1,720,983 research outputs found
Not all pericytes are born equal: Pericytes from human adult tissues present different differentiation properties
Full text linkPericytes (PCs) have been recognized for a long time only as structural cells of the blood vessels. The identification of tight contacts with endothelial cells and the ability to interact with surrounding cells through paracrine signaling revealed additional functions of PCs in maintaining the homeostasis of the perivascular environment. PCs got the front page, in the late 1990s, after the identification and characterization of a new embryonic cell population, the mesoangioblasts, from which PCs present in the adult organism are thought to derive. From these studies, it was clear that PCs were also endowed with multipotent mesodermal abilities. Furthermore, their ability to cross the vascular wall and to reconstitute skeletal muscle tissue after systemic injection opened the way to a number of studies aimed to develop therapeutic protocols for a cell therapy of muscular dystrophy. This has resulted in a major effort to characterize pericytic cell populations from skeletal muscle and other adult tissues. Additional studies also addressed their relationship with other cells of the perivascular compartment and with mesenchymal stem cells. These data have provided initial evidence that PCs from different adult tissues might be endowed with distinctive differentiation abilities. This would suggest that the multipotent mesenchymal ability of PCs might be restrained within different tissues, likely depending on the specific cell renewal and repair requirements of each tissue. This review presents current knowledge on human PCs and highlights recent data on the differentiation properties of PCs isolated from different adult tissues
Mesenchymal stem cells: from the perivascular environment to clinical applications
Full text linkAdult stem cells represent a fundamental biological system that has fascinated scientists over the last decades, and are currently the subject of a large number of studies aimed at better defining the properties of these cells, with a prominent focus on improving their application in regenerative medicine. One of the most used adult stem cells in clinical trials are mesenchymal stem cells (MSCs), which are multipotent cells able to differentiate into mature cells of mesodermal lineages. Following the initial studies on MSCs isolated from bone marrow, similar cells were also isolated from a variety of fetal and adult human tissues. Initially considered as identical and equipotent, MSCs from tissues other than bone marrow actually display differences in terms of their plastic abilities, which can be ascribed to the tissue of origin and/or to the procedures used for their isolation. Moreover, results from additional studies suggest that cultured MSCs represent the in vitro version of a subset of in vivo resident cells localized in the perivascular environment. In this review, we will focus our attention on MSCs from tissues other than bone marrow, their in vivo localization and their current applications in clinics
TAM-associated CASQ1 mutants diminish intracellular Ca2+ content and interfere with regulation of SOCE
Full text linkTubular aggregate myopathy (TAM) is a rare myopathy characterized by muscle weakness and myalgia. Muscle fibers from TAM patients show characteristic accumulation of membrane tubules that contain proteins from the sarcoplasmic reticulum (SR). Gain-of-function mutations in STIM1 and ORAI1, the key proteins participating in the Store-Operated Ca2+ Entry (SOCE) mechanism, were identified in patients with TAM. Recently, the CASQ1 gene was also found to be mutated in patients with TAM. CASQ1 is the main Ca2+ buffer of the SR and a negative regulator of SOCE. Previous characterization of CASQ1 mutants in non-muscle cells revealed that they display altered Ca2+dependent polymerization, reduced Ca2+storage capacity and alteration in SOCE inhibition. We thus aimed to assess how mutations in CASQ1 affect calcium regulation in skeletal muscles, where CASQ1 is naturally expressed. We thus expressed CASQ1 mutants in muscle fibers from Casq1 knockout mice, which provide a valuable model for studying the Ca2+ storage capacity of TAM-associated mutants. Moreover, since Casq1 knockout mice display a constitutively active SOCE, the effect of CASQ1 mutants on SOCE inhibition can be also properly examined in fibers from these mice. Analysis of intracellular Ca2+ confirmed that CASQ1 mutants have impaired ability to store Ca2+and lose their ability to inhibit skeletal muscle SOCE; this is in agreement with the evidence that alterations in Ca2+entry due to mutations in either STIM1, ORAI1 or CASQ1 represents a hallmark of TAM. © The Author(s) 2024
The potential of obscurin as a therapeutic target in muscle disorders
No full textIntroduction: Obscurin, a giant protein of striated muscles, is emerging as an important player in a wide range of processes including myofibril assembly and maintenance, muscle protein degradation and intracellular signaling. Accordingly, obscurin participates to the mechanisms by which muscles adapt to physiological requirements or to pathological cues associated with cardiac and skeletal muscle diseases. Areas covered: The structure of the different obscurin isoforms identified so far, their tissue distribution and the most recent findings on obscurin in invertebrates and mammals will be reviewed. We will provide a synopsis of known molecular interactions between obscurin and other proteins and the biological relevance of these interactions for striated muscle function. The involvement of obscurin in protein degradation mechanisms and intracellular signaling will be also discussed along with initial evidence of a role of obscurin in the pathophysiology of human diseases. Expert opinion: Although still much remains to be discovered about the role of obscurin either as a structural component of the sarcomere or as a mediator of signaling pathways within muscle cells, it can be envisioned that this protein represents an interesting novel pharmacological target for the prevention and treatment of cardiac and skeletal muscle diseases
Multiple regions within junctin drive its interaction with calsequestrin-1 and its localization to triads in skeletal muscle
No full text: Junctin is a transmembrane protein of striated muscles, located at the junctional sarcoplasmic reticulum (SR). It is characterized by a luminal C-terminal tail, through which it functionally interacts with calsequestrin and the ryanodine receptor (RyR). Interaction with calsequestrin was ascribed to the presence of stretches of charged amino acids (aa). However, the regions able to bind calsequestrin have not been defined in detail. We report here that, in non-muscle cells, junctin and calsequestrin assemble in long linear regions within the endoplasmic reticulum, mirroring the formation of calsequestrin polymers. In differentiating myotubes, the two proteins colocalize at triads, where they assemble with other proteins of the junctional SR. By performing GST pull-down assays with distinct regions of the junctin tail, we identified two KEKE motifs that can bind calsequestrin. In addition, stretches of charged aa downstream these motifs were found to also bind calsequestrin and the RyR. Deletion of even one of these regions impaired the ability of junctin to localize at the junctional SR, suggesting that interaction with other proteins at this site represents a key element in junctin targeting
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
p75 neurotrophin receptor is involved in proliferation of undifferentiated mouse embryonic stem cells
No full textNeurotrophins and their receptors are known to play a role in the proliferation and survival of many different cell types of neuronal and non-neuronal lineages. In addition, there is much evidence in the literature showing that the p75 neurotrophin receptor (p75NTR), alone or in association with members of the family of Trk receptors, is expressed in a wide variety of stem cells, although its role in such cells has not been completely elucidated. In the present work we have investigated the expression of p75NTR and Trks in totipotent and pluripotent cells, the mouse pre-implantation embryo and embryonic stem and germ cells (ES and EG cells). p75NTR and TrkA can be first detected in the blastocyst from which ES cell lines are derived. Mouse ES cells retain p75NTR/TrkA expression. Nerve growth factor is the only neurotrophin able to stimulate ES cell growth in culture, without affecting the expression of stem cell markers, alkaline phosphatase, Oct4 and Nanog. Such proliferation effect was blocked by antagonizing either p75NTR or TrkA. Interestingly, immunoreactivity to anti-p75NTR antibodies is lost upon ES cell differentiation. The expression pattern of neurotrophin receptors in murine ES cells differs from human ES cells, that only express TrkB and C, and do not respond to NGF. In this paper we also show that, while primordial germ cells (PGC) do not express p75NTR, when they are made to revert to an ES-like phenotype, becoming EG cells, expression of p75NTR is turned on. © 2009 Elsevier Inc. All rights reserved
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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