Characterization of a proximal Sp1 response element in the mouse Dlk2 gene promoter

<p>Abstract</p> <p>Background</p> <p>DLK2 is an EGF-like membrane protein, closely related to DLK1, which is involved in adipogenesis. Both proteins interact with the NOTCH1 receptor and are able to modulate its activation. The expression of the gene <it>Dlk2 </it>is coordinated with that of <it>Dlk1 </it>in several tissues and cell lines. Unlike <it>Dlk1</it>, the mouse <it>Dlk2 </it>gene and its locus at chromosome 17 are not fully characterized.</p> <p>Results</p> <p>The goal of this work was the characterization of <it>Dlk2 </it>mRNA, as well as the analysis of the mechanisms that control its basal transcription. First, we analyzed the <it>Dlk2 </it>transcripts expressed by several mouse cells lines and tissues, and mapped the transcription start site by 5' Rapid Amplification of cDNA Ends. <it>In silico </it>analysis revealed that <it>Dlk2 </it>possesses a TATA-less promoter containing minimal promoter elements associated with a CpG island, and sequences for Inr and DPE elements. Besides, it possesses six GC-boxes, considered as consensus sites for the transcription factor Sp1. Indeed, we report that Sp1 directly binds to the <it>Dlk2 </it>promoter, activates its transcription, and regulates its level of expression.</p> <p>Conclusions</p> <p>Our results provide the first characterization of <it>Dlk2 </it>transcripts, map the location of the <it>Dlk2 </it>core promoter, and show the role of Sp1 as a key regulator of <it>Dlk2 </it>transcription, providing new insights into the molecular mechanisms that contribute to the expression of the <it>Dlk2 </it>gene.</p

Hyperostosis frontalis interna (HFI). Morgagni – Stewart – Morel (MSM) syndrome

La hiperostosis frontal interna (HFI) se caracteriza por un engrosamiento bilateral y simétrico de la tabla interna del hueso frontal, con una prevalencia del 5-12% en la población general. La HFI ha sido descrita como una condición independiente y como parte del síndrome de Morgagni-Stewart-Morel. Se considera que puede ser el resultado de un desequilibrio hormonal, principalmente asociado al metabolismo. La HFI es generalmente un hallazgo incidental, y aunque suele ser asintomático, a veces puede causar síntomas clínicosHFI is characterized by a bilaterally symmetrical thickening of the inner table of frontal bone. It has been reported in 5 to 12% of the general population. HFI has been postulate to be an independent condition or part of the Morgagni-Stewart-Morel. It is considered a result of a disbalance of hormones mainly linked to metabolism. HFI is usually an asymptomatic incidental finding, although sometimes it can cause clinical symptom

Evaluation of the Nanodomain Structure in In-Zn-O Transparent Conductors

The optimization of novel transparent conductive oxides (TCOs) implies a better understanding of the role that the dopant plays on the optoelectronic properties of these materials. In this work, we perform a systematic study of the homologous series ZnkIn2Ok+3 (IZO) by characterizing the specific location of indium in the structure that leads to a nanodomain framework to release structural strain. Through a systematic study of different terms of the series, we have been able to observe the influence of the k value in the nano-structural features of this homologous series. The stabilization and visualization of the structural modulation as a function of k is discussed, even in the lowest term of the series (k = 3). The strain fields and atomic displacements in the wurtzite structure as a consequence of the introduction of In3+ are evaluated.Depto. de Química InorgánicaFac. de Ciencias QuímicasTRUEMinisterio de Ciencia, Innovación y Tecnología /Ministerio de EconomíaComunidad de Madridpu

The Need for the Closer Monitoring of Novel Drugs in MS: A Siponimod Retrospective Cohort Study (Realhes Study)

Lymphopenia; Multiple sclerosis; PharmacovigilanceLinfopenia; Esclerosis múltiple; FarmacovigilanciaLimfopènia; Esclerosi múltiple; FarmacovigilànciaBackground: Severe cases of lymphopenia have been reported during siponimod clinical trials, which may negatively impact its benefit/risk profile. Objective: We aimed to evaluate the incidence of lymphopenia following the initiation of siponimod treatment in clinical practice. The secondary objectives included the analysis of factors predisposing to and the clinical relevance of lymphopenia events. Methods: In this multicenter retrospective cohort study, information collected from the medical records of 129 patients with MS from 15 tertiary hospitals in Spain who initiated treatment with Siponimod were followed-up for at least 3 months, including at least one lymphocyte count evaluation per patient. Results: Of the 129 patients, 121 (93.6%) reported lymphopenia events, including 110 (85.3%) with grade ≤ 3 and 11 (8.5%) with grade 4 lymphopenia, higher than those reported in the pivotal clinical trial (73.3% and 3.3% for grade ≤ 3 and grade 4 lymphopenia, respectively). The study included an unexpectedly high proportion of male subjects (72.9%), which might have led to an underestimation of the actual magnitude of the risk. Conclusions: In this study, the incidence and severity of lymphopenia after starting siponimod treatment were higher than those reported in previous clinical trials. Therefore, our results reinforce the need for the closer monitoring of novel MS drugs in clinical practice, as well as larger and longer follow-up studies to properly characterize this risk

Hyperostosis frontalis interna (HFI). Morgagni - Stewart- Morel (MSM) syndrome

[ES] La hiperostosis frontal interna (HFI) se caracteriza por un engrosamiento bilateral y simétrico de la tabla interna del hueso frontal, con una prevalencia del 5-12% en la población general. La HFI ha sido descrita como una condición independiente y como parte del síndrome de Morgagni-Stewart-Morel. Se considera que puede ser el resultado de un desequilibrio hormonal, principalmente asociado al metabolismo. La HFI es generalmente un hallazgo incidental, y aunque suele ser asintomático, a veces puede causar síntomas clínicos. [EN] HFI is characterized by a bilaterally symmetrical thickening of the inner table of frontal bone. It has been reported in 5 to 12% of the general population. HFI has been postulate to be an independent condition or part of the Morgagni-Stewart-Morel. It is considered a result of a disbalance of hormones mainly linked to metabolism. HFI is usually an asymptomatic incidental finding, although sometimes it can cause clinical symptoms

Longer intervals between SARS-CoV-2 infection and mRNA-1273 doses improve the neutralization of different variants of concern

The humoral immune response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern elicited by vaccination was evaluated in COVID-19 recovered individuals (Rec) separated 1-3 months (Rec2m) or 4-12 months (Rec9m) postinfection and compared to the response in naïve participants. Antibody-mediated immune responses were assessed in 66 participants by three commercial immunoassays and a SARS-CoV-2 lentiviral-based pseudovirus neutralization assay. Immunoglobulin (Ig) levels against SARS-CoV-2 spike were lower in naïve participants after two doses than in Rec after a single dose (p < 0.05). After two doses in Rec, levels of total Ig to receptor-binding domain were significantly increased in Rec9m compared to Rec2m (p < 0.001). The neutralizing potency observed in Rec9m was consistently higher than in Rec2m against variants of concern (VOCs) Alpha, Beta, Delta, and BA.1 sublineage of Omicron with 2.2-2.8-fold increases. Increasing the interval between SARS-CoV-2 infection and the vaccination with messenger RNA-based vaccines to more than 3 months generates a more efficient heterologous humoral immune response against VOCs by allowing enough time to mount a strong recall memory B cell response.This work is funded by Instituto de Salud Carlos III, a Spanish public body assigned to the Ministry of Science and Innovation that manages and promotes public clinical research related to Public Health, by Grants PI19CIII/00004 (José Alcamí and Francisco Díez‐Fuertes) and PI21CIII/00025 (Javier García‐Pérez and Mayte Pérez‐Olmeda), COVID‐19 Fund (Grants COV20/00679 (Javier García‐Pérez, Mayte Pérez‐Olmeda, José Alcamí, and Francisco Díez‐Fuertes) and COV20/00072 (Javier García‐Pérez, Mayte Pérez‐Olmeda, Almudena Ramírez‐García, María Castillo de la Osa, Rocio Layunta Acero, Laura Vicente‐Izquierdo, Cristina Avendaño‐Solá, and José Alcamí), and CIBERINFEC, co‐financed by the European Regional Development Fund (FEDER) “A way to make Europe.”S

Burnout in Palliative Care Nurses, Prevalence and Risk Factors: A Systematic Review with Meta-Analysis

Palliative care nurses are exposed to hard situations, death, and duel feelings in their daily practice. These, and other work stressors, can favor burnout development. Thus, it is important to analyze the prevalence and risk factors of burnout in palliative care nurses and estimate its prevalence. A systematic review and meta-analysis was done with quantitative primary studies. n = 15 studies were included with n = 6 studies including information for the meta-analysis. The meta-analytic prevalence estimation of emotional exhaustion was 24% (95% CI 16–34%), for depersonalization was 30% (95% CI 18–44%) and for low personal accomplishment was 28% with a sample of n = 693 palliative care nurses. The main variables related with burnout are occupational variables followed by psychological variables. Some interventions to improve working conditions of palliative care nurses should be implemented to reduce burnout

Bacteria-instructed B cells cross-prime naïve CD8+ T cells triggering effective cytotoxic responses.

In addition to triggering humoral responses, conventional B cells have been described in vitro to cross-present exogenous antigens activating naïve CD8+ T cells. Nevertheless, the way B cells capture these exogenous antigens and the physiological roles of B cell-mediated cross-presentation remain poorly explored. Here, we show that B cells capture bacteria by trans-phagocytosis from previously infected dendritic cells (DC) when they are in close contact. Bacterial encounter "instructs" the B cells to acquire antigen cross-presentation abilities, in a process that involves autophagy. Bacteria-instructed B cells, henceforth referred to as BacB cells, rapidly degrade phagocytosed bacteria, process bacterial antigens and cross-prime naïve CD8+ T cells which differentiate into specific cytotoxic cells that efficiently control bacterial infections. Moreover, a proof-of-concept experiment shows that BacB cells that have captured bacteria expressing tumor antigens could be useful as novel cellular immunotherapies against cancer.We are grateful to advanced light microscopy and cytometry facilities of CNB for technical supporting. The research is supported by grants: SAF2017-84091- R, and PID2020-116393RB-I00/AEI/10.13039/501100011033, financed by MCIN, BFERO2020.04, financed by FERO foundation and PI20/0036 from ISCIII. RGF is supported by BES-2016-076526 from the Spanish Ministry of Economy Industry and Competitiveness, JOP is supported by fellowship LCF/BQ/SO16/ 52270012 from La Caixa, BHF is supported by FPU18/00895 and AMP by FPU18/03199 from Ministry of Science, Innovation and Universities. LdC has been supported by Juan de la Cierva grant IJC2018-035386-I and a contract associated to SEV-2017-0712. EVC, AMP, AMAM, and NMM belong to the Spanish National Research Council (CSIC)’s Cancer Hub. Synopsis image made with biorender.com by Eduardo Roman Camacho and Esteban Veiga. We thanks Prof. Dan Portnoy who kindly provided bacterial strains.S

Influence of cation substitution on the complex structure and luminescent properties of the Zn_kIn_2O_(k+3) system

The effect of In^(3+) substitution by Ga^(3+) or Al^(3+) on the structure and luminescent properties of Zn_7In_(2-x)M_xO_10 (M = Ga or Al; 0 <= x <= 1) oxides has been investigated by means of high spatial resolution X-ray spectroscopy and high-angle annular dark-field images, combined with magic angle spinning nuclear magnetic resonance spectroscopy. Local structural variations have been identified for the Al- and Ga-doped samples through the analysis of atomically resolved chemical maps and the identification of their structural environment within the wurtzite lattice. In3+ is distributed in a zig-zag modulation, while Al^(3+) and Ga^(3+) are located in a flat distribution at the center of the wurtzite block. Density functional theory calculations provide unambiguous evidence for the preferential flat location of Ga^(3+) and Al^(3+) associated with the different strains introduced in the structure as a result of their ionic radii. The characterization of the photoluminescence response reveals the appearance of new radiative recombination pathways for the doped materials because of the presence of new defect levels in the band gap of the Zn_7In_2O_10 structure

What remains of the future: sustainability through heritage

Coordinators : Felipe Criado Boado (INCIPIT, CSIC), Blanca Ramírez Barat (CENIM, CSIC).Heritage is increasingly being recognized as a key element for social cohesion, sustainable socioeconomic development and people’s welfare. Resources dedicated to heritage conservation have gone from being considered an expense to being regarded as an investment, with a high revenue. The heritage industry has been an active part of this transformations in recent decades, it has generated employment, contributed to the worldwide expansion of tourism and has become a coveted sign of identity for political communities. Today there is no social or political process that does not use heritage in some way. Hence the actuality of the subject, and the importance of an organization such as the CSIC having research capabilities in this field