NTHL1 biallelic mutations seldom cause colorectal cancer, serrated polyposis or a multi-tumor phenotype, in absence of colorectal adenomas

In 2015 Weren et al. described a hereditary cancer syndrome caused by biallelic mutations in the DNA base excision repair gene NTHL1, characterized by attenuated adenomatous polyposis and increased colorectal cancer (CRC) risk, largely resembling the recessive syndrome caused by MUTYH mutations1. To date, 33 homozygous or compound heterozygous NTHL1 mutation carriers have been reported (21 families)1,2,3,4,5,6,7,8. More than 5 colonic adenomas (range: 6 to >50) were identified in 24 of the 28 (85%) mutation carriers who underwent colonoscopy screening, and CRC was diagnosed in 19 (68%) of them. Noteworthy, 17 carriers (57%) were diagnosed with multiple primary malignant tumors in extracolonic locations, being the most recurrently found breast and endometrial tumors, head neck squamous cell carcimomas, meningiomas, and bladder and basal cell carcinomas, suggesting that the NTHL1-associated syndrome is a multi-tumor disease rather than a solely CRC syndrome. On the other hand, the fact that at least ¼ (7/28) of the reported biallelic mutation carriers who underwent colonoscopy screening had ≤10 adenomas, and that ≥5 hyperplastic polyps were detected in five carriers (polyp number range: 5->30), lead us to suspect a possible association of NTHL1 mutations with nonpolyposis CRC and serrated/hyperplastic polyposis. Based on previous evidence and with the aim of refining the phenotypic characteristics of the NTHL1-associated syndrome, here we evaluated the implication of NTHL1 biallelic mutations in the predisposition to personal or familial history of multiple tumor types, familial/early-onset nonpolyposis CRC, and serrated/hyperplastic polyposis

Partial Activation of SA- and JA-Defensive Pathways in Strawberry upon Colletotrichum acutatum Interaction

[EN] Understanding the nature of pathogen host interaction may help improve strawberry (Fragaria x anahassa) cultivars. Plant resistance to pathogenic agents usually operates through a complex network of defense mechanisms mediated by a diverse array of signaling molecules. In strawberry, resistance to a variety of pathogens has been reported to be mostly polygenic and quantitatively inherited, making it difficult to associate molecular markers with disease resistance genes. Colletotrichum acutaturn spp. is a major strawberry pathogen, and completely resistant cultivars have not been reported. Moreover, strawberry defense network components and mechanisms remain largely unknown and poorly understood. Assessment of the strawberry response to C. acutatum included a global transcript analysis, and acidic hormones SA and JA measurements were analyzed after challenge with the pathogen. Induction of transcripts corresponding to the SA and JA signaling pathways and key genes controlling major steps within these defense pathways was detected. Accordingly, SA and JA accumulated in strawberry after infection. Contrastingly, induction of several important SA, JA, and oxidative stress-responsive defense genes, including FaPR1-1, FaLOX2, FaJAR1, FaPDF1, and FaGST1, was not detected, which suggests that specific branches in these defense pathways (those leading to FaPR1-2, FaPR2-1, FaPR2-2, FaAOS, FaPR5, and FaPR10) were activated. Our results reveal that specific aspects in SA and JA dependent signaling pathways are activated in strawberry upon interaction with C. acutatum. Certain described defense-associated transcripts related to these two known signaling pathways do not increase in abundance following infection. This finding suggests new insight into a specific putative molecular strategy for defense against this pathogen.Authors are grateful to Dr. JM Lopez-Aranda (IFAPA-Centro de Churriana) for providing micropropagated strawberry plants and to Nicolas Garcia-Caparros for technical assistance. Authors also want to thank Kevin M. Folta for his insightful comments on the paper. This work was supported by Junta de Andalucia, Spain [Proyectos de Excelencia P07-AGR-02482/P12-AGR-2174, and grants to Grupo-BIO278].Amil-Ruiz, F.; Garrido-Gala, J.; Gadea Vacas, J.; Blanco-Portales, R.; Munoz-Merida, A.; Trelles, O.; De Los Santos, B.... (2016). Partial Activation of SA- and JA-Defensive Pathways in Strawberry upon Colletotrichum acutatum Interaction. Frontiers in Plant Science. 7(1036). https://doi.org/10.3389/fpls.2016.01036S71036Acosta, I. F., & Farmer, E. E. (2010). Jasmonates. The Arabidopsis Book, 8, e0129. doi:10.1199/tab.0129Al-Shahrour, F., Diaz-Uriarte, R., & Dopazo, J. (2004). 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Dynamic Virtual Network Reconfiguration Over SDN Orchestrated Multitechnology Optical Transport Domains

Network virtualization is an emerging technique that enables multiple tenants to share an underlying physical infrastructure, isolating the traffic running over different virtual infrastructures/tenants. This technique aims to improve network utilization, while reducing the complexities in terms of network management for operators. Applied to this context, software defined networking (SDN) paradigm can ease network configurations by enabling network programmability and automation, which reduces the amount of operations required from both service and infrastructure providers. SDN techniques are decreasing vendor lock-in issues due to specific configuration methods or protocols. Application-based Network Operations (ABNO) is a toolbox of key network functional components with the goal of offering application-driven network management. Service provisioning using ABNO may involve direct configuration of data plane elements or delegate it to several control plane modules. We validate the applicability of ABNO to multi-tenant virtual networks in multi-technology optical domains based on two scenarios, in which multiple control plane instances are orchestrated by the architecture. Congestion Detection and Failure Recovery, are chosen to demonstrate fast recalculation and reconfiguration, while hiding the configurations in the physical layer from the upper layer.Grant numbers : supported by the Spanish Ministry of Economy and Competitiveness through the project FARO (TEC2012-38119)

Racism: A Teenagers\u27 Perspective Results of Preliminary Research from Madrid, Spain

In mid-June, 2005, the members of the INTER Center received a collaboration proposal from FETE-UGT8, with the objective of carrying out a brief exploratory study on the perceptions and experiences that young people and adolescents, mainly immigrants, have concerning possible experiences of discrimination and racism in their immediate surroundings. The initial objectives of the project were expanded due to the dynamics of the project itself. New focuses of attention and social, educational and personal dynamics, which can condition to a certain extent the experiences that immigrant adolescents undergo, were detected. The project initially consisted of a series of interviews with adolescents between 12 and 18 years of age. A total of 20 interviews were carried out, some of them group interviews. We consider this project focus, although positive, to be limited, and we think that it would have been necessary to broaden the sample and consider other people in the young people’s social and family environment (family members, friends, classmates, professors, all of them of different origins, including the host country)

Charge and spin configurations in the coupled quantum dots with Coulomb correlations induced by tunneling current

We investigated the peculiarities of non-equilibrium charge states and spin configurations in the system of two strongly coupled quantum dots (QDs) weakly connected to the electrodes in the presence of Coulomb correlations. We analyzed the modification of non-equilibrium charge states and different spin configurations of the system in a wide range of applied bias voltage and revealed well pronounced ranges of system parameters where negative tunneling conductivity appears due to the Coulomb correlations.Comment: 10 pages, 6 figure

The complexity of mesoporous silica nanomaterials unravelled by single molecule microscopy

Mesoporous silica nanomaterials are a novel class of materials that offer a highly complex porous network with nanometre-sized channels into which a wide amount of differently sized guests can be incorporated. This makes them an ideal host for various applications for example in catalysis, chromatography and nanomedicine. For these applications, analyzing the host properties and understanding the complicated host–guest interactions is of pivotal importance. In this perspective we review some of our recent work that demonstrates that single molecule microscopy techniques can be utilized to characterize the porous silica host with unprecedented detail. Furthermore, the single molecule studies reveal sample heterogeneities and are a highly efficient tool to gain direct mechanistic insights into the host–guest interactions. Single molecule microscopy thus contributes to a thorough understanding of these nanomaterials enabling the development of novel tailor-made materials and hence optimizing their applicability significantly

Factors associated with the development of septic shock in patients with candidemia: A post hoc analysis from two prospective cohorts

Background: Almost one third of the patients with candidemia develop septic shock. The understanding why some patients do and others do not develop septic shock is very limited. The objective of this study was to identify variables associated with septic shock development in a large population of patients with candidemia. Methods: A post hoc analysis was performed on two prospective, multicenter cohort of patients with candidemia from 12 hospitals in Spain and Italy. All episodes occurring from September 2016 to February 2018 were analyzed to assess variables associated with septic shock development defined according to The Third International Consensus Definition for Sepsis and Septic Shock (Sepsis-3). Results: Of 317 candidemic patients, 99 (31.2%) presented septic shock attributable to candidemia. Multivariate logistic regression analysis identifies the following factors associated with septic shock development: age > 50 years (OR 2.57, 95% CI 1.03-6.41, p = 0.04), abdominal source of the infection (OR 2.18, 95% CI 1.04-4.55, p = 0.04), and admission to a general ward at the time of candidemia onset (OR 0.21, 95% CI, 0.12-0.44, p = 0.001). Septic shock development was independently associated with a greater risk of 30-day mortality (OR 2.14, 95% CI 1.08-4.24, p = 0.02). Conclusions: Age and abdominal source of the infection are the most important factors significantly associated with the development of septic shock in patients with candidemia. Our findings suggest that host factors and source of the infection may be more important for development of septic shock than intrinsic virulence factors of organisms

Gas phase Elemental abundances in Molecular cloudS (GEMS) : III. Unlocking the CS chemistry: the CS plus O reaction

Context. Carbon monosulphide (CS) is among the most abundant gas-phase S-bearing molecules in cold dark molecular clouds. It is easily observable with several transitions in the millimeter wavelength range, and has been widely used as a tracer of the gas density in the interstellar medium in our Galaxy and external galaxies. However, chemical models fail to account for the observed CS abundances when assuming the cosmic value for the elemental abundance of sulfur. Aims. The CS+O -> CO + S reaction has been proposed as a relevant CS destruction mechanism at low temperatures, and could explain the discrepancy between models and observations. Its reaction rate has been experimentally measured at temperatures of 150-400 K, but the extrapolation to lower temperatures is doubtful. Our goal is to calculate the CS+O reaction rate at temperatures Methods. We performed ab initio calculations to obtain the three lowest potential energy surfaces (PES) of the CS+O system. These PESs are used to study the reaction dynamics, using several methods (classical, quantum, and semiclassical) to eventually calculate the CS + O thermal reaction rates. In order to check the accuracy of our calculations, we compare the results of our theoretical calculations for T similar to 150-400 K with those obtained in the laboratory. Results. Our detailed theoretical study on the CS+O reaction, which is in agreement with the experimental data obtained at 150-400 K, demonstrates the reliability of our approach. After a careful analysis at lower temperatures, we find that the rate constant at 10 K is negligible, below 10(-15) cm(3) s(-1), which is consistent with the extrapolation of experimental data using the Arrhenius expression. Conclusions. We use the updated chemical network to model the sulfur chemistry in Taurus Molecular Cloud 1 (TMC 1) based on molecular abundances determined from Gas phase Elemental abundances in Molecular CloudS (GEMS) project observations. In our model, we take into account the expected decrease of the cosmic ray ionization rate, zeta(H2), along the cloud. The abundance of CS is still overestimated when assuming the cosmic value for the sulfur abundance.Peer reviewe