The ₉₅RGD₉₇ sequence on the A alpha chain of fibrinogen is essential for binding to its erythrocyte receptor

Background: Erythrocyte aggregation, a cardiovascular risk factor, is increased by high plasma fibrinogen levels. Here, the effect of different fibrinogen mutations on binding to its human erythrocyte receptor was assessed in order to identify the interaction sites. Methods: Three fibrinogen variants were tested, specifically mutated in their putative integrin recognition sites on the Aα chain (mutants D97E, D574E and D97E/D574E) and compared with wild-type fibrinogen. Results: Atomic force microscopy-based force spectroscopy measurements showed a significant decrease both on the fibrinogen–erythrocyte binding force and on its frequency for fibrinogen with the D97E mutation, indicating that the corresponding arginine–glycine–aspartate sequence (residues 95–97) is involved in this interaction, and supporting that the fibrinogen receptor on erythrocytes has a β3 subunit. Changes in the fibrin clot network structure obtained with the D97E mutant were observed by scanning electron microscopy. Conclusion: These findings may lead to innovative perspectives on the development of new therapeutic approaches to overcome the risks of fibrinogen-driven erythrocyte hyperaggregation

Portuguese validation of FACES-IV in adult children caregivers facing parental cancer

The purpose of the present study was to examine the psychometric properties of the FACES-IV in Portuguese caregivers of cancer patients. In this cross-sectional study, a sample of 214 adult children caregivers of cancer patients receiving chemotherapy, completed FACES-IV, Family Communication Scale (FCS), Family Satisfaction Scale (FSS), and Satisfaction with Social Support Scale (SSSS). Internal consistencies above .70 were found for all FACES-IV scales, except for Enmeshed and Rigid scales, as well as for the FCS, FSS, and SSSS (except for Intimacy). Strong correlations between FACES-IV and the validation scales FCS and FSS were found except for the Enmeshed and Rigid scales. Confirmatory analysis yielded an acceptable model for the six theoretical subscales. The discriminant analysis between problematic and non-problematic family systems showed results similar to the original study. These findings suggest that FACES-IV is a valid measure of family functioning in oncological family caregiving’s contexts.Acknowledgments This study was funded by a grant from the Portuguese Foundation for Science and Technology (reference SFRH/BD/43275/2008)

Self-organized network evolution coupled to extremal dynamics

The interplay between topology and dynamics in complex networks is a fundamental but widely unexplored problem. Here, we study this phenomenon on a prototype model in which the network is shaped by a dynamical variable. We couple the dynamics of the Bak-Sneppen evolution model with the rules of the so-called fitness network model for establishing the topology of a network; each vertex is assigned a fitness, and the vertex with minimum fitness and its neighbours are updated in each iteration. At the same time, the links between the updated vertices and all other vertices are drawn anew with a fitness-dependent connection probability. We show analytically and numerically that the system self-organizes to a non-trivial state that differs from what is obtained when the two processes are decoupled. A power-law decay of dynamical and topological quantities above a threshold emerges spontaneously, as well as a feedback between different dynamical regimes and the underlying correlation and percolation properties of the network.Comment: Accepted version. Supplementary information at http://www.nature.com/nphys/journal/v3/n11/suppinfo/nphys729_S1.htm

Lactate signalling regulates fungal β-glucan masking and immune evasion

AJPB: This work was supported by the European Research Council (STRIFE, ERC- 2009-AdG-249793), The UK Medical Research Council (MR/M026663/1), the UK Biotechnology and Biological Research Council (BB/K017365/1), the Wellcome Trust (080088; 097377). ERB: This work was supported by the UK Biotechnology and Biological Research Council (BB/M014525/1). GMA: Supported by the CNPq-Brazil (Science without Borders fellowship 202976/2014-9). GDB: Wellcome Trust (102705). CAM: This work was supported by the UK Medical Research Council (G0400284). DMM: This work was supported by UK National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC/K000306/1). NARG/JW: Wellcome Trust (086827, 075470,101873) and Wellcome Trust Strategic Award in Medical Mycology and Fungal Immunology (097377). ALL: This work was supported by the MRC Centre for Medical Mycology and the University of Aberdeen (MR/N006364/1).Peer reviewedPostprin

The Mechanisms of Codon Reassignments in Mitochondrial Genetic Codes

Many cases of non-standard genetic codes are known in mitochondrial genomes. We carry out analysis of phylogeny and codon usage of organisms for which the complete mitochondrial genome is available, and we determine the most likely mechanism for codon reassignment in each case. Reassignment events can be classified according to the gain-loss framework. The gain represents the appearance of a new tRNA for the reassigned codon or the change of an existing tRNA such that it gains the ability to pair with the codon. The loss represents the deletion of a tRNA or the change in a tRNA so that it no longer translates the codon. One possible mechanism is Codon Disappearance, where the codon disappears from the genome prior to the gain and loss events. In the alternative mechanisms the codon does not disappear. In the Unassigned Codon mechanism, the loss occurs first, whereas in the Ambiguous Intermediate mechanism, the gain occurs first. Codon usage analysis gives clear evidence of cases where the codon disappeared at the point of the reassignment and also cases where it did not disappear. Codon disappearance is the probable explanation for stop to sense reassignments and a small number of reassignments of sense codons. However, the majority of sense to sense reassignments cannot be explained by codon disappearance. In the latter cases, by analysis of the presence or absence of tRNAs in the genome and of the changes in tRNA sequences, it is sometimes possible to distinguish between the Unassigned Codon and Ambiguous Intermediate mechanisms. We emphasize that not all reassignments follow the same scenario and that it is necessary to consider the details of each case carefully.Comment: 53 pages (45 pages, including 4 figures + 8 pages of supplementary information). To appear in J.Mol.Evo

Identification of the Transcriptional Regulator NcrB in the Nickel Resistance Determinant of Leptospirillum ferriphilum UBK03

The nickel resistance determinant ncrABCY was identified in Leptospirillum ferriphilum UBK03. Within this operon, ncrA and ncrC encode two membrane proteins that form an efflux system, and ncrB encodes NcrB, which belongs to an uncharacterized family (DUF156) of proteins. How this determinant is regulated remains unknown. Our data indicate that expression of the nickel resistance determinant is induced by nickel. The promoter of ncrA, designated pncrA, was cloned into the promoter probe vector pPR9TT, and co-transformed with either a wild-type or mutant nickel resistance determinant. The results revealed that ncrB encoded a transcriptional regulator that could regulate the expression of ncrA, ncrB, and ncrC. A GC-rich inverted repeat sequence was identified in the promoter pncrA. Electrophoretic mobility shift assays (EMSAs) and footprinting assays showed that purified NcrB could specifically bind to the inverted repeat sequence of pncrA in vitro; this was confirmed by bacterial one-hybrid analysis. Moreover, this binding was inhibited in the presence of nickel ions. Thus, we classified NcrB as a transcriptional regulator that recognizes the inverted repeat sequence binding motif to regulate the expression of the key nickel resistance gene, ncrA

Study of 16 Portuguese activated sludge systems based on filamentous bacteria populations and their relationships with environmental parameters

A survey in 16 activated sludge waste water treatment plants (WWTP) was conducted to contribute to the knowledge of the environmental parameters that determine the composition of the filamentous community. A total of 128 samples of mixed liquor from municipal WWTP were collected during 2 years, and 22 filamentous morphotypes were identified. The most frequent and abundant filamentous bacteria were, in both cases and by this order, type 0041/0675, type 0092, Microthrix parvicella and 1851, nocardioforms and Haliscomenobacter hydrossis. Concerning dominance, type 1851 was the most frequently dominant morphotype, followed by M. parvicella and types 0092 and 0041/0675. These were also, and by this order, the dominant morphotypes during bulking occurrences. Significant correlations were obtained between the abundance of filamentous bacteria and environmental parameters, but multivariate statistical analysis only confirmed the correlation between type 0092 and Sludge Volume Index (SVI), emphasizing the association of this filament with bulking. The discussion of the results in light of published works was complicated by the random use of terms such as frequency, abundance, and dominance with different and often unclear meanings. This reinforces the need of clarifying these terms when discussing the causes of filamentous overgrowth in WWTP.Portuguese Foundation for Science and Technology (FCT) and the European Community fund FEDER, through Program COMPETE, in the ambit of the Projects FCOMP-01-0124-FEDER-007025 (PTDC/AMB/68393/2006), PEst-OE/EQB/LA0023/2013, RECI/BBB-EBI/0179/2012 (FCOMP-01-0124-FEDER-027462), and the Project BBioEnv - Biotechnology and Bioengineering for a sustainable world,REF. NORTE-07-0124- FEDER-000048, co-funded by the Programa Operacional Regional do Norte (ON.2 – O Novo Norte), QREN, FEDER. PhD grant SFRH/BD/64848/200

Anxiety and self-esteem as mediators of the relation between family communication and indecisiveness in adolescence

Abstract In this study, we explored the unique and common contributions of anxiety, self-esteem, and family communication on indecisiveness among adolescents. Three hundred and fifty pupils from 13 to 16 years of age completed selfreport measures on indecisiveness, quality of family communication, trait anxiety, and self-esteem. The findings in this study showed that students\u2019 indecisiveness is predicted by family communication mediated by anxiety and self-esteem. These results have important implications for practice as it stresses the importance of anxiety and self-esteem. Nevertheless, the counselors could also focus on enhancing relationship-building skills by introducing the adolescents\u2019 career formation as an adolescent\u2013parent joint project.L\u2019anxie\ub4te\ub4 et l\u2019estime de soi comme me\ub4diateurs de la relation entre communication au sein de la famille et indecision chronique a` l\u2019adolescence. Dans cette e\ub4tude, nous avons explore\ub4 les contributions uniques et communes de l\u2019anxiete\ub4, de l\u2019estime de soi et de la communication au sein de la famille sur l\u2019indecision chronique aupres d\u2019adolescents. Trois cent cinquante e\ub4le`ves a\u2c6ge\ub4s de 13 a` 16 ans ont rempli des mesures d\u2019auto-e\ub4valuation de l\u2019inde\ub4cision chronique, de la qualite\ub4 de la communication familiale, de l\u2019anxie\ub4te\ub4-trait et de l\u2019estime de soi. Les re\ub4sultats de cette e\ub4tude ont montre\ub4 que l\u2019inde\ub4cision des e\ub4tudiants est explique\ub4e par la communication au sein de la famille et que ce lien est me\ub4diatise\ub4 par l\u2019anxie\ub4te\ub4 et l\u2019estime de soi. Ces re\ub4sultats ont des implications importantes pour la pratique car ils soulignent l\u2019importance de l\u2019anxie\ub4te\ub4 et l\u2019estime de soi. Ne\ub4anmoins, les conseillers pourraient e\ub4galement se concentrer sur l\u2019ame\ub4lioration des compe\ub4tences de construction relationnelle en introduisant la formation professionnelle des adolescents comme un projet conjoint adolescent-parent.Resumen. Ansiedad y Autoestima como Mediadores de la Relacio\ub4n entre Comunicacio\ub4n Familiar e Indecisio\ub4n en la Adolescencia. En este estudio, exploramos las contribuciones u\ub4nicas y comunes de la ansiedad, la autoestima y la comunicacio\ub4n de familia en la indecisio\ub4n de los adolescentes. Tres y cientos cincuenta alumnos entre los 13 y 16 an\u2dcos completaron auto-evaluaciones sobre la indecisio\ub4n, la calidad de comunicacio\ub4n familiar, los rasgos de ansiedad y la autoestima. Los resultados en este estudio muestran que la indecisio\ub4n en los estudiantes es prevista por la comunicacio\ub4n familiar mediada por la ansiedad y la autoestima. Estos resultados tiene importantes implicaciones para la practica ya que destacan la importancia de la ansiedad y la autoestima. Sin embargo, los consejeros podr\u131\ub4an tambie\ub4n focalizarse en el aumento de sus habilidades para construir relaciones mediante la introduccio\ub4n de la formacio\ub4n profesional para adolescentes como un proyecto conjunto del adolescente-padre.Angst und Selbstwertgefu\ua8 hl als Mediatoren der Beziehung zwischen Kommunikation in der Familie und Unentschlossenheit in der Adoleszenz. In dieser Studie untersuchten wir die spezifischen und gemeinsamen Beitra\ua8ge von Angst, Selbstwertgefu\ua8hl und Kommunikation in der Familie auf Unentschlossenheit unter Jugendlichen. Dreihundertfu\ua8nfzig Schu\ua8ler, zwischen 13 bis 16 Jahre alt, fu\ua8llten Skalen zur Unentschlossenheit, Qualita\ua8t der Kommunikation in der Familie, A\ua8 ngstlichkeit und Selbstwertgefu\ua8hl aus. Die Ergebnisse dieser Studie zeigten, dass Unentschlossenheit der Schu\ua8ler von Kommunikation in der Familie vorhergesagt wird, vermittelt durch Angst und Selbstwertgefu\ua8 hl. Diese Ergebnisse haben wichtige Implikationen fu\ua8r die Praxis, da sie die Bedeutung von Angst und Selbstwertgefu\ua8hl hervorheben. Dennoch ko\ua8nnten sich die Beratungspersonen durch die Einfu\ua8hrung der beruflichen Bildung der Jugendlichen als ein gemeinsames Projekt von Jugendliche-Elternteil auch auf die Verbesserung der Fa\ua8higkeiten zum Aufbau von Beziehungen konzentrieren

Fungal iron availability during deep seated candidiasis is defined by a complex interplay involving systemic and local events

Peer reviewedPublisher PD

Blockade of insulin-like growth factors increases efficacy of paclitaxel in metastatic breast cancer.

Breast cancer remains the leading cause of cancer death in women owing to metastasis and the development of resistance to established therapies. Macrophages are the most abundant immune cells in the breast tumor microenvironment and can both inhibit and support cancer progression. Thus, gaining a better understanding of how macrophages support cancer could lead to the development of more effective therapies. In this study, we find that breast cancer-associated macrophages express high levels of insulin-like growth factors 1 and 2 (IGFs) and are the main source of IGFs within both primary and metastatic tumors. In total, 75% of breast cancer patients show activation of insulin/IGF-1 receptor signaling and this correlates with increased macrophage infiltration and advanced tumor stage. In patients with invasive breast cancer, activation of Insulin/IGF-1 receptors increased to 87%. Blocking IGF in combination with paclitaxel, a chemotherapeutic agent commonly used to treat breast cancer, showed a significant reduction in tumor cell proliferation and lung metastasis in pre-clinical breast cancer models compared to paclitaxel monotherapy. Our findings provide the rationale for further developing the combination of paclitaxel with IGF blockers for the treatment of invasive breast cancer, and Insulin/IGF1R activation and IGF+ stroma cells as potential biomarker candidates for further evaluation