Multi-wavelength Study of Transition Region Penumbral Subarcsecond Bright Dots Using IRIS and NST

Using high-resolution transition region (TR) observations taken by the Interface Region Imaging Spectrograph (IRIS) mission, Tian et al. (2014b) revealed numerous short-lived subarcsecond bright dots (BDs) above sunspots (mostly located in the penumbrae), which indicate yet unexplained small-scale energy releases. Moreover, whether these subarcsecond TR brightenings have any signature in the lower atmosphere and how they are formed are still not fully resolved. This paper presents a multi-wavelength study of the TR penumbral BDs using a coordinated observation of a near disk-center sunspot with IRIS and the 1.6 m New Solar Telescope (NST) at the Big Bear Solar Observatory. NST provides high-resolution chromospheric and photospheric observations with narrow-band H-alpha imaging spectroscopy and broad-band TiO images, respectively, complementary to IRIS TR observations. A total of 2692 TR penumbral BDs are identified from a 37-minute time series of IRIS 1400 A slitjaw images. Their locations tend to be associated more with downflowing and darker fibrils in the chromosphere, and weakly associated with bright penumbral features in the photosphere. However, temporal evolution analyses of the BDs show that there is no consistent and convincing brightening response in the chromosphere. These results are compatible with a formation mechanism of the TR penumbral BDs by falling plasma from coronal heights along more vertical and dense magnetic loops. The BDs may also be produced by small-scale impulsive magnetic reconnection taking place sufficiently high in the atmosphere that has no energy release in the chromosphere.Comment: 8 pages, 5 figures, accepted to Ap

Intracellular complexes of the early-onset torsion dystonia-associated AAA+ ATPase TorsinA

A single GAG codon deletion in the gene encoding torsinA is linked to most cases of early-onset torsion dystonia. TorsinA is an ER-localized membrane-associated ATPase from the AAA+ superfamily with an unknown biological function. We investigated the formation of oligomeric complexes of torsinA in cultured mammalian cells and found that wild type torsinA associates into a complex with a molecular weight consistent with that of a homohexamer. Interestingly, the dystonia-linked variant torsinAΔE displayed a reduced propensity to form the oligomers compared to the wild type protein. We also discovered that the deletion of the N-terminal membrane-associating region of torsinA abolished oligomer formation. Our results demonstrate that the dystonia-linked mutation in the torsinA gene produces a protein variant that is deficient in maintaining its oligomeric state and suggest that ER membrane association is required to stabilize the torsinA complex

The era of nano-bionic: 2D materials for wearable and implantable body sensors

Nano-bionics have the potential of revolutionizing modern medicine. Among nano-bionic devices, body sensors allow to monitor in real-time the health of patients, to achieve personalized medicine, and even to restore or enhance human functions. The advent of two-dimensional (2D) materials is facilitating the manufacturing of miniaturized and ultrathin bioelectronics, that can be easily integrated in the human body. Their unique electronic properties allow to efficiently transduce physical and chemical stimuli into electric current. Their flexibility and nanometric thickness facilitate the adaption and adhesion to human body. The low opacity permits to obtain transparent devices. The good cellular adhesion and reduced cytotoxicity are advantageous for the integration of the devices in vivo. Herein we review the latest and more significant examples of 2D material-based sensors for health monitoring, describing their architectures, sensing mechanisms, advantages and, as well, the challenges and drawbacks that hampers their translation into commercial clinical devices

The prokineticin receptor agonist Bv8 decreases IL-10 and IL-4 production in mice splenocytes by activating prokineticin receptor-1

<p>Abstract</p> <p>Background</p> <p>Bv8, prokineticin-1, or endocrine gland-vascular endothelial growth factor, and prokineticin-2 are recently isolated peptide agonists of two G protein-coupled receptors, prokineticin receptor-1 (PROKR 1) and PROKR 2, and have been described as affecting a number of myeloid cell functions. We evaluated the impact of Bv8 on lymphoid cells by investigating its ability to modulate T cell cytokine balance in mouse.</p> <p>Results</p> <p>The production of T-helper1 cytokines (IL-2, IFN-γ and IL-1β), the T-helper 2 cytokine IL-4, and the anti-inflammatory cytokine IL-10 by mouse splenocytes was evaluated after polyclonal stimulation or immunisation with the keyhole limpet hemocyanin protein antigen by measuring cytokine levels. When added <it>in vitro </it>to Con-A-stimulated splenocytes, Bv8 significantly increased IL-1β and decreased IL-4 and IL-10; IL-2 and IFN-γ were not affected. Similar results were obtained when Bv8 was administered <it>in vivo</it>. In KLH-immunised mice, splenocytes restimulated <it>in vitro </it>with KLH and Bv8 produced significantly smaller amounts of IL-4 and IL-10. KLH-induced IL-10 and IL-4 production was also significantly blunted in animals administered Bv8 <it>in vivo </it>at the time of KLH immunisation or two weeks later. The Bv8-induced effects were lost in mice lacking the PROKR 1 gene, thus indicating that PROKR 1 is the receptor involved in the modulation of cytokines.</p> <p>Conclusion</p> <p>These findings indicate that Bv8/prokineticin-1 is a novel modulator of lymphoid functions, and may be a suitable target for new immunopharmacological strategies.</p

Evidence of Non-Thermal Particles in Coronal Loops Heated Impulsively by Nanoflares

The physical processes causing energy exchange between the Sun's hot corona and its cool lower atmosphere remain poorly understood. The chromosphere and transition region (TR) form an interface region between the surface and the corona that is highly sensitive to the coronal heating mechanism. High resolution observations with the Interface Region Imaging Spectrograph (IRIS) reveal rapid variability (about 20 to 60 seconds) of intensity and velocity on small spatial scales at the footpoints of hot dynamic coronal loops. The observations are consistent with numerical simulations of heating by beams of non-thermal electrons, which are generated in small impulsive heating events called "coronal nanoflares". The accelerated electrons deposit a sizable fraction of their energy in the chromosphere and TR. Our analysis provides tight constraints on the properties of such electron beams and new diagnostics for their presence in the nonflaring corona.Comment: Published in Science on October 17: http://www.sciencemag.org/content/346/6207/1255724 . 26 pages, 10 figures. Movies are available at: http://www.lmsal.com/~ptesta/iris_science_mov

Sustainable urban prototypes and informal settlements

In Metro Manila, the pressure for rapid urbanization has led to an explosion of two opposite, yet related phenomena: the development of intensive clusters of high-rise buildings and the formation of dispersed patterns of informal settlements. In the near future, the Pasig River Rehabilitation Program will lead to dramatic shifts in the city’s fabric, including the relocation of large sectors occupied by informal communities. Under this program, BaSECo compound – was selected as a priority area for substantial urban renewal. As a result, the local community was living under the threat of eviction for many years. Although this government-led initiative aimed to resettle the residents on-site instead of relocating them outside the city, the need to establish an integrated approach to implement long- and short-term strategies for the community is still pressing

Camellia japonica: a phytochemical perspective and current applications facing its industrial exploitation

In response to the increased popularity of medicinal plants, a number of conservation groups are recommending the investigation on poorly characterized and widely distributed species, as it is the case of camellias. In particular, Camellia japonica L. is a widespread species found in Galicia (NW Spain), where it has been largely exploited with ornamental purposes. Recent findings on its phytochemical characterization showed thousands of bioactive ingredients, mostly represented by phenolic compounds, together with terpenoids, and fatty acids. These molecules present associated biological activities, acting as antioxidant, antimicrobial, anti-inflammatory, and anticancer agents. This review is aimed at describing the main bioactive compounds of C. japonica, as well as the health-enhancing properties attributed to this medicinal plant. Novel strategies are needed to implement an efficient industrialization process for C. japonica, ranging from small-scale approaches to the establishment of large plantations, thus involving important sectors, such as the food, pharmaceutical and cosmetic industries.The research leading to these results was supported by MICINN supporting the Ram´on y Cajal grant for M.A. Prieto (RYC-2017-22891) and and the Juan de la Cierva Incorporaci´on Hui Cao (IJC2020-046055- I); by Xunta de Galicia for supporting the pre-doctoral grant of A.G. Pereira (ED481A-2019/0228); by European Union that supports the work of P. Garcia-Perez through the “Margarita Salas” grant from the “NextGenerationEU” program.info:eu-repo/semantics/publishedVersio

Dual Inhibition of Focal Adhesion Kinase and Epidermal Growth Factor Receptor Pathways Cooperatively Induces Death Receptor-mediated Apoptosis in Human Breast Cancer Cells

The focal adhesion kinase (FAK) and epidermal growth factor receptor (EGFR) are protein-tyrosine kinases that are overexpressed and activated in human breast cancer. To determine the role of EGFR and FAK survival signaling in breast cancer, EGFR was stably overexpressed in BT474 breast cancer cells, and each signaling pathway was specifically targeted for inhibition. FAK and EGFR constitutively co-immunoprecipitated in EGFR-overexpressing BT474 cells. In low EGFR-expressing BT474-pcDNA3 vector control cells, inhibition of FAK by the FAK C-terminal domain caused detachment and apoptosis via pathways involving activation of caspase-3 and -8, cleavage of poly(ADP-ribose) polymerase, and caspase-3-dependent degradation of AKT. This apoptosis could be rescued by the dominant-negative Fas-associated death domain, indicating involvement of the death receptor pathway. EGFR overexpression did not inhibit detachment induced by the FAK C-terminal domain, but did suppress apoptosis, activating AKT and ERK1/2 survival pathways and inhibiting cleavage of FAK, caspase-3 and -8, and poly(ADP-ribose) polymerase. Furthermore, this protective effect of EGFR signaling was reversed by EGFR kinase inhibition with AG1478. In addition, inhibition of FAK and EGFR in another breast cancer cell line (BT20) endogenously overexpressing these kinases also induced apoptosis via the same mechanism as in the EGFR-overexpressing BT474 cells. The results of this study indicate that dual inhibition of FAK and EGFR signaling pathways can cooperatively enhance apoptosis in breast cancers

Methionine Adenosyltransferase α1 Is Targeted to the Mitochondrial Matrix and Interacts with Cytochrome P450 2E1 to Lower Its Expression

Methionine adenosyltransferase α1 (MATα1, encoded by MAT1A) is responsible for hepatic biosynthesis of S‐adenosyl methionine, the principal methyl donor. MATα1 also act as a transcriptional cofactor by interacting and influencing the activity of several transcription factors. Mat1a knockout (KO) mice have increased levels of cytochrome P450 2E1 (CYP2E1), but the underlying mechanisms are unknown. The aims of the current study were to identify binding partners of MATα1 and elucidate how MATα1 regulates CYP2E1 expression. We identified binding partners of MATα1 by coimmunoprecipitation (co‐IP) and mass spectrometry. Interacting proteins were confirmed using co‐IP using recombinant proteins, liver lysates, and mitochondria. Alcoholic liver disease (ALD) samples were used to confirm relevance of our findings. We found that MATα1 negatively regulates CYP2E1 at mRNA and protein levels, with the latter being the dominant mechanism. MATα1 interacts with many proteins but with a predominance of mitochondrial proteins including CYP2E1. We found that MATα1 is present in the mitochondrial matrix of hepatocytes using immunogold electron microscopy. Mat1a KO hepatocytes had reduced mitochondrial membrane potential and higher mitochondrial reactive oxygen species, both of which were normalized when MAT1A was overexpressed. In addition, KO hepatocytes were sensitized to ethanol and tumor necrosis factor α–induced mitochondrial dysfunction. Interaction of MATα1 with CYP2E1 was direct, and this facilitated CYP2E1 methylation at R379, leading to its degradation through the proteasomal pathway. Mat1a KO livers have a reduced methylated/total CYP2E1 ratio. MATα1’s influence on mitochondrial function is largely mediated by its effect on CYP2E1 expression. Patients with ALD have reduced MATα1 levels and a decrease in methylated/total CYP2E1 ratio. Conclusion: Our findings highlight a critical role of MATα1 in regulating mitochondrial function by suppressing CYP2E1 expression at multiple levels