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A significant impediment to solving the coronal heating problem is that we currently only observe active region loops in their cooling phase. Previous studies showed that the evolution of cooling loop densities and apex temperatures is insensitive to the magnitude, duration, and location of energy deposition. Still, potential clues to how energy is released are encoded in the properties of the cooling phase. The appearance of coronal rain, one of the most spectacular phenomena of the cooling phase, occurs when plasma has cooled below 1 MK, which sets constraints on the heating frequency, for example. Most observations of coronal rain have been made by imaging instruments. Here we report rare Hinode/EUV Imaging Spectrometer (EIS) observations of a loop arcade where coronal rain forms following an X2.1 limb flare. A bifurcation in plasma composition measurements between photospheric at 1.5 MK and coronal at 3.5 MK suggests that we are observing postflare-driven coronal rain. Increases in nonthermal velocities and densities with decreasing temperature (2.7–0.6 MK) suggest that we are observing the formation and subsequent evolution of the condensations. Doppler velocity measurements imply that a 10% correction of apparent flows in imaging data is reasonable. Emission measure analysis at 0.7 MK shows narrow temperature distributions, indicating coherent behavior reminiscent of that observed in coronal loops. The limitations on spatio-temporal resolution of EIS suggest that we are observing the largest features or rain showers. These observations provide insights into the heating rate, source, turbulence, and collective behavior of coronal rain from observations of the loop cooling phase. [ABSTRACT FROM AUTHOR]

The plasma composition of the solar corona is different from that of the solar photosphere. Elements that have a low first ionization potential (FIP) are preferentially transported to the corona and therefore show enhanced abundances in the corona compared to the photosphere. The level of enhancement is measured using the FIP bias parameter. In this work, we use data from the EUV Imaging Spectrometer on Hinode to study the plasma composition in an active region following an episode of significant new flux emergence into the preexisting magnetic environment of the active region. We use two FIP bias diagnostics: Si x 258.375 Å/S x 264.233 Å (temperature of approximately 1.5 MK) and Ca xiv 193.874 Å/Ar xiv 194.396 Å (temperature of approximately 4 MK). We observe slightly higher FIP bias values with the Ca/Ar diagnostic than Si/S in the newly emerging loops, and this pattern is much stronger in the preexisting loops (those that had been formed before the flux emergence). This result can be interpreted in the context of the ponderomotive force model, which proposes that the plasma fractionation is generally driven by Alfvén waves. Model simulations predict this difference between diagnostics using simple assumptions about the wave properties, particularly that the fractionation is driven by resonant/nonresonant waves in the emerging/preexisting loops. We propose that this results in the different fractionation patterns observed in these two sets of loops. [ABSTRACT FROM AUTHOR]

Phosphorylation reactions performed by protein kinases are one of the most studied post-translational modifications within cells. Much is understood about conserved residues within protein kinase domains that perform catalysis of the phosphotransfer reaction, yet the identity of the target substrates and downstream biological effects vary widely among cells, tissues, and organisms. Here, we characterize key residues essential for NUAK kinase activity in Drosophila melanogaster myogenesis and homeostasis. Creation of a NUAK kinase-dead mutation using Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 results in lethality at the embryo to larval transition, while loss of NUAK catalytic function later in development produces aggregation of the chaperone protein αB-crystallin/CryAB in muscle tissue. Yeast 2-hybrid assays demonstrate a physical interaction between NUAK and CryAB. We further show that a phosphomimetic version of NUAK promotes the phosphorylation of CryAB and this post-translational modification occurs at 2 previously unidentified phosphosites that are conserved in the primary sequence of human CryAB. Mutation of these serine residues in D. melanogaster NUAK abolishes CryAB phosphorylation, thus, proving their necessity at the biochemical level. These studies together highlight the importance of kinase activity regulation and provide a platform to further explore muscle tissue proteostasis. [ABSTRACT FROM AUTHOR]

Bieler particularly identifies the environmental movement and non-governmental organizations (NGOs) - presumably socio-political NGOs - as equally involved in the struggle, especially given 'capitalism's capacity to accumulate in the midst of the most blatant ecological destruction, [...]' (p. 20). As indicated by the nearly 30-page biography, Andreas Bieler's book is not the first to challenge privatization of water in Europe. [Extracted from the article]

Cell growth and proliferation must be balanced during development to attain a final adult size with the appropriate proportions of internal organs to maximize fitness and reproduction. While multiple signaling pathways coordinate Drosophila development, it is unclear how multi-organ communication within and between tissues converge to regulate systemic growth. One such growth pathway, mediated by insulin-like peptides that bind to and activate the insulin receptor in multiple target tissues, is a primary mediator of organismal size. Here we uncover a signaling role for the NUAK serine/threonine kinase in muscle tissue that impinges upon insulin pathway activity to limit overall body size, including a reduction in the growth of individual organs. In skeletal muscle tissue, manipulation of NUAK or insulin pathway components influences sarcomere number concomitant with modulation of thin and thick filament lengths, possibly by modulating the localization of Lasp, a nebulin repeat protein known to set thin filament length. This mode of sarcomere remodeling does not occur in other mutants that also exhibit smaller muscles, suggesting that a sensing mechanism exists in muscle tissue to regulate sarcomere growth that is independent of tissue size control. [Display omitted] • NUAK overexpression in muscle tissue blunts insulin signaling and reduces organismal size. • Methuselah-like 8 (mthl8) is a new target of NUAK and FOXO-mediated transcription. • Reduced muscle growth can be uncoupled from alterations in sarcomere number and size. [ABSTRACT FROM AUTHOR]

The type IIa family of receptor protein tyrosine phosphatases (RPTPs), including Lar, RPTPσ and RPTPδ, are well-studied in coordinating actin cytoskeletal rearrangements during axon guidance and synaptogenesis. To determine whether this regulation is conserved in other tissues, interdisciplinary approaches were utilized to study Lar-RPTPs in the Drosophila musculature. Here we find that the single fly ortholog, Drosophila Lar (Dlar), is localized to the muscle costamere and that a decrease in Dlar causes aberrant sarcomeric patterning, deficits in larval locomotion, and integrin mislocalization. Sequence analysis uncovered an evolutionarily conserved Lys-Gly-Asp (KGD) signature in the extracellular region of Dlar. Since this tripeptide sequence is similar to the integrin-binding Arg-Gly-Asp (RGD) motif, we tested the hypothesis that Dlar directly interacts with integrin proteins. However, structural analyses of the fibronectin type III domains of Dlar and two vertebrate orthologs that include this conserved motif indicate that this KGD tripeptide is not accessible and thus unlikely to mediate physical interactions with integrins. These results, together with the proteomics identification of basement membrane (BM) proteins as potential ligands for type IIa RPTPs, suggest a complex network of protein interactions in the extracellular space that may mediate Lar function and/or signaling in muscle tissue. [ABSTRACT FROM AUTHOR]

Accurate forecasting of space weather requires knowledge of the source regions where solar energetic particles (SEP) and eruptive events originate. Recent work has linked several major SEP events in 2014, January, to specific features in the host active region (AR 11944). In particular, plasma composition measurements in and around the footpoints of hot, coronal loops in the core of the active region were able to explain the values later measured in situ by the Wind spacecraft. Due to important differences in elemental composition between SEPs and the solar wind, the magnitude of the Si/S elemental abundance ratio emerged as a key diagnostic of SEP seed population and solar wind source locations. We seek to understand if the results are typical of other active regions, even if they are not solar wind sources or SEP productive. In this paper, we use a novel composition analysis technique, together with an evolutionary magnetic field model, in a new approach to investigate a typical solar active region (AR 11150), and identify the locations of highly fractionated (high Si/S abundance ratio) plasma. Material confined near the footpoints of coronal loops, as in AR 11944, that in this case have expanded to the AR periphery, show the signature, and can be released from magnetic field opened by reconnection at the AR boundary. Since the fundamental characteristics of closed field loops being opened at the AR boundary is typical of active regions, this process is likely to be general. [ABSTRACT FROM AUTHOR]

The central cholinergic system includes the basal forebrain nuclei, mainly projecting to the cortex, the mesopontine tegmental nuclei, mainly projecting to the thalamus and subcortical structures, and other groups of projecting neurons and interneurons. This system regulates many functions of human behavior such as cognition, locomotion, and sleep. In Parkinson's disease (PD), disruption of central cholinergic transmission has been associated with cognitive decline, gait problems, freezing of gait (FOG), falls, REM sleep behavior disorder (RBD), neuropsychiatric manifestations, and olfactory dysfunction. Neuropathological and neuroimaging evidence suggests that basal forebrain pathology occurs simultaneously with nigrostriatal denervation, whereas pathology in the pontine nuclei may occur before the onset of motor symptoms. These studies have also detailed the clinical implications of cholinergic dysfunction in PD. Degeneration of basal forebrain nuclei and consequential cortical cholinergic denervation are associated with and may predict the subsequent development of cognitive decline and neuropsychiatric symptoms. Gait problems, FOG, and falls are associated with a complex dysfunction of both pontine and basal forebrain nuclei. Olfactory impairment is associated with cholinergic denervation of the limbic archicortex, specifically hippocampus and amygdala. Available evidence suggests that cholinergic dysfunction, alongside failure of the dopaminergic and other neurotransmitters systems, contributes to the generation of a specific set of clinical manifestations. Therefore, a "cholinergic phenotype" can be identified in people presenting with cognitive decline, falls, and RBD. In this review, we will summarize the organization of the central cholinergic system and the clinical correlates of cholinergic dysfunction in PD. [ABSTRACT FROM AUTHOR]

Active regions are thought to be one contributor to the slow solar wind. Upflows in EUV coronal spectral lines are routinely observed at their boundaries, and provide the most direct way for upflowing material to escape into the heliosphere. The mechanisms that form and drive these upflows, however, remain to be fully characterized. It is unclear how quickly they form, or how long they exist during their lifetimes. They could be initiated low in the atmosphere during magnetic flux emergence, or as a response to processes occurring high in the corona when the active region is fully developed. On 2019 March 31 a simple bipolar active region (AR 12737) emerged and upflows developed on each side. We used observations from Hinode, SDO, IRIS, and Parker Solar Probe (PSP) to investigate the formation and development of the upflows from the eastern side. We used the spectroscopic data to detect the upflow, and then used the imaging data to try to trace its signature back to earlier in the active region emergence phase. We find that the upflow forms quickly, low down in the atmosphere, and that its initiation appears associated with a small field-opening eruption and the onset of a radio noise storm detected by PSP. We also confirmed that the upflows existed for the vast majority of the time the active region was observed. These results suggest that the contribution to the solar wind occurs even when the region is small, and continues for most of its lifetime. [ABSTRACT FROM AUTHOR]

Differences about fresh water rarely if ever lead to war between neighbouring nations. However, lack of agreement about equitable water use will sooner or later disrupt water management systems. Similarly, unless fresh water is managed sustainably by both nations, their social and economic development will lag, with ultimate effects on any peace agreement. This Viewpoint describes an existing proposal for joint approaches by Israel and Palestine to managing their transboundary water, as well as current unilateral actions by the two governments that work against equitable and sustainable water management. [ABSTRACT FROM AUTHOR]

Responsiveness to PD-1 blockade depends on a cell subset known as Tpex cells, but how these cells are sustained is less understood. In this issue of Immunity , Dähling et al. show how dendritic cells form a niche for Tpex preservation. [ABSTRACT FROM AUTHOR]

Suboptimal CD4+ T cell activation leads to a hyporesponsive state in mice characterized by incomplete differentiation, limited cytokine production, and changes in T helper (Th) subsets. Together, these factors impair CD4+ T cell trafficking to the tumor and enable the immune evasion of tumor cells. Sustained inflammation, antigen stimulation, and suppressive factors induce CD4+ T cell dysfunctions during tumor progression in murine models. Despite sharing some phenotypic similarities with CD8+ T cells in mouse and human, CD4+ T cell dysfunctions are distinct and should be viewed through the lens of Th subset differentiation. Since CD4+ T cells can help multiple parameters of the innate and adaptive immune response, reinvigorating CD4+ T cells holds great potential in enhancing various immunotherapies, including immune checkpoint blockade, cancer vaccines, and the use of CAR T cells. CD4+ T cells are crucial for enhancing the functions of antigen-presenting cells, increasing CD8+ T cell effector differentiation, driving B cell activation and antibody affinity maturation, and temporally sustaining immune efficacy during cancer progression. As a result, CD4+ T cells serve as a central nexus that directs the initiation and coordination of an immune response. Thus, a deeper understanding of the nature, impact, and restorability of CD4+ T cell dysfunction holds vast potential in guiding therapeutic strategies to effectively harness the potential of these cells in cancer treatments. CD4+ T cells are crucial in generating and sustaining immune responses. They orchestrate and fine-tune mammalian innate and adaptive immunity through cell-based interactions and the release of cytokines. The role of these cells in contributing to the efficacy of antitumor immunity and immunotherapy has just started to be uncovered. Yet, many aspects of the CD4+ T cell response are still unclear, including the differentiation pathways controlling such cells during cancer progression, the external signals that program them, and how the combination of these factors direct ensuing immune responses or immune-restorative therapies. In this review, we focus on recent advances in understanding CD4+ T cell regulation during cancer progression and the importance of CD4+ T cells in immunotherapies. [ABSTRACT FROM AUTHOR]

The article presents a study that explores the source of the major solar energetic particle events from super active region. It mentions that Shock waves associated with fast coronal mass ejections (CMEs) accelerate solar energetic particles (SEPs) in the long duration, gradual events that pose hazards to crewed spaceflight and near-Earth technological assets.

Histopathology differentiates TV from EDV, as TV would be expected to demonstrate hyphae and spores in the stratum corneum.1,2 Flat warts can have a similar clinical and histologic appearance to EDV. A 11-year-old girl with human immunodeficiency virus (HIV) was evaluated by pediatric dermatology for the evaluation of a chronic rash present for at least 5 years. Clinicopathologic correlation with examination and histology findings in the setting of HIV infection favored a diagnosis of EDV. [Extracted from the article]

Plasma outflows from the edges of active regions have been suggested as a possible source of the slow solar wind. Spectroscopic measurements show that these outflows have an enhanced elemental composition, which is a distinct signature of the slow wind. Current spectroscopic observations, however, do not have sufficient spatial resolution to distinguish what structures are being measured or determine the driver of the outflows. The High-resolution Coronal Imager (Hi-C) flew on a sounding rocket in 2018 May and observed areas of active region outflow at the highest spatial resolution ever achieved (250 km). Here we use the Hi-C data to disentangle the outflow composition signatures observed with the Hinode satellite during the flight. We show that there are two components to the outflow emission: a substantial contribution from expanded plasma that appears to have been expelled from closed loops in the active region core and a second contribution from dynamic activity in active region plage, with a composition signature that reflects solar photospheric abundances. The two competing drivers of the outflows may explain the variable composition of the slow solar wind. [ABSTRACT FROM AUTHOR]

The inability to remove protein aggregates in post-mitotic cells such as muscles or neurons is a cellular hallmark of aging cells and is a key factor in the initiation and progression of protein misfolding diseases. While protein aggregate disorders share common features, the molecular level events that culminate in abnormal protein accumulation cannot be explained by a single mechanism. Here we show that loss of the serine/threonine kinase NUAK causes cellular degeneration resulting from the incomplete clearance of protein aggregates in Drosophila larval muscles. In NUAK mutant muscles, regions that lack the myofibrillar proteins F-actin and Myosin heavy chain (MHC) instead contain damaged organelles and the accumulation of select proteins, including Filamin (Fil) and CryAB. NUAK biochemically and genetically interacts with Drosophila Starvin (Stv), the ortholog of mammalian Bcl-2-associated athanogene 3 (BAG3). Consistent with a known role for the co-chaperone BAG3 and the Heat shock cognate 71 kDa (HSC70)/HSPA8 ATPase in the autophagic clearance of proteins, RNA interference (RNAi) of Drosophila Stv, Hsc70-4, or autophagy-related 8a (Atg8a) all exhibit muscle degeneration and muscle contraction defects that phenocopy NUAK mutants. We further demonstrate that Fil is a target of NUAK kinase activity and abnormally accumulates upon loss of the BAG3-Hsc70-4 complex. In addition, Ubiquitin (Ub), ref(2)p/p62, and Atg8a are increased in regions of protein aggregation, consistent with a block in autophagy upon loss of NUAK. Collectively, our results establish a novel role for NUAK with the Stv-Hsc70-4 complex in the autophagic clearance of proteins that may eventually lead to treatment options for protein aggregate diseases. Author summary: Non-dividing muscle and nerve cells have limited options to clear harmful biological insults. One such insult is the progressive accumulation of damaged and misfolded proteins that ultimately destroy cellular function and may result in cell or organismal death. Understanding how and why normal protein turnover occurs in healthy tissue is essential for the eventual treatment of age-related and/or degenerative diseases that result from abnormal protein accumulation. Using the large, easily manipulated muscles in fruit fly larvae, we find that loss of the evolutionarily conserved NUAK protein results in cellular degeneration due to the abnormal accumulation of certain proteins, including Fil and CryAB. Moreover, we identify Stv/BAG3 and its binding partner Hsc70-4 to be crucial for NUAK function as overexpression of Stv rescues the NUAK degenerative muscle phenotype. This work is the first to uncover NUAK as a key regulator of protein degradation through autophagy and may provide a novel therapeutic target for the treatment of protein aggregate myopathies. [ABSTRACT FROM AUTHOR]

Introduction: Live attenuated zoster vaccine (Zostavax) was used to test the hypothesis that constitutive level of interleukin 10 (IL-10), which may be high in elderly subjects, impairs vaccine efficacy. If constitutive IL-10 impairs vaccine efficacy, the effectiveness of viral vaccines might be improved by transient inhibition of IL-10 before vaccination.Methods: Zostavax was given to 26 patients (age, 60-80 years). IL-10 and immunity to varicella zoster virus (VZV) were measured at baseline and after vaccination. Fluorescent antibody to membrane antigen (FAMA) assays and glycoprotein enzyme-linked immunosorbent assays (gpELISAs) were used to assess humoral immunity; anti-varicella virus T-cell responses were studied in a subset of subjects. In a prospective animal model, T-cell responses to chimeric vaccines against lymphocytic choriomeningitis virus (LCMV) were assessed in mice that express or lack IL-10.Results: FAMA assays revealed significant boosting (by 4-fold) of humoral immunity, which occurred only in subjects (10 of 26) with a low constitutive IL-10 level (ie, <20 pg/mL); moreover, the Zostavax-induced FAMA and gpELISA responses were inversely related to the constitutive IL-10 level. Significant VZV-specific T-cell responses followed vaccination only in subjects with a low constitutive IL-10 level. Vaccine-induced LCMV-specific T-cell responses in mice lacking IL-10 were greater than in wild-type animals.Conclusions: A high constitutive IL-10 level adversely affects vaccine efficacy. [ABSTRACT FROM AUTHOR]