To identify mesenchymal stromal cells (MSC) from degenerate human nucleus pulposus (NP) and compare them with bone marrow (BM) MSC.
To test whether MSC obtained from NP and BM from the same subjects ...share similar biologic characteristics.
Recent studies have proposed biologic strategies for the treatment of intervertebral disc degeneration, including cell therapy. Bone marrow (BM) MSC could be an attractive approach to restore disc function, and there is evidence that NP may contain MSC-like cells.
Tissue samples were obtained from degenerate lumbar NP and from iliac crest of the same 16 patients with degenerative disc diseases, undergoing discectomy and fusion procedures. MSC isolated from both sources were compared regarding their expansion time, immunophenotype, differentiation ability, and molecular analysis.
In all cases, MSC from NP were isolated and expanded. They fulfil nearly all morphological, inmunophenotypical, and differentiation criteria described by the International Society of Cell Therapy for MSC, with the exception that NP-MSC are not able to differentiate into adipocytes. Slight differences were observed with BM-MSC from the same subjects.
The NP contains mesenchymal stem cells. These cells were quite similar to mesenchymal stem cells from BM, with the exception of their adipogenic differentiation ability. These findings suggest that we may treat intervertebral disc degeneration by cell therapy (MSC from BM) and by stimulating endogenous MSC from NP.
The Ypd1 phosphorelay protein is a central constituent of fungal two-component signal transduction pathways. Inhibition of Ypd1 in Saccharomyces cerevisiae and Cryptococcus neoformans is lethal due ...to the sustained activation of the 'p38-related' Hog1 stress-activated protein kinase (SAPK). As two-component signalling proteins are not found in animals, Ypd1 is considered to be a prime antifungal target. However, a major fungal pathogen of humans, Candida albicans, can survive the concomitant sustained activation of Hog1 that occurs in cells lacking YPD1. Here we show that the sustained activation of Hog1 upon Ypd1 loss is mediated through the Ssk1 response regulator. Moreover, we present evidence that C. albicans survives SAPK activation in the short-term, following Ypd1 loss, by triggering the induction of protein tyrosine phosphatase-encoding genes which prevent the accumulation of lethal levels of phosphorylated Hog1. In addition, our studies reveal an unpredicted, reversible, mechanism that acts to substantially reduce the levels of phosphorylated Hog1 in ypd1Δ cells following long-term sustained SAPK activation. Indeed, over time, ypd1Δ cells become phenotypically indistinguishable from wild-type cells. Importantly, we also find that drug-induced down-regulation of YPD1 expression actually enhances the virulence of C. albicans in two distinct animal infection models. Investigating the underlying causes of this increased virulence, revealed that drug-mediated repression of YPD1 expression promotes hyphal growth both within murine kidneys, and following phagocytosis, thus increasing the efficacy by which C. albicans kills macrophages. Taken together, these findings challenge the targeting of Ypd1 proteins as a general antifungal strategy and reveal novel cellular adaptation mechanisms to sustained SAPK activation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
El viaje es un tema fundamental en la cultura decimonónica. Junto a los posibles itinerarios reales se despliegan, ante el caminante, trayectos imaginarios, nocturnos, iniciáticos, marcados por el ...terror y la desesperanza. Desde los mundos inferiores hasta el cielo, pasando por la travesía de la muerte, el viajero recorre cárceles y cuevas, infiernos y tumbas, en un camino que conduce al viandante hacía el más allá.
Una de las cuestiones más controvertidas en relación a la aplicación de las normas de competencia a empresas pluricorporativas es la eventual utilización del principio de unidad económica como vía de ...extensión de responsabilidad entre las distintas sociedades. Actualmente, asistimos a una nueva inquietud que valora la extensión de responsabilidad aguas abajo, es decir, la posible legitimación pasiva de la filial para soportar el ejercicio de una acción follow on por una infracción cometida por su matriz y por la que ella no ha sido sancionada. La cuestión es objeto de un encendido debate doctrinal y judicial entre defensores de una responsabilidad del grupo como tal y posturas más apegadas a las categorías tradicionales de imputación de responsabilidad. El objeto de este trabajo es el examen de dicho debate y la valoración crítica de las diferentes posiciones y argumentos utilizados.
Tomando como punto de partida el marco teórico de la decolonialidad (Quijano, Mignolo, Maldonado-Torres y Walsh), este ensayo examina las complejas relaciones de poder que se presentan en el ...largometraje Palmeras en la nieve (2015), dirigido por Fernando González Molina, que está basado en la novela homónima de Luz Gabás. El artículo sostiene que el legado colonial que se proyecta en el drama épico del pasado pervive en la colonialidad que permea los conflictos dramáticos del presente histórico que se narra en el largometraje; una colonialidad que tiñe las actitudes ideológicas, éticas y culturales relacionadas con el pasado colonial español en Guinea Ecuatorial.
Using the theoretical framework of (de)coloniality (Quijano, Mignolo, Maldonado-Torres and Walsh), this article analyses the interrelatedness of colonial and decolonial discourses in Fernando González Molina’s Palmeras en la nieve (2015), a film based on Luz Gabás’s novel. This article argues that the historical epic drama exposes how colonial legacy continues in the coloniality that permeates conflicts located in the parts of the film set in the present day. Coloniality stains the ideological, ethical, and cultural attitudes related to the Spanish colonial past in Equatorial Guinea.
Previous deception research on repeated interviews found that liars are not less consistent than truth tellers, presumably because liars use a "repeat strategy" to be consistent across interviews. ...The goal of this study was to design an interview procedure to overcome this strategy. Innocent participants (truth tellers) and guilty participants (liars) had to convince an interviewer that they had performed several innocent activities rather than committing a mock crime. The interview focused on the innocent activities (alibi), contained specific central and peripheral questions, and was repeated after 1 week without forewarning. Cognitive load was increased by asking participants to reply quickly. The liars' answers in replying to both central and peripheral questions were significantly less accurate, less consistent, and more evasive than the truth tellers' answers. Logistic regression analyses yielded classification rates ranging from around 70% (with consistency as the predictor variable), 85% (with evasive answers as the predictor variable), to over 90% (with an improved measure of consistency that incorporated evasive answers as the predictor variable, as well as with response accuracy as the predictor variable). These classification rates were higher than the interviewers' accuracy rate (54%).
In the context of an epidemiological study carried out by several wildlife recovery centers in Spain, trichomonads resembling Trichomonas gallinae were found in the oropharyngeal cavity of 2 Egyptian ...vultures (Neophron percnopterus) and 14 cinereous vultures (Aegypius monachus) which did not show any symptoms of trichomonosis. In order to characterize them, these isolates along with seven other T. gallinae isolates obtained from different hosts and from different geographical origin were analyzed. Genetic analyses were performed by sequencing the small subunit ribosomal RNA (SSU-rRNA) and the internal transcribed spacers (ITS1 and ITS2) and the 5.8S rRNA regions. The morphological study of the isolates in both light and scanning electron microscopy was also performed. The sequences obtained in the genetic analysis coincide with previously published sequences of an isolate named as Trichomonas sp., obtained from a bearded vulture (Gypaetus barbatus), and showed clear differences to the T. gallinae sequences (97 and 90–91 % homology, respectively, for SSU-rRNA and ITS regions) and display higher similarity with Trichomonas vaginalis and Trichomonas stableri than with T. gallinae. Multivariate statistical analysis of the morphometric study also reveals significant differences between the trichomonads of vultures and the isolates of T. gallinae. The isolates from vultures presented smaller values for each variable except for the length of axostyle projection, which was higher. These results together with the different nature of their hosts suggest the possibility of a new species of trichomonad which we hereby name Trichomonas gypaetinii, whose main host are birds of the subfamily Gypaetinae.
Vascular microthrombotic lesions in lupus nephritis with or without antiphospholipid antibodies may relate to worse renal outcomes. Whether microthrombotic lesions are a consequence of renal ...inflammation or independently contribute to renal damage is unclear. Our aim was to investigate the relationship between microthrombotic renal vascular lesions and nephritis progression in MRL/lpr mice.
MRL/lpr mice were analyzed for the presence of renal microvascular, glomerular and tubulointerstitial lesions and the effect of anti-aggregation (aspirin or clopidogrel) and dexamethasone on renal clinical and pathological manifestations was evaluated. Intravascular platelet aggregates (CD41), peri- (F4/80), and intraglomerular (Mac-2) macrophage infiltration, and C3 deposition were quantified by immunohistochemistry. Renal function was assessed by measuring proteinuria, and serum levels of creatinine and albumin. Anti-dsDNA and anti-cardiolipin antibodies, and thromboxane B2 levels were quantified by ELISA.
Frequency of microthrombotic renal lesions in MRL/lpr mice was high and was associated with immune-mediated renal damage. Proteinuria positively correlated with glomerular macrophage infiltration and was higher in mice with proliferative glomerular lesions. All mice had detectable anti-dsDNA and anti-cardiolipin IgG, regardless the presence of microthrombosis. Proteinuria and glomerular macrophage infiltration were significantly reduced in all treatment groups. Dexamethasone and platelet anti-aggregation similarly reduced glomerular damage and inflammation, but only platelet anti-aggregation significantly reduced anti-cardiolipin antibodies, renal complement deposition and thromboxane B2 levels.
Platelet anti-aggregation reduced renal inflammatory damage, renal complement deposition, anti-cardiolipin antibodies, and thromboxane B2 levels and in MRL/lpr mice, suggesting that platelet activation has a pathogenic effect on immune-mediated nephritis. Our results point to MRL/lpr mice with lupus nephritis as an appropriate model to analyze the potential impact of anti-thrombotic intervention on renal inflammation.
Vitamin K antagonists (VKA) are the most widely used anticoagulants for the prevention of thrombotic events. Several renal adverse effects have been associated with the use of VKA. The main aim of ...our study was to explore the association between international normalized ratio (INR) levels and microscopic hematuria in patients with VKA.
We performed a cross-sectional study of patients treated with VKA that attended the outpatient clinic for routine INR control. A simple urinalysis was performed on the day of the INR control and the precise number of red cells in the urine sediment was quantified. Demographic data, kidney function tests, comorbidities, anticoagulant dose and concomitant treatment were registered.
A total of 337 patients were included with median INR levels of 2.6 (IQR 2.1-3.3). 11.9% of the patients presented microscopic hematuria (≥14 RBCs/µl). There was a significant correlation between INR levels and the number of red blood cells in the urine sediment (r = 0.201, p = 0.024). In the univariate analysis, microscopic hematuria was associated with having an INR >3.5 (19% vs. 10.2%, p = 0.046), bacteriuria (15.2% vs. 3.6%, p = 0.015), leukocyturia (14.8% vs. 6.6%, p = 0.026), hypertension (16.2% vs. 9.5%, p = 0.053), and the use of renin-angiotensin system (RAS) blockers (6.9% vs. 17.2%, p = 0.004). Multivariate logistic regression showed an association between microscopic hematuria and RAS blockade (OR 0.38, CI 95% 0.163-0.886, p = 0.025), independent from INR levels, hypertension, leukocyturia or bacteriuria.
INR overdose was significantly associated with the presence of microscopic hematuria. RAS blockade is an independent protective factor for the presence of microscopic hematuria in anticoagulated patients.
Introduction
The ability of mesenchymal stromal cells (MSC) to suppress T‐cell function has prompted their therapeutic use for graft‐versus‐host disease (GVHD) control. However, as MSC also modulate ...the activity of NK cells, which play an important role in graft‐versus‐leukemia (GVL) reaction, their administration could hamper this beneficial effect of allogeneic hematopoietic stem cell transplantation. MSC can be expanded from several sources, especially bone marrow and fat, but it is not well established if the cell source makes a difference in their immunoregulatory capacity.
Objective
The aim of this study was to compare the immunomodulatory effect of MSC derived from bone marrow (BM‐CSM) or adipose tissue (AT‐MSC) on NK cells, to determine whether the use of MSC from one or the other origin could be more favorable to preserve NK cell activity and, therefore, GVL.
Methods
Human NK cells were stimulated with IL‐15 in the presence of BM‐MSC or AT‐MSC. The effect of both MSC populations on NK cell proliferation, cell cycle progression, and CD56 expression was analyzed by flow cytometry. Cytokine secretion was measured by ELISA, and cytotoxic activity was assessed by calcein release assays.
Results
Although both BM‐MSC and AT‐MSC induced a similar inhibition of NK cell proliferation, only BM‐MSC decreased significantly NK cell cytotoxic activity and showed a trend for a higher reduction of IFN‐γ secretion.
Conclusion
These results suggest that, in the context of GVHD inhibition, the use of AT‐MSC rather than BM‐MSC could further preserve NK cell activity and, thus, favor GVL.
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