Editorial: Glial plasticity in depression

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Microtubule Depolymerization Potentiates Alpha-Synuclein Oligomerization

Parkinson's disease (PD) is associated with perturbed mitochondria function and alpha-synuclein fibrillization. We evaluated potential mechanistic links between mitochondrial dysfunction and alpha-synuclein aggregation. We studied a PD cytoplasmic hybrid (cybrid) cell line in which platelet mitochondria from a PD subject were transferred to NT2 neuronal cells previously depleted of endogenous mitochondrial DNA. Compared to a control cybrid cell line, the PD line showed reduced ATP levels, an increased free/polymerized tubulin ratio, and alpha-synuclein oligomer accumulation. Taxol (which stabilizes microtubules) normalized the PD tubulin ratio and reduced alpha-synuclein oligomerization. A nexus exists between mitochondrial function, cytoskeleton homeostasis, and alpha-synuclein oligomerization. In our model, mitochondrial dysfunction triggers an increased free tubulin, which destabilizes the microtubular network and promotes alpha-synuclein oligomerization

Increased responsiveness of murine eosinophils to MIPâ 1β (CCL4) and TCAâ 3 (CCL1) is mediated by their specific receptors, CCR5 and CCR8

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141970/1/jlb1019.pd

The role of CCL22 (MDC) for the recruitment of eosinophils during allergic pleurisy in mice

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142274/1/jlb0356.pd

Scaffolding strategies for tissue engineering and regenerative medicine applications

During the past two decades, tissue engineering and the regenerative medicine field have invested in the regeneration and reconstruction of pathologically altered tissues, such as cartilage, bone, skin, heart valves, nerves and tendons, and many others. The 3D structured scaffolds and hydrogels alone or combined with bioactive molecules or genes and cells are able to guide the development of functional engineered tissues, and provide mechanical support during in vivo implantation. Naturally derived and synthetic polymers, bioresorbable inorganic materials, and respective hybrids, and decellularized tissue have been considered as scaffolding biomaterials, owing to their boosted structural, mechanical, and biological properties. A diversity of biomaterials, current treatment strategies, and emergent technologies used for 3D scaffolds and hydrogel processing, and the tissue-specific considerations for scaffolding for Tissue engineering (TE) purposes are herein highlighted and discussed in depth. The newest procedures focusing on the 3D behavior and multi-cellular interactions of native tissues for further use for in vitro model processing are also outlined. Completed and ongoing preclinical research trials for TE applications using scaffolds and hydrogels, challenges, and future prospects of research in the regenerative medicine field are also presented.This research was funded by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) (NORTE-01-0145-FEDER-000023) and by the Portuguese Foundation for Science and Technology ((M-ERA-NET/0022/2016), Transitional Rule DL 57/2016 (CTTI-57/18-I3BS(5)), and (IF/01285/2015))

The nonpolymorphic MHC Qa-1b mediates CD8+ T cell surveillance of antigen-processing defects

The nonclassical major histocompatibility complex (MHC) Qa-1b accommodates monomorphic leader peptides and functions as a ligand for germ line receptors CD94/NKG2, which are expressed by natural killer cells and CD8+ T cells. We here describe that the conserved peptides are replaced by a novel peptide repertoire of surprising diversity as a result of impairments in the antigen-processing pathway. This novel peptide repertoire represents immunogenic neoantigens for CD8+ T cells, as we found that these Qa-1b–restricted T cells dominantly participated in the response to tumors with processing deficiencies. A surprisingly wide spectrum of target cells, irrespective of transformation status, MHC background, or type of processing deficiency, was recognized by this T cell subset, complying with the conserved nature of Qa-1b. Target cell recognition depended on T cell receptor and Qa-1b interaction, and immunization with identified peptide epitopes demonstrated in vivo priming of CD8+ T cells. Our data reveal that Qa-1b, and most likely its human homologue human leukocyte antigen-E, is important for the defense against processing-deficient cells by displacing the monomorphic leader peptides, which relieves the inhibition through CD94/NKG2A on lymphocytes, and by presenting a novel repertoire of immunogenic peptides, which recruits a subset of cytotoxic CD8+ T cells

Posterior talar process as a suitable cell source for treatment of cartilage and osteochondral defects of the talus

Osteochondral defects of the ankle are common lesions affecting the talar cartilage and subchondral bone. Current treatments include cell-based therapies but are frequently associated with donor-site morbidity. Our objective is to characterize the posterior process of the talus (SP) and the os trigonum (OT) tissues and investigate its potential as a new source of viable cells for application in tissue engineering and regenerative medicine.SP and OT tissues obtained from six patients were characterized by micro-computed tomography, and histological, histomorphometric and immunohistochemical analyses. Isolated cells proliferation and viability were evaluated by MTS assay, DNA quantification and Live/Dead staining. The TUNEL assay was performed to evaluate cell death by apoptosis. Moreover, the production of extracellular matrix was evaluated by toluidine blue staining, whereas cells phenotype was investigated by flow cytometry. Ankle explants characterization showed the presence of a cartilage tissue layer in both SP and OT tissues, which represent, at least 20% in average of the explant. The presence of type II collagen was detected in the extracellular matrix. Isolated cells presented a round morphology typical of chondrocytes. In in vitro studies, cells were viable and proliferating up to 21 days of culturing. No signs of apoptosis were detected. Flow cytometry analysis revealed that isolated cells maintained the expression of several chondrocytic markers during culturing. The results indicate that the SP and OT tissues are a reliable source of viable chondrocytes, which can find promising applications in ACI/MACI strategies with minimal concerns regarding donor zone complications.Portuguese Foundation for Science and Technology (FCT) through the project OsteoCart (Grant No. PTDC/CTM-BPC/115977/2009), Fundación MAPFRE (Ayudas a la Investigación Ignacio H. de Larramendi, Prevención, Salud y Medio Ambiente, Spain) under the project 'Preventing the progression of the knee osteoarthritis: advanced therapies combining injectable hydrogels, autologous stem cells and PRP' (Grant No. BIL/13/SA/235). This study was also carried out with the support of Fundo Europeu de Desenvolvimento Regional (FEDER) through Programa Operacional do Norte through the project Articulate (Grant No. 23189

Anatomy Teaching at the School of Health Sciences of University of Minho

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