Differentiation of lactotrope precursor GHFT cells in response to Fibroblast Growth Factor-2

The mechanisms that control the emergence of different anterior pituitary cells from a common stem cell population are largely unknown. The immortalized GHFT cells derived from targeted expression of SV40 T antigen to mouse pituitary display characteristics of somatolactotropic progenitors in that they express the transcription factor GHF-1 (Pit-1) but not growth hormone (GH) or prolactin (PRL). We searched for factors capable of inducing lactotropic differentiation of GHFT cells. PRL gene expression was not observed in cells subjected to a variety of stimuli, which induce PRL gene expression in mature lactotropes. Only fibroblast growth factor-2 (FGF-2) was able to initiate the transcription, synthesis, and release of PRL in GHFT cells. However, induction of PRL expression was incomplete in FGF-2-treated cells, suggesting that additional factors are necessary to attain high levels of PRL transcription in fully differentiated lactotropes. We also show that the FGF-2 response element is located in the proximal PRL promoter. Stimulation of PRL expression by FGF-2 requires endogenous Ets factors and these factors as well as GHF-1 are expressed at low levels in the committed precursor, suggesting that these low levels are limiting for full PRL expression. Moreover, FGF-2 effect on lactotrope differentiation is mediated, at least partially, by stimulation of the Ras-signaling pathway. Our results suggest that, indeed, GHFT cells represent a valid model for studying lactotropic differentiation and that FGF-2 could play a key role both in initiating lactotrope differentiation and maintaining PRL expression

Monitoring of RAS mutant clones in plasma of patients with RAS mutant metastatic colorectal cancer

Circulating tumor DNA; Liquid biopsy; Metastatic colorectal cancerADN tumoral circulante; Biopsia liquida; Cáncer colorrectal metastásicoADN tumoral circulant; Biòpsia líquida; Càncer colorectal metastàticPurpose Some patients with histologically confirmed primary mCRC and mutated RAS reported undetectable RAS mutant clones in plasma after receiving anti-VEGF treatment. The aim was to prospectively assess it with its potential therapeutic implications. Methods RAS mutant genes in solid biopsy (before first-line treatment: FOLFOX/CAPOX + bevacizumab) were compared in liquid biopsy (before second-line treatment: panitumumab + FOLFIRI), using Idylla™ system. Discordant results between solid/liquid biopsies were assessed by the next-generation sequencing (NGS) test (solid/liquid biopsies). Results Twenty-three patients were assessed (seven had RAS mutant discrepancies between solid/liquid biopsies). The NGS test confirmed that 3/23 (13%) patients had undetectable RAS mutant clones in liquid biopsy and 3/23 (13%) presented discrepancies in solid biopsy (Idylla™ system vs. NGS test). Conclusion Thirteen percentage of patients had undetectable RAS mutant clones in liquid biopsy after first-line treatment. However, some discrepancies between solid and liquid biopsies have been observed. These results suggest a need to improve accuracy of RAS analyses, especially in solid biopsies.This work was supported by Amgen S.A. Amgen did not have any role in study design; collection, analysis, and interpretation of data; writing the report; and the decision to submit the report for publication

Microbialite-like structures in Cladophora sp. (Ulvophyceae) mats from a subtropical Andean basin: ecological implications

The solubility equilibrium of calcite is influenced by physicochemical, climatic and biological factors. Annual cycles of exceptionally prolonged drought, in conjunction with naturally occurring diffuse organic pollution, generate the unique conditions for the precipitation of lithified carbonate structures (microbialites). The aim of this article is to analyze the possible implications of calcite precipitation produced in mats of Cladophora sp. in an Andean subtropical basin, considering it is the first time this phenomenon is described for the region. We collected samples from selected sites at the Lules River Basin, in four sampling dates between the years 2003 and 2004, within a monitoring work of 15 years. Samples were analyzed using an electron microscope and X-ray diffraction analysis. We found that Gomphonema sp. attached to Cladophora sp. contributes to precipitation of calcite and formation of microbialite like structures, in the studied area. This work presents an initial discussion of the discovery of microbialites-like structures attached to Cladophora sp. mats in a subtropical Andean stream and the environmental conditions that lead to their production, as well as the possible ecological implications of these microbialites.Fil: Fernandez, Hugo Rafael. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto de Biodiversidad Neotropical. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo. Instituto de Biodiversidad Neotropical. Instituto de Biodiversidad Neotropical; ArgentinaFil: González Achem, Ana L.. Fundación Miguel Lillo. Dirección de Zoología. Instituto de Invertebrados; ArgentinaFil: Correa, M.. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo; ArgentinaFil: Albarracín, Virginia Helena. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo; Argentin

Azores cetaceans field guide

Os Cetáceos (baleias e golfinhos) são um dos 5 grupos de mamíferos marinhos, juntamente com os pinípedes (focas, otárias e morsas), os sirénios (manatins e dugongos), as lontras e os ursos polares. Evidências moleculares e fósseis sugerem que baleias e golfinhos incluem-se dentro dos artiodáctilos, o grupo de mamíferos com cascos em número par, e.g. porcos, vacas e hipopótamos.ABSTRACT: Cetaceans (whales, dolphins, and porpoises) are one of the 5 groups of marine mammals, which also include pinnipeds (seals, sea lions, and walruses), sirenians (dugongs and manatees), sea otters, and polar bears. Fossil and molecular evidence suggests that whales and dolphins are a group within the artiodactyls (the group of eventoed, hoofed mammals that includes pigs, cattle and hippopotamus).N/

High-precision isotopic analysis sheds new light on mercury metabolism in long-finned pilot whales (Globicephala melas)

Eduardo Bolea-Fernandez acknowledges BOF-UGent for his postdoctoral grant. We acknowledge Arnout Laureys for his support, Jonas Kunigkeit and Magali Perez for isolation of HgSe particles, and Dr. Andrew Brownlow for given access to the Pilot Whale samples.Peer reviewedPublisher PD

La falta de coordinación como problema de salud

Presentamos el caso de una mujer de 92 años, que sufre un problema de salud agudo y acude a los servicios de urgencias de 2 centros sanitarios. La falta de acceso de los profesionales sanitarios a la historia clínica/farmacológica de la paciente, origina cambios en la medicación y una prescripción en cascada que tiene como consecuencia el deterioro de la salud en una paciente estable. Cuando un paciente acude a distintos profesionales para resolver un problema de salud, la falta de un sistema común de repositorio de esa información con acceso directo de los profesionales lastra la resolución de los problemas de salud

La falta de coordinación como problema de salud

Presentamos el caso de una mujer de 92 años, que sufre un problema de salud agudo y acude a los servicios de urgencias de 2 centros sanitarios. La falta de acceso de los profesionales sanitarios a la historia clínica/farmacológica de la paciente, origina cambios en la medicación y una prescripción en cascada que tiene como consecuencia el deterioro de la salud en una paciente estable. Cuando un paciente acude a distintos profesionales para resolver un problema de salud, la falta de un sistema común de repositorio de esa información con acceso directo de los profesionales lastra la resolución de los problemas de salud

Albumin downregulates Klotho in tubular cells

Background. Kidney tubular cells are the main sources of Klotho, a protein with phosphaturic action. Genetic Klotho deficiency causes premature cardiovascular aging in mice. Human chronic kidney disease (CKD) is characterized by acquired Klotho deficiency. Despite the lack of uremic toxin accumulation, Category G1 CKD [(normal glomerular filtration rate (GFR)] is already associated with decreased Klotho and with premature cardiovascular aging. Methods. We have explored whether albuminuria, a criterion to diagnose CKD when GFR is normal, may directly decrease Klotho expression in human CKD, preclinical models and cultured tubular cells. Results. In a CKD cohort, albuminuria correlated with serum phosphate after adjustment for GFR, age and sex. In this regard, urinary Klotho was decreased in patients with pathological albuminuria but preserved GFR. Proteinuria induced in rats by puromycin aminonucleoside and in mice by albumin overload was associated with interstitial inflammation and reduced total kidney Klotho messenger ribonucleic acid (mRNA) expression. Western blot disclosed reduced kidney Klotho protein in proteinuric rats and mice and immunohistochemistry localized the reduced kidney Klotho expression to tubular cells in proteinuric animals. In cultured murine and human tubular cells, albumin directly decreased Klotho mRNA and protein expression. This was inhibited by trichostatin A, an inhibitor of histone deacetylases, but unlike cytokine-induced Klotho downregulation, not by inhibitors of nuclear factor kappa-light-chain-enhancer of activated B cells. Conclusions. In conclusion, albumin directly decreases Klotho expression in cultured tubular cells. Thismay explain, or at least contribute to, the decrease in Klotho and promote fibroblast growth factor 23 resistance in early CKD categories, as observed in preclinical and clinical proteinuric kidney diseaseThis work was supported by FIS PI13/00047, CP14/00133, PI15/00298, PI16/02057, FEDER funds ISCIII-RETIC REDinREN RD12/0021, RD16/0009, Comunidad de Madrid (S2010/BMD-2378), Sociedad Espanola de Nefrología, EUTOX, FRIAT. Programa Intensificacion Actividad Investigadora (ISCIII/Agencia Lain-Entralgo/CM) to A.O., Miguel Servet MS14/00133, MS12/03262 to M.D.S.-N. and A.B.S., Joan Rodes to B.F.F. A.O. and M.D.S.-N. report grants from the Spanish government and grants from the Spanish Society of Nephrology during the conduct of the stud