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Professional traders need to process a large amount of visual information in their daily activity to judge how risky it is to trade specific investment products. Despite some studies investigating the effects of display clutter on traders, visual attention and memory were never investigated in controlled experimental tasks in this population. Following a preliminary study with 30 participants, visual selective attention and visual working memory were measured and compared between two groups of 15 traders and 15 non-traders (salespeople, acting as a control group) from a large-scale banking group in three experimental tasks measuring selective attention in complex visual contexts, simulating display clutter situations (Visual search), cognitive interference (Stroop task), and a delayed recall visual working memory task. In the Visual search task, traders displayed faster response times (RTs) than non-traders for small display sets, while their performance overlapped for large sets. In the Stroop task, traders showed faster RTs than non-traders but were nevertheless affected by cognitive interference. The memory task highlighted no significant differences between the groups. Therefore, this study found an advantage in traders' attention when processing visual information in small sets with no retention. This result could influence trading activity-determining an immediate use of relevant visual information in decision making-and traders' display layout organization.
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Memoria a Corto Plazo , Humanos , Tiempo de Reacción , Test de StroopRESUMEN
The regulation of the informational flow from the mitochondria to the nucleus (mitonuclear communication) is not fully characterized in the heart. We have determined that mitochondrial ribosomal protein S5 (MRPS5/uS5m) can regulate cardiac function and key pathways to coordinate this process during cardiac stress. We demonstrate that loss of Mrps5 in the developing heart leads to cardiac defects and embryonic lethality while postnatal loss induces cardiac hypertrophy and heart failure. The structure and function of mitochondria is disrupted in Mrps5 mutant cardiomyocytes, impairing mitochondrial protein translation and OXPHOS. We identify Klf15 as a Mrps5 downstream target and demonstrate that exogenous Klf15 is able to rescue the overt defects and re-balance the cardiac metabolome. We further show that Mrps5 represses Klf15 expression through c-myc, together with the metabolite L-phenylalanine. This critical role for Mrps5 in cardiac metabolism and mitonuclear communication highlights its potential as a target for heart failure therapies.
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Insuficiencia Cardíaca , Biosíntesis de Proteínas , Humanos , Cardiomegalia/genética , Cardiomegalia/metabolismo , Insuficiencia Cardíaca/genética , Insuficiencia Cardíaca/metabolismo , Miocitos Cardíacos/metabolismo , Proteínas Mitocondriales/genética , Proteínas Mitocondriales/metabolismoRESUMEN
In this study, we sought to determine the role of tRNA-derived fragments in the regulation of gene expression during skeletal muscle cell proliferation and differentiation. We employed cell culture to examine the function of mt-Ty 5' tiRNAs. Northern blotting, RT-PCR as well as RNA-Seq, were performed to determine the effects of mt-Ty 5' tiRNA loss and gain on gene expression. Standard and transmission electron microscopy (TEM) were used to characterize cell and sub-cellular structures. mt-Ty 5'tiRNAs were found to be enriched in mouse skeletal muscle, showing increased levels in later developmental stages. Gapmer-mediated inhibition of tiRNAs in skeletal muscle C2C12 myoblasts resulted in decreased cell proliferation and myogenic differentiation; consistent with this observation, RNA-Seq, transcriptome analyses, and RT-PCR revealed that skeletal muscle cell differentiation and cell proliferation pathways were also downregulated. Conversely, overexpression of mt-Ty 5'tiRNAs in C2C12 cells led to a reversal of these transcriptional trends. These data reveal that mt-Ty 5'tiRNAs are enriched in skeletal muscle and play an important role in myoblast proliferation and differentiation. Our study also highlights the potential for the development of tiRNAs as novel therapeutic targets for muscle-related diseases.
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Mioblastos Esqueléticos , Ratones , Animales , Línea Celular , Diferenciación Celular , Músculo Esquelético/fisiología , Proliferación CelularRESUMEN
Internal mobility often depends on predicting future job satisfaction, for such employees subject to internal mobility programs. In this study, we compared the predictive power of different classes of models, i.e., (i) traditional Structural Equation Modeling (SEM), with two families of Machine Learning algorithms: (ii) regressors, specifically least absolute shrinkage and selection operator (Lasso) for feature selection and (iii) classifiers, specifically Bagging meta-model with the k-nearest neighbors algorithm (k-NN) as a base estimator. Our aim is to investigate which method better predicts job satisfaction for 348 employees (with operational duties) and 35 supervisors in the training set, and 79 employees in the test set, all subject to internal mobility programs in a large Italian banking group. Results showed average predictive power for SEM and Bagging k-NN (accuracy between 61 and 66%; F1 scores between 0.51 and 0.73). Both SEM and Lasso algorithms highlighted the predictive power of resistance to change and orientation to relation in all models, together with other personality and motivation variables in different models. Theoretical implications are discussed for using these variables in predicting successful job relocation in internal mobility programs. Moreover, these results showed how crucial it is to compare methods coming from different research traditions in predictive Human Resources analytics.
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Mindfulness interventions were shown to be effective in improving well-being and reducing perceived stress in several conditions. These effects were also found in online mindfulness-based training, especially in employees in organizational environments. The aim of this study was to test the effectiveness of an online mindfulness intervention on healthy employees, especially after the first Italian Covid-19 lockdown. Participants in the intervention group underwent an 8-week mindfulness online training program based on the Mindfulness-Based Stress Reduction (MBSR) protocol compared to a control (no-intervention) group. All participants filled in weekly surveys for the whole intervention duration via online questionnaires to measure their habits, mindfulness (FFMQ-15), emotion regulation (ERQ), positive and negative affect (PANAS), depression, anxiety and stress (DASS-21), resilience (RSA) and insomnia (ISI). 69 participants in the intervention group and 63 in the no-treatment control group were considered in the longitudinal analyses. We found significant differences between the intervention and control groups over time in the measures of mindfulness (in particular the nonreactivity subscale), positive affect, depression, and insomnia. Moreover, we found that the frequency of practice and ease perceived in practicing were positively correlated to several indices of well-being (mindfulness, positive affect, cognitive reappraisal) and negatively correlated to several indices of stress (negative affect, depression, anxiety, stress, insomnia, expressive suppression). These results show the importance and effectiveness of online mindfulness training programs to cope with stress among employees, especially after the Covid-19 lockdown.
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COVID-19 , Intervención basada en la Internet , Atención Plena , Trastornos del Inicio y del Mantenimiento del Sueño , Ansiedad/psicología , COVID-19/prevención & control , Control de Enfermedades Transmisibles , Depresión/psicología , Humanos , Atención Plena/métodos , Estrés Psicológico/psicología , Estrés Psicológico/terapiaRESUMEN
How do affect and cognition interact in managerial decision making? Over the last decades, scholars have investigated how managers make decisions. However, what remains largely unknown is the interplay of affective states and cognition during the decision-making process. We offer a systematization of the contributions produced on the role of affect and cognition in managerial decision making by considering the recent cross-fertilization of management studies with the neuroscience domain. We implement a Systematic Literature Review of 23 selected contributions dealing with the role of affect and cognition in managerial decisions that adopted neuroscience techniques/points of view. Collected papers have been analyzed by considering the so-called reflexive (X-) and reflective (C-) systems in social cognitive neuroscience and the type of decisions investigated in the literature. Results obtained help to support an emerging "unified" mind processing theory for which the two systems of our mind are not in conflict and for which affective states have a driving role toward cognition. A research agenda for future studies is provided to scholars who are interested in advancing the investigation of affect and cognition in managerial decision making, also through neuroscience techniques - with the consideration that these works should be at the service of the behavioral strategy field.
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With the present work, we aim to mark a beginning line on the study of decision-making of potential consumers in the insurance sector, with the long-term purpose of defining the optimal cognitive processes to be undertaken when deciding whether to purchase insurance or not. Decision-making in conditions of uncertainty is influenced by the dual-self model doers/planner integrated with the hot-cold states and prospect utility function. Thus, we present a theoretical model of choice-making to evaluate the level of optimal self-control necessary to be exerted if the individual is either in the hot or in the cold state depending on the arousal. This theoretical choice-making model lays the ground for the decision journey by following the long-term utility and avoiding gross mistakes that could lead the consumer not to insure, when the odds suggest doing it, or vice versa, in situations when it would not be necessary.
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Enhancing cognitive memory through virtual reality represents an issue, that has never been investigated in organizational settings. Here, we compared a virtual memoryscape (treatment) - an immersive virtual environment used by subjects as a shared memory tool based on spatial navigation - with respect to the traditional individual-specific mnemonic tool based on the "method of loci" (control). A memory task characterized by high ecological validity was administered to 82 subjects employed by large banking group. Memory recall was measured, for both groups, immediately after the task (Phase 1) and one week later (Phase 2). Results show that (i) in Phase 1, the method of loci was more efficient in terms of recalling information than the to the virtual memoryscape; (ii) in Phase 2, there was no difference. Compared to the method of loci, the virtual memoryscape presents the advantages - relevant for organizations - of being collective, controllable, dynamic, and non-manipulable.
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The frontal alpha asymmetry (FAA) is a neurophysiological measure of motivation and preference. Despite the FAA is associated to commercial pleasantness, conflicting evidence emerged in the literature regarding its relationship with behavior. To study the association between FAA and consumers' decision, we manipulated a commercial script to elicit diverse consumers' attitudes and decisions and to evaluate whether the FAA score is associated to their final investment. A little informative script (S1) was used to polarize consumers' attitudes and investments toward unfavorable scores, while a more personalized message (S2) to elicit in customers a favorable attitude and higher investments. Twenty-one participants listened to the scripts, and their FAA, attitude, and monetary investment were measured. In S1, the FAA did not correlate with neither attitude nor the investment decision, while a robust negative correlation between these variables was found in S2. No other peripheral body and neural measures associated with attitude or final decision. Our data suggest that the FAA correlates with attitude and decision, when a commercial script is customized and provides an adequate information, likely leading the consumer to a more reasoned and planned decision-making process. When facilitating a favorable attitude toward an offer, the negative correlation of FAA and behavior may reflect the involvement of a control system, whose role is to monitor and govern possible conflicts between approach and avoidance motivations. This observation provides additional indication on the value of FAA as a marker of consumer behaviors, and how it could be affected by experimental and contextual bias.
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MicroRNAs (miRNAs) negatively regulate gene expression at the post-transcriptional level, primarily by base-pairing with the 3'-untranslated region (3'-UTR) of their target mRNAs. Many miRNAs are expressed in a tissue/organ-specific manner and are associated with an increasing number of cell proliferation, differentiation, and tissue development events. Cardiac muscle expresses distinct genes encoding structural proteins and a subset of signal molecules that control tissue specification and differentiation. The transcriptional regulation of cardiomyocyte development has been well established, yet only until recently has it been uncovered that miRNAs participate in the regulatory networks. A subset of miRNAs are either specifically or highly expressed in cardiac muscle, providing an opportunity to understand how gene expression is controlled by miRNAs at the post-transcriptional level in this muscle type. miR-1, miR-133, miR-206, and miR-208 have been found to be muscle-specific, and thus have been called myomiRs. The discovery of myomiRs as a previously unrecognized component in the regulation of gene expression adds an entirely new layer of complexity to our understanding of cardiac muscle development. Investigating myomiRs will not only reveal novel molecular mechanisms of the miRNA-mediated regulatory network in cardiomyocyte development, but also raise new opportunities for therapeutic intervention for cardiovascular disease.
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MicroARNs/fisiología , Miocitos Cardíacos/fisiología , Biología de Sistemas , Animales , HumanosRESUMEN
Idiopathic pulmonary fibrosis (IPF) is a refractory and lethal interstitial lung disease characterized by alveolar epithelial cells apoptosis, fibroblast proliferation and extra-cellular matrix protein deposition. EBV, localised to alveolar epithelial cells of pulmonary fibrosis patients is associated with a poor prognosis. A strategy based on microarray-differential gene expression analysis to identify molecular drivers of EBV-associated lung fibrosis was utilized. Alveolar epithelial cells were infected with EBV to identify genes whose expression was altered following TGFbeta1-mediated lytic phase. EBV lytic reactivation by TGFbeta1 drives a selective alteration in CUX1 variant (a) (NCBI accession number NM_181552) expression, inducing activation of non-canonical Wnt pathway mediators, implicating it in Epithelial Mesenchymal Transition (EMT), the molecular event underpinning scar production in tissue fibrosis. The role of EBV in EMT can be attenuated by antiviral strategies and inhibition of Wnt signaling by using All-Trans Retinoic Acids (ATRA). Activation of non-canonical Wnt signaling pathway by EBV in epithelial cells suggests a novel mechanism of EMT via CUX1 signaling. These data present a framework for further description of the link between infectious agents and fibrosis, a significant disease burden.
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Herpesvirus Humano 4/patogenicidad , Proteínas de Homeodominio/metabolismo , Proteínas Nucleares/metabolismo , Alveolos Pulmonares/metabolismo , Alveolos Pulmonares/virología , Proteínas Represoras/metabolismo , Proteínas Wnt/metabolismo , Adulto , Anciano , Antivirales/farmacología , Secuencia de Bases , Células Cultivadas , Cartilla de ADN/genética , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Células Epiteliales/patología , Células Epiteliales/virología , Infecciones por Virus de Epstein-Barr/complicaciones , Femenino , Expresión Génica/efectos de los fármacos , Herpesvirus Humano 4/efectos de los fármacos , Proteínas de Homeodominio/genética , Interacciones Huésped-Patógeno , Humanos , Fibrosis Pulmonar Idiopática/etiología , Fibrosis Pulmonar Idiopática/metabolismo , Fibrosis Pulmonar Idiopática/patología , Fibrosis Pulmonar Idiopática/virología , Masculino , Mesodermo/efectos de los fármacos , Mesodermo/metabolismo , Mesodermo/patología , Mesodermo/virología , Persona de Mediana Edad , Proteínas Nucleares/genética , Regiones Promotoras Genéticas , Alveolos Pulmonares/efectos de los fármacos , Alveolos Pulmonares/patología , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN Interferente Pequeño/genética , Proteínas Represoras/genética , Transducción de Señal/efectos de los fármacos , Factores de Transcripción , Factor de Crecimiento Transformador beta1/farmacología , Proteínas Wnt/antagonistas & inhibidores , Proteínas Wnt/genéticaRESUMEN
EBV infection has been implicated in the pathogenesis of Idiopathic Pulmonary Fibrosis (IPF). Viral infection may occur from the early or late stage in IPF development. Whether alveolar epithelial cells, AECs, normally express EBV main receptor, CD21, remains uncertain. Such situations prompted us to exploit an efficient direct infection system to investigate EBV receptor repertoire in primary human AECs. Using human primary type 2 AECs, which have been grown in basal medium supplemented with 10 ng/ml Keratinocyte Growth Factor, and type 1 AECs, supplemented with Epithelial Growth Factor, both AEC lines express CD21 mRNA and protein with a significant increase in type 2 cells. Type 2 AECs have been exposed to TGFbeta1 and IL-4, whose expression is associated with IPF development. CD21 is highly expressed in type 2 AECs following IL-4 exposure. EBV bound to type 2 AECs membrane increases significantly following pre-treatment with IL-4 (p<0.001) and decreasing antagonizing CD21 receptor (p<0.01). 200 microg/ml G418-mediated selection of EBV-Neomycin resistant infected cells selected IL-4 pre-exposed type 2 AECs. Our study of a viral cell line model provides evidence to suggest that CD21-dependent viral entry plays a crucial role in type 2 AECs, indicative of an IL-4 response EBV infection in IPF.
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Células Epiteliales/efectos de los fármacos , Infecciones por Virus de Epstein-Barr/patología , Herpesvirus Humano 4/fisiología , Interleucina-4/farmacología , Alveolos Pulmonares/efectos de los fármacos , Receptores de Complemento 3d/fisiología , Células Cultivadas , Células Epiteliales/inmunología , Células Epiteliales/metabolismo , Células Epiteliales/virología , Infecciones por Virus de Epstein-Barr/genética , Infecciones por Virus de Epstein-Barr/inmunología , Infecciones por Virus de Epstein-Barr/metabolismo , Herpesvirus Humano 4/efectos de los fármacos , Humanos , Fibrosis Pulmonar Idiopática/etiología , Fibrosis Pulmonar Idiopática/inmunología , Fibrosis Pulmonar Idiopática/virología , Alveolos Pulmonares/inmunología , Alveolos Pulmonares/metabolismo , Alveolos Pulmonares/virología , Receptores de Complemento 3d/antagonistas & inhibidores , Receptores de Complemento 3d/genética , Receptores de Complemento 3d/metabolismo , Mucosa Respiratoria/efectos de los fármacos , Mucosa Respiratoria/inmunología , Mucosa Respiratoria/metabolismo , Mucosa Respiratoria/virología , Células Th2/metabolismo , Regulación hacia Arriba/efectos de los fármacos , Regulación hacia Arriba/inmunología , Acoplamiento Viral/efectos de los fármacosRESUMEN
The quality of tissue studied impacts greatly on oligonucleotide microarray results, emphasizing the importance of harvesting techniques. The analyzed RNA extracted from human lung samples preserved via 4 different storage conditions (RNAlater, phosphate-buffered saline, TRIzol, liquid nitrogen). RNA was assessed by denaturing gel electrophoresis, Agilent bioanalysis, real-time polymerase chain reaction (PCR), and Test3 Affymetrix chip hybridization. Results revealed better quality RNA from RNAlater samples on gel electrophoresis and bioanalysis. RNAlater samples also showed greater yield (r18s via PCR P < .05) and resulted in better Test3 chips hybridization (p < .05), suggesting RNAlater was superior at preserving lung tissue nucleic acid.
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Pulmón , Preservación de Órganos/métodos , Anciano , Electroforesis , Femenino , Humanos , Masculino , Análisis por Micromatrices/métodos , Persona de Mediana Edad , Desnaturalización de Ácido Nucleico , Hibridación de Ácido Nucleico/métodos , Análisis de Secuencia por Matrices de Oligonucleótidos , Soluciones Preservantes de Órganos/uso terapéutico , Reacción en Cadena de la Polimerasa , ARN/análisisRESUMEN
Idiopathic pulmonary fibrosis (IPF) is a refractory and lethal interstitial lung disease characterized by alveolar epithelial cells apoptosis, fibroblast proliferation, and ECM protein deposition. Epstein-Barr virus (EBV) has previously been localized to alveolar epithelial cells of IPF patients and is associated with a poor prognosis. In this study, we utilized a microarray-based differential gene expression analysis strategy to identify molecular drivers of EBV-associated lung fibrosis. Two cell lines, primary human alveolar epithelial cells type 2 and A549 cells, were infected with EBV. EBV lytic phase induction increased active and total transforming growth factor-beta1 (TGFbeta1) transcript expression in association with reduced cell proliferation and increased caspase 3/7 activity. Exposing EBV-infected cells to ganciclovir resulted in TGFbeta1 deregulation and reduced expression of EBV early response genes, BRLF1 and BZLF1. We targeted the BRLF1 and BZLF1 gene products, Rta and Zta, by silencing RNA, and this resulted in the normalization of TGFbeta1 transcript and cell proliferation levels. Our study using a viral cell line model complements existing human and animal model data and further provides evidence to suggest that viral epithelial cell injury may play a role in IPF.
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Herpesvirus Humano 4/patogenicidad , Alveolos Pulmonares/metabolismo , Alveolos Pulmonares/virología , Factor de Crecimiento Transformador beta1/genética , Antivirales/farmacología , Apoptosis/efectos de los fármacos , Secuencia de Bases , Línea Celular , Proliferación Celular , Células Cultivadas , Cartilla de ADN/genética , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Células Epiteliales/patología , Células Epiteliales/virología , Infecciones por Virus de Epstein-Barr/tratamiento farmacológico , Infecciones por Virus de Epstein-Barr/genética , Infecciones por Virus de Epstein-Barr/patología , Ganciclovir/farmacología , Genes Inmediatos-Precoces , Herpesvirus Humano 4/efectos de los fármacos , Herpesvirus Humano 4/genética , Humanos , Alveolos Pulmonares/efectos de los fármacos , Alveolos Pulmonares/lesiones , ARN Interferente Pequeño/genética , Regulación hacia Arriba/efectos de los fármacosRESUMEN
A high incidence of decreased bone mineral density (BMD) has increasingly been associated with HIV infection. In this study mesenchymal stem cell (MSC) and human osteoblast (hOB) cell lines were treated with HIV tat, HIV rev, HIV p55-gag, HIV gp120 and HTLV env (100 ng/ml, 24 h). Cells were then analyzed for calcium deposition, alkaline phosphatase (ALP) activity, and lipid levels using established methods. Real-time PCR with gene-specific primers was used to quantify the mRNA levels of the transcription factors RUNX-2 and PPARgamma, transcription factors known to be pro-osteogenic and pro-adipogenic, respectively. The levels of secreted bone markers and transcription factor activity were determined using commercial assays. In OBs, HIV p55-gag and gp120 were seen to reduce calcium deposition, ALP activity, levels of secreted BMP-2, -7, and RANK-L, and the expression and activity of RUNX-2. The levels of osteocalcin were also significantly reduced by p55-gag treatment, while gp120 also increased PPARgamma activity. Lipid levels were also increased by gp120 treatment. The ability of MSCs to develop into functioning OBs was also affected by the presence of HIV proteins, with p55-gag inducing a decrease in osteogenesis, while rev induced an increase. HIV proteins can potentially modulate OB development and function in vitro via modulation of bone maker secretion and RUNX-2 and PPARgamma transcription factor activity.
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Proteínas del Virus de la Inmunodeficiencia Humana/fisiología , Células Madre Mesenquimatosas/fisiología , Osteoblastos/fisiología , Osteogénesis , Fosfatasa Alcalina/metabolismo , Proteínas Morfogenéticas Óseas/metabolismo , Calcificación Fisiológica , Calcio/metabolismo , Diferenciación Celular , Línea Celular , Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Humanos , Metabolismo de los Lípidos , Células Madre Mesenquimatosas/metabolismo , Osteoblastos/metabolismo , Osteocalcina/metabolismo , PPAR gamma/genética , PPAR gamma/metabolismo , Ligando RANK/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
BACKGROUND: Idiopathic Pulmonary Fibrosis (IPF) is a progressive diffuse disease involving the lung parenchyma. Despite recent advances, the molecular mechanisms of the initiation and progression of this disease remain elusive. Previous studies have demonstrated TGFbeta1 as a key effector cytokine in the development of lung fibrosis. METHODS: In this study we have used a transgenic mouse based strategy to identify the effect of overexpression of this key effector mediator on the development of pulmonary fibrosis in response to exogenous injury. We bred two lines (line 25 and 18) of transgenic mice (Tr+) that overexpressed active TGFbeta1. Three-month old transgenic and wild type mice were subsequently wounded with intraperitoneal bleomycin. Mice were sacrificed at 6 weeks post-bleomycin and their lungs analysed histologically and biochemically. RESULTS: The severity of lung fibrosis was significantly greater in the Tr+ mice compared to the wild type mice. Using an oligonucleotide microarray based strategy we identified discrete patterns of gene expression contributing to TGFbeta1 associated pulmonary fibrosis. CONCLUSION: This data emphasises the importance of a host predisposition in the form of endogenous TGFbeta1, in the development of pulmonary fibrosis in response to an exogenous injury.
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HIV-infected patients are at increased risk of decreased bone mineral density. Some studies have implicated antiretroviral therapy as a contributor to the decreased bone mineral density seen in treated HIV-1 patients. In this study we explore the interactions between protease inhibitors (PI) and primary human osteoblast gene expression, highlighting a group of dysregulated genes that potentially are key factors in reducing bone formation. Runx-2 mRNA expression, calcium deposition, and alkaline phosphatase (ALP) activity decreased significantly in human osteoblast cultures after exposure to the PIs nelfinavir (NFV) and indinavir (IDV). Saquinavir (SQV), ritonavir (RTV), indinavir (IDV), or nelfinavir (NFV) exposure induced significant changes in genotypic expression as assessed by gene-chip microarray analysis. The altered genes from each group were compared to each other and a list of 8 upregulated and 13 downregulated genes only after NFV and IDV exposure was identified. This set includes TIMP-3, which has previously been demonstrated to be involved in osteoblast differentiation and extracellular matrix development processes. Silencing TIMP-3 mRNA expression using siRNA duplexes enhanced calcium deposition and ALP activity significantly, even after exposure to NFV and IDV. Our data suggest a link between reduced osteoblastic phenotype and a group of 21 altered genes following NFV and IDV treatment, and also suggest TIMP-3 may be involved in the PI-induced inhibition of osteoblast function.
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Fosfatasa Alcalina/metabolismo , Calcio/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Inhibidores de la Proteasa del VIH/farmacología , Osteoblastos/efectos de los fármacos , Inhibidor Tisular de Metaloproteinasa-3/metabolismo , Línea Celular , Regulación hacia Abajo , Perfilación de la Expresión Génica , Infecciones por VIH/tratamiento farmacológico , Humanos , Indinavir/farmacología , Nelfinavir/farmacología , Análisis de Secuencia por Matrices de Oligonucleótidos , Osteoblastos/metabolismo , Ritonavir/farmacología , Saquinavir/farmacología , Inhibidor Tisular de Metaloproteinasa-3/genética , Regulación hacia ArribaRESUMEN
HIV-infected patients are at increased risk of decreased bone mineral density. Several studies have implicated antiretroviral therapy as a contributor to the decreased bone mineral density seen in treated HIV-1 patients. Whilst the exact molecular mechanisms underlying decreased bone density remain to be elucidated, inflammation has been postulated to be an important pathogenomic mechanism. In this study, we have explored primary human osteoblast gene expression in response to protease inhibitors (PIs), by oligonucleotide microarray analysis. A list of dysregulated genes, correlated with the inflammatory response, increased significantly after NFV and RTV exposure. Analysis of gene and protein expression determined a selectively increase of the pro-inflammatory cytokines monocyte chemoattractant protein (MCP)-1 and interleukin-8 (IL-8) following exposure to a pharmacological concentration of NFV and RTV. These data suggested that generation of local inflammatory cascades may contribute to the development of decreased bone mineral density in highly active antiretroviral therapy (HAART)-treated HIV patients.