Constraints on coronal turbulence models from source sizes of noise storms at 327 MHz

We seek to reconcile observations of small source sizes in the solar corona at 327 MHz with predictions of scattering models that incorporate refractive index effects, inner scale effects and a spherically diverging wavefront. We use an empirical prescription for the turbulence amplitude $C_{N}^{2}(R)$ based on VLBI observations by Spangler and coworkers of compact radio sources against the solar wind for heliocentric distances $R \approx$ 10--50 $R_{\odot}$. We use the Coles & Harmon model for the inner scale $l_{i}(R)$, that is presumed to arise from cyclotron damping. In view of the prevalent uncertainty in the power law index that characterizes solar wind turbulence at various heliocentric distances, we retain this index as a free parameter. We find that the inclusion of spherical divergence effects suppresses the predicted source size substantially. We also find that inner scale effects significantly reduce the predicted source size. An important general finding for solar sources is that the calculations substantially underpredict the observed source size. Three possible, non-exclusive, interpretations of this general result are proposed. First and simplest, future observations with better angular resolution will detect much smaller sources. Consistent with this, previous observations of small sources in the corona at metric wavelengths are limited by the instrument resolution. Second, the spatially-varying level of turbulence $C_{N}^{2}(R)$ is much larger in the inner corona than predicted by straightforward extrapolation Sunwards of the empirical prescription, which was based on observations between 10--50 $R_{\odot}$. Either the functional form or the constant of proportionality could be different. Third, perhaps the inner scale is smaller than the model, leading to increased scattering.Comment: Accepted for publication in the Journal of Geophysical Research (Space Physics). Figures 5, 8 and 9 revised. Conclusions unchange

Near-Limb Zeeman and Hanle Diagnostics

"Weak" magnetic-field diagnostics in faint objects near the bright solar disk are discussed in terms of the level of non-object signatures, in particular, of the stray light in telescopes. Calculated dependencies of the stray light caused by diffraction at the 0.5-, 1.6-, and 4-meter entrance aperture are presented. The requirements for micro-roughness of refractive and reflective primary optics are compared. Several methods for reducing the stray light (the Lyot coronagraphic technique, multiple stages of apodizing in the focal and exit pupil planes, apodizing in the entrance aperture plane with a special mask), and reducing the random and systematic errors are noted. An acceptable level of stray light in telescopes is estimated for the V-profile recording with a signal-to-noise ratio greater than three. Prospects for the limb chromosphere magnetic measurements are indicated.Comment: 11 pages, 3 figure

SIRT7 mediates L1 elements transcriptional repression and their association with the nuclear lamina

Altres ajuts: La Marató de TV3.Long interspersed elements-1 (LINE-1, L1) are retrotransposons that hold the capacity of self-propagation in the genome with potential mutagenic outcomes. How somatic cells restrict L1 activity and how this process becomes dysfunctional during aging and in cancer cells is poorly understood. L1s are enriched at lamin-associated domains, heterochromatic regions of the nuclear periphery. Whether this association is necessary for their repression has been elusive. Here we show that the sirtuin family member SIRT7 participates in the epigenetic transcriptional repression of L1 genome-wide in both mouse and human cells. SIRT7 depletion leads to increased L1 expression and retrotransposition. Mechanistically, we identify a novel interplay between SIRT7 and Lamin A/C in L1 repression. Our results demonstrate that SIRT7-mediated H3K18 deacetylation regulates L1 expression and promotes L1 association with elements of the nuclear lamina. The failure of such activity might contribute to the observed genome instability and compromised viability in SIRT7 knockout mice. Overall, our results reveal a novel function of SIRT7 on chromatin organization by mediating the anchoring of L1 to the nuclear envelope, and a new functional link of the nuclear lamina with transcriptional repression

SIRT7 mediates L1 elements transcriptional repression and their association with the nuclear lamina

Long interspersed elements-1 (LINE-1, L1) are retrotransposons that hold the capacity of self-propagation in the genome with potential mutagenic outcomes. How somatic cells restrict L1 activity and how this process becomes dysfunctional during aging and in cancer cells is poorly understood. L1s are enriched at lamin-associated domains, heterochromatic regions of the nuclear periphery. Whether this association is necessary for their repression has been elusive. Here we show that the sirtuin family member SIRT7 participates in the epigenetic transcriptional repression of L1 genome-wide in both mouse and human cells. SIRT7 depletion leads to increased L1 expression and retrotransposition. Mechanistically, we identify a novel interplay between SIRT7 and Lamin A/C in L1 repression. Our results demonstrate that SIRT7-mediated H3K18 deacetylation regulates L1 expression and promotes L1 association with elements of the nuclear lamina. The failure of such activity might contribute to the observed genome instability and compromised viability in SIRT7 knockout mice. Overall, our results reveal a novel function of SIRT7 on chromatin organization by mediating the anchoring of L1 to the nuclear envelope, and a new functional link of the nuclear lamina with transcriptional repression

Rheumatoid Factor as a Potentiator of Anti–Citrullinated Protein Antibody–Mediated Inflammation in Rheumatoid Arthritis

Objective. The co-occurrence of rheumatoid factor (RF) and anti–citrullinated protein antibody (ACPA) positivity in rheumatoid arthritis (RA) is well described. However, the mechanisms underlying the potential interaction between these 2 distinct autoantibodies have not been well defined. The aim of this study was to evaluate the epidemiologic and molecular interaction of ACPAs and RF and its association with both disease activity and measures of RA-associated inflammation. Methods. In a cohort of 1,488 US veterans with RA, measures of disease activity and serum levels of cytokines and multiplex ACPAs were compared between the following groups of patients: double-negative (anti–cyclic citrullinated peptide [anti-CCP]-/RF-), anti-CCP+/RF-, anti-CCP-/RF+, or double-positive (anti-CCP+/RF+). Additional studies were performed using an in vitro immune complex (IC) stimulation assay in which macrophages were incubated with ACPA ICs in the presence or absence of monoclonal IgM-RF, and tumor necrosis factor α production measured as a readout of macrophage activation. Results. Compared with the double-negative subgroup (as well as each single-positive subgroup), the double-positive subgroup exhibited higher disease activity as well as higher levels of C-reactive protein and inflammatory cytokines (all P \u3c 0.001). In vitro stimulation of macrophages by ACPA ICs increased cytokine production, and the addition of monoclonal IgM-RF significantly increased macrophage tumor necrosis factor α production (P = 0.003 versus ACPA ICs alone). Conclusion. The combined presence of ACPAs and IgM-RF mediates increased proinflammatory cytokine production in vitro and is associated with increased systemic inflammation and disease activity in RA. Our data suggest that IgM-RF enhances the capacity of ACPA ICs to stimulate macrophage cytokine production, thereby providing a mechanistic link by which RF enhances the pathogenicity of ACPA ICs in RA

Structural Determination of the Broadly Reactive Anti-IGHV1-69 Anti-idiotypic Antibody G6 and Its Idiotope

The heavy chain IGHV1-69 germline gene exhibits a high level of polymorphism and shows biased use in protective antibody (Ab) responses to infections and vaccines. It is also highly expressed in several B cell malignancies and autoimmune diseases. G6 is an anti-idiotypic monoclonal Ab that selectively binds to IGHV1-69 heavy chain germline gene 51p1 alleles that have been implicated in these Ab responses and disease processes. Here, we determine the co-crystal structure of humanized G6 (hG6.3) in complex with anti-influenza hemagglutinin stem-directed broadly neutralizing Ab D80. The core of the hG6.3 idiotope is a continuous string of CDR-H2 residues starting with M53 and ending with N58. G6 binding studies demonstrate the remarkable breadth of binding to 51p1 IGHV1-69 Abs with diverse CDR-H3, light chain, and antigen binding specificities. These studies detail the broad expression of the G6 cross-reactive idiotype (CRI) that further define its potential role in precision medicine

Why do people drive when they can't see clearly?

© 2018 Elsevier Ltd Purpose: Refractive blur is associated with decreased hazard perception and impairments in driving performance, but little is known about why people who have spectacles to correct their distance vision drive with uncorrected vision. Methods: We conducted six focus groups. Participants were 30 drivers (mean age 45) who reported having driven uncorrected at least twice in the past six months despite having spectacles to correct their distance vision. Focus groups were audio recorded, transcribed verbatim and analysed thematically. Results: We identified three themes. 1. Responsibility: participants did not feel obliged to drive with optimal vision and believed that others have a responsibility to ensure drivers maintain clear vision. 2. Safe Enough: participants felt safe to drive uncorrected, did not believe they need to wear spectacles to see sufficiently clearly and that they would know if their uncorrected eyesight fails to meet minimum standards. 3. Situations: participants discussed how they would drive uncorrected for short and familiar journeys, when they feel alert, in daylight and in good weather. Conclusions: Beliefs about the importance of driving with clear vision compete with the benefits of not wearing spectacles. Eyecare professionals should provide more direct advice to patients regarding the need to wear their visual correction for driving

Augmented TLR9-induced Btk activation in PIR-B–deficient B-1 cells provokes excessive autoantibody production and autoimmunity

Pathogens are sensed by Toll-like receptors (TLRs) expressed in leukocytes in the innate immune system. However, excess stimulation of TLR pathways is supposed to be connected with provocation of autoimmunity. We show that paired immunoglobulin (Ig)-like receptor B (PIR-B), an immunoreceptor tyrosine-based inhibitory motif–harboring receptor for major histocompatibility class I molecules, on relatively primitive B cells, B-1 cells, suppresses TLR9 signaling via Bruton's tyrosine kinase (Btk) dephosphorylation, which leads to attenuated activation of nuclear factor κB p65RelA but not p38 or Erk, and blocks the production of natural IgM antibodies, including anti-IgG Fc autoantibodies, particularly rheumatoid factor. The autoantibody production in PIR-B–deficient (Pirb−/−) mice was further augmented in combination with the Faslpr mutation, which might be linked to the development of autoimmune glomerulonephritis. These results show the critical link between TLR9-mediated sensing and a simultaneously evoked, PIR-B–mediated inhibitory circuit with a Btk intersection in B-1 cells, and suggest a novel way toward preventing pathogenic natural autoantibody production

Cognitive ability across the life course and cortisol levels in older age

Elevated cortisol levels have been hypothesised to contribute to cognitive ageing, but study findings are inconsistent. In the present study, we examined the association between salivary cortisol in older age and cognitive ability across the life course. We used data from 370 members of the 36-Day Sample of the Scottish Mental Survey 1947, who underwent cognitive testing at age 11, and were then followed up at around age 78, completing further cognitive tests and providing diurnal salivary cortisol samples. We hypothesised that higher cortisol levels would be associated with lower cognitive ability in older age and greater cognitive decline from childhood to older age, but also lower childhood cognitive ability. Few of the tested associations were significant, and of those that were, most suggested a positive relationship between cortisol and cognitive ability. Only one cognitive measure showed any sign of cortisol-related impairment. However, after correcting for multiple comparisons, no results remained significant. These findings suggest that cortisol may not play an important role in cognitive ageing across the life course

An association between polymorphism of the heme oxygenase-1 and -2 genes and age-related macular degeneration

Iron may be implicated in the generation of oxidative stress by the catalyzing the Haber–Weiss or Fenton reaction. On the other hand, oxidative stress has been implicated in the pathogenesis of age-related macular degeneration (AMD) and heme oxygenase-1 (HO-1), encoded by the HMOX1 gene and heme oxygenase-2 (HO-2), encoded by the HMOX2 gene are important markers of iron-related oxidative stress and its consequences. Therefore, variability of the HMOX1 and HMOX2 genes might be implicated in the pathogenesis of AMD through the modulation of the cellular reaction to oxidative stress. In the present work, we investigated the association between AMD and a G → C transversion at the 19 position in the HMOX1 gene (the 19G>C-HMOX1 polymorphism, rs2071747) and a A → G transition at the −42 + 1444 position in the HMOX2 gene (the −42 + 1444A>G-HMOX2 polymorphism, rs2270363) and its modulation by some environmental factors. 279 patients with AMD and 105 controls were recruited in this study and the polymorphisms were typed by restriction fragment length polymorphism and allele-specific polymerase chain reaction (PCR). We observed an association between the occurrence of dry AMD and the G/A genotype of the −42 + 1444A>G-HMOX2 polymorphism (odds ratio (OR) 2.72), whereas the G/G genotype reduced the risk of dry AMD (OR 0.41). The G/C genotype and the C allele of the 19 G>C-HMOX1 polymorphism and the G/G genotype and the G allele of the −42 + 1444A>G-HMOX2 polymorphism were associated with progression of AMD from dry to wet form (OR 4.83, 5.20, 2.55, 1.69, respectively). On the other hand, the G/G genotype and the G allele of the 19 G>C-HMOX1 polymorphism and the A/G genotype and the A allele of the −42 + 1444A>G-HMOX2 polymorphism protected against AMD progression (OR 0.19, 0.19, 0.34, 0.59, respectively). Therefore, the 19G>C-HMOX1 and the −42 + 1444A>G-HMOX2 polymorphisms may be associated with the occurrence and progression of AMD