/0112/2020

EFEITO DO TREINAMENTO FÍSICO AERÓBICO EM CORONARIOPATAS SUBMETIDOS A UM PROGRAMA DE REABILITAÇÃO CARDIOVASCULAR

Study Model: Retrospective. Study objectives: Evaluate the effect of aerobic physical training in cardiovascular variables in patients with coronary artery disease participants of a Cardiovascular Rehabilitation Program. Methods: Patients with stable coronary artery disease were included and were analyzed the cardiovascular variables of exercise testing, carried out before and after a minimum period of 12 weeks of aerobic physical training in a Cardiovascular Rehabilitation Program, from February 2002 to July 2005. Results: A significant increment (p <0.0001) of maximal oxygen consumption (VO2 max) was observed after the cardiovascular rehabilitation (30.1 ± 9.5 versus 35.5 ± 8.8 ml/kg/min). The difference of the VO2 max had negative correlation with the initial physical capacity, with greater benefits in patients with smaller initial values of VO2  max. Significant differences were not observed in maximal systolic blood pressure and double product, and a small difference was observed in maximal heart rate. The improvement in ischemic threshold was more pronounced, with an increment of 7.4 ml/kg/min in oxygen consumption, with statistical significance (p < 0.0001) (21.0 ± 6.9 versus 28.4 ± 8.2 ml/kg/min). Conclusions: The cardiovascular rehabilitation improved physical capacity and ischemic threshold in patients participants of a Cardiovascular Rehabilitation Program. The benefit in physical capacity was greater in patients with smaller initial values of maximal oxygen consumption.    Modelo do estudo: Retrospectivo. Objetivos do estudo: Avaliar o efeito do treinamento físico aeróbico nas variáveis cardiovasculares em pacientes coronariopatas participantes do Programa de Reabilitação Cardiovascular. Metodologia: Foram incluídos pacientes portadores de coronariopatia estável e foram avaliadas as variáveis cardiovasculares de testes ergométricos seriados, realizados antes e após um período mínimo de 12 semanas de treinamento físico aeróbico em um Programa de Reabilitação Cardiovascular, de fevereiro de 2002 a julho de 2005. Resultados: Documentou-se incremento significativo (p < 0,0001) do consumo de oxigênio pico (VO2 pico) após a reabilitação cardiovascular (30,1 ± 9,5 versus 35,5 ± 8,8 ml/kg/min). Este delta do VO2 pico apresentou correlação negativa com a capacidade física inicial, com maiores ganhos nos pacientes com menores valores iniciais de VO2 pico. Não foram observadas diferenças significativas na pressão arterial sistólica e no duplo produto pico, e uma diferença de pequena magnitude foi observada na freqüência cardíaca pico. A melhora no limiar isquêmico do miocárdio, avaliada pelo consumo de oxigênio na positivação, foi ainda mais expressiva, com incremento de 7,4 ml/kg/min (p < 0,0001) (21,0 ± 6,9 versus 28,4 ± 8,2 ml/kg/min). Conclusões: A reabilitação cardiovascular melhorou a capacidade física e o limiar isquêmico de pacientes participantes do Programa de Reabilitação Cardiovascular. O benefício na capacidade física foi maior  nos pacientes com menores valores iniciais de consumo de oxigênio pico.   

Characterization of crop residues from false banana/Ensete ventricosum/in Ethiopia in view of a full-resource valorization

Research ArticleFalse banana /Ensete ventricosum [Welw.] Cheesman/ is exploited as a food crop in Ethiopia where it represents an important staple food. The plant is harvested and large amounts of biomass residues are originated, mainly from the pseudo stem (i.e., fiber bundles obtained from the leaf sheaths after being scrapped to produce starchy food) and the inflorescence stalk. These materials were studied in relation to their summative chemical composition, composition of lignin, lipophilic and polar extracts. Moreover, their structural characteristics, in view of their valorization, were scrutinized. The analytical studies were performed with the aid of FTIR, GC/MS, Py-GC/MS and SEM. The fiber bundles are aggregates of mainly long and slender fibers with low ash, extractives and lignin contents (3.8%. 4.4% and 10.5% respectively) and high holocellulose and α-cellulose contents (87.5% and 59.6% respectively). The hemicelluloses in the fibers are mostly highly acetylated xylans and the lignin is of the H-type (H:G:S, 1:0.7:0.8). This lignin composition is in line with the FTIR peaks at 1670 cm-1 and 1250 cm-1.The inflorescence stalk has high ash content (12.3% in the main stalk and 24.6% in fines) with a major proportion of potassium, high extractives (25.9%), and low lignin and α-cellulose contents (5.8% and 17.9% respectively). The stalk includes numerous starch granules in the cellular structure with the predominant presence of parenchyma. The potential valorization routes for these materials are clearly different. The fiber bundles could be used as a fiber source for paper pulp production with the possibility of a prior hemicelluloses removal while the inflorescence stalk has nutritional value for food and fodder. Furthermore, it can also be used for sugar fermentation productsinfo:eu-repo/semantics/publishedVersio