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Coronal loops, seen in solar coronal images, are believed to represent emission from magnetic flux tubes with compact cross sections. We examine the 3D structure of plasma above an active region in a radiative magnetohydrodynamic simulation to locate volume counterparts for coronal loops. In many cases, a loop cannot be linked to an individual thin strand in the volume. While many thin loops are present in the synthetic images, the bright structures in the volume are fewer and of complex shape. We demonstrate that this complexity can form impressions of thin bright loops, even in the absence of thin bright plasma strands. We demonstrate the difficulty of discerning from observations whether a particular loop corresponds to a strand in the volume, or a projection artifact. We demonstrate how apparently isolated loops could deceive observers, even when observations from multiple viewing angles are available. While we base our analysis on a simulation, the main findings are independent from a particular simulation setup and illustrate the intrinsic complexity involved in interpreting observations resulting from line-of-sight integration in an optically thin plasma. We propose alternative interpretation for strands seen in Extreme Ultraviolet images of the corona. The “coronal veil” hypothesis is mathematically more generic, and naturally explains properties of loops that are difficult to address otherwise—such as their constant cross section and anomalously high density scale height. We challenge the paradigm of coronal loops as thin magnetic flux tubes, offering new understanding of solar corona, and by extension, of other magnetically confined bright hot plasmas.

The to and fro of RNA polymerase RNA polymerase II (RNA pol II) moves forwards along the DNA strand during gene transcription, synthesizing messenger RNA as it goes. It can also move backwards and stall — a useful property for regulatory purposes or if it hits an obstacle such as a nucleosome. This arrested state is reactivated by transcription factor IIS (TFIIS). Now, the crystal structure of a backtracked yeast RNA pol II complex containing observable backtracked RNA has been determined at 3.3 Å resolution, as well as the structure of a backtracked complex containing TFIIS. The structures reveal possible mechanisms of transcriptional stalling and transcription reactivation. During gene transcription, RNA polymerase (Pol) II moves forward along DNA and synthesizes mRNA. However, Pol II can also move backwards and stall, which is important for regulatory purposes or when the polymerase hits an obstacle such as a nucleosome. This arrested state is reactivated by the transcription factor TFIIS. Here, a crystal structure is presented of a backtracked yeast Pol II complex in which the backtracked RNA can be observed, plus a structure of a backtracked complex that contains TFIIS. A model is presented for Pol II backtracking, arrest and reactivation during transcription elongation. During gene transcription, RNA polymerase (Pol) II moves forwards along DNA and synthesizes messenger RNA. However, at certain DNA sequences, Pol II moves backwards, and such backtracking can arrest transcription. Arrested Pol II is reactivated by transcription factor IIS (TFIIS), which induces RNA cleavage that is required for cell viability 1 . Pol II arrest and reactivation are involved in transcription through nucleosomes 2 , 3 and in promoter-proximal gene regulation 4 , 5 , 6 . Here we present X-ray structures at 3.3 Å resolution of an arrested Saccharomyces cerevisiae Pol II complex with DNA and RNA, and of a reactivation intermediate that additionally contains TFIIS. In the arrested complex, eight nucleotides of backtracked RNA bind a conserved ‘backtrack site’ in the Pol II pore and funnel, trapping the active centre trigger loop and inhibiting mRNA elongation. In the reactivation intermediate, TFIIS locks the trigger loop away from backtracked RNA, displaces RNA from the backtrack site, and complements the polymerase active site with a basic and two acidic residues that may catalyse proton transfers during RNA cleavage. The active site is demarcated from the backtrack site by a ‘gating tyrosine’ residue that probably delimits backtracking. These results establish the structural basis of Pol II backtracking, arrest and reactivation, and provide a framework for analysing gene regulation during transcription elongation.

Gene transcription by RNA polymerase II is regulated by activator proteins that recruit the coactivator complexes SAGA (Spt–Ada–Gcn5–acetyltransferase) 1 , 2 and transcription factor IID (TFIID) 2 – 4 . SAGA is required for all regulated transcription 5 and is conserved among eukaryotes 6 . SAGA contains four modules 7 – 9 : the activator-binding Tra1 module, the core module, the histone acetyltransferase (HAT) module and the histone deubiquitination (DUB) module. Previous studies provided partial structures 10 – 14 , but the structure of the central core module is unknown. Here we present the cryo-electron microscopy structure of SAGA from the yeast Saccharomyces cerevisiae and resolve the core module at 3.3 Å resolution. The core module consists of subunits Taf5, Sgf73 and Spt20, and a histone octamer-like fold. The octamer-like fold comprises the heterodimers Taf6–Taf9, Taf10–Spt7 and Taf12–Ada1, and two histone-fold domains in Spt3. Spt3 and the adjacent subunit Spt8 interact with the TATA box-binding protein (TBP) 2 , 7 , 15 – 17 . The octamer-like fold and its TBP-interacting region are similar in TFIID, whereas Taf5 and the Taf6 HEAT domain adopt distinct conformations. Taf12 and Spt20 form flexible connections to the Tra1 module, whereas Sgf73 tethers the DUB module. Binding of a nucleosome to SAGA displaces the HAT and DUB modules from the core-module surface, allowing the DUB module to bind one face of an ubiquitinated nucleosome. Structural studies on the yeast transcription coactivator complex SAGA (Spt–Ada–Gcn5–acetyltransferase) provide insights into the mechanism of initiation of regulated transcription by this multiprotein complex, which is conserved among eukaryotes.

COPII mediates Endoplasmic Reticulum to Golgi trafficking of thousands of cargoes. Five essential proteins assemble into a two-layer architecture, with the inner layer thought to regulate coat assembly and cargo recruitment, and the outer coat forming cages assumed to scaffold membrane curvature. Here we visualise the complete, membrane-assembled COPII coat by cryo-electron tomography and subtomogram averaging, revealing the full network of interactions within and between coat layers. We demonstrate the physiological importance of these interactions using genetic and biochemical approaches. Mutagenesis reveals that the inner coat alone can provide membrane remodelling function, with organisational input from the outer coat. These functional roles for the inner and outer coats significantly move away from the current paradigm, which posits membrane curvature derives primarily from the outer coat. We suggest these interactions collectively contribute to coat organisation and membrane curvature, providing a structural framework to understand regulatory mechanisms of COPII trafficking and secretion. Cytosolic coat proteins capture secretory cargo and sculpt membrane carriers for intracellular transport, such as COPII which mediates Endoplasmic Reticulum to Golgi trafficking of thousands of cargoes. Here authors visualise the complete, membrane-assembled COPII coat by cryo-electron tomography and subtomogram averaging, revealing the full network of interactions within and between coat layers.

Low back pain (LBP), as a leading cause of disability, is a common musculoskeletal disorder that results in major social and economic burdens. Recent research has identified inflammation and related signaling pathways as important factors in the onset and progression of disc degeneration, a significant contributor to LBP. Inflammatory mediators also play an indispensable role in discogenic LBP. The suppression of LBP is a primary goal of clinical practice but has not received enough attention in disc research studies. Here, an overview of the advances in inflammation-related pain in disc degeneration is provided, with a discussion on the role of inflammation in IVD degeneration and pain induction. Puncture models, mechanical models, and spontaneous models as the main animal models to study painful disc degeneration are discussed, and the underlying signaling pathways are summarized. Furthermore, potential drug candidates, either under laboratory investigation or undergoing clinical trials, to suppress discogenic LBP by eliminating inflammation are explored. We hope to attract more research interest to address inflammation and pain in IDD and contribute to promoting more translational research.

Small-scale internetwork (IN) magnetic fields are considered to be the main building blocks of quiet Sun magnetism. For this reason, it is crucial to understand how they appear on the solar surface. Here, we employ a high-resolution, high-sensitivity, long-duration Hinode/NFI magnetogram sequence to analyze the appearance modes and spatiotemporal evolution of individual IN magnetic elements inside a supergranular cell at the disk center. From identification of flux patches and magnetofrictional simulations, we show that there are two distinct populations of IN flux concentrations: unipolar and bipolar features. Bipolar features tend to be bigger and stronger than unipolar features. They also live longer and carry more flux per feature. Both types of flux concentrations appear uniformly over the solar surface. However, we argue that bipolar features truly represent the emergence of new flux on the solar surface, while unipolar features seem to be formed by the coalescence of background flux. Magnetic bipoles appear at a faster rate than unipolar features (68 as opposed to 55 Mx cm−2 day−1), and provide about 70% of the total instantaneous IN flux detected in the interior of the supergranule.

Despite the widespread observations on the osteogenic effects of magnesium ion (Mg 2+ ), the diverse roles of Mg 2+ during bone healing have not been systematically dissected. Here, we reveal a previously unknown, biphasic mode of action of Mg 2+ in bone repair. During the early inflammation phase, Mg 2+ contributes to an upregulated expression of transient receptor potential cation channel member 7 (TRPM7), and a TRPM7-dependent influx of Mg 2+ in the monocyte-macrophage lineage, resulting in the cleavage and nuclear accumulation of TRPM7-cleaved kinase fragments (M7CKs). This then triggers the phosphorylation of Histone H3 at serine 10, in a TRPM7-dependent manner at the promoters of inflammatory cytokines, leading to the formation of a pro-osteogenic immune microenvironment. In the later remodeling phase, however, the continued exposure of Mg 2+ not only lead to the over-activation of NF-κB signaling in macrophages and increased number of osteoclastic-like cells but also decelerates bone maturation through the suppression of hydroxyapatite precipitation. Thus, the negative effects of Mg 2+ on osteogenesis can override the initial pro-osteogenic benefits of Mg 2+ . Taken together, this study establishes a paradigm shift in the understanding of the diverse and multifaceted roles of Mg 2+ in bone healing. Supplementation of magnesium (Mg2+) or its inclusion in biomaterials has beneficial effects for bone formation, but it has also been reported that it can have detrimental effects. Here, the authors analyse dose- and time-dependent effects of Mg2+ on bone regeneration and show that it can stimulate monocyte-macrophage lineage cells to support bone formation in the early phases of repair, but inhibit bone repair and mineralization in later stages by promoting a pro-inflammatory environment.

This is a prospective study to establish prediction models that map the refined Scoliosis Research Society 22-item (SRS-22r) onto EuroQoL-5 dimension 5-level (EQ-5D-5L) utility scores in adolescent idiopathic scoliosis (AIS) patients. Comparison of treatment outcomes in AIS can be determined by cost-utility analysis. However, the mainstay spine-specific health-related quality of life outcome measure, the SRS-22r questionnaire does not provide utility assessment. In this study, AIS patients were prospectively recruited to complete both the EQ-5D-5L and SRS-22r questionnaires by trained interviewers. Ordinary least squares regression was undertaken to develop mapping models, which the validity and robustness were assessed by using the 10-fold cross-validation procedure. EQ-5D-5L utility scores were regressed on demographics, Cobb angle, curve types, treatment modalities, and five domains of the SRS-22r questionnaire. Three models were developed using stepwise selection method. EQ-5D-5L scores were regressed on 1) main effects of SRS-22r subscale scores, 2) as per 1 plus squared and interaction terms, and 3) as per 2 plus demographic and clinical characteristics. Model goodness-of-fit was assessed using R-square, adjusted R-square, and information criteria; whereas the predictive performance was evaluated using root mean square error (RMSE), mean absolute error (MAE), and the proportion of absolute error within the threshold of 0.05 and 0.10. A total of 227 AIS patients with mean age of 15.6 years were recruited. The EQ-5D-5L scores were predicted by four domains of SRS-22r (main effects of 'Function', 'Pain', 'Appearance' and 'Mental Health', and squared term of 'Function' and 'Pain'), and Cobb angle in Model 3 with the best goodness-of-fit (R-square/adjusted R-square: 62.1%/60.9%). Three models demonstrated an acceptance predictive performance in error analysis applying 10-fold cross-validation to three models where RMSE and MAE were between 0.063-0.065 and between 0.039-0.044, respectively. Model 3 was therefore recommended out of three mapping models established in this paper. To our knowledge, this is the first study to map a spine-specific health-related quality of life measure onto EQ-5D-5L for AIS patients. With the consideration and incorporation of demographic and clinical characteristics, over 60% variance explained by mapping model 3 enabled the satisfactory prediction of EQ-5D-5L utility scores from existing SRS-22r data for health economic appraisal of different treatment options.

Solar and stellar flares are the most intense emitters of X-rays and extreme ultraviolet radiation in planetary systems1,2. On the Sun, strong flares are usually found in newly emerging sunspot regions3. The emergence of these magnetic sunspot groups leads to the accumulation of magnetic energy in the corona. When the magnetic field undergoes abrupt relaxation, the energy released powers coronal mass ejections as well as heating plasma to temperatures beyond tens of millions of kelvins. While recent work has shed light on how magnetic energy and twist accumulate in the corona4 and on how three-dimensional magnetic reconnection allows for rapid energy release5,6, a self-consistent model capturing how such magnetic changes translate into observable diagnostics has remained elusive. Here, we present a comprehensive radiative magnetohydrodynamics simulation of a solar flare capturing the process from emergence to eruption. The simulation has sufficient realism for the synthesis of remote sensing measurements to compare with observations at visible, ultraviolet and X-ray wavelengths. This unifying model allows us to explain a number of well-known features of solar flares7, including the time profile of the X-ray flux during flares, origin and temporal evolution of chromospheric evaporation and condensation, and sweeping of flare ribbons in the lower atmosphere. Furthermore, the model reproduces the apparent non-thermal shape of coronal X-ray spectra, which is the result of the superposition of multi-component super-hot plasmas8 up to and beyond 100 million K.A state-of-the-art magnetohydrodynamic simulation of a solar flare from emergence to eruption is able to reproduce observations at visible, UV and X-ray wavelengths, and suggests that non-thermal particles at high energy may play a less prominent role than usually assumed in flare models.

Optical coherence tomography angiography (OCTA) has emerged as a novel, non-invasive imaging modality that allows the detailed study of flow within the vascular structures of the eye. Compared to conventional dye angiography, OCTA can produce more detailed, higher resolution images of the vasculature without the added risk of dye injection. In our review, we discuss the advantages and disadvantages of this new technology in comparison to conventional dye angiography. We provide an overview of the current OCTA technology available, compare the various commercial OCTA machines technical specifications and discuss some future software improvements. An approach to the interpretation of OCTA images by correlating images to other multimodal imaging with attention to identifying potential artefacts will be outlined and may be useful to ophthalmologists, particularly those who are currently still unfamiliar with this new technology. This review is based on a search of peer-reviewed published papers relevant to OCTA according to our current knowledge, up to January 2017, available on the PubMed database. Currently, many of the published studies have focused on OCTA imaging of the retina, in particular, the use of OCTA in the diagnosis and management of common retinal diseases such as age-related macular degeneration and retinal vascular diseases. In addition, we describe clinical applications for OCTA imaging in inflammatory diseases, optic nerve diseases and anterior segment diseases. This review is based on both the current literature and the clinical experience of our individual authors, with an emphasis on the clinical applications of this imaging technology.