Role of hippocampal NF-κB and GluN2B in the memory acquisition impairment of experiences gathered prior to cocaine administration in rats

Cocaine can induce severe neurobehavioral changes, among others, the ones involved in learning and memory processes. It is known that during drug consumption, cocaine-associated memory and learning processes take place. However, much less is known about the effects of this drug upon the mechanisms involved in forgetting.The present report focuses on the mechanisms by which cocaine affects memory consolidation of experiences acquired prior to drug administration. We also study the involvement of hippocampus in these processes, with special interest on the role of Nuclear factor kappa B (NF-κB), N-methyl-D-aspartate glutamate receptor 2B (GluN2B), and their relationship with other proteins, such as cyclic AMP response element binding protein (CREB). For this purpose, we developed a rat experimental model of chronic cocaine administration in which spatial memory and the expression or activity of several proteins in the hippocampus were assessed after 36 days of drug administration. We report an impairment in memory acquisition of experiences gathered prior to cocaine administration, associated to an increase in GluN2B expression in the hippocampus. We also demonstrate a decrease in NF-κB activity, as well as in the expression of the active form of CREB, confirming the role of these transcription factors in the cocaine-induced memory impairment

Calidad y sostenibilidad : una propuesta metodológica interdisciplinar para la innovación competitiva de los municipios turísticos maduros

En el contexto de las primeras manifestaciones de una fase recesiva relacionada con la falta de competitividad de los destinos de sol y playa convencionales en países desarrollados en comparación con los análogos de países emergentes, se esgrimen como alternativa la evolución hacia un modelo de excelencia, identificado con calidad ambiental y calidad en el servicio. En el artículo se presenta una propuesta metodológica que tiene como objetivo fundamental reorientar la actitud de los agentes sociales de los municipios correspondientes a estos destinos hacia aquella que facilite la asunción por éstos de los criterios de calidad y sostenibilidad en sus prácticas económicas y territoriales. Esta metodología tiene un carácter interdisciplinar desde dos dimensiones. Una definida por la combinación de metodologías procedentes de dos áreas temáticas: los estudios turísticos y los estudios sobre procesos de innovación en el marco del desarrollo local. Otra, aportada por la composición del equipo, integrado por geógrafos, antropólogos y economistas.Environmental quality (sustainability) and service quality are being argued as a way to do more competitive the mature sun and beach destination, that are living the competition of young destinations. This paper presents a methodologic proposal whose main aim is helping to the local stakeholders in these destination to modify their behaviour in order to take on their economic and environmental skills these issues of sustainability and quality. This methodology is interdisciplinary in two ways: On the one hand, it arranges the methodologies belonging to tourist studies with that of the local development studies. On the other hand, it arranges the methodologies belonging to the study workteam: geographers, anthropologists and economists

Morphological Description of Frontal EEG Interictal and Ictal Discharges in an Adult Cohort of 175 Patients

EEG morphology; Electroencephalography; Frontal lobe seizuresMorfología EEG; Electroencefalografía; Convulsiones del lóbulo frontalMorfologia EEG; Electroencefalografia; Convulsions del lòbul frontalClinical and electroencephalogram (EEG) features in frontal lobe epilepsy (FLE) vary considerably among patients, making the diagnosis a challenge. The objective of this study was to describe interictal and ictal EEG activity, identifying variables that could help to differentiate and diagnose frontal lobe epilepsy cases. A prospective cross-sectional study from patients with frontal interictal epileptiform discharges (IED) referred to the Vall d’Hebron University Hospital (Barcelona, Spain) after a clinical event compatible with epileptic seizures was designed. The interictal and ictal activity were analyzed to provide a detailed EEG description of the cases, using different statistical analyses. The morphological seizure pattern at the ictal onset remained globally unchanged over time in seizures arising from the frontal lobe for each patient. Isolated sharp waves were the most frequent waveforms in the expression of IED. Frontal lobe seizures are frequently short and sometimes appear grouped in clusters within the same recording. Often the ictal expression of the electrical activity in frontal lobe seizure is subtle and challenging to interpret. A description of the main findings is summarized to identify seizures arising from the frontal lobe and avoid false negatives findings in EEG interpretations.This research received no external funding

SAlBi educa (Tailored Nutrition App for Improving Dietary Habits): Initial Evaluation of Usability

In recent years, the use of applications to improve dietary habits has increased. Although numerous nutrition apps are available on the market, only few have been developed by health and nutrition professionals based on scientific evidence and subsequently tested to prove their usability. The main objective of this study was to design, develop, and evaluate the usability of a tailored nutrition application to be used to promote healthy eating habits. In order to decide app design and content, three focus groups took place with fifteen professionals from primary healthcare, nutrition, and food science and computer science, as well as expert users. For the general and feedback message design, a reference model based on the scientific literature was developed. To address the multi-perspective approach of users' and external healthcare professionals' feedback, a one-day pilot testing with potential users and healthcare professionals was conducted with four focus groups. To evaluate the relevance and potential usability of the app a 1-month pilot test was conducted in a real-life environment. A total of 42 volunteers participated in the one-day pilot testing, and 39 potential users participated in the 1-month pilot test. The SAlBi educa app developed includes an online dietary record, a self-monitoring tool to evaluate dietary patterns, general and feedback messages, and examples of traditional Mediterranean recipes. The usability study showed that volunteers think that SAlBi educa is pleasant (59%) and easy to learn to use (94%). Over 84% of the volunteers declared that the nutritional messages were clear and useful. Volunteers stated that general and tailored recommendations, as well as self-monitoring, were SAlBi educa's most motivating and useful features. SAlBi educa is an innovative, user-friendly nutritional education tool with the potential to engage and help individuals to follow dietary habits based on the Mediterranean model.Junta de Andalucía PIN-0050-201

The evolution of the North Atlantic Oscillation for the last 700 years inferred from D/H isotopes in the sedimentary record of Lake Azul (Azores archipelago, Portugal).

TheD plant leaf wax variations provide insights on precipitation and evaporation evolution through time. This proxy has been used to reconstruct the temporal evolution of the North Atlantic Oscillation (NAO) climate mode since this mode rules most of the climate variability in the central North Atlantic area. A total lipid extraction preparation and the correspondent analyses in the IRMS have been done for 100 samples from the uppermost 1.5 m of the sedimentary infill of Lake Azul (Azores archipelago, Portugal). According to the chronological model, established by 210Pb profile and 4 AMS 14C dates, this record contains the environmental history of the last 730 years. The reconstructed precipitation variations obtained from D/H isotope values, suggest that this area has suffered significant changes in its distribution and intensity rainfall patterns through time. The end of the Medieval Climate Anomaly (MCA, 1100- 1300 AD) is characterized by a progressive enrichmentof D/H isotope values which meant decreasing arid conditions. These rainfalls’ increase might be interpreted by a shift from positive to negative dominance of the NAO. The Little Ice Age (LIA, 1300 - 1850 AD) was characterized by two humid periods (1300- 1550 AD and 1650 - 1850 AD) separated by a relatively dry period. These precipitation oscillations are clearly visible by marked changes in the D/H isotope values. The LIA was followed by the persistence of the positive NAO mode, exhibited by the depletion of the D/H isotope signal, which indicated an overall decrease of the precipitation in the central North Atlantic area. Surprisingly, the D/H of the last 100 years, characterized by the present global warming and a persistent positive NAO mode, display large fluctuations most possibly linked to an enhancement of the storminess which is in concordance with the data fluctuations observed in the instrumental record for the last 80 years in the archipelago. This climatic evolution is in accordance with other NAO records of the North Atlantic region (Trouet et al., 2012) highlighting the validity of the D/H isotopes as precipitation proxy.Peer Reviewe

Phenotypic profile of expanded NK cells in chronic lymphoproliferative disorders: a surrogate marker for NK-cell clonality

This is an open-access article distributed under the terms of the Creative Commons Attribution License.Currently, the lack of a universal and specific marker of clonality hampers the diagnosis and classification of chronic expansions of natural killer (NK) cells. Here we investigated the utility of flow cytometric detection of aberrant/altered NK-cell phenotypes as a surrogate marker for clonality, in the diagnostic work-up of chronic lymphoproliferative disorders of NK cells (CLPD-NK). For this purpose, a large panel of markers was evaluated by multiparametric flow cytometry on peripheral blood (PB) CD56 NK cells from 60 patients, including 23 subjects with predefined clonal (n = 9) and polyclonal (n = 14) CD56 NK-cell expansions, and 37 with CLPD-NK of undetermined clonality; also, PB samples from 10 healthy adults were included. Clonality was established using the human androgen receptor (HUMARA) assay. Clonal NK cells were found to show decreased expression of CD7, CD11b and CD38, and higher CD2, CD94 and HLADR levels vs. normal NK cells, together with a restricted repertoire of expression of the CD158a, CD158b and CD161 killer-associated receptors. In turn, NK cells from both clonal and polyclonal CLPD-NK showed similar/overlapping phenotypic profiles, except for high and more homogeneous expression of CD94 and HLADR, which was restricted to clonal CLPD-NK. We conclude that the CD94/HLADR phenotypic profile proved to be a useful surrogate marker for NK-cell clonality.This work has been partially supported by the following grants: FIS 02/1244-FEDER, DTS 15/00119-FEDER, RTICC RD06/0020/0035-FEDER and RTICC RD12/0036/0048-FEDER from the Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Madrid, Spain; SA103/03 and SA079U14 from the Consejería de Educación, Junta de Castilla y León, Valladolid, Spain. The research activities of the EuroFlow Consortium were supported by the European Commission (grant STREP EU-FP6, LSHB-CT-2006–018708, entitled ‘Flow cytometry for fast and sensitive diagnosis and follow-up of hematological malignancies’).Peer Reviewe

Conflicts Of Interest In Research On Electronic Cigarettes

INTRODUCTION The tobacco control community has raised some concerns about whether studies on electronic cigarettes (e-cigarettes) published in scientific journals hide conflicts of interest (COI) and whether such reports are biased. This study assessed potential COI in the e-cigarette scientific literature. METHODS Cross-sectional study was conducted on e-cigarette publications indexed in PubMed up to August 2014. We extracted information about the authors (affiliations, location, etc.), publication characteristics (type, topic, subject, etc.), results and conclusions, presence of a COI statement, and funding by and/or financial ties to pharmaceutical, tobacco, and/or e-cigarette companies. An algorithm to determine the COI disclosure status was created based on the information in the publication. Prevalence ratios (PRs) and confidence intervals (CIs) were calculated to identify associations with COI disclosure, controlling for several independent variables. RESULTS Of the 404 publications included in the analysis, 37.1% (n=150) had no COI disclosure statement, 38.6% declared no COI, 13.4% declared potential COI with pharmaceutical companies, 3.0% with tobacco companies, and 10.6% with e-cigarette companies. The conclusions in publications with COI, which were mainly tied to pharmaceutical companies, were more likely to be favourable to e-cigarette use (PR=2.23; 95% CI: 1.43-3.46). Publications that supported the use of e-cigarettes for both harm reduction (PR= 1.81; 95% CI: 1.14-2.89) and smoking cessation (PR= 2.02; 95% CI: 1.26-3.23) were more likely to have conclusions that were favourable to e-cigarettes. CONCLUSIONS One-third of the publications reporting studies on e-cigarettes did not have a COI disclosure statement, and this proportion was even higher in news articles, editorials and other types of publications. Papers with conclusions that were favourable to e-cigarette use were more likely to have COI. Journal editors and reviewers should consider evaluating publications, including funding sources, to determine whether the results and conclusions may be biased

Non-conventional yeasts as hosts for heterologous protein production.

Yeasts are an attractive group of lower eukaryotic microorganisms, some of which are used in several industrial processes that include brewing, baking and the production of a variety of biochemical compounds. More recently, yeasts have been developed as host organisms for the production of foreign (heterologous) proteins. Saccharomyces cerevisiae has usually been the yeast of choice, but an increasing number of alternative non-Saccharomyces yeasts has now become accessible for modern molecular genetics techniques. Some of them exhibit certain favourable traits such as high-level secretion or very strong and tightly regulated promoters, offering significant advantages over traditional bakers' yeast. In the present work, the current status of Kluyveromyces lactis, Yarrowia lipolytica, Hansenula polymorpha and Pichia pastoris (the best-known alternative yeast systems) is reviewed. The advantages and limitations of these systems are discussed in relation to S. cerevisiae.Spanish Society for Microbiolog

A novel targeted RNA-Seq panel identifies a subset of adult patients with acute lymphoblastic leukemia with BCR-ABL1-like characteristics

BCR-ABL1-like B-cell precursor acute lymphoblastic leukemia (BCP-ALL) remains poorly characterized in adults. We sought to establish the frequency and outcome of adolescent and adult BCR-ABL1-like ALL using a novel RNA-Seq signature in a series of patients with BCP-ALL. To this end, we developed and tested an RNA-Seq custom panel of 42 genes related to a BCR-ABL1-like signature in a cohort of 100 patients with BCP-ALL and treated with risk-adapted ALL trials. Mutations related to BCR-ABL1-like ALL were studied in a panel of 33 genes by next-generation sequencing (NGS). Also, CRLF2 overexpression and IKZF1/CDKN2A/B deletions were analyzed. Twenty out of 79 patients (12-84 years) were classified as BCR-ABL1-like (25%) based on heatmap clustering, with significant overexpression of ENAM, IGJ, and CRLF2 (P ≤ 0.001). The BCR-ABL1-like subgroup accounted for 29% of 15-60-year-old patients, with the following molecular characteristics: CRLF2 overexpression (75% of cases), IKZF1 deletions (64%), CDKN2A/B deletions (57%), and JAK2 mutations (57%). Among patients with postinduction negative minimal residual disease, those with the BCR-ABL1-like ALL signature had a higher rate of relapse and lower complete response duration than non-BCR-ABL1-like patients (P = 0.007). Thus, we have identified a new molecular signature of BCR-ABL1-like ALL that correlates with adverse prognosis in adult patients with ALL

A novel targeted RNA-Seq panel identifies a subset of adult patients with acute lymphoblastic leukemia with BCR-ABL1-like characteristics

BCR-ABL1-like B-cell precursor acute lymphoblastic leukemia (BCP-ALL) remains poorly characterized in adults. We sought to establish the frequency and outcome of adolescent and adult BCR-ABL1-like ALL using a novel RNA-Seq signature in a series of patients with BCP-ALL. To this end, we developed and tested an RNA-Seq custom panel of 42 genes related to a BCR-ABL1-like signature in a cohort of 100 patients with BCP-ALL and treated with risk-adapted ALL trials. Mutations related to BCR-ABL1-like ALL were studied in a panel of 33 genes by next-generation sequencing (NGS). Also, CRLF2 overexpression and IKZF1/CDKN2A/B deletions were analyzed. Twenty out of 79 patients (12-84 years) were classified as BCR-ABL1-like (25%) based on heatmap clustering, with significant overexpression of ENAM, IGJ, and CRLF2 (P <= 0.001). The BCR-ABL1-like subgroup accounted for 29% of 15-60-year-old patients, with the following molecular characteristics: CRLF2 overexpression (75% of cases), IKZF1 deletions (64%), CDKN2A/B deletions (57%), and JAK2 mutations (57%). Among patients with postinduction negative minimal residual disease, those with the BCR-ABL1-like ALL signature had a higher rate of relapse and lower complete response duration than non-BCR-ABL1-like patients (P = 0.007). Thus, we have identified a new molecular signature of BCR-ABL1-like ALL that correlates with adverse prognosis in adult patients with ALL