Inflammatory extracellular vesicles prompt heart dysfunction via TRL4-dependent NF-κB activation.

Background: After myocardial infarction, necrotic cardiomyocytes release damage-associated proteins that stimulate innate immune pathways and macrophage tissue infiltration, which drives inflammation and myocardial remodeling. Circulating inflammatory extracellular vesicles play a crucial role in the acute and chronic phases of ischemia, in terms of inflammatory progression. In this study, we hypothesize that the paracrine effect mediated by these vesicles induces direct cytotoxicity in cardiomyocytes. Thus, we examined whether reducing the generation of inflammatory vesicles within the first few hours after the ischemic event ameliorates cardiac outcome at short and long time points. Methods: Myocardial infarction was induced in rats that were previously injected intraperitoneally with a chemical inhibitor of extracellular-vesicle biogenesis. Heart global function was assessed by echocardiography performed at 7, 14 and 28 days after MI. Cardiac outcome was also evaluated by hemodynamic analysis at sacrifice. Cytotoxic effects of circulating EV were evaluated ex-vivo in a Langendorff, system by measuring the level of cardiac troponin I (cTnI) in the perfusate. Mechanisms undergoing cytotoxic effects of EV derived from pro-inflammatory macrophages (M1) were studied in-vitro in primary rat neonatal cardiomyocytes. Results: Inflammatory response following myocardial infarction dramatically increased the number of circulating extracellular vesicles carrying alarmins such as IL-1α, IL-1β and Rantes. Reducing the boost in inflammatory vesicles during the acute phase of ischemia resulted in preserved left ventricular ejection fraction in vivo. Hemodynamic analysis confirmed functional recovery by displaying higher velocity of left ventricular relaxation and improved contractility. When added to the perfusate of isolated hearts, post-infarction circulating vesicles induced significantly more cell death in adult cardiomyocytes, as assessed by cTnI release, comparing to circulating vesicles isolated from healthy (non-infarcted) rats. In vitro inflammatory extracellular vesicles induce cell death by driving nuclear translocation of NF-κB into nuclei of cardiomyocytes. Conclusion: Our data suggest that targeting circulating extracellular vesicles during the acute phase of myocardial infarction may offer an effective therapeutic approach to preserve function of ischemic heart

What makes SMEs more likely to collaborate? Analysing the role of regional policy

The last twenty years have witnessed the diffusion of regional innovation policies supporting networks of innovators. The underlying aim of these policies is to encourage firms, particularly SMEs, to undertake collaborations with organisations possessing complementary knowledge. Focusing on a set of SMEs that have participated, over time, in several innovation networks funded by the same regional government, the paper investigates how their relationships have evolved with respect to the following aspects: (i) reiteration of pre-existing relationships as opposed to experimentation of new relationships; (ii) collaboration with organisations possessing complementary rather than similar knowledge and competencies; (iii) creation of local relationships rather than experimentation of extra-local collaborations; (iv) reliance upon intermediaries to connect with other organisations. Our findings reveal that the involvement in these policy-supported networks changed the firms’ relational patterns, leading them to collaborate with a wider variety of agents than those with whom they were linked before the policies. Sectoral heterogeneity had a negative effect on the probability to collaborate, while co-localisation increased the likelihood to collaborate. Mutual involvement with intermediaries also had a positive effect. However, in the case of firm-to-university relationships only specialized intermediaries were likely to perform a positive role and, therefore, encourage networking

Author Correction: 150,000-year palaeoclimate record from northern Ethiopia supports early, multiple dispersals of modern humans from Africa

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper

Decolonizing Science and Science Education in a Postcolonial Space (Trinidad, a Developing Caribbean Nation, Illustrates)

The article addresses how remnant or transformed colonialist structures continue to shape science and science education, and how that impact might be mitigated within a postcolonial environment in favor of the development of the particular community being addressed. Though cognizant of, and resistant to, the ongoing colonial impact globally and nationally (and any attempts at subjugation, imperialism, and marginalization), this article is not about anticolonial science. Indeed, it is realized that the postcolonial state of science and science education is not simply defined, and may exist as a mix of the scientific practices of the colonizer and the colonized. The discussion occurs through a generic postcolonial lens and is organized into two main sections. First, the discussion of the postcolonial lens is eased through a consideration of globalization which is held here as the new colonialism. The article then uses this lens to interrogate conceptions of science and science education, and to suggest that the mainstream, standard account of what science is seems to represent a globalized- or arguably a Western, modern, secular-conception of science. This standard account of science can act as a gatekeeper to the indigenous ways of being, knowing, and doing of postcolonial populations. The article goes on to suggest that as a postcolonial response, decolonizing science and science education might be possible through practices that are primarily contextually respectful and responsive. That is, localization is suggested as one possible antidote to the deleterious effects of globalization. Trinidad, a postcolonial developing Caribbean nation, is used as illustration

Lepton Flavor Violation in Supersymmetric SO(10) Grand Unified Models

The study for lepton flavor violation combined with the neutrino oscillation may provide more information about the lepton flavor structure of the grand unified theory. In this paper, we study two lepton flavor violation processes, $\tau\to \mu\gamma$ and $Z\to \tau\mu$, in the context of supersymmetric SO(10) grand unified models. We find the two processes are both of phenomenological interest. In particular the latter may be important in some supersymmetric parameter space where the former is suppressed. Thus, Z-dacay may offer another chance for looking for lepton flavor violation.Comment: 26 pages, 10 figure

Education policy as an act of white supremacy: whiteness, critical race theory and education reform

The paper presents an empirical analysis of education policy in England that is informed by recent developments in US critical theory. In particular, I draw on ‘whiteness studies’ and the application of Critical Race Theory (CRT). These perspectives offer a new and radical way of conceptualising the role of racism in education. Although the US literature has paid little or no regard to issues outside North America, I argue that a similar understanding of racism (as a multifaceted, deeply embedded, often taken-for-granted aspect of power relations) lies at the heart of recent attempts to understand institutional racism in the UK. Having set out the conceptual terrain in the first half of the paper, I then apply this approach to recent changes in the English education system to reveal the central role accorded the defence (and extension) of race inequity. Finally, the paper touches on the question of racism and intentionality: although race inequity may not be a planned and deliberate goal of education policy neither is it accidental. The patterning of racial advantage and inequity is structured in domination and its continuation represents a form of tacit intentionality on the part of white powerholders and policy makers. It is in this sense that education policy is an act of white supremacy. Following others in the CRT tradition, therefore, the paper’s analysis concludes that the most dangerous form of ‘white supremacy’ is not the obvious and extreme fascistic posturing of small neonazi groups, but rather the taken-for-granted routine privileging of white interests that goes unremarked in the political mainstream

Highlights from the Pierre Auger Observatory

The Pierre Auger Observatory is the world's largest cosmic ray observatory. Our current exposure reaches nearly 40,000 km$^2$ str and provides us with an unprecedented quality data set. The performance and stability of the detectors and their enhancements are described. Data analyses have led to a number of major breakthroughs. Among these we discuss the energy spectrum and the searches for large-scale anisotropies. We present analyses of our X$_{max}$ data and show how it can be interpreted in terms of mass composition. We also describe some new analyses that extract mass sensitive parameters from the 100% duty cycle SD data. A coherent interpretation of all these recent results opens new directions. The consequences regarding the cosmic ray composition and the properties of UHECR sources are briefly discussed.Comment: 9 pages, 12 figures, talk given at the 33rd International Cosmic Ray Conference, Rio de Janeiro 201

Ultrahigh-energy neutrino follow-up of Gravitational Wave events GW150914 and GW151226 with the Pierre Auger Observatory

On September 14, 2015 the Advanced LIGO detectors observed their first gravitational-wave (GW) transient GW150914. This was followed by a second GW event observed on December 26, 2015. Both events were inferred to have arisen from the merger of black holes in binary systems. Such a system may emit neutrinos if there are magnetic fields and disk debris remaining from the formation of the two black holes. With the surface detector array of the Pierre Auger Observatory we can search for neutrinos with energy above 100 PeV from point-like sources across the sky with equatorial declination from about -65 deg. to +60 deg., and in particular from a fraction of the 90% confidence-level (CL) inferred positions in the sky of GW150914 and GW151226. A targeted search for highly-inclined extensive air showers, produced either by interactions of downward-going neutrinos of all flavors in the atmosphere or by the decays of tau leptons originating from tau-neutrino interactions in the Earth's crust (Earth-skimming neutrinos), yielded no candidates in the Auger data collected within $\pm 500$ s around or 1 day after the coordinated universal time (UTC) of GW150914 and GW151226, as well as in the same search periods relative to the UTC time of the GW candidate event LVT151012. From the non-observation we constrain the amount of energy radiated in ultrahigh-energy neutrinos from such remarkable events.Comment: Published version. Added journal reference and DOI. Added Report Numbe

Multi-resolution anisotropy studies of ultrahigh-energy cosmic rays detected at the Pierre Auger Observatory

We report a multi-resolution search for anisotropies in the arrival directions of cosmic rays detected at the Pierre Auger Observatory with local zenith angles up to $80^\circ$ and energies in excess of 4 EeV ($4 \times 10^{18}$ eV). This search is conducted by measuring the angular power spectrum and performing a needlet wavelet analysis in two independent energy ranges. Both analyses are complementary since the angular power spectrum achieves a better performance in identifying large-scale patterns while the needlet wavelet analysis, considering the parameters used in this work, presents a higher efficiency in detecting smaller-scale anisotropies, potentially providing directional information on any observed anisotropies. No deviation from isotropy is observed on any angular scale in the energy range between 4 and 8 EeV. Above 8 EeV, an indication for a dipole moment is captured; while no other deviation from isotropy is observed for moments beyond the dipole one. The corresponding $p$-values obtained after accounting for searches blindly performed at several angular scales, are $1.3 \times 10^{-5}$ in the case of the angular power spectrum, and $2.5 \times 10^{-3}$ in the case of the needlet analysis. While these results are consistent with previous reports making use of the same data set, they provide extensions of the previous works through the thorough scans of the angular scales.Comment: Published version. Added journal reference and DOI. Added Report Numbe