A numerical algorithm for a Signorini problem associated with Maxwell–Norton materials by using generalized Newton’s methods

The goal of this work is to present new numerical approaches to obtain computationally efficient adaptive procedures to solve contact problems associated with Maxwell–Norton materials. We will describe in detail the numerical methods used to solve such problems and derive iterative algorithms. To validate the proposed algorithms we will present some test examples with known analytical solutions. Finally, we will compare the efficiency of the algorithms presented in this paper with others previously proposed by the authors.This research was supported by Xunta de Galicia (projects PGIDT00PXI20701PR, PGIDT02PXIC20701PN) and CYCIT-FEDER (projects DPI2001-2908, DPI2004-01993).S

Pervasive RNA Regulation of Metabolism Enhances the Root Colonization Ability of Nitrogen-Fixing Symbiotic α-Rhizobia

The rhizosphere and rhizoplane are nutrient-rich but selective environments for the root microbiome. Here, we deciphered a posttranscriptional network regulated by the homologous trans-small RNAs (sRNAs) AbcR1 and AbcR2, which rewire the metabolism of the nitrogen-fixing α-rhizobium Sinorhizobium meliloti during preinfection stages of symbiosis with its legume host alfalfa. The LysR-type regulator LsrB, which transduces the cell redox state, is indispensable for AbcR1 expression in actively dividing bacteria, whereas the stress-induced transcription of AbcR2 depends on the alternative σ factor RpoH1. MS2 affinity purification coupled with RNA sequencing unveiled exceptionally large and overlapping AbcR1/2 mRNA interactomes, jointly representing ⁓6% of the S. meliloti protein-coding genes. Most mRNAs encode transport/metabolic proteins whose translation is silenced by base pairing to two distinct anti-Shine Dalgarno motifs that function independently in both sRNAs. A metabolic model-aided analysis of the targetomes predicted changes in AbcR1/2 expression driven by shifts in carbon/nitrogen sources, which were confirmed experimentally. Low AbcR1/2 levels in some defined media anticipated overexpression growth phenotypes linked to the silencing of specific mRNAs. As a proof of principle, we confirmed AbcR1/2-mediated downregulation of the l-amino acid AapQ permease. AbcR1/2 interactomes are well represented in rhizosphere-related S. meliloti transcriptomic signatures. Remarkably, a lack of AbcR1 specifically compromised the ability of S. meliloti to colonize the root rhizoplane. The AbcR1 regulon likely ranks the utilization of available substrates to optimize metabolism, thus conferring on S. meliloti an advantage for efficient rhizosphere/rhizoplane colonization. AbcR1 regulation is predicted to be conserved in related α-rhizobia, which opens unprecedented possibilities for engineering highly competitive biofertilizers

CDH1 somatic alterations in Mexican patients with diffuse and mixed sporadic gastric cancer

Background: Diffuse gastric cancer (DGC) is associated with the reduction or absence of the expression of the cell adhesion protein E-cadherin (encoded by the CDH1 gene). Molecular characteristics are less well described for mixed gastric cancer (MGC). The main somatic alterations that have been described in the CDH1 gene are mutations, loss of heterozygosity (LOH) and promoter methylation. The aim was to analyze CDH1 somatic alterations in Mexican patients with diffuse and mixed gastric cancer. Methods: We searched for mutations in the CDH1 gene in tumor DNA from DGC (n = 13) and MGC (n = 7) patients by next generation sequencing (NGS). Validation of findings was performed using Sanger sequencing. LOH was analyzed using dinucleotide repeat markers surrounding the CDH1 gene, and methylation was investigated by DNA bisulfite conversion and sequencing. E-cadherin protein deficiency was analyzed by immunohistochemistry. Results: Seventeen point variants were identified by NGS, 13 of them were validated by Sanger sequencing. Only 1/13 had not been previously reported (c.-137C > A), and 12/13 were already reported as polymorphisms. Two DGC cases presented LOH at the locus 16q22.1 (13.3%). CDH1 promoter methylation was positive in (7/11) 63.6% and (4/6) 66.6% of the cases with DGC and MGC, respectively. E-cadherin protein deficiency was observed in 58.3% of DGC cases while 100% in MGC cases. Conclusions: While no pathogenic somatic mutations were found that could explain the diffuse histology of gastric cancer in DGC and MGC, methylation was the most common somatic inactivation event of the CDH1 gene, and LOH was rare. The previously unreported c.-137C > A variant modify the CDH1 gene expression since it alters the binding sites for transcription factors.This work was supported by the “Consejo Nacional de Ciencia y Tecnología (CONACYT)” (grant Ciencia Básica 2013–1-222972) and by the “Fondo de Investigación en Salud (FIS), Instituto Mexicano del Seguro Social (IMSS)” (grant FIS/IMSS/PROT/G13/1189), that contributed to the design of the study, collection, analysis, interpretation of data and writing the manuscript. We thank the following institutions: 1) Coordinación de Investigación en Salud (CIS), Instituto Mexicano del Seguro Social (IMSS) for the support given to ARBC, through the Professional Development in the International Research of Graduate Students (PRODESI) program; 2) Fundación IMSS, A.C. for the research grant awarded to JYSL and MTMT; 3) FEDER - Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 - Operational Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT/ Ministério da Ciência, Tecnologia e Inovação in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274); 4) The project NORTE-01-0145-FEDER-000029, supported by Norte Portugal Regional Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF); 5) FCT fellowships (SFRH/BPD/86543/2012 to JC; SFRH/BPD/89764/2012 to PO; PD/ BD/128007/2016 to AS). IPATIMUP integrates the i3S Research Unit, which is partially supported by FCT, the Portuguese Foundation for Science and Technology

Aplicación de biología molecular en veterinaria: Pcr como método de diagnóstico para investigar presencia de Escherichia Coli productora de Verotoxina (Vtec) en caninos de zonas rurales y periurbanas. Su implicancia en salud pública

El síndrome urémico hemolítico (SUH) se caracteriza por anemia hemolítica microangiopática, plaquetopenia y daño renal. Constituye la primera causa de insuficiencia renal aguda en la edad pediátrica y la segunda de insuficiencia renal crónica. Escherichia coli productor de verotoxina es el primer agente etiológico de SUH. Los objetivos del presente trabajo son determinar si los perros pueden constituir un riesgo para la salud pública como portadores de VTEC y poner a punto la técnica de la reacción en cadena de la polimerasa (PCR). Hasta la fecha se han tomado 26 muestras de zonas peri urbanas y de caninos de la Sociedad Mendocina Protectora de Animales (SMPA). Las muestras fueron obtenidas mediante hisopado rectal de caninos y fueron sembradas en el medio de cultivo selectivo Agar Mac Conkey Sorbitol y Agar Levine e incubadas 24 horas a 37°C

Relación entre la respiración del suelo y propiedades indicadoras de la calidad del suelo en un viñedo de la D.O.Ca. Rioja con manejos alternativos

11 páginas, 6 figuras, 2 tablas.-- Trabajo presentado al IV Congreso Ibérico de la Ciencia del Suelo: "Suelo: Funciones y Manejo" celebrado en Granada del 21 al 24 de septiembre de 2010.En un suelo de viñedo representativo de la D.O.Ca Rioja se han estudiado la capacidad de dos manejos de suelo alternativos, cubiertas vegetales y la aplicación de sustrato de postcultivo de champiñón (SPCH) para incrementar el carbono orgánico del suelo y mejorar la calidad del mismo. Se muestreó la capa más superficial del suelo (0-5 cm), y se encontró que ambos manejos incrementaron la materia orgánica total y las hcciones lábiles como el Carbono soluble y el Nitrógeno potencialmente mineralizable. Sin embargo las cubiertas vegetales presentan mayor actividad enzimática B-Glucosidasa y Ureasa; las cuales mostraron altas correlaciones con la respiración del suelo.El presente trabajo se realizado gracias al INIA y el Fondo Social Europeo a través del programa de Doctores INIA-CCAA. También gracias a la financiación del Gobierno de la Rioja a través del proyecto regional R-07-09 y del INIA (proyecto RTA 2009-00101-00-00).Peer reviewe

The use of fluoroproline in MUC1 antigen enables efficient detection of antibodies in patients with prostate cancer

A structure-based design of a new generation of tumor-associated glycopeptides with improved affinity against two anti-MUC1 antibodies is described. These unique antigens feature a fluorinated proline residue, such as a (4S)-4-fluoro-l-proline or 4,4-difluoro-l-proline, at the most immunogenic domain. Binding assays using biolayer interferometry reveal 3-fold to 10-fold affinity improvement with respect to the natural (glyco)peptides. According to X-ray crystallography and MD simulations, the fluorinated residues stabilize the antigen-antibody complex by enhancing key CH/π interactions. Interestingly, a notable improvement in detection of cancer-associated anti-MUC1 antibodies from serum of patients with prostate cancer is achieved with the non-natural antigens, which proves that these derivatives can be considered better diagnostic tools than the natural antigen for prostate cancer.We thank the Ministerio de Economía y Competitividad (projects CTQ2015-67727-R, UNLR13-4E-1931, CTQ2013-44367-C2-2-P, CTQ2015-64597-C2-1P, and BFU2016-75633-P). I.A.B. thanks the Asociación Española Contra el Cancer en La Rioja for a grant. I.S.A. and G.J.L.B. thank FCT Portugal (Ph.D. studentship and FCT Investigator, respectively) and EPSRC. G.J.L.B. holds a Royal Society URF and an ERC StG (TagIt). F.C. and G.J.L.B thank the EU (Marie-Sklodowska Curie ITN, Protein Conjugates). R.H-G. thanks Agencia Aragonesa para la Investigación y Desarrollo (ARAID) and the Diputación General de Aragón (DGA, B89) for financial support. The research leading to these results has also received funding from the FP7 (2007-2013) under BioStruct-X (grant agreement no. 283570 and BIOSTRUCTX_5186). We thank synchrotron radiation source DIAMOND (Oxford) and beamline I04 (number of experiment mx10121-19). The Hokkaido University group acknowledges JSPS KAKENHI grant no. 25220206 and JSPS Wakate B KAKENHI grant no. 24710242. We also thank CESGA (Santiago de Compostela) for computer support.Peer reviewedPeer Reviewe

High-affinity RNA binding by a hyperthermophilic single-stranded DNA-binding protein

Single-stranded DNA-binding proteins (SSBs), including replication protein A (RPA) in eukaryotes, play a central role in DNA replication, recombination, and repair. SSBs utilise an oligonucleotide/oligosaccharide-binding (OB) fold domain to bind DNA, and typically oligomerise in solution to bring multiple OB fold domains together in the functional SSB. SSBs from hyperthermophilic crenarchaea, such as Sulfolobus solfataricus, have an unusual structure with a single OB fold coupled to a flexible C-terminal tail. The OB fold resembles those in RPA, whilst the tail is reminiscent of bacterial SSBs and mediates interaction with other proteins. One paradigm in the field is that SSBs bind specifically to ssDNA and much less strongly to RNA, ensuring that their functions are restricted to DNA metabolism. Here, we use a combination of biochemical and biophysical approaches to demonstrate that the binding properties of S. solfataricus SSB are essentially identical for ssDNA and ssRNA. These features may represent an adaptation to a hyperthermophilic lifestyle, where DNA and RNA damage is a more frequent event.Publisher PDFPeer reviewe