Staphylococcus saprophyticus from clinical and environmental origins have distinct biofilm composition

Biofilm formation has been shown to be critical to the success of uropathogens. Although Staphylococcus saprophyticus is a common cause of urinary tract infections, its biofilm production capacity, composition, genetic basis, and origin are poorly understood. We investigated biofilm formation in a large and diverse collection of S. saprophyticus (n = 422). Biofilm matrix composition was assessed in representative strains (n = 63) belonging to two main S. saprophyticus lineages (G and S) recovered from human infection, colonization, and food-related environment using biofilm detachment approach. To identify factors that could be associated with biofilm formation and structure variation, we used a pangenome-wide association study approach. Almost all the isolates (91%; n = 384/422) produced biofilm. Among the 63 representative strains, we identified eight biofilm matrix phenotypes, but the most common were composed of protein or protein-extracellular DNA (eDNA)-polysaccharides (38%, 24/63 each). Biofilms containing protein-eDNA-polysaccharides were linked to lineage G and environmental isolates, whereas protein-based biofilms were produced by lineage S and infection isolates (p < 0.05). Putative biofilm-associated genes, namely, aas, atl, ebpS, uafA, sasF, sasD, sdrH, splE, sdrE, sdrC, sraP, and ica genes, were found with different frequencies (3-100%), but there was no correlation between their presence and biofilm production or matrix types. Notably, icaC_1 was ubiquitous in the collection, while icaR was lineage G-associated, and only four strains carried a complete ica gene cluster (icaADBCR) except one that was without icaR. We provided evidence, using a comparative genomic approach, that the complete icaADBCR cluster was acquired multiple times by S. saprophyticus and originated from other coagulase-negative staphylococci. Overall, the composition of S. saprophyticus biofilms was distinct in environmental and clinical isolates, suggesting that modulation of biofilm structure could be a key step in the pathogenicity of these bacteria. Moreover, biofilm production in S. saprophyticus is ica-independent, and the complete icaADBCR was acquired from other staphylococci

Foodborne Origin and Local and Global Spread of Staphylococcus saprophyticus Causing Human Urinary Tract Infections

Staphylococcus saprophyticus is a primary cause of community-acquired urinary tract infections (UTIs) in young women. S. saprophyticus colonizes humans and animals but basic features of its molecular epidemiology are undetermined. We conducted a phylogenomic analysis of 321 S. saprophyticus isolates collected from human UTIs worldwide during 1997-2017 and 232 isolates from human UTIs and the pig-processing chain in a confined region during 2016-2017. We found epidemiologic and genomic evidence that the meat-production chain is a major source of S. saprophyticus causing human UTIs; human microbiota is another possible origin. Pathogenic S. saprophyticus belonged to 2 lineages with distinctive generic features that are globally and locally disseminated. Pangenome-wide approaches identified a strong association between pathogenicity and antimicrobial resistance, phages, platelet binding proteins, and an increased recombination rate. Our study provides insight into the origin, transmission, and population structure of pathogenic S. saprophyticus and identifies putative new virulence factors

Genes related to cell-mediated cytotoxicity and interferon response are induced in the retina of European sea bass upon intravitreal infection with nodavirus

Viral diseases are responsible for high rates of mortality and subsequent economic losses in modern aquaculture. The nervous necrosis virus (NNV) produces viral encephalopathy and retinopathy (VER), which affects the central nervous system, is considered one of the most serious viral diseases in marine aquaculture. Although some studies have localized NNV in the retina cells, none has dealt with immunity in the retina. Thus, for the first time, we intravitreally infected healthy specimens of European sea bass (Dicentrarchus labrax) with NNV with the aim of characterizing the immune response in the retina. Ultrastructural analysis detected important retinal injuries and structure degradation, including pycnosis, hydropic degeneration and vacuolization in some cell layers as well as myelin sheaths in the optic nerve fibres. Immunohistochemistry demonstrated that NNV re- plicated in the eyes. Regarding retinal immunity, NNV infection elicited the transcription of genes encoding proteins involved in the interferon (IFN) and cell-mediated cytotoxicity (CMC) responses as well as B and T cell markers, demonstrating that viral replication influences innate and adaptive responses. Further studies are needed to understand the retina immunity and whether the main retinal function, vision, is affected by noda- virus.Versión del edito

Trust transitivity in social networks

Non-centralized recommendation-based decision making is a central feature of several social and technological processes, such as market dynamics, peer-to-peer file-sharing and the web of trust of digital certification. We investigate the properties of trust propagation on networks, based on a simple metric of trust transitivity. We investigate analytically the percolation properties of trust transitivity in random networks with arbitrary degree distribution, and compare with numerical realizations. We find that the existence of a non-zero fraction of absolute trust (i.e. entirely confident trust) is a requirement for the viability of global trust propagation in large systems: The average pair-wise trust is marked by a discontinuous transition at a specific fraction of absolute trust, below which it vanishes. Furthermore, we perform an extensive analysis of the Pretty Good Privacy (PGP) web of trust, in view of the concepts introduced. We compare different scenarios of trust distribution: community- and authority-centered. We find that these scenarios lead to sharply different patterns of trust propagation, due to the segregation of authority hubs and densely-connected communities. While the authority-centered scenario is more efficient, and leads to higher average trust values, it favours weakly-connected "fringe" nodes, which are directly trusted by authorities. The community-centered scheme, on the other hand, favours nodes with intermediate degrees, in detriment of the authorities and its "fringe" peers.Comment: 11 pages, 9 figures (with minor corrections

Dependencia funcional, deterioro cognitivo y características de la marcha en adultos mayores con enfermedades crónicas

Objetivo: Identificar el nivel y relación de dependencia funcional (DF), deterioro cognitivo (DC) y características de la marcha en adultos mayores (AM) con enfermedades crónicas, habitantes del área metropolitana de Saltillo, Coahuila. Método: Diseño descriptivo correlacional. Muestra constituida por 105 AM de 60 años o más, usuarios de los Centros de Atención e Integración Familiar (CAIF). El tamaño de la muestra se determinó a través del paquete estadístico nQuery Advisor 7.0 considerando análisis de correlación bivariada, nivel de significancia de 0.5 y potencia del 95%. El muestreo fue por conveniencia. La recolección de datos se realizó a través de una cédula de datos socio-demográficas conjuntamente con cuatro instrumentos: para DF 1. Actividades Básicas de la Vida Diaria (AVD) y 2. Actividades Instrumentales de la Vida Diaria (AIVD); para DC 3. Mini Mental State Examination MMS-E; para las características de la marcha, 4. Sistema para Análisis de Marcha GaitRite ©, alphas de 0.730, 0.765, 0.720 y 0.811, respectivamente. Resultados. La edad promedio de los AM participantes es de 75 años (X = 75 ± 6) y escolaridad de 5 años (X = 5 ± 3). La mayor parte son mujeres (81.9%); que viven sin pareja (74.3%) y reportan alguna enfermedad crónico-degenerativa (65%) como Diabetes, 32.4%; Hipertensión, 61% y Enfermedades Articulares, 42%. La prevalencia de: dependencia severa en ABVD 5.7% y AIVD 21.9 %; DC 24 %; Los AM con mayor edad y menor escolaridad, reportan mayor grado de DC (r= .251; p<.05; r= -.259; p<.05, respectivamente) y dependencia para realizar ABVD (r=.297; p<.05) y AIVD (r=.351; p<.05); Por lo menos, el 30% de AM presentabó dificultades para mantener el equilibrio. Además, el 60% presentó dificultades para sentarse porque tienen problemas al medir la distancia entre su propio cuerpo y la silla, caen en la silla o se apoye en él con movimientos inseguros. 29% presentaba dificultades para elevar su pie derecho completamente. Discusión y Conclusiones. Los resultados de este estudio confirman lo que la literatura reporta acerca de la prevalencia y asociación de DF, DC y presencia de enfermedades crónicas características del AM como Diabetes e Hipertensión. Es necesario profundizar en el análisis de este estudio incorporando mediciones acerca del tiempo de diagnóstico de la enfermedad crónica, co-morbilidad, síntomas de depresión y diferencias de género, entre otros aspectos. También los factores asociados a la problemática de la marcha. Para el profesional de Enfermería, la continuidad de este fenómeno de estudio, fortalecerá el cuerpo de conocimientos disciplinares y la atención a las complejas necesidades de cuidado a la salud que demanda este segmento de la población. Palabras Clave: Adulto Mayor, Dependencia Funcional, Deterioro Cognitivo, Marcha

VAMOS: a Pathfinder for the HAWC Gamma-Ray Observatory

VAMOS was a prototype detector built in 2011 at an altitude of 4100m a.s.l. in the state of Puebla, Mexico. The aim of VAMOS was to finalize the design, construction techniques and data acquisition system of the HAWC observatory. HAWC is an air-shower array currently under construction at the same site of VAMOS with the purpose to study the TeV sky. The VAMOS setup included six water Cherenkov detectors and two different data acquisition systems. It was in operation between October 2011 and May 2012 with an average live time of 30%. Besides the scientific verification purposes, the eight months of data were used to obtain the results presented in this paper: the detector response to the Forbush decrease of March 2012, and the analysis of possible emission, at energies above 30 GeV, for long gamma-ray bursts GRB111016B and GRB120328B.Comment: Accepted for pubblication in Astroparticle Physics Journal (20 pages, 10 figures). Corresponding authors: A.Marinelli and D.Zaboro

Susceptibility to type 1 diabetes conferred by the PTPN22 C1858T polymorphism in the Spanish population

<p>Abstract</p> <p>Background</p> <p>The protein tyrosine phosphatase N22 gene (<it>PTPN22</it>) encodes a lymphoid-specific phosphatase (LYP) which is an important downregulator of T cell activation. A <it>PTPN22 </it>polymorphism, C1858T, was found associated with type 1 diabetes (T1D) in different Caucasian populations. In this study, we aimed at confirming the role of this variant in T1D predisposition in the Spanish population.</p> <p>Methods</p> <p>A case-control was performed with 316 Spanish white T1D patients consecutively recruited and 554 healthy controls, all of them from the Madrid area. The <it>PTPN22 </it>C1858T SNP was genotyped in both patients and controls using a TaqMan Assay in a 7900 HT Fast Real-Time PCR System.</p> <p>Results</p> <p>We replicated for the first time in a Spanish population the association of the 1858T allele with an increased risk for developing T1D [carriers of allele T vs. CC: OR (95%) = 1.73 (1.17–2.54); p = 0.004]. Furthermore, this allele showed a significant association in female patients with diabetes onset before age 16 years [carriers of allele T vs. CC: OR (95%) = 2.95 (1.45–6.01), female patients vs female controls p = 0.0009]. No other association in specific subgroups stratified for gender, HLA susceptibility or age at onset were observed.</p> <p>Conclusion</p> <p>Our results provide evidence that the <it>PTPN22 </it>1858T allele is a T1D susceptibility factor also in the Spanish population and it might play a different role in susceptibility to T1D according to gender in early-onset T1D patients.</p

Inactivation of CDK/pRb Pathway Normalizes Survival Pattern of Lymphoblasts Expressing the FTLD-Progranulin Mutation c.709-1G>A

8 figuras, 2 tablasBackground Mutations in the progranulin (PGRN) gene, leading to haploinsufficiency, cause familial frontotemporal lobar degeneration (FTLD-TDP), although the pathogenic mechanism of PGRN deficit is largely unknown. Allelic loss of PGRN was previously shown to increase the activity of cyclin-dependent kinase (CDK) CDK6/pRb pathway in lymphoblasts expressing the c.709-1G>A PGRN mutation. Since members of the CDK family appear to play a role in neurodegenerative disorders and in apoptotic death of neurons subjected to various insults, we investigated the role of CDK6/pRb in cell survival/death mechanisms following serum deprivation. Methodology/Principal Findings We performed a comparative study of cell viability after serum withdrawal of established lymphoblastoid cell lines from control and carriers of c.709-1G>A PGRN mutation, asymptomatic and FTLD-TDP diagnosed individuals. Our results suggest that the CDK6/pRb pathway is enhanced in the c.709-1G>A bearing lymphoblasts. Apparently, this feature allows PGRN-deficient cells to escape from serum withdrawal-induced apoptosis by decreasing the activity of executive caspases and lowering the dissipation of mitochondrial membrane potential and the release of cytochrome c from the mitochondria. Inhibitors of CDK6 expression levels like sodium butyrate or the CDK6 activity such as PD332991 were able to restore the vulnerability of lymphoblasts from FTLD-TDP patients to trophic factor withdrawal. Conclusion/Significance The use of PGRN-deficient lymphoblasts from FTLD-TDP patients may be a useful model to investigate cell biochemical aspects of this disease. It is suggested that CDK6 could be potentially a therapeutic target for the treatment of the FTLD-TDPThis work has been supported by grants from Ministry of Education and Science (SAF2007-61701, SAF2010-15700, SAF2011-28603), Fundación Eugenio Rodríguez Pascual, and Basque Government (Saiotek program 2008–2009). NE holds a fellowship of the JAE predoctoral program of the CSICPeer reviewe