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"Rodríguez, Esther"
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The image of Elizabeth I in Early Modern Spain
\"The Image of Elizabeth I in Early Modern Spain explores the fictionalized, historical, and visual representations of Elizabeth I and their impact on the Spanish collective imagination.\"--Provided by publisher.
Book
Deficient pulmonary IFN‐β expression in COPD patients
COPD patients are prone to acute infectious exacerbations that impair their quality of life and hamper prognosis. The purpose of the present study was to investigate the in situ IFN-β response in the lungs of stable COPD and non-COPD patients. Lung samples from 70 subjects (9 control never smokers, 19 control smokers without COPD, 21 patients with moderate COPD and 21 patients with very severe COPD) were studied for the expression of IFN-β, its main transcription factor, IRF-7, and two products of its autocrine function, namely RIG-I and MDA-5, by immunohistochemical techniques and quantitative real-time PCR. IFN-β, IRF-7, RIG-I and MDA-5 were widely detected in most lung cell types. In epithelial tissues and alveolar macrophages, IFN-β and IRF-7 labeling scores were decreased up to 65% and 74%, respectively, for COPD patients, paralleling an analogous reduction (43% and 65%, respectively) in the amount of their lung mRNA. Moreover, this decreased production of IFN-β in COPD patients correlated with a similar decrease in the expression of RIG-I and MDA-5, two essential members of the innate immune system. Our study indicates that most lung cells from stable COPD patients show a constitutive decreased expression of IFN-β, IRF-7, RIG-I and MDA-5, suggesting that this deficiency is the main cause of their acute viral exacerbations.
Journal Article
Health-Promoting Properties of Proanthocyanidins for Intestinal Dysfunction
The intestinal barrier is constantly exposed to potentially harmful environmental factors, including food components and bacterial endotoxins. When intestinal barrier function and immune homeostasis are compromised (intestinal dysfunction), inflammatory conditions may develop and impact overall health. Evidence from experimental animal and cell culture studies suggests that exposure of intestinal mucosa to proanthocyanidin (PAC)-rich plant products, such as grape seeds, may contribute to maintaining the barrier function and to ameliorating the pathological inflammation present in diet-induced obesity and inflammatory bowel disease. In this review, we aim to update the current knowledge on the bioactivity of PACs in experimental models of intestinal dysfunction and in humans, and to provide insights into the underlying biochemical and molecular mechanisms.
Journal Article
Hierarchical organization and skilled workforces for constructing the Tartessic earthen building at Casas del Turuñuelo (Guareña, Spain)
This article presents the results of the geoarchaeological study of earthen building materials used in a Tartessic public building at Casas del Turuñuelo. The construction dates back to the fifth century BCE and is one of the monumental buildings of Tartessic culture, characterized by its complex architecture, prestige goods, and intentional destruction after a feast and animal sacrifice. We applied an integrated methodology combining macro and micro approaches to investigate earthen construction processes, such as techniques, labour organization, workers’ specialization, and environmental exploitation. The sample mainly consists of mudbricks, but we also include other forms of earthen materials such as mud plasters, mud mortars, and geological soils for comparison. In total, 64 samples from different building parts were studied through X-ray fluorescence, X-ray diffraction, thin-section petrography, and CHN analyses. The results reveal that the workforce involved in the construction process used different resources and presented different skill levels, but was centrally planned and organized. This study reflects on the communities’ knowledge of the environment, the logistic effort and technical skill employed in the building process, and the existence of strong political structures capable of managing the erection of the complex Tartessic buildings.
Journal Article
Mass animal sacrifice at casas del Turuñuelo (Guareña, Spain): A unique Tartessian (Iron Age) site in the southwest of the Iberian Peninsula
Zooarchaeological analyses of the skeletal remains of 52 animals unearthed in the courtyard of an Iron Age Tartessian building known as Casas del Turuñuelo (Badajoz, Spain) shed light on a massive sacrifice forming part of a series of rituals linked to the site’s last period of activity and final abandonment. The rites took place towards the end of the 5th century BCE when both the building (intentionally destroyed) and the sacrificed animals were intentionally buried under a tumulus 90 m in diameter and 6 m high. The main objective of the zooarchaeological and microstratigraphic analyses was to determine the phasing of the sacrificial depositions. Evidence gathered from taphonomic assessments and a series of radiocarbon datings indicate that the sacrifices fall into three consecutive phases spanning several years. The findings of the zooarchaeological analyses clearly point to a selection of equid and cattle males. Adult equids predominate (MNI = 41) followed by adult and sub-adult cattle (MNI = 6). Pigs, in turn, are only represented by a few adults and sub-adult females (MNI = 4). Among the animals is a single dog of undetermined sex between 3 and 4 years of age. The fact that the animals are mostly adults discards the likelihood that they died from natural causes or an epidemic. In addition, the scenographic deposition of certain equids in pairs, as well as evidence of the burning of plant offerings, suggest an intentional ritualistic sacrifice. Nine of the initial depositions of Phase 1 in the SE quadrant were scattered and certain of their bones bear marks characteristic of both prolonged open air exposure and scavengers. Another 31 animals from Phases 1 and 2 are represented by almost complete, articulated skeletons, indicating they were promptly covered. Phase 3, by contrast, reveals both almost complete and partial animals bearing clear signs of processing for human consumption. This study thus sheds light on both the sequence of the animal sacrifices and the protocols linked to rites accompanied by the celebration of banquets. Certain features associated with the sealing of this building under a tumulus offer evidence of the decline of the Tartessian Culture. This study thus advances notions serving to contextualize ritual animal sacrifices in the framework of practice observed at other Iron Age sites in the Iberian Peninsula and elsewhere throughout Europe.
Journal Article
Intervention through an intelligent technological platform for socio-emotional development and health promotion in adolescents with Type 1 Diabetes Mellitus (emoTICare): A study protocol for randomized controlled trial
During adolescence, individuals face various challenges that require adequate psychosocial and emotional adjustment. Additionally, the presence of a chronic illness during this stage, such as Type 1 Diabetes Mellitus (T1DM), introduces additional medical and psychological needs, which can increase vulnerability. In this context, serious games emerge as a promising tool to address educational and psychoemotional aspects while maintaining the motivation and playability typical of a video game. Currently, no technological tool simultaneously addresses both the educational and psycho-emotional needs of adolescents with T1DM.
This study aims to design and validate a psychological intervention program using a technological platform that incorporates artificial intelligence. Through the serious game emoTICare, the goal is to promote physical and emotional health in adolescents with T1DM by enhancing the development of socio-emotional skills.
Test this tool, adolescents with T1DM will be recruited through diabetes associations across Spain. The participants, 372 adolescents aged between 12 and 16, will be randomly assigned to either a control or an experimental group. The experimental group will complete the emoTICare program. Over six weeks, participants will engage in psychoeducational activities using the tools provided by the serious game. Data Will be collected at three points: baseline (T1) and after six weeks (T2) (for the control group, T2 will be at the same time as the experimental group's post-intervention), and aT3 (after six months of T2). The program's effectiveness will be analyzed using various statistical packages.
The study hypothesizes that adolescents will maintain or improve their physical and emotional health indicators following the emoTICare program. Specifically, statistically significant improvements (p ≤ .05) are expected in the following variables: health-related quality of life, social skills and communication, emotional awareness, resilience, self-esteem, and coping and problem-solving abilities. Additionally, a statistically significant reduction (p ≤ .05) is anticipated in variables related to the perceived threat of the disease, as well as emotional and behavioral problems. The experimental group is expected to present improvements in all these areas when comparing pre- and posttreatment evaluations, and also in comparison to the control group on the waiting list.
Journal Article
Glucagon-like peptide-1 regulation by food proteins and protein hydrolysates
Glucagon-like peptide-1 (GLP-1) is an enterohormone with a key role in several processes controlling body homeostasis, including glucose homeostasis and food intake regulation. It is secreted by the intestinal cells in response to nutrients, such as glucose, fat and amino acids. In the present review, we analyse the effect of protein on GLP-1 secretion and clearance. We review the literature on the GLP-1 secretory effects of protein and protein hydrolysates, and the mechanisms through which they exert these effects. We also review the studies on protein from different sources that has inhibitory effects on dipeptidyl peptidase-4 (DPP4), the enzyme responsible for GLP-1 inactivation, with particular emphasis on specific sources and treatments, and the gaps there still are in knowledge. There is evidence that the protein source and the hydrolytic processing applied to them can influence the effects on GLP-1 signalling. The gastrointestinal digestion of proteins, for example, significantly changes their effectiveness at modulating this enterohormone secretion in both in vivo and in vitro studies. Nevertheless, little information is available regarding human studies and more research is required to understand their potential as regulators of glucose homeostasis.
Journal Article
Intrinsically disordered regions in the yeast transcriptional regulator Ixr1 support prion-like behavior
Ixr1 is a yeast transcriptional regulator previously identified as a player in the response to stress conditions, such as oxidative stress, hypoxia, iron limitation or DNA damage. Little is known about the structure of the Ixr1 protein apart from their HMG-boxes, which conform two well-known folded DNA binding domains. Intrinsically disordered regions (IDRs) are predicted in Ixr1 by algorithms and analytical methods. Ixr1 protein is non-globular and prone to aggregation, sustaining a concentration-dependent equilibrium between monomeric and dimeric forms. Treatment with 150 µM glutaraldehyde, to stabilize and fix weak protein-protein interactions, induces Ixr1 to form large oligomers. Indeed, Ixr1 forms amyloids as demonstrated both by in vitro and in vivo approaches. Chimeras constructed between Ixr1 and the C-terminal domain of Sup35, which provides the translation termination function to the yeast prion [
PSI
+
], show that IDRs from Ixr1 substitute the N-terminal region of Sup35 that is responsible of its priogenic nature. Finally, Artificial Intelligence (AI) assisted modeling of Ixr1 with Ssn8 (Srb11), which was already identified as a protein interacting with Ixr1 and related to yeast stress response, reveals that their interaction might diminish the disordered/priogenic nature of Ixr1 and increase the Ixr1 folding in the heterodimer.
Journal Article
Effectiveness and Safety of the Sequential Use of a Second and Third Anti-TNF Agent in Patients With Inflammatory Bowel Disease: Results From the Eneida Registry
BackgroundThe effectiveness of the switch to another anti–tumor necrosis factor (anti-TNF) agent is not known. The aim of this study was to analyze the effectiveness and safety of treatment with a second and third anti-TNF drug after intolerance to or failure of a previous anti-TNF agent in inflammatory bowel disease (IBD) patients.MethodsWe included patients diagnosed with IBD from the ENEIDA registry who received another anti-TNF after intolerance to or failure of a prior anti-TNF agent.ResultsA total of 1122 patients were included. In the short term, remission was achieved in 55% of the patients with the second anti-TNF. The incidence of loss of response was 19% per patient-year with the second anti-TNF. Combination therapy (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.8–3; P < 0.0001) and ulcerative colitis vs Crohn’s disease (HR, 1.6; 95% CI, 1.1–2.1; P = 0.005) were associated with a higher probability of loss of response. Fifteen percent of the patients had adverse events, and 10% had to discontinue the second anti-TNF. Of the 71 patients who received a third anti-TNF, 55% achieved remission. The incidence of loss of response was 22% per patient-year with a third anti-TNF. Adverse events occurred in 7 patients (11%), but only 1 stopped the drug.ConclusionsApproximately half of the patients who received a second anti-TNF achieved remission; nevertheless, a significant proportion of them subsequently lost response. Combination therapy and type of IBD were associated with loss of response. Remission was achieved in almost 50% of patients who received a third anti-TNF; nevertheless, a significant proportion of them subsequently lost response.Almost half of the 1122 patients who switched to a second anti-TNF after primary failure, secondary failure, or intolerance to the first anti-TNF achieved remission after switching. Factors associated with loss of response were type of IBD and combo therapy.
Journal Article
The amino acid substitutions A30W, K28A, and M35C alter amyloid-β peptide toxicity in cell culture and in an in vivo model of amyloidosis in Caenorhabditis elegans
The buildup of toxic aggregates formed by the amyloid-β peptide 1-42 (Aβ
) is a central process in Alzheimer's disease (AD) pathology. The peptide's self-assembly and toxicity are highly dependent on its primary amino acid sequence and can be altered by modifying key residues. Specifically, the single amino acid substitutions A30W, K28A, and M35C can reduce the aggregation and toxicity of the Aβ
peptide. In this study, we further evaluated the effects of these mutations in a C6 rat glioma cell line and in the
strains CL2006 and CL4176, which express muscular Aβ
as an
model. Our results showed that the A30W, K28A, and M35C substitutions reduce apoptosis induction in cell culture, in contrast to the WT Aβ42 peptide. In
, the three variants extended the lifespan of CL2006 worms by reducing fibrillar aggregates or altering aging, whereas the M35C peptide delayed the paralysis of CL4176 worms. Additionally, the substitutions altered oxidative stress and autophagy in control worms. Taken together, these results suggest that the A30W, K28A, and M35C substitutions reduce Aβ42 toxicity in cell culture and in
and could protect the nematode against Aβ42 toxicity.
Journal Article