PARL deficiency in mouse causes Complex III defects, coenzyme Q depletion, and Leigh-like syndrome

The mitochondrial intramembrane rhomboid protease PARL has been implicated in diverse functions in vitro, but its physiological role in vivo remains unclear. Here we show that ablation in mouse causes a necrotizing encephalomyelopathy similar to Leigh syndrome, a mitochondrial disease characterized by disrupted energy production. Mice with conditional PARL deficiency in the nervous system, but not in muscle, develop a similar phenotype as germline KOs, demonstrating the vital role of PARL in neurological homeostasis. Genetic modification of two major PARL substrates, PINK1 and PGAM5, do not modify this severe neurological phenotype. brain mitochondria are affected by progressive ultrastructural changes and by defects in Complex III (CIII) activity, coenzyme Q (CoQ) biosynthesis, and mitochondrial calcium metabolism. PARL is necessary for the stable expression of TTC19, which is required for CIII activity, and of COQ4, which is essential in CoQ biosynthesis. Thus, PARL plays a previously overlooked constitutive role in the maintenance of the respiratory chain in the nervous system, and its deficiency causes progressive mitochondrial dysfunction and structural abnormalities leading to neuronal necrosis and Leigh-like syndrome

Doença de Fabry, revisão de uma doença olho-rim

Fabry’s disease is a recessive X -linked disorder that results from a deficiency of the hydrolase alpha- -galactosidase A (α -Gal A). The absence of α -Gal A enzyme activity leads to accumulation of glycosphingolipid globotryaosylceramide (GL -3) in the lysosomes of a variety of cell types. It can cause skin and ocular lesions, progressive renal, cardiac or cerebrovascular disorders. The authors report the case of a 39 -year -old female who was referred to a nephrology appointment by her ophthalmologist, after the diagnosis of cornea verticillata and posterior subcapsular cataract. This case illustrates the importance of a multidisciplinary evaluation to an effective clinical screening. In males, most symptoms begin in childhood; in females the onset can be observed later and presentation is more variable. Various manifestations often lead to misdiagnosis or are frequently delayed for many years. Enzyme replacement therapy highlights the importance of early diagnosis so that treatment can be initiated before irreversible organ damage occurs

Community psychiatry in the team of Brandoa: services provided in December 2008

O Serviço de Psiquiatria do Hospital Prof. Doutor Fernando Fonseca, EPE (HFF) foi o primeiro serviço em Portugal com base no hospital geral a desenvolver um modelo integrado de cuidados de saúde mental na comunidade, orientado para as necessidades da população e apoiado em equipas multidisciplinares. Este modelo assenta na continuidade de cuidados pela mesma equipa, no seguimento assertivo dos doentes na comunidade, na articulação com os cuidados de saúde primários e numa grande diversidade de intervenções1. A actividade do Serviço decorre a nível hospitalar e comunitário, mantendo-se uma estreita articulação entre as várias unidades que o constituem, de forma a garantir a indispensável continuidade de cuidados. A nível comunitário, as Equipas da Amadora, Brandoa, Damaia e Queluz constituem a Unidade Funcional Comunitária e estão sediadas nos Centros de Saúde da área onde desenvolvem a sua actividade. O presente trabalho tem como objectivos caracterizar a população activa seguida pela Equipa Comunitária da Brandoa em Dezembro de 2008, em termos socio-demográficos e clínicos e a partir dos dados obtidos, fazer uma breve reflexão no sentido de questionar a actividade desenvolvida e melhorar as práticas assistenciais no futuro

Environmental effects in galaxies: Molecular Gas, Star Formation, and Activity

In order to study whether there is any correlation between nuclear activities, gas content, and the environment where galaxies reside, we have obtained optical and millimetric spectra for a well-defined sample of intermediate Hubble type spirals in dense environments and in the field. We found that these spirals in dense environments have on average: less molecular gas per blue luminosity, higher atomic gas fraction, lower current star formation rate, and the same star formation efficiency as field galaxies. Although none of these results stand out as a single strong diagnostic, given their statistical significance, taken together they indicate a trend for diminished gas content and star formation activity in galaxies in high density environments. Our results suggest that galaxies in dense environments have either (i) consumed their molecular gas via star formation in the past or (ii) that dense environments leads to an inhibition of molecular gas from atomic phase. The similarities in star formation efficiency of the dense environments and field galaxies suggest that the physical processes controling the formation of stars from the molecular gas are local rather than global. We also found that star formation rate per blue luminosity increases linearly as the total amount of gas increases in LINERs. This result, based on a small sample, suggests that LINERs are powered by star formation rather than an AGN.Comment: 12 pages, 12 figures, A&A accepte

Influência de fungos micorrízicos arbusculares e da adubação fosfatada em acessos de Passiflora cincinnata mast.

O objetivo desse trabalho foi verificar a resposta do maracujazeiro-do-mato (P. cincinnata Mast.) à inoculação com Glomus etunicatum e à adubação fosfatada

Metabolic control of T cell immune response through glycans in inflammatory bowel disease

Mucosal T lymphocytes from patients with ulcerative colitis (UC) were previously shown to display a deficiency in branched N-glycosylation associated with disease severity. However, whether this glycosylation pathway shapes the course of the T cell response constituting a targeted-specific mechanism in UC remains largely unknown. In this study, we demonstrated that metabolic supplementation of ex vivo mucosal T cells from patients with active UC with N-acetylglucosamine (GlcNAc) resulted in enhancement of branched N-glycosylation in the T cell receptor (TCR), leading to suppression of T cell growth, inhibition of the T helper 1 (Th1)/Th17 immune response, and controlled T cell activity. We further demonstrated that mouse models displaying a deficiency in the branched N-glycosylation pathway (MGAT5-/-, MGAT5+/-) exhibited increased susceptibility to severe forms of colitis and early-onset disease. Importantly, the treatment of these mice with GlcNAc reduced disease severity and suppressed disease progression due to a controlled T cell-mediated immune response at the intestinal mucosa. In conclusion, our human ex vivo and preclinical results demonstrate the targeted-specific immunomodulatory properties of this simple glycan, proposing a therapeutic approach for patients with UC.We thank Dr. Hiroaki Korekane and Fumi (RIKEN) for support in preparation of the fluorescent oligosaccharide acceptor substrate. We thank Dr. Michael Pierce for kindly providing the MGAT5 knockout mice. We also thank Paula Paíga (REQUIMTE/LAQV) for technical support with the HPLC system. The Institute of Molecular Pathology and Immunology of the University of Porto integrates the i3S research unit, which is partially supported by the Portuguese Foundation for Science and Technology (FCT). This article is a result of the project NORTE-01-0145-FEDER-000029, supported by the Norte Portugal Regional Programme (NORTE 2020) under the PORTUGAL 2020 Partnership Agreement through the European Regional Development Fund. This work was also funded by Fundo Europeu de Desenvolvimento Regional (FEDER) funds through the COMPETE 2020—Operacional Programme for Competitiveness and Internationalization (POCI), Portugal 2020, and by Portuguese funds through the FCT in the framework of the project (POCI-01/ 0145-FEDER-016601 and PTDC/DTP-PIC/0560/2014). S.S.P. acknowledges the European Crohn’s and Colitis Organization (ECCO) for ECCO Grant 2017, the Broad Medical Research Program at the Crohn’s and Colitis Foundation of America, and the Portuguese Group of Study in IBD (GEDII) for funding. A.M.D. [PD/BD/105982/2014], A.C. [SFRH/BPD/91623/2012], and M.S.P. [SFRH/ BD/110148/2015] received funding from the FCT. M. Lima thanks the CHP for the research support.info:eu-repo/semantics/publishedVersio

Neuregulin1/ErbB system: importance in the control of cardiovascular function

The family of Neuregulins (NRG), growth factors like epidermal growth factor, is known to induce growth and differentiation of epithelial, glial, neuronal, and skeletal muscle cells. This family comprises four members, being NRG1 the most largely studied, particularly at the cardiovascular level. The biological effects of NRG1 in the adult heart are mediated by the tyrosine kinase receptors ErbB. In the adult heart, NRG1 is expressed by cells of the endocardial endothelium and the cardiac microvascular endothelium, and the receptors ErbB2/ErbB4 are expressed by ventricular cardiomyocytes and are located in T-tubule system and intercalated disks in close proximity to the system components of excitation-contraction coupling. The importance of the NRG/ErbB signaling axis at the cardiovascular level became evident after discovering that patients treated with trastuzumab (inhibitory antibody against ErbB2, used in the treatment of breast cancer) can develop ventricular dysfunction and have higher risk of cardiomyopathy when co-administered with anthracyclines. Subsequent studies in vitro and in vivo have clarified the effects and the respective signaling pathways associated with the NRG/ErbB system in the adult heart. Some cardiovascular functions of the NRG1/ErbB system have been described at the vascular (stimulation of angiogenesis and ateroprotector effect) and myocardium level (negative inotropic effect) as well as effect on the survival, cell growth and organization of the cardiomyocytes (myofibrillar organization and cell-to-cell contact between cardiomyocytes). Furthermore, the interaction of this system with other neurohumoral mediators has been studied. Thus, there seems to be a physiological role in modulating the sympathovagal balance and an interaction with endothelin-1 signaling. All these effects result from the activation of different intracellular signaling cascades, as a consequence of the binding of NRG1 to ErbB receptors. Some cardiac signaling pathways identified until now include molecules such as MEK / Erk 1/2, phosphatidylinositol 3-kinase/ Akt, focal adhesion kinase, Gab (Grb-2-associated binder) family, vascular endothelial growth factor and NO production by endothelial nitric oxide synthase. Thus, the aim of this paper was to make an up-to-date review of existing information on NRG1/ErbB signaling axis, with particular focus on its cardiovascular effects

Genome of the Avirulent Human-Infective Trypanosome—Trypanosoma rangeli

Background: Trypanosoma rangeli is a hemoflagellate protozoan parasite infecting humans and other wild and domestic mammals across Central and South America. It does not cause human disease, but it can be mistaken for the etiologic agent of Chagas disease, Trypanosoma cruzi. We have sequenced the T. rangeli genome to provide new tools for elucidating the distinct and intriguing biology of this species and the key pathways related to interaction with its arthropod and mammalian hosts.  Methodology/Principal Findings: The T. rangeli haploid genome is ,24 Mb in length, and is the smallest and least repetitive trypanosomatid genome sequenced thus far. This parasite genome has shorter subtelomeric sequences compared to those of T. cruzi and T. brucei; displays intraspecific karyotype variability and lacks minichromosomes. Of the predicted 7,613 protein coding sequences, functional annotations could be determined for 2,415, while 5,043 are hypothetical proteins, some with evidence of protein expression. 7,101 genes (93%) are shared with other trypanosomatids that infect humans. An ortholog of the dcl2 gene involved in the T. brucei RNAi pathway was found in T. rangeli, but the RNAi machinery is non-functional since the other genes in this pathway are pseudogenized. T. rangeli is highly susceptible to oxidative stress, a phenotype that may be explained by a smaller number of anti-oxidant defense enzymes and heatshock proteins.  Conclusions/Significance: Phylogenetic comparison of nuclear and mitochondrial genes indicates that T. rangeli and T. cruzi are equidistant from T. brucei. In addition to revealing new aspects of trypanosome co-evolution within the vertebrate and invertebrate hosts, comparative genomic analysis with pathogenic trypanosomatids provides valuable new information that can be further explored with the aim of developing better diagnostic tools and/or therapeutic targets

Curso semipresencial promove reflexão sobre a prática no ensino de álgebra

Este artigo tem origem na satisfação do grupo de Álgebra, do Setor Matemática, do Projeto Fundão, ao terminar duas edições de um curso semipresencial sobre ensino de Álgebra para professores e futuros professores do Estado do Rio de Janeiro. Durante três anos, o grupo realizou um estudo sobre o desenvolvimento do pensamento algébrico que teve como resul-tado a publicação de um livro, em 2008, para servir de subsídio a professores interessados em inovar sua prática nas aulas de Álgebra, do 6º ano do ano, do Ensino Fundamental ao 3º ano do Ensino Médio. Como o conhecimento pedagógico do conteúdo (Shulman, 1986) desenvolvido ao longo do trabalho foi rico e significativo, o grupo resolveu compartilhá-lo com outros professores, por meio do curso. O seu sucesso em 2010fez com que o repetísse-mos, em 2011, para outros professores. Registramos aqui as ideias fundamentais sobre as quais giraram as reflexões do curso e observações, considerações e constatações possíveis a partir dele

A serious games platform for cognitive rehabilitation with preliminary evaluation

In recent years Serious Games have evolved substantially, solving problems in diverse areas. In particular, in Cognitive Rehabilitation, Serious Games assume a relevant role. Traditional cognitive therapies are often considered repetitive and discouraging for patients and Serious Games can be used to create more dynamic rehabilitation processes, holding patients' attention throughout the process and motivating them during their road to recovery. This paper reviews Serious Games and user interfaces in rehabilitation area and details a Serious Games platform for Cognitive Rehabilitation that includes a set of features such as: natural and multimodal user interfaces and social features (competition, collaboration, and handicapping) which can contribute to augment the motivation of patients during the rehabilitation process. The web platform was tested with healthy subjects. Results of this preliminary evaluation show the motivation and the interest of the participants by playing the games.- This work has been supported by FCT - Fundacao para a Ciencia e Tecnologia in the scope of the projects: PEst-UID/CEC/00319/2015 and PEst-UID/CEC/00027/2015. The authors would like to thank also all the volunteers that participated in the study