Wnt/β-catenin signaling stimulates the expression and synaptic clustering of the autism-associated Neuroligin 3 gene

Indexación: Scopus.Synaptic abnormalities have been described in individuals with autism spectrum disorders (ASD). The cell-adhesion molecule Neuroligin-3 (Nlgn3) has an essential role in the function and maturation of synapses and NLGN3 ASD-associated mutations disrupt hippocampal and cortical function. Here we show that Wnt/β-catenin signaling increases Nlgn3 mRNA and protein levels in HT22 mouse hippocampal cells and primary cultures of rat hippocampal neurons. We characterized the activity of mouse and rat Nlgn3 promoter constructs containing conserved putative T-cell factor/lymphoid enhancing factor (TCF/LEF)-binding elements (TBE) and found that their activity is significantly augmented in Wnt/β-catenin cell reporter assays. Chromatin immunoprecipitation (ChIP) assays and site-directed mutagenesis experiments revealed that endogenous β-catenin binds to novel TBE consensus sequences in the Nlgn3 promoter. Moreover, activation of the signaling cascade increased Nlgn3 clustering and co-localization with the scaffold PSD-95 protein in dendritic processes of primary neurons. Our results directly link Wnt/β-catenin signaling to the transcription of the Nlgn3 gene and support a functional role for the signaling pathway in the dysregulation of excitatory/inhibitory neuronal activity, as is observed in animal models of ASD.https://www.nature.com/articles/s41398-018-0093-y.pd

The Zero-Removing Property and Lagrange-Type Interpolation Series

The classical Kramer sampling theorem, which provides a method for obtaining orthogonal sampling formulas, can be formulated in a more general nonorthogonal setting. In this setting, a challenging problem is to characterize the situations when the obtained nonorthogonal sampling formulas can be expressed as Lagrange-type interpolation series. In this article a necessary and sufficient condition is given in terms of the zero removing property. Roughly speaking, this property concerns the stability of the sampled functions on removing a finite number of their zeros

Synchronous or collision solid neoplasms and lymphomas: A systematic review of 308 case reports.

The presence of a lymphoma associated with a solid synchronous neoplasm or collision neoplasm has been rarely in the literature, and a detailed characterization of these cases is lacking to date. To describe the main clinicopathological features of synchronous/collision tumors. A systematic search in PubMed, Scielo, and Virtual Health Library literature databases for cases or case series of synchronous or collision lymphoma and other solid neoplasms reported up to March 2021 was performed. Three reviewers independently screened the literature, extracted data, and assessed the quality of the included studies. The systematic review was performed following the Preferred Reporting Items for Systematic Meta-Analyses guidelines. Mean age of patients was 62.9 years (52.9% men). A total of 308 cases were included (62% synchronous and 38% collision). The most frequent location of both synchronous and collision tumors was the gastrointestinal tract with the most common solid neoplasm being adenocarcinoma, and the most frequent lymphoma diffuse large B-cell lymphoma (21.7%) and mucosa-associated lymphoid tissue lymphoma (20.4%). Of the total number of mucosa-associated lymphoid tissue lymphomas and gastric adenocarcinomas, the presence of Helicobacter pylori infection was documented in 47.3% of them. Only 2% of all cases had a previous history of lymphoma. Thus, in most cases (98%), lymphoma was discovery incidentally. In addition, nodal lymphoma was associated with metastasis in 29 (9.4%) cases as collision tumor, most commonly (90%) in locoregional lymph nodes of the solid neoplasm. The frequent association of some type of B-cell lymphoma and adenocarcinoma in synchronous/collision tumors of the gastrointestinal tract points to common pathogenic mechanisms in both neoplasia, particularly related to chronic inflammation in this location. In most cases, lymphoma identified in locoregional lymph nodes or distant of a carcinoma seems to represent an incidental finding during the carcinoma diagnostic/therapeutic approach. A synergy between carcinoma and lymphoma (involving inflammation and immunosuppression mechanisms) may favor tumor progression and dissemination. A better understating of the interactions lymphoma/carcinoma in the setting of synchronous/collision tumors may help to improve patient management and prognosis

The Three-Step Workflow: A Pragmatic Approach to Allocating Academic Hospitals’ Affiliations for Bibliometric Purposes

This paper presents a method for classifying the varying degrees of interdependency between academic hospitals and universities in the context of the Leiden Ranking. A key question for ranking universities is whether or not to allocate the publication output of affiliated hospitals to universities.Hospital nomenclatures vary worldwide to denote some form of collaboration with a university: academic hospitals, teaching hospitals, university hospitals, and academic medical centres do not correspond to universally standard definitions. Thus, rather than seeking a normative definition of academic hospitals, we are proposing a workflow that aligns the university-hospital relationship with one of three general models: full integration of the hospital and the medical faculty into a single organization; health science centres in which hospitals and medical faculty remain separate entities albeit within the same governance structure; and structures in which universities and hospitals are separate entities which collaborate with one another. This classification system provides a standard by which we can allocate publications which note affiliations with academic hospitals.Our three-step workflow effectively translates the three above-mentioned models into two types of instrumental relationships for the assignation of publications: “associate” and “component”. When a hospital and a medical faculty are fully integrated or when a hospital is part of a health science centre, the relationship is classified as component. When a hospital follows the model of collaboration and support, the relationship is classified as associate. The compilation of data following these standards allows for a more uniform comparison between worldwide educational and research systems.Seventh Framework Programme (FP7)313082Merit, Expertise and Measuremen

Disparities among 2009 pandemic influenza A (H1N1) hospital admissions: A mixed methods analysis - Illinois, April-December 2009

During late April 2009, the first cases of 2009 pandemic influenza A (H1N1) (pH1N1) in Illinois were reported. On-going, sustained local transmission resulted in an estimated 500,000 infected persons. We conducted a mixed method analysis using both quantitative (surveillance) and qualitative (interview) data; surveillance data was used to analyze demographic distribution of hospitalized cases and follow-up interview data was used to assess health seeking behavior. Invitations to participate in a telephone interview were sent to 120 randomly selected Illinois residents that were hospitalized during April-December 2009. During April-December 2009, 2,824 pH1N1 hospitalizations occurred in Illinois hospitals; median age (interquartile range) at admission was 24 (range: 6-49) years. Hospitalization rates/100,000 persons for blacks and Hispanics, regardless of age or sex were 2-3 times greater than for whites (blacks, 36/100,000 (95% Confidence Interval ([95% CI], 33-39)); Hispanics, 35/100,000 [95%CI,32-37] (; whites, 13/100,000[95%CI, 12-14); p<0.001). Mortality rates were higher for blacks (0.9/100,000; p<0.09) and Hispanics (1/100,000; p<0.04) when compared with the mortality rates for whites (0.6/ 100,000). Of 33 interview respondents, 31 (94%) stated that they had heard of pH1N1 before being hospitalized, and 24 (73%) did not believed they were at risk for pH1N1. On average, respondents reported experiencing symptoms for 2 days (range: 1-7) before seeking medical care. When asked how to prevent pH1N1 infection in the future, the most common responses were getting vaccinated and practicing hand hygiene. Blacks and Hispanics in Illinois experienced disproportionate pH1N1 hospitalization and mortality rates. Public health education and outreach efforts in preparation for future influenza pandemics should include prevention messaging focused on perception of risk, and ensure community wide access to prevention messages and practices

Adaptive downregulation of Cl- /HCO3 - exchange activity in rat hepatocytes under experimental obstructive cholestasis

In obstructive cholestasis, there is an integral adaptive response aimed to diminish the bile flow and minimize the injury of bile ducts caused by increased intraluminal pressure and harmful levels of bile salts and bilirrubin. Canalicular bicarbonate secretion, driven by the anion exchanger 2 (AE2), is an influential determinant of the canalicular bile salt-independent bile flow. In this work, we ascertained whether AE2 expression and/or activity is reduced in hepatocytes from rats with common bile duct ligation (BDL), as part of the adaptive response to cholestasis. After 4 days of BDL, we found that neither AE2 mRNA expression (measured by quantitative real-time PCR) nor total levels of AE2 protein (assessed by western blot) were modified in freshly isolated hepatocytes. However, BDL led to a decrease in the expression of AE2 protein in plasma membrane fraction as compared with SHAM control. Additionally, AE2 activity (J(OH)-, mmol/L/min), measured in primary cultured hepatocytes from BDL and SHAM rats, was decreased in the BDL group versus the control group (1.9 +/- 0.3 vs. 3.1 +/- 0.2, p<0.005). cAMP-stimulated AE2 activity, however, was not different between SHAM and BDL groups (3.7 +/- 0.3 vs. 3.5 +/- 0.3), suggesting that cAMP stimulated insertion into the canalicular membrane of AE2-containing intracellular vesicles, that had remained abnormally internalized after BDL. In conclusion, our results point to the existence of a novel adaptive mechanism in cholestasis aimed to reduce biliary pressure, in which AE2 internalization in hepatocytes might result in decreased canalicular HCO3- output and decreased bile flow.This work was supported by grants from Spanish Carlos III Health Institute (ISCIII) [J. M. Banales (FIS PI15/01132, PI18/01075 and Miguel Servet Program CON14/00129) cofinanced by "Fondo Europeo de Desarrollo Regional" (FEDER); "Instituto de Salud Carlos III" [CIBERehd: J. M. Banales], Spain; BIOEF (Basque Foundation for Innovation and Health Research: EiTB Maratoia BIO15/CA/016/BD to J. M. Banales), Department of Health of the Basque Country (J. M. Banales: 2017111010) and Euskadi RIS3 (J. M. Banales: 2016222001, 2017222014, 2018222029). "Fundacion Cientifica de la Asociacion Espanola Contra el Cancer" (AECC Scientific Foundation, to J. M. Banales). F. A. Crocenzi was recipient of a Young Investigator Scholarship from Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), Argentina. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

De novo assembly and functional annotation of Myrciaria dubia fruit transcriptome reveals multiple metabolic pathways for L-ascorbic acid biosynthesis

Background Myrciaria dubia is an Amazonian fruit shrub that produces numerous bioactive phytochemicals, but is best known by its high L-ascorbic acid (AsA) content in fruits. Pronounced variation in AsA content has been observed both within and among individuals, but the genetic factors responsible for this variation are largely unknown. The goals of this research, therefore, were to assemble, characterize, and annotate the fruit transcriptome of M. dubia in order to reconstruct metabolic pathways and determine if multiple pathways contribute to AsA biosynthesis. Results In total 24,551,882 high-quality sequence reads were de novo assembled into 70,048 unigenes (mean length = 1150 bp, N50 = 1775 bp). Assembled sequences were annotated using BLASTX against public databases such as TAIR, GR-protein, FB, MGI, RGD, ZFIN, SGN, WB, TIGR_CMR, and JCVI-CMR with 75.2 % of unigenes having annotations. Of the three core GO annotation categories, biological processes comprised 53.6 % of the total assigned annotations, whereas cellular components and molecular functions comprised 23.3 and 23.1 %, respectively. Based on the KEGG pathway assignment of the functionally annotated transcripts, five metabolic pathways for AsA biosynthesis were identified: animal-like pathway, myo-inositol pathway, L-gulose pathway, D-mannose/L-galactose pathway, and uronic acid pathway. All transcripts coding enzymes involved in the ascorbate-glutathione cycle were also identified. Finally, we used the assembly to identified 6314 genic microsatellites and 23,481 high quality SNPs. Conclusions This study describes the first next-generation sequencing effort and transcriptome annotation of a non-model Amazonian plant that is relevant for AsA production and other bioactive phytochemicals. Genes encoding key enzymes were successfully identified and metabolic pathways involved in biosynthesis of AsA, anthocyanins, and other metabolic pathways have been reconstructed. The identification of these genes and pathways is in agreement with the empirically observed capability of M. dubia to synthesize and accumulate AsA and other important molecules, and adds to our current knowledge of the molecular biology and biochemistry of their production in plants. By providing insights into the mechanisms underpinning these metabolic processes, these results can be used to direct efforts to genetically manipulate this organism in order to enhance the production of these bioactive phytochemicals. The accumulation of AsA precursor and discovery of genes associated with their biosynthesis and metabolism in M. dubia is intriguing and worthy of further investigation. The sequences and pathways produced here present the genetic framework required for further studies. Quantitative transcriptomics in concert with studies of the genome, proteome, and metabolome under conditions that stimulate production and accumulation of AsA and their precursors are needed to provide a more comprehensive view of how these pathways for AsA metabolism are regulated and linked in this species

Informe del seguiniento científico de la acción piloto RAI-AP-76/2007: Pesca experimental con arte de arrastre de fondo en Mallorca (Islas Baleares, Mediterráneo occidental)

RESUMEN.- Del 14 de octubre al 30 de diciembre de 2008, se han llevado a cabo 49 pescas experimentales de arrastre de fondo, a bordo del B/P Punta d’es Vent, en caladeros de la plataforma y talud del sur de Mallorca (Islas Baleares). Se utilizaron dos artes de pesca, de manera alterna. La red “tangonera” tradicional, que utiliza éste y otros barcos de arrastre en el área, con un peso de 900 kg y copo de malla rómbica de 40 mm, acoplada a 360 m de malletas y unas puertas clásicas ovaladas polivalentes de 670 kg. Una red experimental, cuyo peso se estimó en 800 kg, de paños más finos y de mayor abertura de malla en el cuerpo y la manga y un copo de malla cuadrada de 40 mm, acoplada a 310 m de malletas y unas puertas EXPLORER de 588 kg. Del total de pescas, 43 fueron consideradas válidas para el análisis de datos, en base a tres estratos batimétricos: plataforma profunda (80-200 m), talud superior (300-500 m) y talud medio (600-800 m), cuyas principales especies objetivo fueron la merluza (Merluccius merluccius), la cigala (Nephrops norvegicus) y la gamba roja (Aristeus antennatus), respectivamente. Se ha estimado la composición de la captura estandarizada (kg/h y n/h) y los índices medios de captura total, descartes y desembarcos, y de las especies objetivo, por estrato batimétrico y arte. Se calcularon también las distribuciones de tallas de los ejemplares capturados, así como de su fracción comercializada y descartada, y para las tres especies objetivo se modelaron las curvas y parámetros de selección con copo de malla cuadrada de 40 mm. Con sistema SCANMAR se estimaron parámetros de los artes trabajando sobre el fondo (distancia entre puertas, inclinación y ángulos de ataque de puertas, tensión en puertas y calones, abertura horizontal y vertical de la red, simetría y filtrado de la red en boca, manga e inicio del copo) y con un medidor de caudal se registró el consumo de combustible durante la pesca. En cada marea se estimó la biomasa desembarcada y su valor económico de primera venta, así como los costes de explotación relacionados con el consumo de combustible. El análisis de esta información se ha realizado mediante técnicas uni- y multi-variantes. Los resultados han mostrado que el cambio de geometría en la malla del copo (de rómbica a cuadrada) mejora la selectividad de la pesquería de arrastre: se incrementan las tallas de primera captura (Merluccius merluccius: de 10.6 a 13.4 cm LT con malla rómbica y cuadrada de 40 mm, respectivamente; Nephrops norvegicus: 15-19 a 23.2 mm LCT; Aristeus antennatus: de 17.2 a 20.0 mm LCT) y se reducen los descartes (Merluccius merluccius: de 135.6 a 55.6 ejemplares/h con malla rómbica y cuadrada de 40 mm, respectivamente). El arte experimental ha permitido también reducir el impacto directo sobre el fondo marino, no sólo debido a la reducción del peso de la red y las puertas (↓11-12%) sino también de la superficie de contacto de las puertas y la longitud de las malletas (↓14%), disminuir la tensión en las puertas (↓9%) y aumentar el filtrado de agua a través de la red (~0.3 nudos). Como consecuencia de ello, se ha mantenido, e incluso aumentado, la distancia entre puertas (↑7%) y la abertura horizontal de la red (↑10%), con un menor régimen de revoluciones del motor principal durante la pesca (↓3%) y, por tanto, de consumo de combustible (↓11%). La mejor selectividad y mayor eficiencia energética del arte experimental respecto al tradicional se han obtenido sin una pérdida significativa de los rendimientos comerciales, en la mayoría de los casos. No obstante, hay que señalar también un aspecto negativo del arte experimental, que es el incremento del área barrida respecto del tradicional. Por ello, es necesario (y posible) reducir aún más las dimensiones y peso de las puertas y longitud de las malletas, lo que unido a otras posibles modificaciones (e.g. paños de red sin nudo, que ofrezcan menor resistencia a la tracción), podría conllevar una disminución (a corto plazo) de los rendimientos, si bien esta pérdida se compensaría con una mayor reducción del consumo de combustible. Por último, señalar que los resultados obtenidos pueden contribuir a mejorar la pesquería de arrastre de fondo, con el objetivo de hacerla ecológica y económicamente sostenible.INFORME DEL SEGUIMENT CIENTÍFIC DE L’ACCIÓ PILOT RAI-AP-76/2007: PESCA EXPERIMENTAL AMB ART DE RÒSSEC DE FONS A MALLORCA (ILLES BALEARS, MEDITERRÀNI OCCIDENTAL).- Del 14 d’octubre al 30 de desembre de 2008, s’han realitzat 49 pesques experimentals de ròssec de fons, a bord del V/P Punta d’es Vent, als caladors de plataforma y talús del sud de Mallorca (Illes Balears). S’utilitzaren dos arts de pesca, de manera alterna. La xarxa “tangonera” tradicional, que utilitza aquest i altres vaixells de ròssec, amb un pes de 900 kg i cóp de malla ròmbica de 40 mm, acoblada a 360 m de malletes y unes portes clàssiques ovalades polivalents de 670 kg. Una xarxa experimental, el pes de la qual es va estimar en 800 kg, de xarxa més fina i de major obertura de malla en el cos i la màniga i un cóp de malla quadrada de 40 mm, acoblada a 310 m de malletes i unes portes EXPLORER de 588 kg. Del total de pesques, 43 van ser considerades vàlides per a l’anàlisi de dades, en base a tres estrats batimètrics: plataforma profunda (80-200 m), talús superior (300-500 m) i talús mitjà (600-800 m), les principals espècies dels quals van ser el lluç (Merluccius merluccius), l’escamerlà (Nephrops norvegicus) i la gamba vermella (Aristeus antennatus), respectivament. S’ha estimat la composició de la captura estandarditzada (kg/h i n/h) i los índexs mitjans de captura total, rebuigs i desembarcaments, i de les espècies objectiu, per estrat batimètric i art. Es van calcular també les distribucions de talles dels exemplars capturats, així com de la seva fracció comercialitzada i rebutjada, i per a les tres espècies objectiu es modelaren les corbes i paràmetres de selecció amb cóp de malla quadrada de 40 mm. Amb sistema SCANMAR s’estimaren paràmetres dels arts treballant sobre el fons (distància entre portes, inclinació i angles d’atac de portes, tensió en portes i calons, obertura horitzontal i vertical de la xarxa, simetria i filtrat de la xarxa en boca, màniga i començament del cóp) i amb un mesurador de caudal s’enregistrà el consum de combustible durant la pesca. En cada marea s’estimà la biomassa desembarcada y el seu valor econòmic de primera venda, així com els costs de d’explotació relacionats amb el consum de combustible. L’anàlisi d’aquesta informació s’ha realitzat mitjançant tècniques uni- i multi-variants. Els resultats han mostrat que el canvi de geometria en la malla del cóp (de ròmbica a quadrada) millora la selectivitat de la pesqueria de ròssec: s’incrementen les talles de primera captura (Merluccius merluccius: de 10.6 a 13.4 cm LT amb malla ròmbica i quadrada de 40 mm, respectivament; Nephrops norvegicus: 15-19 a 23.2 mm LCT; Aristeus antennatus: de 17.2 a 20.0 mm LCT) i es redueixen els rebuigs (Merluccius merluccius: de 135.6 a 55.6 exemplars/h amb malla ròmbica i quadrada de 40 mm, respectivament). L’art experimental ha permès també reduir l’impacte directe sobre el fons marí, no només per la reducció del pes de la xarxa i les portes (↓11-12%) si no també de la superfície de contacte de les portes i la longitud de les malletes (↓14%), disminuir la tensió en las portes (↓9%) i augmentar el filtratge d’aigua a través de la xarxa (~0.3 nuus). Com a conseqüència d’això, s’ha mantingut, i inclús augmentat, la distància entre portes (↑7%) i l’obertura horitzontal de la xarxa (↑10%), amb un menor règim de revolucions del motor principal durant la pesca (↓3%) i, por tant, de consum de combustible (↓11%). La millor selectivitat i major eficiència energètica del art experimental respecte al tradicional s’han obtingut sense pèrdua significativa dels rendiments comercials, en la majoria dels casos. No obstant, hi ha que senyalar també un aspecte negatiu de l’art experimental, que és l’increment de l’àrea escombrada respecte del tradicional. Por això, és necessari (i possible) reduir més les dimensions i el pes de les portes i la longitud de les malletes, la qual cosa, juntament a altres possibles modificacions (e.g. teles de xarxa sense nuus, que ofereixen menor resistència a la tracció), podria resultar en una disminució (a curt termini) dels rendiments, si bé aquesta pèrdua es compensaria amb una major reducció del consum de combustible. Per acabar, assenyalar que els resultats obtinguts poden contribuir a millorar la pesqueria de ròssec de fons, amb l’objectiu de fer-la ecològica i econòmicament sostenible