Porto, Portugal

The Abel Salazar Biomedical science Institute is a graduate medical and life science school of the University of Porto. The Institute is especially geared to scientific research and investigation.Along with traditional medicine, including specialities such as oncology, public health and mental health, it also teaches acupuncture, marine biology, veterinary medicine, biochemistry and bioengineering. It is named after Abel Salazar , a Portuguese physician, lecturer, researcher and painter who worked and lived in Porto.On the main hall of the Institute, the famous maxim of Abel Salazar can be read:"The one who only knows Medicine, not even Medicine does he know." Wikipedia.


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Miura S.K.,University of California at Los Angeles | Martins A.,University of California at Los Angeles | Martins A.,Abel Salazar Biomedical Sciences Institute | Zhang K.X.,University of California at Los Angeles | And 2 more authors.
Cell | Year: 2013

The Drosophila Dscam1 gene encodes a vast number of cell recognition molecules through alternative splicing. These exhibit isoform-specific homophilic binding and regulate self-avoidance, the tendency of neurites from the same cell to repel one another. Genetic experiments indicate that different cells must express different isoforms. How this is achieved is unknown, as expression of alternative exons in vivo has not been shown. Here, we modified the endogenous Dscam1 locus to generate splicing reporters for all variants of exon 4. We demonstrate that splicing does not occur in a cell-type-specific fashion, that cells sharing the same anatomical location in different individuals express different exon 4 variants, and that the splicing pattern in a given neuron can change over time. We conclude that splicing is probabilistic. This is compatible with a widespread role in neural circuit assembly through self-avoidance and is incompatible with models in which specific isoforms of Dscam1 mediate homophilic recognition between processes of different cells. © 2013 Elsevier Inc.


Correia A.L.,Lawrence Berkeley National Laboratory | Correia A.L.,Abel Salazar Biomedical Sciences Institute | Mori H.,Lawrence Berkeley National Laboratory | Chen E.I.,State University of New York at Stony Brook | And 2 more authors.
Genes and Development | Year: 2013

Matrix metalloproteinases (MMPs) are crucial mediators in sculpting tissue architecture and are required for many physiological and pathological processes. MMP3 has been shown to regulate branching morphogenesis in the mammary gland. Ectopic expression of proteolytically active MMP3 in mouse mammary epithelia triggers supernumerary lateral branching and, eventually, tumors. Using a three-dimensional collagen-I (Col-1) gel assay that simulates epithelial invasion and branching, we show that it is the hemopexin domain that directs these processes. Using three different engineered constructs containing a variation on MMP3 structural domains, we confirmed the importance of the hemopexin domain also in primary organoids of the mammary gland. A proteomic screen of MMP3-binding partners surprisingly revealed that the intracellular chaperone heat-shock protein 90 β (HSP90β) is present extracellularly, and its interaction with the hemopexin domain of MMP3 is critical for invasion. Blocking of HSP90β with inhibitory antibodies added to the medium abolished invasion and branching. These findings shift the focus from the proteolytic activity of MMP3 as the central player to its hemopexin domain and add a new dimension to HSP90β's functions by revealing a hitherto undescribed mechanism of MMP3 regulation. Our data also may shed light on the failure of strategies to use MMP inhibitors in cancer treatment and other related disorders. © 2013 by Cold Spring Harbor Laboratory Press.


Goncalves A.P.,Abel Salazar Biomedical Sciences Institute
G3 (Bethesda, Md.) | Year: 2014

We pinpoint CZT-1 (cell death-activated zinc cluster transcription factor) as a novel transcription factor involved in tolerance to cell death induced by the protein kinase inhibitor staurosporine in Neurospora crassa. Transcriptional profiling of staurosporine-treated wild-type cells by RNA-sequencing showed that genes encoding the machinery for protein synthesis are enriched among the genes repressed by the drug. Functional category enrichment analyses also show that genes encoding components of the mitochondrial respiratory chain are downregulated by staurosporine, whereas genes involved in endoplasmic reticulum activities are upregulated. In contrast, a staurosporine-treated Δczt-1 deletion strain is unable to repress the genes for the respiratory chain and to induce the genes related to the endoplasmic reticulum, indicating a role for CZT-1 in the regulation of activity of these organelles. The Δczt-1 mutant strain displays increased reactive oxygen species accumulation on insult with staurosporine. A genome-wide association study of a wild population of N. crassa isolates pointed out genes associated with a cell death role of CZT-1, including catalase-1 (cat-1) and apoptosis-inducing factor-homologous mitochondrion-associated inducer of death 2 (amid-2). Importantly, differences in the expression of czt-1 correlates with resistance to staurosporine among wild isolate strains. Our results reveal a novel transcription factor that regulates drug resistance and cell death in response to staurosporine in laboratory strains as well as in wild isolates of N. crassa. Copyright © 2014 Gonçalves et al.


Silva K.,Abel Salazar Biomedical Sciences Institute | De Sousa L.,Abel Salazar Biomedical Sciences Institute
Biology Letters | Year: 2011

Empathy has long attracted the attention of philosophers and psychologists, and more recently, of evolutionary biologists. Interestingly, studies suggest that empathy is a phylogenetically continuous phenomenon, ranging across animals from automatic emotional activation in response to the emotions of others, to perspective-taking that becomes increasingly complex with increasing brain size. Although suggestions have been made that the domestic dog may have the capacity to empathize with humans, no discussion has yet addressed the topic, nor have experimental routes been proposed to further explore the level of emotional and cognitive processing underlying dogs' seemingly empathic behaviour towards humans. In this opinion piece, we begin by contextualizing our topic of interest within the larger body of literature on empathy. Thereafter we: (i) outline the reasons for why we believe dogs may be capable of empathizing with humans, perhaps even at some level beyond emotional contagion; (ii) review available evidence both pro and against our opinion; and (iii) propose routes for future studies to accurately address the topic. Also, we consider the use of dogs to further explore open questions regarding empathy in humans. © 2011 The Royal Society.


Tomas A.M.,University of Porto | Tomas A.M.,Abel Salazar Biomedical Sciences Institute | Castro H.,University of Porto
Antioxidants and Redox Signaling | Year: 2013

Significance: In the single mitochondrion of protozoan trypanosomatid parasites there are several sites for the generation and elimination of reactive oxygen species (ROS), a class of molecules that exhibit a dual role in cells, either as regulatory mediators or as cytotoxic effectors. Recent Advances: Formation of ROS in trypanosomatid mitochondria can be induced by various drug compounds. Importantly, it can also be triggered by specific physiologic stimuli, indicating that this phenomenon may occur in living parasites as well. Elimination of ROS in these organelles is attributed to the activity of two iron-dependent superoxide dismutases (FeSODs) and up to three different peroxidases (a cytochrome c peroxidase and two thiol peroxidases). Critical Issues: Data regarding the formation of ROS in trypanosomatid mitochondria are limited and nonsystematic. Another critical issue refers to the exact contribution of mitochondrial FeSODs and peroxidases for ROS removal, given that their antioxidant activity is not essential when abrogated individually. This suggests some level of functional overlapping or that ROS produced in mitochondria under normal conditions can be removed noncatalytically. Also still unsolved is the mechanism by which mitochondrial thiol peroxidases are regenerated to their reduced (active) form. Future Directions: The production of intramitochondrial ROS under physiologic conditions and their implication in parasite biology should be further clarified. The relative importance of enzymatic versus nonenzymatic mechanisms for ROS elimination in trypanosomatid mitochondria also requires investigation. Simultaneous depletion of several redundant antioxidant enzymes and determination of noncatalytic antioxidants are possible ways to achieve this. Antioxid. Redox Signal. 19, 696-707. © Copyright 2013, Mary Ann Liebert, Inc. 2013.


Magalhaes J.,Abel Salazar Biomedical Sciences Institute | Saraiva M.J.,Abel Salazar Biomedical Sciences Institute
Journal of Neuropathology and Experimental Neurology | Year: 2011

Extracellular chaperones such as clusterin may contribute to extracellular protein homeostasis in neurodegenerative disorders. It has been implicated in fibrillogenesis and extracellular misfolded protein clearance in Alzheimer disease. We investigated the localization and potential functions of clusterin in familial amyloidotic polyneuropathy (FAP), a neurodegenerative disorder characterized by extracellular deposition of mutant transthyretin (TTR) in the peripheral nervous system. We observed increased clusterin expression in human FAP nerves, in the dorsal root ganglia of mutant TTR transgenic mice with TTR deposition, and in human neuroblastoma cells incubated with oligomeric TTR. Clusterin colocalized with extracellular TTR aggregates in human FAP nerves and was detected in aggregates extracted from FAP tissues. Abolition of clusterin expression using small interfering RNA in a HEK293 cell line that secretes wild-type TTR resulted in increased TTR aggregation in the medium, thus suggesting a protective role for clusterin in inhibition of TTR aggregation. However, under the conditions examined, toxicity of oligomeric TTR in neuroblastoma cells was unaltered by clusterin gene silencing. These data suggest that clusterin can influence TTR aggregation but may not modulate TTR aggregate toxicity or play a role in TTR clearance in FAP. Further studies will elucidate neuroprotective mechanisms conferred by clusterin in FAP and other neurodegenerative diseases. Copyright © 2011 by the American Association of Neuropathologists, Inc.


Barreira Da Silva R.,University of Zürich | Barreira Da Silva R.,Abel Salazar Biomedical Sciences Institute | Munz C.,University of Zürich
Cellular and Molecular Life Sciences | Year: 2011

Natural killer (NK) cells have originally been identified by their spontaneous cytolytic potential against tumor cells, which, however, might result from pre-activation due to prior pathogen exposure. Resting NK cells, on the contrary, require activation by bystander antigen-presenting cells to reach their full functional competence. In this review, we will summarize studies on how dendritic cells (DCs), the most potent type of antigen-presenting cell, communicate with human NK cells to activate them in secondary lymphoid organs and to integrate signals from activated NK cells at sites of inflammation for their own maturation. Furthermore, we will review aspects of the immunological synapse, which mediates this cross-talk. These studies provide the mechanistic understanding of how mature DCs can activate NK cells and survive to go on for the activation of adaptive immunity. This feature of DCs, to activate different waves of immune responses, could be harnessed for immunotherapies, including vaccinations. © 2011 Springer Basel AG.


Bidarra S.J.,University of Porto | Barrias C.C.,University of Porto | Granja P.L.,University of Porto | Granja P.L.,Abel Salazar Biomedical Sciences Institute
Acta Biomaterialia | Year: 2014

Alginate hydrogels are extremely versatile and adaptable biomaterials, with great potential for use in biomedical applications. Their extracellular matrix-like features have been key factors for their choice as vehicles for cell delivery strategies aimed at tissue regeneration. A variety of strategies to decorate them with biofunctional moieties and to modulate their biophysical properties have been developed recently, which further allow their tailoring to the desired application. Additionally, their potential use as injectable materials offers several advantages over preformed scaffold-based approaches, namely: Easy incorporation of therapeutic agents, such as cells, under mild conditions; minimally invasive local delivery; and high contourability, which is essential for filling in irregular defects. Alginate hydrogels have already been explored as cell delivery systems to enhance regeneration in different tissues and organs. Here, the in vitro and in vivo potential of injectable alginate hydrogels to deliver cells in a targeted fashion is reviewed. In each example, the selected crosslinking approach, the cell type, the target tissue and the main findings of the study are highlighted. © 2013 Acta Materialia Inc.


Vieira M.,Abel Salazar Biomedical Sciences Institute | Saraiva M.J.,IBMC Institute Biologia Molecular e Celular
FEBS Letters | Year: 2013

Transthyretin is the carrier protein of thyroxine and retinol in plasma and cerebrospinal fluid and has been described also as a neuroprotective molecule. 14-3-3 Proteins are very important in many cellular processes, being their absence related with deficits in memory and learning. The analysis of the relationship between these two proteins is the main objective of this work. We found that hippocampi of young TTR null mice presented lower levels of 14-3-3ζ protein, but no changes in gene expression when compared to TTR wild type littermates were noted. Cellular studies ascribed this finding to increased degradation of 14-3-3ζ in lysosomes in the absence of TTR, increasing autophagy. © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.


Morais-De-Sa E.,Institute Biologia Molecular e Celular IBMC | Sunkel C.,Institute Biologia Molecular e Celular IBMC | Sunkel C.,Abel Salazar Biomedical Sciences Institute
EMBO Reports | Year: 2013

Cytokinesis is asymmetric along the apical-basal axis of epithelial cells, positioning the midbody near the apical domain. However, little is known about the mechanism and purpose of this asymmetry. We use live imaging of Drosophila follicle cell division to show that asymmetric cytokinesis does not result from intrinsic polarization of the main contractile ring components. We show that adherens junctions (AJs) maintain close contact with the apical side of the contractile ring during cytokinesis. Asymmetric distribution of AJ components within follicle cells and in the otherwise unpolarized S2 cells is sufficient to recruit the midbody, revealing that asymmetric cytokinesis is determined by apical AJs in the epithelia. We further show that ectopic midbody localization induces epithelial invaginations, shifting the position of the apical interface between daughter cells relative to the AB axis of the tissue. Thus, apical midbody localization is essential to maintain epithelial tissue architecture during proliferation. © 2013 European Molecular Biology Organization.

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