DDR2 controls breast tumor stiffness and metastasis by regulating integrin mediated mechanotransduction in CAFs

Biomechanical changes in the tumor microenvironment influence tumor progression and metastases. Collagen content and fiber organization within the tumor stroma are major contributors to biomechanical changes (e., tumor stiffness) and correlated with tumor aggressiveness and outcome. What signals and in what cells control collagen organization within the tumors, and how, is not fully understood. We show in mouse breast tumors that the action of the collagen receptor DDR2 in CAFs controls tumor stiffness by reorganizing collagen fibers specifically at the tumor-stromal boundary. These changes were associated with lung metastases. The action of DDR2 in mouse and human CAFs, and tumors in vivo, was found to influence mechanotransduction by controlling full collagen-binding integrin activation via Rap1-mediated Talin1 and Kindlin2 recruitment. The action of DDR2 in tumor CAFs is thus critical for remodeling collagen fibers at the tumor-stromal boundary to generate a physically permissive tumor microenvironment for tumor cell invasion and metastases

Assessing Nitrogen Limitation in Inoculated Soybean in Southern Brazil

Core Ideas Soybean yield did not respond to low starter fertilizer N rates in soils with high organic matter content. Nitrogen limitation tended to be greater in low compared with medium-high yield levels. Nitrogen limitation is potentially related to lower contribution of N coming from biological nitrogen fixation (BNF) and mineralization. Overcoming potential N limitation in soybean [Glycine max (L.) Merr.] is a critical factor for sustaining plant nutrient demand and improving productivity. Following this rationale, a set of studies were executed in southern Brazil with the goals of quantifying yield response to early season fertilizer N rates (up to 40 kg ha−1), “starter N fertilization,” and to understand if soybean seed yields are limited by N (testing a non-limiting N scenario) when grown in soils with medium to high organic matter content. The main key outcomes of this research were: (i) starter N fertilization did not increase yields compared with non-fertilized soybean, potentially highlighting the absence of an early season N limitation; and (ii) N limitation was observed when soybean yields were compared with non-limiting N scenario and it tended to be greater in low compared with medium-high yield levels, potentially connected with co-limitations on both N sources (N2 fixation and mineralization) to satisfy soybean N demand. Producing soybean in a sustainable manner implies focus on production practices to conserve and, potentially, to increase soil organic matter on a long-term basis. Furthermore, it requires enhancing the biological N2 fixation process for satisfying the large plant N demand for achieving high soybean yields. Future research should be focused on understanding factors governing biological N2 fixation and N mineralization processes in soybean grown in soils with medium-high organic matter content.Fil: Ambrosini, Vítor Gabriel. Universidade Federal do Rio Grande do Sul; BrasilFil: Vieira Fontoura, Sandra Mara. Fundação Agrária de Pesquisa Agropecuária; BrasilFil: Paulo de Moraes, Renato. Fundação Agrária de Pesquisa Agropecuária; BrasilFil: Carciochi, Walter Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata; ArgentinaFil: Ciampitti, Ignacio Antonio. Kansas State University; Estados UnidosFil: Bayer, Cimélio. Universidade Federal do Rio Grande do Sul; Brasi

The twelve principles of CO2 Chemistry

This paper introduces a set of 12 Principles, based on the acronym CO2 CHEMISTRY, which are intended to form a set of criteria for assessing the viability of different processes or reactions for using CO2 as a feedstock for making organic chemicals. The principles aim to highlight the synergy of Carbon Dioxide Utilisation (CDU) with the components of green and sustainable chemistry as well as briefly pointing out the connection to the energy sector

Myeloid STAT3 promotes formation of colitis-associated colorectal cancer in mice

Myeloid cells lacking STAT3 promote antitumor responses of NK and T cells but it is unknown if this crosstalk affects development of autochthonous tumors. We deleted STAT3 in murine myeloid cells (STAT3(Δm)) and examined the effect on the development of autochthonous colorectal cancers (CRCs). Formation of Azoxymethane/Dextransulfate (AOM/DSS)-induced CRCs was strongly suppressed in STAT3(Δm) mice. Gene expression profiling showed strong activation of T cells in the stroma of STAT3(Δm) CRCs. Moreover, STAT3(Δm) host mice were better able to control the growth of transplanted MC38 colorectal tumor cells which are known to be killed in a T cell-dependent manner. These data suggest that myeloid cells lacking STAT3 control formation of CRCs mainly via cross activation of T cells. Interestingly, the few CRCs that formed in STAT3(Δm) mice displayed enhanced stromalization but appeared normal in size indicating that they have acquired ways to escape enhanced tumor surveillance. We found that CRCs in STAT3(Δm) mice consistently activate STAT3 signaling which is implicated in immune evasion and might be a target to prevent tumor relapse

Changes of hemodynamic and cerebral oxygenation after exercise in normobaric and hypobaric hypoxia: associations with acute mountain sickness

Objective: Normobaric (NH) and hypobaric hypoxia (HH) are associated with acute mountain sickness (AMS) and cognitive dysfunction. Only few variables, like heart-rate-variability, are correlated with AMS. However, prediction of AMS remains difficult. We therefore designed an expedition-study with healthy volunteers in NH/HH to investigate additional non-invasive hemodynamic variables associated with AMS.Methods: Eleven healthy subjects were examined in NH (FiO(2) 13.1%;equivalent of 3.883m a.s.l;duration 4h) and HH (3.883ma.s.l.;duration 24h) before and after an exercise of 120min. Changes in parameters of electrical cardiometry (cardiac index (CI), left-ventricular ejection time (LVET), stroke volume (SV), index of contractility (ICON)), near-infrared spectroscopy (cerebral oxygenation, rScO(2)), Lake-Louise-Score (LLS) and cognitive function tests were assessed. One-Way-ANOVA, Wilcoxon matched-pairs test, Spearman's-correlation-analysis and Student's t-test were performed.Results: HH increased heart rate (HR), mean arterial pressure (MAP) and CI and decreased LVET, SV and ICON, whereas NH increased HR and decreased LVET. In both NH and HH cerebral oxygenation decreased and LLS increased significantly. After 24h in HH, 6 of 11 subjects (54.6%) developed AMS. LLS remained increased until 24h in HH, whereas cognitive function remained unaltered. In HH, HR and LLS were inversely correlated (r=-0.692;p<0.05). More importantly, the rScO2-decrease after exercise in NH significantly correlated with LLS after 24h in HH (r=-0.971;p<0.01) and rScO2 correlated significantly with HR (r=0.802;p<0.01), CI (r=0.682;p<0.05) and SV (r=0.709;p<0.05) after exercise in HH.Conclusion: sBoth acute NH and HH altered hemodynamic and cerebral oxygenation and induced AMS. Subjects, who adapted their CI had higher rScO2 and lower LLS. Furthermore, rScO2 after exercise under normobaric conditions was associated with AMS at high altitudes

Design Principles for Ligand-Sensing, Conformation-Switching Ribozymes

Nucleic acid sensor elements are proving increasingly useful in biotechnology and biomedical applications. A number of ligand-sensing, conformational-switching ribozymes (also known as allosteric ribozymes or aptazymes) have been generated by some combination of directed evolution or rational design. Such sensor elements typically fuse a molecular recognition domain (aptamer) with a catalytic signal generator (ribozyme). Although the rational design of aptazymes has begun to be explored, the relationships between the thermodynamics of aptazyme conformational changes and aptazyme performance in vitro and in vivo have not been examined in a quantitative framework. We have therefore developed a quantitative and predictive model for aptazymes as biosensors in vitro and as riboswitches in vivo. In the process, we have identified key relationships (or dimensionless parameters) that dictate aptazyme performance, and in consequence, established equations for precisely engineering aptazyme function. In particular, our analysis quantifies the intrinsic trade-off between ligand sensitivity and the dynamic range of activity. We were also able to determine how in vivo parameters, such as mRNA degradation rates, impact the design and function of aptazymes when used as riboswitches. Using this theoretical framework we were able to achieve quantitative agreement between our models and published data. In consequence, we are able to suggest experimental guidelines for quantitatively predicting the performance of aptazyme-based riboswitches. By identifying factors that limit the performance of previously published systems we were able to generate immediately testable hypotheses for their improvement. The robust theoretical framework and identified optimization parameters should now enable the precision design of aptazymes for biotechnological and clinical applications

Theoretical Models and Operational Frameworks in Public Health Ethics

The article is divided into three sections: (i) an overview of the main ethical models in public health (theoretical foundations); (ii) a summary of several published frameworks for public health ethics (practical frameworks); and (iii) a few general remarks. Rather than maintaining the superiority of one position over the others, the main aim of the article is to summarize the basic approaches proposed thus far concerning the development of public health ethics by describing and comparing the various ideas in the literature. With this in mind, an extensive list of references is provided

A near-infrared/optical/X-ray survey in the centre of sigma Orionis

Because of the intense brightness of the OB-type multiple star system sigma Ori, the low-mass stellar and substellar populations close to the centre of the very young sigma Orionis cluster is poorly know. I present an IJHKs survey in the cluster centre, able to detect from the massive early-type stars down to cluster members below the deuterium burning mass limit. The near-infrared and optical data have been complemented with X-ray imaging. Ten objects have been found for the first time to display high-energy emission. Previously known stars with clear spectroscopic youth indicators and/or X-ray emission define a clear sequence in the I vs. I-Ks diagram. I have found six new candidate cluster members that follow this sequence. One of them, in the magnitude interval of the brown dwarfs in the cluster, displays X-ray emission and a very red J-Ks colour, indicative of a disc. Other three low-mass stars have excesses in the Ks band as well. The frequency of X-ray emitters in the area is 80+/-20 %. The spatial density of stars is very high, of up to 1.6+/-0.1 arcmin-2. There is no indication of lower abundance of substellar objects in the cluster centre. Finally, I also report two cluster stars with X-ray emission located at only 8000-11000 AU to sigma Ori AB, two sources with peculiar colours and an object with X-ray emission and near-infrared magnitudes similar to those of previously-known substellar objects in the cluster.Comment: Accepted for publication in Astron. Nachr. It has not been edited for language ye

Upper limits on the strength of periodic gravitational waves from PSR J1939+2134

The first science run of the LIGO and GEO gravitational wave detectors presented the opportunity to test methods of searching for gravitational waves from known pulsars. Here we present new direct upper limits on the strength of waves from the pulsar PSR J1939+2134 using two independent analysis methods, one in the frequency domain using frequentist statistics and one in the time domain using Bayesian inference. Both methods show that the strain amplitude at Earth from this pulsar is less than a few times $10^{-22}$.Comment: 7 pages, 1 figure, to appear in the Proceedings of the 5th Edoardo Amaldi Conference on Gravitational Waves, Tirrenia, Pisa, Italy, 6-11 July 200