56 research outputs found

    Career inhibitors and career enablers for executive women

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    This paper is intended to contribute to the study of career inhibitors and career enablers for women. The analysis is based on data obtained from a survey conducted by the International Center of Work and Family at IESE Business School. The main conclusions of the analysis are: - Women have readier access to general management posts in small companies. - The feeling of working a "double work day" is widespread among women managers, especially in large companies. - Lack of sympathy on the part of colleagues and superiors when women give priority to their family responsibilities undermines women managers' satisfaction with their professional life. - The main career inhibitor is corporate culture (the "glass ceiling"). - The importance that executive women ascribe to career inhibitors decreases with age and professional rank. - The average woman manager's main support is her husband, who in most cases is also a manager. - The principal career enablers are: motivation, training, mental strength and value system.top management; career; family; women;

    SDCBP Modulates Stemness and Chemoresistance in Head and Neck Squamous Cell Carcinoma through Src Activation

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    CÚl·lules mare del càncer; QuimioresistÚnciaCélulas madre del cåncer; QuimiorresistenciaCancer stem cells; ChemoresistanceTo characterize the mechanisms that govern chemoresistance, we performed a comparative proteomic study analyzing head and neck squamous cell carcinoma (HNSCC) cells: CCL-138 (parental), CCL-138-R (cisplatin-resistant), and cancer stem cells (CSCs). Syntenin-1 (SDCBP) was upregulated in CCL-138-R cells and CSCs over parental cells. SDCBP depletion sensitized biopsy-derived and established HNSCC cell lines to cisplatin (CDDP) and reduced CSC markers, Src activation being the main SDCBP downstream target. In mice, SDCBP-depleted cells formed tumors with decreased mitosis, Ki-67 positivity, and metastasis over controls. Moreover, the fusocellular pattern of CCL-138-R cell-derived tumors reverted to a more epithelial morphology upon SDCBP silencing. Importantly, SDCBP expression was associated with Src activation, poor differentiated tumor grade, advanced tumor stage, and shorter survival rates in a series of 382 HNSCC patients. Our results reveal that SDCBP might be a promising therapeutic target for effectively eliminating CSCs and CDDP resistance.This research was supported by grants from the Instituto de Salud Carlos III (ISCIII): PI15/01262 and CP03/00101 (M.E.LL.), PI19/00560 (J.G.-P.), and CIBERONC (M.E.LL. and IDI2018/155 J.P.R.) and was co-financed by the European Regional Fund (ERDF) and AECC (Spanish Association of Cancer Research) Founding Ref. GC16173720CARR (M.E.LL.). Y.G.M. and C.M. were supported by the VHIR and iP-FIS (ISCIII) fellowships, respectively. We acknowledge the Principado de Asturias BioBank (PT17/0015/0023)

    A clinical trial to evaluate the effect of the Mediterranean diet on smokers lung function

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    Mediterranian diet; Smoke; Lung functionDieta mediterrĂĄnea; Fumar; FunciĂłn pulmonarDieta mediterrĂ nia; Fumar; FunciĂł pulmonarData on the association between lung function and some dietary patterns have been published. However, it is not yet well known if whether the Mediterranean Diet (MD) pattern can preserve or improve lung function. Our purpose is to evaluate the effect of increased MD adherence on lung function in smokers. A multicenter, parallel, cluster-randomized, controlled clinical trial is proposed. A total of 566 active smokers (>10 packs-year), aged 25-75 years will be included, without previous respiratory disease and who sign an informed consent to participate. Twenty Primary Care Centres in Tarragona (Spain) will be randomly assigned to a control or an intervention group (1:1). All participants will receive advice to quit smoking, and the intervention group, a nutritional intervention (2 years) designed to increase MD adherence by: (1) annual visit to deliver personalized nutritional education, (2) annual telephone contact to reinforce the intervention, and (3) access to an online dietary blog. We will evaluate (annually for 2 years): pulmonary function by forced spirometry and MD adherence by a 14-item questionnaire and medical tests (oxidation, inflammation and consumption biomarkers). In a statistical analysis by intention-to-treat basis, with the individual smoker as unit of analysis, pulmonary function and MD adherence in both groups will be compared; logistic regression models will be applied to analyze their associations. We hope to observe an increased MD adherence that may prevent the deterioration of lung function in smokers without previous respiratory disease. This population may benefit from a dietary intervention, together with the recommendation of smoking cessation

    Actin-binding protein α-actinin-1 interacts with the metabotropic glutamate receptor type 5b and modulates the cell surface expression and function of the receptor

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    Receptors for neurotransmitters require scaffolding proteins for membrane microdomain targeting and for regulating receptor function. Using a yeast two-hybrid screen, α-actinin-1, a major F-actin cross-linking protein, was identified as a binding partner for the C-terminal domain of metabotropic glutamate receptor type 5b (mGlu5b receptor). Co-expression, co-immunoprecipitation, and pull-down experiments showed a close and specific interaction between mGlu5b receptor and α-actinin-1 in both transfected HEK-293 cells and rat striatum. The interaction of α-actinin-1 with mGlu5b receptor modulated the cell surface expression of the receptor. This was dependent on the binding of α-actinin-1 to the actin cytoskeleton. In addition, the α-actinin-1/mGlu5b receptor interaction regulated receptor-mediated activation of the mitogen-activated protein kinase pathway. Together, these findings indicate that there is an α-actinin-1-dependent mGlu5b receptor association with the actin cytoskeleton modulating receptor cell surface expression and functioning

    Influence of early neurological complications on clinical outcome following lung transplant

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    BACKGROUND. Neurological complications after lung transplantation are common. The full spectrum of neurological complications and their impact on clinical outcomes has not been extensively studied. METHODS. We investigated the neurological incidence of complications, categorized according to whether they affected the central, peripheral or autonomic nervous systems, in a series of 109 patients undergoing lung transplantation at our center between January 1 2013 and December 31 2014. RESULTS. Fifty-one patients (46.8%) presented at least one neurological complication. Critical illness polyneuropathy-myopathy (31 cases) and phrenic nerve injury (26 cases) were the two most prevalent complications. These two neuromuscular complications lengthened hospital stays by a median period of 35.5 and 32.5 days respectively. However, neurological complications did not affect patients' survival. CONCLUSIONS. The real incidence of neurological complications among lung transplant recipients is probably underestimated. They usually appear in the first two months after surgery. Despite not affecting mortality, they do affect the mean length of hospital stay, and especially the time spent in the Intensive Care Unit. We found no risk factor for neurological complications except for long operating times, ischemic time and need for transfusion. It is necessary to develop programs for the prevention and early recognition of these complications, and the prevention of their precipitant and risk factors

    Control of a hippocampal recurrent excitatory circuit by cannabinoid receptor-interacting protein Gap43

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    The type-1 cannabinoid receptor (CB1R) is widely expressed in excitatory and inhibitory nerve terminals, and by suppressing neurotransmitter release, its activation modulates neural circuits and brain function. While the interaction of CB1R with various intracellular proteins is thought to alter receptor signaling, the identity and role of these proteins are poorly understood.Using a highthroughput proteomic analysis complemented with an array of in vitro and in vivo approaches in the mouse brain, we report that the C-terminal, intracellular domain of CB1R interacts specifically with growth-associated protein of 43 kDa (GAP43). The CB1R-GAP43 interaction occurs selectively at mossy cell axon boutons, which establish excitatory synapses with dentate granule cells in the hippocampus. This interaction impairs CB1R-mediated suppression of mossy cell to granule cell transmission, thereby inhibiting cannabinoidmediated anti-convulsant activity inmice. Thus, GAP43 acts as a synapse typespecific regulatory partner of CB1R that hampers CB1R-mediated effects on hippocampal circuit function

    Metabolites related to purine catabolism and risk of type 2 diabetes incidence; modifying efects of the TCF7L2-rs7903146 polymorphism

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    Studies examining associations between purine metabolites and type 2 diabetes (T2D) are limited. We prospectively examined associations between plasma levels of purine metabolites with T2D risk and the modifying effects of transcription factor-7-like-2 (TCF7L2) rs7903146 polymorphism on these associations. This is a case-cohort design study within the PREDIMED study, with 251 incident T2D cases and a random sample of 694 participants (641 non-cases and 53 overlapping cases) without T2D at baseline (median follow-up: 3.8 years). Metabolites were semi-quantitatively profiled with LC-MS/MS. Cox regression analysis revealed that high plasma allantoin levels, including allantoin-to-uric acid ratio and high xanthine-to-hypoxanthine ratio were inversely and positively associated with T2D risk, respectively, independently of classical risk factors. Elevated plasma xanthine and inosine levels were associated with a higher T2D risk in homozygous carriers of the TCF7L2-rs7903146 T-allele. The potential mechanisms linking the aforementioned purine metabolites and T2D risk must be also further investigated

    DNA Aptamers against the Lup an 1 Food Allergen

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    Using in vitro selection, high affinity DNA aptamers to the food allergen Lup an 1, ß-conglutin, were selected from a pool of DNA, 93 bases in length, containing a randomised sequence of 49 bases. ß-conglutin was purified from lupin flour and chemically crosslinked to carboxylated magnetic beads. Peptide mass fingerprinting was used to confirm the presence of the ß-conglutin. Single stranded DNA was generated from the randomised pool using T7 Gene 6 Exonuclease and was subsequently incubated with the magnetic beads and the captured DNA was released and amplified prior to a further round of Systematic Evolution of Ligands by Exponential Enrichment (SELEX). Evolution was monitored using enzyme linked oligonucleotide assay and surface plasmon resonance. Once a plateau in evolution was reached, the isolated DNA sequences were cloned and sequenced. The consensus motif was identified via alignment of the sequences and the affinities of these sequences for immobilised ß-conglutin were determined using surface plasmon resonance. The selected aptamer was demonstrated to be highly specific, showing no cross-reactivity with other flour ingredients or with other conglutin fractions of lupin. The secondary structures of the selected aptamers were predicted using m-fold. Finally, the functionality of the selected aptamers was demonstrated using a competitive assay for the quantitative detection of ß-conglutin. . Future work will focus on structure elucidation and truncation of the selected sequences to generate a smaller aptamer for application to the analysis of the Lup an 1 allergen in foodstuffs

    Influence of early neurological complications on clinical outcome following lung transplant

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    Sistema NerviĂłs AutĂČnom; Risc de malalties cardiovasculars; Procediments mĂšdics quirĂșrgics i invasiusSistema nervioso autĂłnomo; Riesgo de enfermedad cardiovascular; Procedimientos mĂ©dicos quirĂșrgicos e invasivosAutonomic Nervous System; Cardiovascular disease risk; Surgical and invasive medical proceduresBackground Neurological complications after lung transplantation are common. The full spectrum of neurological complications and their impact on clinical outcomes has not been extensively studied. Methods We investigated the neurological incidence of complications, categorized according to whether they affected the central, peripheral or autonomic nervous systems, in a series of 109 patients undergoing lung transplantation at our center between January 1 2013 and December 31 2014. Results Fifty-one patients (46.8%) presented at least one neurological complication. Critical illness polyneuropathy-myopathy (31 cases) and phrenic nerve injury (26 cases) were the two most prevalent complications. These two neuromuscular complications lengthened hospital stays by a median period of 35.5 and 32.5 days respectively. However, neurological complications did not affect patients’ survival. Conclusions The real incidence of neurological complications among lung transplant recipients is probably underestimated. They usually appear in the first two months after surgery. Despite not affecting mortality, they do affect the mean length of hospital stay, and especially the time spent in the Intensive Care Unit. We found no risk factor for neurological complications except for long operating times, ischemic time and need for transfusion. It is necessary to develop programs for the prevention and early recognition of these complications, and the prevention of their precipitant and risk factors.JG is the recipient of a grant from the Spanish Fondo de Investigaciones Sanitarias (FIS PI13-01272-FEDER)
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