LocoMouse: a novel system for studying the role of cerebellum in gait coordination

Smooth and efficient walking requires the coordination of movement across different parts of the body. The cerebellum plays an important role in this process, yet the specific neural circuit mechanisms of whole-body coordination are poorly understood. Although sophisticated genetic tools exist to manipulate the cerebellar circuit in mice, analyses of mouse gait have typically been limited to gross performance measures and lack detail about precision and timing of limb movements. In this project, I developed an automated, high-throughput, markerless 3D tracking system (LocoMouse) for quantifying locomotion in freely walking mice. Using LocoMouse, I showed that locomotor parameters for individual limbs vary systematically with mouse walking speed and body size. In visibly ataxic Purkinje cell degeneration (pcd) and reeler mice, I found that 3D limb trajectories and, especially, interlimb and whole-body coordination are specifically impaired. Our findings suggest a failure to predict the consequences of movement across joints, limbs, and body. These experiments were essential to establish a quantitative framework for whole-body locomotor coordination in mice (Machado, Darmohray et al. eLife 2015). The LocoMouse system was then combined with optogenetic tools to ask how different output regions of the cerebellum differentially contribute to locomotor coordination. I expressed ChR2 in Purkinje cells and stimulated their terminals in the medial, interposed, and lateral cerebellar nuclei of freely walking mice. Here, I identified locomotor parameters that were specifically related to the manipulation of each nucleus. Acute disruption of neural activity in medial and interposed nuclei immediately perturbed ongoing locomotion. In contrast, similar manipulation of Purkinje cell inputs to the lateral nucleus had no observable effect on ongoing locomotor behavior. These results are broadly consistent with previous anatomical and lesion studies suggesting a medial-to-lateral functional organization of cerebellar outputs. Taken together, these experiments isolated impairments in interlimb and whole-body coordination in mice with cerebellar manipulations. In contrast, spinal cord mutant mice revealed impairments at the intralimb level with no alteration in the interlimb coordination. I characterized distinct motor deficits associated with manipulations in different brain regions and identified and quantified core features of cerebellar ataxia in mice. These experiments establish the LocoMouse system, combined with genetic manipulations, as a powerful system to dissect cerebellar circuit mechanisms of coordinated locomotion

Development of bacterial cellulose wound dressings with controlled delivery of vitamin D3

Book of Abstracts of CEB Annual Meeting 2017[Excerpt] Wounds, in particular traumatic (e.g. burns) and chronic ones, are a major cause of morbidity and impaired life quality. They often result in long hospitalization stays, taking up substantial health resources in developed countries. This proposal aims at developing a safe, easy-to-use and nonexpensive approach to efficiently address this problem, by attaining faster and proper wound healing. Recent studies showed that an antimicrobial peptide (AMP), LLKKK18, released from conjugates with dextrin embedded in a Carbopol hydrogel significantly improved burn wound healing. In addition to antimicrobial activity, this peptide stimulates vascularization, thus supporting a faster healing and tissue regeneration[1]. As such, one can hypothesize that a hydrogel comprising drugs that stimulate the expression of LL37 will improve wound healing while keeping the wound area infection-free. This work comprised the approach towards the development of a novel bacterial nanocellulose (BNC) dressing. BNC, already used clinically for the treatment of burn wounds due to the unique properties like high water holding capacity, high crystallinity, ultrafine fiber network, high resistance, high moldability and biocompatibility[2]. In this work BNC will be used as drug carriers for the controlled release of drugs, namely of vitamin D3, an inducer of an endogenous expression of AMP LL37, known for accelerating the wound healing process, and as a protective barrier against exogenous agents (dust, microorganism) that can impair wound healing. [...]info:eu-repo/semantics/publishedVersio

Beyond new neurons in the adult hippocampus: imipramine acts as a pro-astrogliogenic factor and rescues cognitive impairments induced by stress exposure

Depression is a prevalent, socially burdensome disease. Different studies have demonstrated the important role of astrocytes in the pathophysiology of depression as modulators of neurotransmission and neurovascular coupling. This is evidenced by astrocyte impairments observed in brains of depressed patients and the appearance of depressive-like behaviors upon astrocytic dysfunctions in animal models. However, little is known about the importance of de novo generated astrocytes in the mammalian brain and in particular its possible involvement in the precipitation of depression and in the therapeutic actions of current antidepressants (ADs). Therefore, we studied the modulation of astrocytes and adult astrogliogenesis in the hippocampal dentate gyrus (DG) of rats exposed to an unpredictable chronic mild stress (uCMS) protocol, untreated and treated for two weeks with antidepressants—fluoxetine and imipramine. Our results show that adult astrogliogenesis in the DG is modulated by stress and imipramine. This study reveals that distinct classes of ADs impact differently in the astrogliogenic process, showing different cellular mechanisms relevant to the recovery from behavioral deficits induced by chronic stress exposure. As such, in addition to those resident, the newborn astrocytes in the hippocampal DG might also be promising therapeutic targets for future therapies in the neuropsychiatric field.ARMS: ELC, NDA, PP, AMP, JSC, MM, AJR, JFO, and L.P. received fellowships from the Portuguese Foundation for Science and Technology (FCT) (IF/00328/2015 to J.F.O.; 2020.02855.CEECIND to LP). This work was funded by FCT (IF/01079/2014, PTDC/MED-NEU/31417/2017 Grant to JFO), BIAL Foundation Grants (037/18 to J.F.O. and 427/14 to L.P.), “la Caixa” Foundation Health Research Grant (LCF/PR/HR21/52410024) and Nature Research Award for Driving Global Impact—2019 Brain Sciences (to L.P.). This was also co-funded by the Life and Health Sciences Research Institute (ICVS), and by FEDER, through the Competitiveness Internationalization Operational Program (POCI), and by National funds, through the Foundation for Science and Technology (FCT)—project UIDB/50026/2020 and UIDP/50026/2020. Moreover, this work has been funded by ICVS Scientific Microscopy Platform, member of the national infrastructure PPBI—Portuguese Platform of Bioimaging (PPBI-POCI-01-0145-FEDER-022122; by National funds, through the Foundation for Science and Technology (FCT)—project UIDB/50026/2020 and UIDP/50026/2020; “la Caixa” Foundation (ID 100010434 to A.J.R.), under the agreement LCF/PR/HR20/52400020; and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement No 101003187 to A.J.R.)

Effect of PEDOT:PSS with secondary dopants and DBD plasma treatment on the conductive properties of polyester fabrics

[Excerpt] Introduction Smart textiles have the capability to interact with the surrounding environment and react in different ways, namely in electrical conduction. The conductive properties of these materials are useful in medical, healthcare, and protective clothing.This research was funded by FEDER funds through the Operational Competitiveness Program– COMPETE, under the projects POCI-01-0247-FEDER-068924, and by National Funds through Fundação para a Ciência e Tecnologia (FCT), under the project UID/CTM/00264/2020. Ana Isabel Ribeiro and Cátia Alves acknowledge FCT, MCTES, FSE, and UE PhD grant SFRH/BD/145269/2019 and 2022.10454.BD

a detailed view of the methodology

Rheumatic and musculoskeletal diseases (RMD) are prevalent and leading causes of disability and consumption of healthcare and social resources. EpiReumaPt is a national population-based survey developed by the Portuguese Society of Rheumatology that aimed to estimate the prevalence of RMDs and determine their impact on function, quality of life, mental health and use of healthcare resources. This article describes in detail the design, methodology and planned analyses of EpiReumaPt. Recruitment started in September 2011 and finished in December 2013. This study involved a three-stage approach. The first step was a face-to-face survey performed by trained interviewers at the household of 10,661 subjects who where randomly selected by a stratified multistage sampling. A highly sensitive screening questionnaire for RMDs was used. Secondly, participants who screened positive (64%) for at least one RMD as well as 20% of individuals with a negative screening were invited for assessment by a rheumatologist. In total, 3,877 subjects participated in this second phase, where they were also invited to donate a blood sample to be stored at the Biobanco-IMM. History and physical examination, followed by appropriate laboratory and imaging tests were performed. At the end of the visit, the rheumatologist established a diagnosis. Finally, a team of three experienced rheumatologists reviewed all the clinical data and defined the diagnoses according to previously validated criteria. The EpiReumaPt dataset, containing data from several questionnaires, various clinical measurements and information from laboratory and imaging tests, comprises an invaluable asset for research. The large amount of information collected from each participant and the large number of participants, with a wide age range covering and being representative of the adults from the entire country, makes EpiReumaPt the largest study of RMDs performed in Portugal.publishersversionpublishe

going beyond BASDAI

This work was supported by a Research Grant from the InvestigatorInitiated Studies program of Merck Sharp & Dohme (Grant No. 56078). The sponsor did not interfere with the study question, analysis or interpretation of results. AS is supported by a doctoral grant from Fundação para a Ciência e Tecnologia (Foundation for Science and Technology) (SFRH/BD/108246/2015).OBJECTIVES: To compare definitions of high disease activity of the Ankylosing Spondylitis Disease Activity Score (ASDAS) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in selecting patients for treatment with biologic disease-modifying antirheumatic drugs (bDMARDs). METHODS: Patients from Rheumatic Diseases Portuguese Register (Reuma.pt) with a clinical diagnosis of axial spondyloarthritis (axSpA) were included. Four subgroups (cross-tabulation between ASDAS (≥2.1) and BASDAI (≥4) definitions of high disease activity) were compared regarding baseline characteristics and response to bDMARDs at 3 and 6 months estimated in multivariable regression models. RESULTS: Of the 594 patients included, the majority (82%) had both BASDAI≥4 and ASDAS ≥2.1. The frequency of ASDAS ≥2.1, if BASDAI<4 was much larger than the opposite (ie, ASDAS <2.1, if BASDAI≥4): 62% vs 0.8%. Compared to patients fulfilling both definitions, those with ASDAS ≥2.1 only were more likely to be male (77% vs 51%), human leucocyte antigen B27 positive (79% vs 65%) and have a higher C reactive protein (2.9 (SD 3.5) vs 2.1 (2.9)). Among bDMARD-treated patients (n=359), responses across subgroups were globally overlapping, except for the most 'stringent' outcomes. Patients captured only by ASDAS responded better compared to patients fulfilling both definitions (eg, ASDAS inactive disease at 3 months: 61% vs 25% and at 6 months: 42% vs 25%). CONCLUSION: The ASDAS definition of high disease activity is more inclusive than the BASDAI definition in selecting patients with axSpA for bDMARD treatment. The additionally 'captured' patients respond better and have higher likelihood of predictors thereof. These results support using ASDAS≥2.1 as a criterion for treatment decisions.publishersversionpublishe

Arbustus unedo essence: morphological and genetic characterization of the strawberry tree of Castelo de Paiva

O medronheiro é um arbusto da região mediterrânica que pode ser encontrada por todo o país. Ao contrário do que verifica na região sul do país, no concelho de Castelo de Paiva é atribuída uma reduzida importância económica a esta espécie. Com o intuito de preservar e potenciar a produção desta espécie e contribuir para a dinamização da economia do concelho, procedeu-se à caracterização morfológica e genética de uma amostra da população de medronheiros de Castelo de Paiva. A caracterização morfológica e genética foi realizada para um total de 10 genótipos. Para tal recolheram-se 70 folhas aleatoriamente em cada árvore. Em 40 folhas mediu-se o comprimento, largura, comprimento do pedúnculo, peso fresco, peso seco e determinou-se a área foliar. Dos caracteres morfológicos analisados, aqueles que se revelaram mais úteis na distinção dos vários genótipos foram: comprimento do pedúnculo, peso fresco e peso seco. As restantes 30 folhas foram utilizadas para a caracterização genética. Esta caracterização foi realizada recorrendo a um marcador de DNA, ISSR. Os 5 primeiros exemplaresutilizados na técnica de ISSR demonstraram-se polimórficos. Os resultados da caracterização genética sugerem que a variabilidade genética na população é média a alta.The strawberry tree is a shrub native in the Mediterranean region and it can be found throughout Portugal. Unlike the case in the southern region of the country, in Castelo de Paiva a minor economic importance is given to this species. In order to preserve, to enhance the production of this species and to contribute to the boosting of the economy of the region, we proceeded to the characterization of a small sample population of this fruit tree of Castelo de Paiva in what concerns to its morphology and genetics. The morphological and genetic characterization was performed for a total of 10 genotypes. For this, 70 leaves were randomly collected from each tree. For 40 leaves, it was measured the length, the width, the peduncle length, the wet weight, the dry weight and determined the leaf area. Of the morphological characteristics analyzed, the ones that proved most useful in distinguishing the various genotypes were: the length peduncle, the wet weight and the dry weight. The remaining 30 leaves were used in the genetic characterization. This characterization was performed using a DNA marker, the ISSR. The 5 primers used in the ISSR technique proved to be polymorphic. The results from the genetic characterization suggest that variability in population genetics is medium to high

Tuberculosis across the seas: CPLP-TB - a joint effort in cataloguing mycobacterium tuberculosis genetic diversity in the lusophone space

The Community of Portuguese Language Speaking Countries (CPLP) comprises nine countries across four continents, accounting for 7.2% of the world’s land area, and where tuberculosis (TB) is still a cause of public health concern. A marked variation in TB incidence (23 to 551 cases per 100 000 habitants) can be observed across the different member-states and, despite of this, a considerable gap in the knowledge on the Mycobacterium tuberculosis population structure and country-level geospatial distribution still exists. To address this we have gathered a comprehensive set of molecular and phenotypic drug susceptibility data on approximately 1150 different clinical isolates, from different partners, across 5 distinct portuguesespeaking countries. This initial dataset comprises molecular genotypic data obtained by either 12, 15 or 24-loci Mycobacterial Interspersed Repetitive Unit – Variable Number of Tandem repeat (MIRU-VNTR) and/or Spoligotyping. The complete dataset therefore includes M. tuberculosis clinical isolates from Portugal (n≈370), Angola (n≈80), Guinea-Bissau (n≈13), Mozambique (n≈14) and Brazil (n≈680). To make this data available to the scientific community and public health authorities we have developed CPLP-TB, an online database coupled with webbased tools that enable exploratory data analysis. This new tool specifically directed at CPLP countries include advanced data analysis capability together with graphical visualization tools (e.g. dendrogram and choropleth mapping). As a public health tool, it is expected to contribute for a deeper knowledge on the combined population structure and strain circulation between countries, thus enabling the assessment of strain specific trends in a broader macroepidemiological context. Furthermore, this new tool provides a new framework for interlaboratory cooperation on TB molecular epidemiology.N/

Artistas sobre outras obras

Ninguém vive sem passar uma parte muito importante da sua vida fazendo tarefas sem nada de especial, ou habitando espaços quotidianos, caseiros, sem muito interesse. E, contudo, essas ações constituem a identidade profunda, a singularidade radica na banalidade. Na maior parte do tempo, os humanos têm pouco interesse, ocupados em repetir gestos e funções vitais. Convivemos com a alienação há pouco tempo: ela é denunciada na sociedade industrial através da relação prioritária do homem com os objetos, e pela redução crescente da relação do homem consigo próprio, e com os seus semelhantes. O homem, mais rico, hoje, é no fundo muito mais pobre. Assim se apontem instâncias de auto-descolonização, de reflexão, de resistência, de libertação, de emancipação: a arte pode ser uma delas.info:eu-repo/semantics/publishedVersio