Mutually exclusive signaling signatures define the hepatic and pancreatic progenitor cell lineage divergence

Understanding how distinct cell types arise from multipotent progenitor cells is a major quest in stem cell biology. The liver and pancreas share many aspects of their early development and possibly originate from a common progenitor. However, how liver and pancreas cells diverge from a common endoderm progenitor population and adopt specific fates remains elusive. Using RNA sequencing (RNA-seq), we defined the molecular identity of liver and pancreas progenitors that were isolated from the mouse embryo at two time points, spanning the period when the lineage decision is made. The integration of temporal and spatial gene expression profiles unveiled mutually exclusive signaling signatures in hepatic and pancreatic progenitors. Importantly, we identified the noncanonical Wnt pathway as a potential developmental regulator of this fate decision and capable of inducing the pancreas program in endoderm and liver cells. Our study offers an unprecedented view of gene expression programs in liver and pancreas progenitors and forms the basis for formulating lineage-reprogramming strategies to convert adult hepatic cells into pancreatic cells

Brucella abortus Uses a Stealthy Strategy to Avoid Activation of the Innate Immune System during the Onset of Infection

To unravel the strategy by which Brucella abortus establishes chronic infections, we explored its early interaction with innate immunity. Methodology/Principal Findings Brucella did not induce proinflammatory responses as demonstrated by the absence of leukocyte recruitment, humoral or cellular blood changes in mice. Brucella hampered neutrophil (PMN) function and PMN depletion did not influence the course of infection. Brucella barely induced proinflammatory cytokines and consumed complement, and was strongly resistant to bactericidal peptides, PMN extracts and serum. Brucella LPS (BrLPS), NH-polysaccharides, cyclic glucans, outer membrane fragments or disrupted bacterial cells displayed low biological activity in mice and cells. The lack of proinflammatory responses was not due to conspicuous inhibitory mechanisms mediated by the invading Brucella or its products. When activated 24 h post-infection macrophages did not kill Brucella, indicating that the replication niche was not fusiogenic with lysosomes. Brucella intracellular replication did not interrupt the cell cycle or caused cytotoxicity in WT, TLR4 and TLR2 knockout cells. TNF-α-induction was TLR4- and TLR2-dependent for live but not for killed B. abortus. However, intracellular replication in TLR4, TLR2 and TLR4/2 knockout cells was not altered and the infection course and anti-Brucella immunity development upon BrLPS injection was unaffected in TLR4 mutant mice. Conclusion/Significance We propose that Brucella has developed a stealth strategy through PAMPs reduction, modification and hiding, ensuring by this manner low stimulatory activity and toxicity for cells. This strategy allows Brucella to reach its replication niche before activation of antimicrobial mechanisms by adaptive immunity. This model is consistent with clinical profiles observed in humans and natural hosts at the onset of infection and could be valid for those intracellular pathogens phylogenetically related to Brucella that also cause long lasting infections

Anales de Edafología y Agrobiología Tomo 37 Número 9-10

Contribución al estudio de suelos desarrollados sobre roca caliza, por A. Hoyos de Castro, A. Mª Moreno García y J. González Parra.-- Génesis y evolución de un suelo desarrollado sobre material calizo (Sierra deAralar), por A. Hoyo, A. M. Moreno y J. González Parra.-- Características del humus a lo largo de una toposecuencia de andoso es en la lsla de Tenerife, por A. Polo, C. Gª Milla y F. Velasco.-- Relationship between organic carbon, nitrogen, phoophorus, sulphur and organic matter in some soils of Rajasthau, por L. L. Somani and S. N. Saxena.-- Meteorización experimental de sedimentos aluviales ácidos del valle del Guadalquivir, por Juan de Olmedo Pujoly Angelines Hernández.-- Predicting cation exchange capacity of soils from relative amount of clay and organic matter content, por L. L. Souzani.-- Influencia de la época de siembra de Triticum vulgare L. y grado de infección de Avena sterilis L. en la competencia de ambas especies, por R.González Ponce y V. Hernando Fernandez.-- Estudio de la capacidad competitiva de Avena sterilis L. contra Triticum vulgare L. en comparación a la de este ultimo consigo mismo, por R. González Ponce y V. H ernando Fernández.-- Estudio previo sobre la nutrición del Aguacate por análisis foliar, por S. Jaime Palacios, A. Aguilar Villalvilla y E. Esteban Velasco.-- Influencia del clururo sódico sobre la germinación de semillas de pimiemo (Capsicum annuum), por N. Caro, F. G. Fernández y A. Cerda.-- Aclareo químico de frutos en el olivar manzanillo de Sevilla, por A. Troncoso, I. Prieto y J. Liñan.-- Estudio de un sistema de drenaje a nivel parcelario en pasto Nariño (Colombia), por A. Alvarez López, A. Arias Henández y L. Legarda Burbano.-- Utilización digestiva de dietas con pesticidas, por Ciara Mª Rueda, J. F. Aguilar y J. Boza.—Trabajos recapitulativos.-- Genética de khizobium y de la fijación de nitrógeno, por J. Casadesús y J. Olivares.—Notas previa.-- Aplicaciones de la informática en el reconocimiento y evaluación de suelos, por D. de la Rosa, F. Cardona. J. Naranjo y J. Almorza.-- Notas.-- Asociación Internacional de Ciencias del Suelo.-- Mapa mundial de Suelos a escala 1:5.000.000.-- C. S. l. C. Normativa sobre constitución de las comisiones científica y económica: Real Decreto 3450/77.-- Nota informativa de la Comisión Científica (núm. 1) C. S. l. C.-- Nota informativa de la Comisión Científica (núm. 2) C. S. l. C.-- Comisión Económica (Circular núm. 1) 29-JX-1978. C. S. l. C.-- VII Reunión Nacional de Suelos.-- Sociedad Española de Ciencia del Suelo.-- Los profesores Hoyos y García Vicente visitan Polonia.-- XXth International Horticultural Congress y 8th International Colloquium Plant Analysis and Fertilizer Problema.-- Asamblea de la Sociedad Española de Ciencia del Suelo.-- Reunión de la sección VII de la Sociedad Española de Ciencia del Suelo y Estudio de los suelos del Campo de Cartagena.-- VII Curso Internacional de fertilidad de suelos y nutrición vegetal.-- Becas de estudios científicos y técnicos de la Fundación Juan March para 1979.--IV Simposio Nacional de Bioclimatología.-- III Reunión del Grupo Humus (junio de 1979).-- Premio Agrícola Aedos (Convocatoria 1979).--BibliografíaPeer reviewe

Infections, antibiotic treatment and mortality in patients admitted to ICUs in countries considered to have high levels of antibiotic resistance compared to those with low levels

Background: Antimicrobial resistance is an increasing concern in ICUs worldwide. Infection with an antibiotic resistant (ABR) strain of an organism is associated with greater mortality than infection with the non-resistant strain, but there are few data assessing whether being admitted to an intensive care unit (ICU) with high levels of antimicrobial resistance is associated with a worse outcome than being admitted to an ICU with low rates of resistance. The aim of this study was, therefore, to compare the characteristics of infections and antibiotic treatments and patient outcomes in patients admitted to ICUs in countries considered as having high levels of antibiotic resistance and those admitted to ICUs in countries considered as having low levels of antibiotic resistance. Methods: Data from the large, international EPIC II one-day point prevalence study on infections in patients hospitalized in ICUs were used. For the current study, we compared the data obtained from patients from two groups of countries: countries with reported MRSA rates of greater than= 25% (highABR: Greece, Israel, Italy, Malta, Portugal, Spain, and Turkey) and countries with MRSA rates of less than 5% (lowABR: Denmark, Finland, Netherlands, Norway, and Sweden). Results: On the study day, 1187/2204 (53.9%) patients in the HighABR ICUs were infected and 255/558 (45.7%) in the LowABR ICUs (P less than 0.01). Patients in the HighABR ICUs were more severely ill than those in the LowABR ICUs, as reflected by a higher SAPS II score (35.6 vs 32.7, P less than 0.05) and had longer median ICU (12 days vs 5 days) and hospital (24 days vs 16 days) lengths of stay. They also had higher crude ICU (20.0% vs 15.4%) and hospital (27.0% vs 21.5%) mortality rates (both P less than 0.05). However, after multivariable adjustment and matched pair analysis there were no differences in ICU or hospital mortality rates between High or LowABR ICU patients overall or among those with infections. Conclusions: Being hospitalized in an ICU in a region with high levels of antimicrobial resistance is not associated per se with a worse outcome

Infections, antibiotic treatment and mortality in patients admitted to ICUs in countries considered to have high levels of antibiotic resistance compared to those with low levels

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