La Gaceta de México y la promoción de impresos españoles durante la primera mitad del siglo XVIII

La producción bibliográfica del siglo XVIII se sirvió de las Gacetas de México para la promoción de autores y títulos de impresos que aparecíancotidianamente. Bajo los títulos Libros nuevos de México, Libros nuevos de España o Libros nuevos, varios de los fascículos de las Gacetas ofrecen a los lectores información sobre novedades bibliográficas. El presente texto se enfoca particularmente en la identificación del conjunto de noticias sobre impresos españoles que aparecen en las dos primeras Gacetas de México, que en total representan 15 años de publicación y más de 160 fascículos. Se ofrecen datos sobre autores, títulos, temas y lugares de venta de los libros españoles que circularon en México durante la primera mitad del siglo XVIII

Heterologous mammalian Akt disrupts plasma membrane homeostasis by taking over TORC2 signaling in Saccharomyces cerevisiae.

The Akt protein kinase is the main transducer of phosphatidylinositol-3,4,5-trisphosphate (PtdIns3,4,5P) signaling in higher eukaryotes, controlling cell growth, motility, proliferation and survival. By co-expression of mammalian class I phosphatidylinositol 3-kinase (PI3K) and Akt in the Saccharomyces cerevisiae heterologous model, we previously described an inhibitory effect on yeast growth that relied on Akt kinase activity. Here we report that PI3K-Akt expression in yeast triggers the formation of large plasma membrane (PM) invaginations that were marked by actin patches, enriched in PtdIns4,5P and associated to abnormal intracellular cell wall deposits. These effects of Akt were mimicked by overproduction of the PtdIns4,5P effector Slm1, an adaptor of the Ypk1 and Ypk2 kinases in the TORC2 pathway. Although Slm1 was phosphorylated in vivo by Akt, TORC2-dependent Ypk1 activation did not occur. However, PI3K-activated Akt suppressed the lethality derived from inactivation of either TORC2 or Ypk protein kinases. Thus, heterologous co-expression of PI3K and Akt in yeast short-circuits PtdIns4,5P- and TORC2-signaling at the level of the Slm-Ypk complex, overriding some of its functions. Our results underscore the importance of phosphoinositide-dependent kinases as key actors in the homeostasis and dynamics of the PM

A humanized yeast-based toolkit for monitoring phosphatidylinositol 3-kinase activity at both single cell and population levels

Phosphatidylinositol 3-kinase (PI3K) is a key regulator of phosphoinositide-dependent signaling in mammalian cells and its dysfunction is related to multiple syndromes, including cancer. By heterologous expression in Saccharomyces cerevisiae, we have developed a humanized yeast system as a tool for functional studies on higher eukaryotic PI3K. Here we restrict PI3K activity in yeast to specific plasma membrane (PM) microdomains by fusing the p110α PI3K catalytic subunit to either a septin or an eisosome component. We engineered a Dual Reporter for PI3K (DRAPIK), useful to monitor activity on cellular membranes in vivo at a single-cell level, by simultaneous PM staining of the enzyme substrate (PtdIns4,5P2) with GFP and its product (PtdIns3,4,5P3) with mCherry. We also developed a sensitive FLUorescence by PI3K Inhibition (FLUPI) assay based on a GFP transcriptional reporter that is turned off by PI3K activity. This reporter system proved useful to monitor PI3K inhibition in vivo by active compounds. Such novel tools were used to study the performance of yeast PM microdomain-directed PI3K. Our results show that tethering heterologous PI3K to discrete PM domains potentiates its activity on PtdIns4,5P2 but different locations display distinct effects on yeast growth and endocytosis

An Atlas of the circumnuclear regions of 75 Seyfert galaxies in the near-UV with HST Advanced Camera for Surveys

We present an atlas of the central regions of 75 Seyfert galaxies imaged in the near-UV with the Advanced Camera for Surveys of the Hubble Space Telescope at an average resolution of ~10pc. These data complement archival high resolution data from the Space Telescope at optical and near-IR wavelengths, creating an extremely valuable dataset for astronomers with a broad range of scientific interests. Our goal is to investigate the nature of the near-UV light in these objects, its relation to the circumnuclear starburst phenomenon, and the connection of this to the evolution and growth of the galaxy bulge and central black hole. In this paper, we describe the near-UV morphology of the objects and characterize the near-UV emission. We estimate the size and the luminosity of the emitting regions and extract the luminosity profile. We also determine the presence of unresolved compact nuclei. In addition, the circumnuclear stellar cluster population is identified, and the contribution of the stellar clusters to the total light, at this wavelength, is estimated. The size of the sample allows us to draw robust statistical conclusions. We find that {Seyfert 1} galaxies are completely dominated by its bright and compact nucleus, that remains point-like at this resolution, while we find almost no unresolved nucleus in Seyfert 2. The Seyfert types 1 and 2 are quite segregated in an asymmetry vs compactness plot. Stellar clusters are found somewhat more frequently in Sy2 (in ~70% of the galaxies) than in Sy1 (~57%), and contribute more to the total light in Sy2, but this two differences seem to be mostly due to the large contribution of the compact nucleus in Sy1, as the luminosity distribution of the clusters is similar in both Sy types.Comment: Accepted for publication in AJ, 58 pages, 20 figures. High-resolution figures for all the objects are available at http://www.iaa.es/~manuel/publications/paper01.htm

Long-Term outcomes and durability of the mitroflow aortic bioprosthesis

[Abstract] Background. This study aims to determine the incidence and causes of structural valve deterioration (SVD) among all models of Mitroflow bioprostheses (A12/LX/DL), as well as to define their long-term clinical and hemodynamic performance. Methods and Results. We retrospectively reviewed a series of 1023 patients who underwent aortic valve replacement with Mitroflow bioprostheses between 2001 and 2014. A small aortic root was found in 22.4% of patients. There were two cases of severe patient-prosthesis mismatch. Only 31 patients developed SVD. The rate of incidence was 8.1 cases per 1000 patient-years. Cumulative incidence of SVD was 1.4% and 3% at five and 10 years, respectively. Freedom from SVD was 97.4% and 88.2% at five and 10 years, respectively. Anticalcification phospholipid reduction treatment (PRT) for model DL was a protective factor for SVD. Multivariable analysis confirmed age <70 years and use of 19 mm valve as independent predictors of SVD. Cumulative survival was 76.6% at five years and 42.3% at 10 years (mean follow-up 3.8 ± 3.1 years). In multivariable analysis, neither the use of small aortic prosthesis (p = 0.18) nor the occurrence of SVD (p = 0.85) was found to be independent predictors of long-term survival. Conclusions. Mitroflow valves demonstrate an acceptable rate of SVD and satisfactory long-term hemodynamic performance, particularly in patients with small aortic roots, age >70 years, and cases with severe left ventricular hypertrophy. PRT might contribute to improved long-term durability

GCAT|Genomes for life: a prospective cohort study of the genomes of Catalonia

PURPOSE: The prevalence of chronic non-communicable diseases (NCDs) is increasing worldwide. NCDs are the leading cause of both morbidity and mortality, and it is estimated that by 2030, they will be responsible for 80% of deaths across the world. The Genomes for Life (GCAT) project is a long-term prospective cohort study that was designed to integrate and assess the role of epidemiological, genomic and epigenomic factors in the development of major chronic diseases in Catalonia, a north-east region of Spain. PARTICIPANTS: At the end of 2017, the GCAT Study will have recruited 20 000 participants aged 40-65 years. Participants who agreed to take part in the study completed a self-administered computer-driven questionnaire, and underwent blood pressure, cardiac frequency and anthropometry measurements. For each participant, blood plasma, blood serum and white blood cells are collected at baseline. The GCAT Study has access to the electronic health records of the Catalan Public Healthcare System. Participants will be followed biannually at least 20 years after recruitment. FINDINGS TO DATE: Among all GCAT participants, 59.2% are women and 83.3% of the cohort identified themselves as Caucasian/white. More than half of the participants have higher education levels, 72.2% are current workers and 42.1% are classified as overweight (body mass index ≥25 and <30 kg/m2). We have genotyped 5459 participants, of which 5000 have metabolome data. Further, the whole genome of 808 participants will be sequenced by the end of 2017. FUTURE PLANS: The first follow-up study started in December 2017 and will end by March 2018. Residences of all subjects will be geocoded during the following year. Several genomic analyses are ongoing, and metabolomic and genomic integrations will be performed to identify underlying genetic variants, as well as environmental factors that influence metabolites

Insights into the pathological mechanisms of p85α mutations using a yeast-based phosphatidylinositol 3-kinase model

In higher eukaryotes, cell proliferation is regulated by class I phosphatidylinositol 3-kinase (PI3K), which transduces stimuli received from neighboring receptors by local generation of PtdIns(3,4,5)P 3 in cellular membranes. PI3K is a heterodimeric protein consisting of a regulatory and a catalytic subunit (p85 and p110 respectively). Heterologous expression of p110α in Saccharomyces cerevisiae leads to toxicity by conversion of essential PtdIns(4,5)P 2 into futile PtdIns(3,4,5)P 3 , providing a humanized yeast model for functional studies on this pathway. Here, we report expression and functional characterization in yeast of all regulatory and catalytic human PI3K isoforms, and exploitation of the most suitable setting to functionally assay panels of tumor-and germ line-associated PI3K mutations, with indications to the limits of the system. The activity of p110α in yeast was not compromised by truncation of its N-terminal adaptor-binding domain (ABD) or inactivation of the Ras-binding domain (RBD). In contrast, a cluster of positively charged residues at the C2 domain was essential. Expression of a membrane-driven p65α oncogenic-truncated version of p85α, but not the full-length protein, led to enhanced activity of α, β, and δ p110 isoforms. Mutations impairing the inhibitory regulation exerted by the p85α iSH2 domain on the C2 domain of p110α yielded the latter non-responsive to negative regulation, thus reproducing this oncogenic mechanism in yeast. However, p85α germ line mutations associated with short stature, hyperextensibility of joints and/or inguinal hernia, ocular depression, Rieger anomaly, and teething delay (SHORT) syndrome did not increase PI3K activity in this model, supporting the idea that SHORT syndrome-associated p85α mutations operate through mechanisms different from the canonical disruption of inhibitory p85-p110 interactions typical of cancer

A trans-kingdom T6SS effector induces the fragmentation of the mitochondrial network and activates innate immune receptor NLRX1 to promote infection

Bacteria can inhibit the growth of other bacteria by injecting effectors using a type VI secretion system (T6SS). T6SS effectors can also be injected into eukaryotic cells to facilitate bacterial survival, often by targeting the cytoskeleton. Here, we show that the trans-kingdom antimicrobial T6SS effector VgrG4 from Klebsiella pneumoniae triggers the fragmentation of the mitochondrial network. VgrG4 colocalizes with the endoplasmic reticulum (ER) protein mitofusin 2. VgrG4 induces the transfer of Ca2+ from the ER to the mitochondria, activating Drp1 (a regulator of mitochondrial fission) thus leading to mitochondrial network fragmentation. Ca2+ elevation also induces the activation of the innate immunity receptor NLRX1 to produce reactive oxygen species (ROS). NLRX1-induced ROS limits NF-κB activation by modulating the degradation of the NF-κB inhibitor IκBα. The degradation of IκBα is triggered by the ubiquitin ligase SCFβ-TrCP, which requires the modification of the cullin-1 subunit by NEDD8. VgrG4 abrogates the NEDDylation of cullin-1 by inactivation of Ubc12, the NEDD8-conjugating enzyme. Our work provides an example of T6SS manipulation of eukaryotic cells via alteration of the mitochondria