A blowout numerical model for the supernova remnant G352.7-0.1

We present 3D hydrodynamical simulations of the Galactic supernova remnant G352.7−0.1. This remnant is peculiar for having a shell-like inner ring structure and an outer arc in radio observations. In our model, the supernova explosion producing the remnant occurs inside and near the border of a spherical cloud with a density higher than that of the surrounding interstellar medium. A blowout is produced when the remnant reaches the border of the cloud. We have then used the results of our hydrodynamical simulations to calculate synthetic synchrotron radio emission maps, as well as synthetic X-ray maps. For some combinations of the particle acceleration mechanism and the direction of the line of sight, our radio maps display the peculiar morphology of G352.7−0.1 and reproduce the correct relative sizes of the main observed features. At the same time, the calculated X-ray maps reproduce the centrally peaked morphology of the observations.Fil: Toledo Roy, J. C.. Universidad Nacional Autónoma de México; MéxicoFil: Velazquez, P. F.. Universidad Nacional Autónoma de México; MéxicoFil: Esquivel, A.. Universidad Nacional Autónoma de México; MéxicoFil: Giacani, Elsa Beatriz. Consejo Nacional de Investigaciónes Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Astronomía y Física del Espacio. - Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Astronomía y Física del Espacio; Argentin

Origin of the bilateral structure of the supernova remnant G296.5+10

In this work, we have modelled the supernova remnant (SNR) G296.5+10, by means of 3D magnetohydrodynamics (MHD) simulations. This remnant belongs to the bilateral SNR group and has an additional striking feature: the rotation measure (RM) in its eastern and western parts are very different. In order to explain both the morphology observed in radio-continuum and the RM, we consider that the remnant expands into a medium shaped by the superposition of the magnetic field of the progenitor star with a constant Galactic magnetic field. We have also carried out a polarization study from our MHD results, obtaining synthetic maps of the linearly polarized intensity and the Stokes parameters. This study reveals that both the radio morphology and the reported RM for G296.5+10 can be explained if the quasi-parallel acceleration mechanism is taking place in the shock front of this remnant.Fil: Moranchel-Basurto, A.. Universidad Nacional Autónoma de México; MéxicoFil: Velazquez, P.. Universidad Nacional Autónoma de México; MéxicoFil: Giacani, Elsa Beatriz. Universidad de Buenos Aires. Facultad de Arquitectura y Urbanismo; Argentina. Consejo Nacional de Investigaciónes Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Astronomía y Física del Espacio. - Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Astronomía y Física del Espacio; ArgentinaFil: Toledo Roy, J. C.. Universidad Nacional Autónoma de México; MéxicoFil: Schneiter, E.. Universidad Nacional Autónoma de México; MéxicoFil: De Colle, F.. Universidad Nacional Autónoma de México; MéxicoFil: Esquivel, A.. Universidad Nacional Autónoma de México; Méxic

Immunity to the Melanoma Inhibitor of Apoptosis Protein (ML-IAP; livin) in Patients with Malignant Melanoma

Therapeutic targeting of melanoma antigens frequently focuses on the melanocyte differentiation or cancer-testis families. Antigen-loss variants can often result, as these antigens are not critical for tumor cell survival. Exploration of functionally relevant targets has been limited. The melanoma inhibitor of apoptosis protein (ML-IAP; livin) is overexpressed in melanoma, contributing to disease progression and treatment resistance. Improved understanding of the significance of ML-IAP immune responses in patients has possible therapeutic applications. We found ML-IAP frequently expressed in melanoma metastases by immunohistochemistry. To assess spontaneous immunity to ML-IAP, an overlapping peptide library representing full-length protein was utilized to screen cellular responses in stage I–IV patients and healthy controls by ELISPOT. A broad array of $CD4^+$ and $CD8^+$ cellular responses against ML-IAP was observed with novel class I and class II epitopes identified. Specific HLA-A*0201 epitopes were analyzed further for frequency of reactivity. The generation of specific $CD4^+$ and cytotoxic T cells revealed potent functional capability including cytokine responsiveness to melanoma cell lines and tumor cell killing. In addition, recombinant ML-IAP protein used in an ELISA demonstrated high titer antibody responses in a subset of patients. Several melanoma patients who received CTLA-4 blockade with ipilimumab developed augmented humoral immune responses to ML-IAP as a function of treatment which was associated with beneficial clinical outcomes. High frequency immune responses in melanoma patients, associations with favorable treatment outcomes, and its essential role in melanoma pathogenesis support the development of ML-IAP as a disease marker and therapeutic target

Clinical relevance of Neutral Endopeptidase (NEP/CD10) in melanoma

BACKGROUND: Overexpression of Neutral Endopeptidase (NEP) has been reported in metastatic carcinomas, implicating NEP in tumor progression and suggesting a role for NEP inhibitors in its treatment. We investigated the role of NEP expression in the clinical progression of cutaneous melanoma. METHODS: We screened 7 melanoma cell lines for NEP protein expression. NEP-specific siRNA was transfected into the lines to examine the role of gene transcription in NEP expression. Immunohistochemistry was done for 93 specimens and correlated with clinicopathologic parameters. Thirty-seven metastatic melanoma specimens were examined for NEP transcript expression using Affymetrix GeneChips. In a subset of 25 specimens for which both transcript and protein expression was available, expression ratios were used to identify genes that co-express with NEP in GeneChip analysis. RESULTS: NEP was overexpressed in 4/7 human melanoma cell lines, and siRNA knock-down of NEP transcripts led to downregulation of its protein expression. NEP protein overexpression was significantly more common in metastatic versus primary tumors (P = 0.002). Twelve of 37 (32%) metastatic tumors had increased NEP transcript expression, and an association was observed between NEP transcript upregulation and protein overexpression (P < 0.0001). Thirty-eight genes were found to significantly co-express with NEP (p < 0.005). Thirty-three genes positively correlated with NEP, including genes involved in the MAP kinase pathway, antigen processing and presentation, apoptosis, and WNT signaling pathway, and 5 genes negatively correlated with NEP, including genes of focal adhesion and the notch signaling pathways. CONCLUSION: NEP overexpression, which seems to be largely driven by increased transcription, is rare in primary melanoma and occurs late in melanoma progression. Functional studies are needed to better understand the mechanisms of NEP regulation in melanoma

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

Vision, challenges and opportunities for a Plant Cell Atlas

With growing populations and pressing environmental problems, future economies will be increasingly plant-based. Now is the time to reimagine plant science as a critical component of fundamental science, agriculture, environmental stewardship, energy, technology and healthcare. This effort requires a conceptual and technological framework to identify and map all cell types, and to comprehensively annotate the localization and organization of molecules at cellular and tissue levels. This framework, called the Plant Cell Atlas (PCA), will be critical for understanding and engineering plant development, physiology and environmental responses. A workshop was convened to discuss the purpose and utility of such an initiative, resulting in a roadmap that acknowledges the current knowledge gaps and technical challenges, and underscores how the PCA initiative can help to overcome them.</jats:p

Effects of thermal conduction on the X-ray and synchrotron emission from supernova remnants

Several physical mechanisms have been studied in order to explain why composite supernova remnants (SNRs) have shell-like morphologies in the radio continuum while their X-ray emission is centrally peaked. One of the proposed mechanisms has been the presence of thermal conduction, which can raise the density at the center of SNRs, increasing the X-ray emission from these regions. In this work, we have carried out axisymmetric numerical simulations with the adaptive grid Yguazú-a code, which includes advection of the magnetic field and thermal conduction. We have considered cases with anisotropic and isotropic thermal conduction, as well as with no conduction. We have simulated X-ray (as well as radio synchrotron) emission maps from our numerical simulations, which can be directly compared with observations.Fil: Velazquez, Pablo F.. Universidad Nacional Autónoma de México; MéxicoFil: Martinell, Julio J.. Universidad Nacional Autónoma de México; MéxicoFil: Raga, Alejandro C.. Universidad Nacional Autónoma de México; MéxicoFil: Giacani, Elsa Beatriz. Consejo Nacional de Investigaciónes Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Astronomía y Física del Espacio. - Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Astronomía y Física del Espacio; Argentin