Type Ia supernova Hubble diagram with near-infrared and optical observations

We main goal of this paper is to test whether the NIR peak magnitudes of SNe Ia could be accurately estimated with only a single observation obtained close to maximum light, provided the time of B band maximum and the optical stretch parameter are known. We obtained multi-epoch UBVRI and single-epoch J and H photometric observations of 16 SNe Ia in the redshift range z=0.037-0.183, doubling the leverage of the current SN Ia NIR Hubble diagram and the number of SNe beyond redshift 0.04. This sample was analyzed together with 102 NIR and 458 optical light curves (LCs) of normal SNe Ia from the literature. The analysis of 45 well-sampled NIR LCs shows that a single template accurately describes them if its time axis is stretched with the optical stretch parameter. This allows us to estimate the NIR peak magnitudes even with one observation obtained within 10 days from B-band maximum. We find that the NIR Hubble residuals show weak correlation with DM_15 and E(B-V), and for the first time we report a possible dependence on the J_max-H_max color. The intrinsic NIR luminosity scatter of SNe Ia is estimated to be around 0.10 mag, which is smaller than what can be derived for a similarly heterogeneous sample at optical wavelengths. In conclusion, we find that SNe Ia are at least as good standard candles in the NIR as in the optical. We showed that it is feasible to extended the NIR SN Ia Hubble diagram to z=0.2 with very modest sampling of the NIR LCs, if complemented by well-sampled optical LCs. Our results suggest that the most efficient way to extend the NIR Hubble diagram to high redshift would be to obtain a single observation close to the NIR maximum. (abridged)Comment: 39 pages, 15 figures, accepted by A&

Evolutionary instability of Zero Determinant strategies demonstrates that winning isn't everything

Zero Determinant (ZD) strategies are a new class of probabilistic and conditional strategies that are able to unilaterally set the expected payoff of an opponent in iterated plays of the Prisoner's Dilemma irrespective of the opponent's strategy, or else to set the ratio between a ZD player's and their opponent's expected payoff. Here we show that while ZD strategies are weakly dominant, they are not evolutionarily stable and will instead evolve into less coercive strategies. We show that ZD strategies with an informational advantage over other players that allows them to recognize other ZD strategies can be evolutionarily stable (and able to exploit other players). However, such an advantage is bound to be short-lived as opposing strategies evolve to counteract the recognition.Comment: 14 pages, 4 figures. Change in title (again!) to comply with Nature Communications requirements. To appear in Nature Communication

Cover to Volume 3

The fibroblast mitogen platelet-derived growth factor -BB (PDGF-BB) induces a transient expression of the orphan nuclear receptor NR4A1 (also named Nur77, TR3 or NGFIB). The aim of the present study was to investigate the pathways through which NR4A1 is induced by PDGF-BB and its functional role. We demonstrate that in PDGF-BB stimulated NIH3T3 cells, the MEK1/2 inhibitor CI-1040 strongly represses NR4A1 expression, whereas Erk5 downregulation delays the expression, but does not block it. Moreover, we report that treatment with the NF-κB inhibitor BAY11-7082 suppresses NR4A1 mRNA and protein expression. The majority of NR4A1 in NIH3T3 was found to be localized in the cytoplasm and only a fraction was translocated to the nucleus after continued PDGF-BB treatment. Silencing NR4A1 slightly increased the proliferation rate of NIH3T3 cells; however, it did not affect the chemotactic or survival abilities conferred by PDGF-BB. Moreover, overexpression of NR4A1 promoted anchorage-independent growth of NIH3T3 cells and the glioblastoma cell lines U-105MG and U-251MG. Thus, whereas NR4A1, induced by PDGF-BB, suppresses cell growth on a solid surface, it increases anchorage-independent growth

JNK1 phosphorylation of SCG10 determines microtubule dynamics and axodendritic length

C-Jun NH2-terminal kinases (JNKs) are essential during brain development, when they regulate morphogenic changes involving cell movement and migration. In the adult, JNK determines neuronal cytoarchitecture. To help uncover the molecular effectors for JNKs in these events, we affinity purified JNK-interacting proteins from brain. This revealed that the stathmin family microtubule-destabilizing proteins SCG10, SCLIP, RB3, and RB3' interact tightly with JNK. Furthermore, SCG10 is also phosphorylated by JNK in vivo on sites that regulate its microtubule depolymerizing activity, serines 62 and 73. SCG10-S73 phosphorylation is significantly decreased in JNK1-/- cortex, indicating that JNK1 phosphorylates SCG10 in developing forebrain. JNK phosphorylation of SCG10 determines axodendritic length in cerebrocortical cultures, and JNK site-phosphorylated SCG10 colocalizes with active JNK in embryonic brain regions undergoing neurite elongation and migration. We demonstrate that inhibition of cytoplasmic JNK and expression of SCG10-62A/73A both inhibited fluorescent tubulin recovery after photobleaching. These data suggest that JNK1 is responsible for regulation of SCG10 depolymerizing activity and neurite elongation during brain development

Islet antibodies and remaining beta-cell function 8 years after diagnosis of diabetes in young adults: a prospective follow-up of the nationwide Diabetes Incidence Study in Sweden.

Objectives. To establish the prevalence of remaining beta-cell function 8 years after diagnosis of diabetes in young adults and relate the findings to islet antibodies at diagnosis and 8 years later. Design. Population-based cohort study. Setting. Nationwide from all Departments of Medicine and Endocrinology in Sweden. Subjects. A total of 312 young (15-34 years old) adults diagnosed with diabetes during 1987-88. Main outcome measure. Plasma connecting peptide (C-peptide) 8 years after diagnosis. Preserved beta-cell function was defined as measurable C-peptide levels. Three islet antibodies - cytoplasmic islet cell antibodies (ICA), glutamic acid decarboxylase antibodies and tyrosine phosphatase antibodies - were measured. Results. Amongst 269 islet antibody positives (ab+) at diagnosis, preserved beta-cell function was found in 16% (42/269) 8 years later and these patients had a higher body mass index (median 22.7 and 20.5 kg m-2, respectively; P = 0.0003), an increased frequency of one islet antibody (50 and 24%, respectively; P = 0.001), and a lower prevalence of ICA (55 and 6%, respectively; P = 0.007) at diagnosis compared with ab+ without remaining beta-cell function. Amongst the 241 patients without detectable beta-cell function at follow-up, 14 lacked islet antibodies, both at diagnosis and at follow-up. Conclusions. Sixteen per cent of patients with autoimmune type 1 diabetes had remaining beta-cell function 8 years after diagnosis whereas 5.8% with beta-cell failure lacked islet autoimmunity, both at diagnosis and at follow-up

NOX4-dependent ROS production by stromal mammary cells modulates epithelial MCF-7 cell migration

BACKGROUND: The influence of the stromal microenvironment on the progression of epithelial cancers has been demonstrated. Unravelling the mechanisms by which stromal cells affect epithelial behaviour will contribute in understanding cellular malignancy. It has been proposed that redox environment has a role in the acquisition of malignancy. In this work, we studied the influence of epithelial cells on the stromal redox status and the consequence of this phenomenon on MCF-7 cell motility. METHODS: We analysed in a co-culture system, the effect of RMF-EG mammary stromal cells on the migratory capacity of MCF-7 cell line. To test whether the NOX-dependent stromal redox environment influences the epithelial migratory behaviour, we knocked down the expression of NOX4 using siRNA strategy. The effect of TGF-b1 on NOX4 expression and activity was analysed by qPCR, and intracellular ROS production was measured by a fluorescent method. RESULTS: Migration of MCF-7 breast epithelial cells was stimulated when co-cultured with RMF-EG cells. This effect depends on stromal NOX4 expression that, in turn, is enhanced by epithelial soluble factors. Pre-treatment of stromal cells with TGF-b1 enhanced this migratory stimulus by elevating NOX4 expression and intracellular ROS production. TGF-b1 seems to be a major component of the epithelial soluble factors that stimulate NOX4 expression. CONCLUSIONS: Our results have identified that an increased stromal oxidative status, mainly provided by an elevated NOX4 expression, is a permissive element in the acquisition of epithelial migratory properties. The capacity of stromal cells to modify their intracellular ROS production, and accordingly, to increase epithelial motility, seems to depend on epithelial soluble factors among which TGF-b1 have a decisive role.This work was supported by the grant (1080196 to JM) from the Fondo Nacional de Ciencia y Tecnologı´a (FONDECYT) of Chile

Monitoraggio in area sismica di beni monumentali: tecniche NDT e procedure di verifica

Negli ultimi anni il concetto di vulnerabilità sismica è tristemente entrato a far parte delle conoscenze anche dei non addetti ai lavori. Infatti, gli eventi sismici che hanno interessato dagli inizi del ‘900 il territorio Italiano, hanno sistematicamente messo in risalto l’elevata vulnerabilità sismica del nostro patrimonio edilizio, ivi compresi i beni monumentali, nonché, l’inesistenza di qualsiasi attività di programmazione della manutenzione periodica ordinaria e straordinaria delle strutture sismo-resistenti, che garantiscono nel tempo la conservazione delle loro capacità di risposta alle perturbazioni esterne.Il progetto PON sul Monitoraggio in Area Sismica di SIstemi MOnumentali nasce con la prerogativa di produrre uno strumento dedicato alla tutela di strutture a valenza storico – artistica, attraverso un percorso di catalogazione, di analisi del bene inteso come elemento costituito da elementi resistenti e da materiali, di studio del sito dove la struttura è ubicata e di attività di monitoraggio

Mammary tumors that become independent of the type I insulin-like growth factor receptor express elevated levels of platelet-derived growth factor receptors

<p>Abstract</p> <p>Background</p> <p>Targeted therapies are becoming an essential part of breast cancer treatment and agents targeting the type I insulin-like growth factor receptor (IGF-IR) are currently being investigated in clinical trials. One of the limitations of targeted therapies is the development of resistant variants and these variants typically present with unique gene expression patterns and characteristics compared to the original tumor.</p> <p>Results</p> <p>MTB-IGFIR transgenic mice, with inducible overexpression of the IGF-IR were used to model mammary tumors that develop resistance to IGF-IR targeting agents. IGF-IR independent mammary tumors, previously shown to possess characteristics associated with EMT, were found to express elevated levels of PDGFRα and PDGFRβ. Furthermore, these receptors were shown to be inversely expressed with the IGF-IR in this model. Using cell lines derived from IGF-IR-independent mammary tumors (from MTB-IGFIR mice), it was demonstrated that PDGFRα and to a lesser extent PDGFRβ was important for cell migration and invasion as RNAi knockdown of PDGFRα alone or PDGFRα and PDGFRβ in combination, significantly decreased tumor cell migration in Boyden chamber assays and suppressed cell migration in scratch wound assays. Somewhat surprisingly, concomitant knockdown of PDGFRα and PDGFRβ resulted in a modest increase in cell proliferation and a decrease in apoptosis.</p> <p>Conclusion</p> <p>During IGF-IR independence, PDGFRs are upregulated and function to enhance tumor cell motility. These results demonstrate a novel interaction between the IGF-IR and PDGFRs and highlight an important, therapeutically relevant pathway, for tumor cell migration and invasion.</p