Abel Salazar Biomedical Sciences Institute

Porto, Portugal

Abel Salazar Biomedical Sciences Institute

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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Vasconcelos T.,BIAL Portela and Ca S.A. | Vasconcelos T.,Abel Salazar Biomedical Sciences Institute | Vasconcelos T.,University of Porto | Marques S.,University of Porto | And 3 more authors.
Advanced Drug Delivery Reviews | Year: 2016

Amorphous products and particularly amorphous solid dispersions are currently one of the most exciting areas in the pharmaceutical field. This approach presents huge potential and advantageous features concerning the overall improvement of drug bioavailability.Currently, different manufacturing processes are being developed to produce amorphous solid dispersions with suitable robustness and reproducibility, ranging from solvent evaporation to melting processes. In the present paper, laboratorial and industrial scale processes were reviewed, and guidelines for a rationale selection of manufacturing processes were proposed. This would ensure an adequate development (laboratorial scale) and production according to the good manufacturing practices (GMP) (industrial scale) of amorphous solid dispersions, with further implications on the process validations and drug development pipeline. © 2016 Elsevier B.V.


Monteiro M.P.,Abel Salazar Biomedical Sciences Institute | Monteiro M.P.,University College London | Batterham R.L.,University College London
Gastroenterology | Year: 2017

The gastrointestinal tract, the key interface between ingested nutrients and the body, plays a critical role in regulating energy homeostasis. Gut-derived signals convey information regarding incoming nutrients to the brain, initiating changes in eating behavior and energy expenditure, to maintain energy balance. Here we review hormonal, neural, and nutrient signals emanating from the gastrointestinal tract and evidence for their role in controlling feeding behavior. Mechanistic studies that have utilized pharmacologic and/or transgenic approaches targeting an individual hormone/mediator have yielded somewhat disappointing body weight changes, often leading to the hormone/mediator in question being dismissed as a potential obesity therapy. However, the recent finding of sustained weight reduction in response to systemic administration of a long-acting analog of the gut-hormone glucagon-like peptide-1 highlights the therapeutic potential of gut-derived signals acting via nonphysiologic mechanisms. Thus, we also review therapeutics strategies being utilized or developed to leverage gastrointestinal signals in order to treat obesity. © 2017 AGA Institute


Torres C.,Abel Salazar Biomedical Sciences Institute
Blood Coagulation and Fibrinolysis | Year: 2017

: To evaluate the plasma levels of soluble endothelial cell molecules in patients with venous thromboembolism (VTE) out of the acute phase as compared with healthy individuals. We also investigated the possible associations of the soluble endothelial cell molecules among them, as well as with other clinical and laboratory data, including the numbers of circulating endothelial cells (CEC), circulating endothelial progenitor cells (CEP), and CEC expressing activation-related [cluster of differentiation (CD)54 and CD62E] and procoagulant (CD142) markers. In total, 15 patients with VTE and 20 normal individuals were studied. The CEC and CEP were quantified and characterized by flow cytometry. The soluble molecules studied included P-selectin, E-selectin, intercellular cell adhesion molecule 1, vascular cell adhesion molecule 1 and tissue factor (ELISA), and von Willebrand factor antigen (immunoturbidimetry). VTE patients had significantly higher levels of vascular cell adhesion molecule 1 and von Willebrand factor antigen and lower levels of soluble E-selectin than controls. They also showed significantly higher numbers of CEC, as of activated/procoagulant CEC and lower numbers of CEP, compared with controls. We did not find any correlation between the levels of soluble molecules and the numbers of endothelial cell in circulation, but there was with several clinical and laboratory data in VTE patients. Our results would suggest that in VTE patients, the endothelium remains activated and in some hypercoagulable state. The levels of soluble endothelial cell molecules did not seem to be directly related to the numbers of CEC and CEP neither reflected the number of activated CEC, which may be because of the different function that surface and soluble molecules may have. Copyright © 2017 YEAR Wolters Kluwer Health, Inc. All rights reserved.


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.


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.


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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