587 research outputs found

    Magnetic Reconnection, Cosmic Ray Acceleration, and Gamma-Ray emission around Black Holes and Relativistic Jets

    Full text link
    Particle acceleration by magnetic reconnection is now recognized as an important process in magnetically dominated regions of galactic and extragalactic black hole sources. This process helps to solve current puzzles specially related to the origin of the very high energy flare emission in these sources. In this review, we discuss this acceleration mechanism and show recent analytical studies and multidimensional numerical SRMHD and GRMHD (special and general relativistic magnetohydrodynamical) simulations with the injection of test particles, which help us to understand this process both in relativistic jets and coronal regions of these sources. The very high energy and neutrino emission resulting from the accelerated particles by reconnection is also discussed.Comment: Invited Review at the International Conference on Black Holes as Cosmic Batteries: UHECRs and Multimessenger Astronomy - BHCB2018, 12-15 September, 2018, Foz du Iguazu, Brasil, in press in Procs. of Science. arXiv admin note: text overlap with arXiv:1608.0317

    Differential Role of Human Choline Kinase α and β Enzymes in Lipid Metabolism: Implications in Cancer Onset and Treatment

    Get PDF
    11 pages, 6 figures, 1 table.Background The Kennedy pathway generates phosphocoline and phosphoethanolamine through its two branches. Choline Kinase (ChoK) is the first enzyme of the Kennedy branch of synthesis of 1phosphocholine, the major component of the plasma membrane. ChoK family of proteins is composed by ChoKα and ChoKβ isoforms, the first one with two different variants of splicing. Recently ChoKα has been implicated in the carcinogenic process, since it is over-expressed in a variety of human cancers. However, no evidence for a role of ChoKβ in carcinogenesis has been reported. Methodology/Principal Findings Here we compare the in vitro and in vivo properties of ChoKα1 and ChoKβ in lipid metabolism, and their potential role in carcinogenesis. Both ChoKα1 and ChoKβ showed choline and ethanolamine kinase activities when assayed in cell extracts, though with different affinity for their substrates. However, they behave differentially when overexpressed in whole cells. Whereas ChoKβ display an ethanolamine kinase role, ChoKα1 present a dual choline/ethanolamine kinase role, suggesting the involvement of each ChoK isoform in distinct biochemical pathways under in vivo conditions. In addition, while overexpression of ChoKα1 is oncogenic when overexpressed in HEK293T or MDCK cells, ChoKβ overexpression is not sufficient to induce in vitro cell transformation nor in vivo tumor growth. Furthermore, a significant upregulation of ChoKα1 mRNA levels in a panel of breast and lung cancer cell lines was found, but no changes in ChoKβ mRNA levels were observed. Finally, MN58b, a previously described potent inhibitor of ChoK with in vivo antitumoral activity, shows more than 20-fold higher efficiency towards ChoKα1 than ChoKβ. Conclusion/Significance This study represents the first evidence of the distinct metabolic role of ChoKα and ChoKβ isoforms, suggesting different physiological roles and implications in human carcinogenesis. These findings constitute a step forward in the design of an antitumoral strategy based on ChoK inhibition.This work has been supported by grants to JCL from Comunidad de Madrid (GR-SAL-0821-2004), Ministerio de Ciencia e Innovación (SAF2008-03750, RD06/0020/0016), Fundación Mutua Madrileña, and by a grant to ARM from Fundación Mutua Madrileña.Peer reviewe

    INCA (Peru) study: Impact of non-invasive cardiac magnetic resonance assessment in the developing world

    Get PDF
    Background—Advanced cardiac imaging permits optimal targeting of cardiac treatment but needs to be faster, cheaper, and easier for global delivery. We aimed to pilot rapid cardiac magnetic resonance (CMR) with contrast in a developing nation, embedding it within clinical care along with training and mentoring. Methods and Results—A cross-sectional study of CMR delivery and clinical impact assessment performed 2016-2017 in an upper middle-income country. An International partnership (clinicians in Peru and collaborators from the United Kingdom, United States, Brazil, and Colombia) developed and tested a 15-minute CMR protocol in the United Kingdom, for cardiac volumes, function and scar, and delivered it with reporting combined with training, education and mentoring in 2 centers in the capital city, Lima, Peru, 100 patients referred by local doctors from 6 centers. Management changes related to the CMR were reviewed at 12 months. One-hundred scans were conducted in 98 patients with no complications. Final diagnoses were cardiomyopathy (hypertrophic, 26%; dilated, 22%; ischemic, 15%) and 12 other pathologies including tumors, congenital heart disease, iron overload, amyloidosis, genetic syndromes, vasculitis, thrombi, and valve disease. Scan cost was 150USD,andtheaveragescandurationwas18±7minutes.Findingsimpactedmanagementin56150 USD, and the average scan duration was 18±7 minutes. Findings impacted management in 56% of patients, including previously unsuspected diagnoses in 19% and therapeutic management changes in 37%. Conclusions—Advanced cardiac diagnostics, here CMR with contrast, is possible using existing infrastructure in the developing world in 18 minutes for 150, resulting in important changes in patient care

    Thy1+ Nk Cells from Vaccinia Virus-Primed Mice Confer Protection against Vaccinia Virus Challenge in the Absence of Adaptive Lymphocytes

    Get PDF
    While immunological memory has long been considered the province of T- and B- lymphocytes, it has recently been reported that innate cell populations are capable of mediating memory responses. We now show that an innate memory immune response is generated in mice following infection with vaccinia virus, a poxvirus for which no cognate germline-encoded receptor has been identified. This immune response results in viral clearance in the absence of classical adaptive T and B lymphocyte populations, and is mediated by a Thy1+ subset of natural killer (NK) cells. We demonstrate that immune protection against infection from a lethal dose of virus can be adoptively transferred with memory hepatic Thy1+ NK cells that were primed with live virus. Our results also indicate that, like classical immunological memory, stronger innate memory responses form in response to priming with live virus than a highly attenuated vector. These results demonstrate that a defined innate memory cell population alone can provide host protection against a lethal systemic infection through viral clearance

    Eco-bio-social determinants for house infestation by non-domiciliated Triatoma dimidiata in the Yucatan peninsula, Mexico

    Get PDF
    Background Chagas disease is a vector-borne disease of major importance in the Americas. Disease prevention is mostly limited to vector control. Integrated interventions targeting ecological, biological and social determinants of vector-borne diseases are increasingly used for improved control. Methodology/principal findings We investigated key factors associated with transient house infestation by T. dimidiata in rural villages in Yucatan, Mexico, using a mixed modeling approach based on initial null-hypothesis testing followed by multimodel inference and averaging on data from 308 houses from three villages. We found that the presence of dogs, chickens and potential refuges, such as rock piles, in the peridomicile as well as the proximity of houses to vegetation at the periphery of the village and to public light sources are major risk factors for infestation. These factors explain most of the intra-village variations in infestation. Conclusions/significance These results underline a process of infestation distinct from that of domiciliated triatomines and may be used for risk stratification of houses for both vector surveillance and control. Combined integrated vector interventions, informed by an Ecohealth perspective, should aim at targeting several of these factors to effectively reduce infestation and provide sustainable vector control
    corecore