Multiple sclerosis (MS) is a heterogenous autoimmune disease in which autoreactive lymphocytes attack the myelin sheath of the central nervous system. B lymphocytes in the cerebrospinal fluid (CSF) ...of patients with MS contribute to inflammation and secrete oligoclonal immunoglobulins
. Epstein-Barr virus (EBV) infection has been epidemiologically linked to MS, but its pathological role remains unclear
. Here we demonstrate high-affinity molecular mimicry between the EBV transcription factor EBV nuclear antigen 1 (EBNA1) and the central nervous system protein glial cell adhesion molecule (GlialCAM) and provide structural and in vivo functional evidence for its relevance. A cross-reactive CSF-derived antibody was initially identified by single-cell sequencing of the paired-chain B cell repertoire of MS blood and CSF, followed by protein microarray-based testing of recombinantly expressed CSF-derived antibodies against MS-associated viruses. Sequence analysis, affinity measurements and the crystal structure of the EBNA1-peptide epitope in complex with the autoreactive Fab fragment enabled tracking of the development of the naive EBNA1-restricted antibody to a mature EBNA1-GlialCAM cross-reactive antibody. Molecular mimicry is facilitated by a post-translational modification of GlialCAM. EBNA1 immunization exacerbates disease in a mouse model of MS, and anti-EBNA1 and anti-GlialCAM antibodies are prevalent in patients with MS. Our results provide a mechanistic link for the association between MS and EBV and could guide the development of new MS therapies.
Parkinson's disease (PD) is a common neurodegenerative disorder characterized by degeneration of the substantia nigra pars compacta and by accumulation of α-synuclein in Lewy bodies. PD is caused by ...a combination of environmental factors and genetic variants. These variants range from highly penetrant Mendelian alleles to alleles that only modestly increase disease risk. Here, we review what is known about the genetics of PD. We also describe how PD genetics have solidified the role of endosomal, lysosomal, and mitochondrial dysfunction in PD pathophysiology. Finally, we highlight how all three pathways are affected by α-synuclein and how this knowledge may be harnessed for the development of disease-modifying therapeutics.
We study the properties of clumps formed in three-dimensional weakly magnetized magnetohydrodynamic simulations of converging flows in the thermally bistable, warm neutral medium (WNM). We find the ...following. (1) Similarly to the situation in the classical two-phase medium, cold, dense clumps form through dynamically triggered thermal instability in the compressed layer between the convergent flows, and are often characterized by a sharp density jump at their boundaries though not always. (2) However, the clumps are bounded by phase-transition fronts rather than by contact discontinuities, and thus they grow in size and mass mainly by accretion of WNM material through their boundaries. (3) The clump boundaries generally consist of thin layers of thermally unstable gas, but these layers are often widened by the turbulence, and penetrate deep into the clumps. (4) The clumps are approximately in both ram and thermal pressure balance with their surroundings, a condition which causes their internal Mach numbers to be comparable to the bulk Mach number of the colliding WNM flows. (5) The clumps typically have mean temperatures 20 ≲〈T〉≲ 50 K, corresponding to the wide range of densities they contain (20 ≲n≲ 5000 cm−3) under a nearly isothermal equation of state. (6) The turbulent ram pressure fluctuations of the WNM induce density fluctuations that then serve as seeds for local gravitational collapse within the clumps. (7) The velocity and magnetic fields tend to be aligned with each other within the clumps, although both are significantly fluctuating, suggesting that the velocity tends to stretch and align the magnetic field with it. (8) The typical mean field strength in the clumps is a few times larger than that in the WNM. (9) The magnetic field strength in the densest regions within the clumps (n∼ 104 cm−3) has a mean value of B∼ 6 μG but with a large scatter of nearly two orders of magnitude, implying that both sub- and supercritical cores are formed in the simulation. (10) In the final stages of the evolution, the clumps' growth drives them into gravitational instability, at which point star formation sets in, and the pressure in the clumps' centres increases even further.
To evaluate macular and peripapillary vessel perfusion density (VD) in glaucoma suspects (GS) and glaucoma patients; to correlate ganglion cell-inner plexiform layer (GCIPL) and retinal nerve fiber ...layer (RNFL) thicknesses with macular and peripapillary VD; and to evaluate the diagnostic accuracy of the structural and vascular parameters.
A consecutive series of GS, glaucoma patients, and healthy subjects was prospectively recruited from July 1, 2016, to January 31, 2017. All subjects underwent standard automated perimetry, spectral-domain optical coherence tomography (OCT), and 6 × 6-mm optical coherence tomography angiography (OCT-A) centered on the fovea and optic nerve.
Forty controls, 40 GS, and 40 glaucoma patients were enrolled. Peripapillary RNFL, GCIPL, and macular RNFL thicknesses significantly decreased in the glaucoma group compared to controls and GS (P < 0.01). Peripapillary VD in average and in the superior and inferior quadrants decreased in the glaucoma group (P ≤ 0.001); conversely, macular VD was not statistically different across groups (P > 0.05). At the peripapillary area, a correlation between RNFL thickness and VD was found; conversely, no statistically significant correlation was found between GCIPL thicknesses and macular VD (all P > 0.05) in all groups. Peripapillary RNFL and GCIPL showed higher diagnostic capacity compared to peripapillary and macular VDs.
Structural damage is evident both in the peripapillary and in macular areas. Vascular damage seems to be less prominent, as it was seen only for the glaucoma group and at the radial peripapillary plexus. Diagnostic abilities are excellent for structural variables, less so but still good for peripapillary VD, and poor for macular VD.
Obesity is associated with locality and alcohol use; however, less is known about how the interaction of these two factors may compound the risk of obesity among adolescents. This study examines the ...relationship between alcohol use and obesity among adolescents from rural and urban areas in the United States. Data came from a sample of American adolescents aged 12-17 years from the National Survey on Drug Use and Health (2015-2019; n = 39,489). Obesity was regressed on age, sex, race/ethnicity, income, cigarette smoking, locality, and alcohol use, with an interaction term to examine locality x alcohol use. Predicted probabilities were plotted to assess the interaction. Compared to adolescents from urban areas, those from rural areas had 1.35 times higher odds of being obese (95% CI 1.25, 1.47). Predicted probabilities indicated that the probability of being obese was higher for rural adolescents at lower levels of drinking, up to about 40 drinks in the past 12 months.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We present the identification of 634 variable stars in the Milky Way dwarf spheroidal (dSph) satellite Sculptor based on archival ground-based optical observations spanning ∼24 yr and covering ...∼2.5 deg2. We employed the same methodologies as the ‘Homogeneous Photometry’ series published by Stetson. In particular, we have identified and characterized one of the largest (536) RR Lyrae samples so far in a Milky Way dSph satellite. We have also detected four Anomalous Cepheids, 23 SX Phoenicis stars, five eclipsing binaries, three field variable stars, three peculiar variable stars located above the horizontal branch – near to the locus of BL Herculis – that we are unable to classify properly. Additionally, we identify 37 long period variables plus 23 probable variable stars, for which the current data do not allow us to determine the period. We report positions and finding charts for all the variable stars, and basic properties (period, amplitude, mean magnitude) and light curves for 574 of them. We discuss the properties of the RR Lyrae stars in the Bailey diagram, which supports the coexistence of subpopulations with different chemical compositions. We estimate the mean mass of Anomalous Cepheids (∼1.5 M⊙) and SX Phoenicis stars (∼1 M⊙). We discuss in detail the nature of the former. The connections between the properties of the different families of variable stars are discussed in the context of the star formation history of the Sculptor dSph galaxy.
Open clusters (OCs) are crucial for studying the formation and evolution of the Galactic disc. However, the lack of a large number of OCs analysed homogeneously hampers the investigations about ...chemical patterns and the existence of Galactocentric radial and vertical gradients, or an age–metallicity relation. To overcome this, we have designed the Open Cluster Chemical Abundances from Spanish Observatories (OCCASO) survey. We aim to provide homogeneous radial velocities, physical parameters and individual chemical abundances of six or more red clump stars for a sample of 25 old and intermediate-age OCs visible from the Northern hemisphere. To do so, we use high-resolution spectroscopic facilities (R ≥ 62 000) available at Spanish observatories. We present the motivation, design and current status of the survey, together with the first data release of radial velocities for 77 stars in 12 OCs, which represents about 50 per cent of the survey. We include clusters never studied with high-resolution spectroscopy before (NGC 1907, NGC 6991, NGC 7762), and clusters in common with other large spectroscopic surveys like the Gaia-ESO Survey (NGC 6705) and Apache Point Observatory Galactic Evolution Experiment (NGC 2682 and NGC 6819). We perform internal comparisons between instruments to evaluate and correct internal systematics of the results, and compare our radial velocities with previous determinations in the literature, when available. Finally, radial velocities for each cluster are used to perform a preliminary kinematic study in relation with the Galactic disc.
The Internet and computer networks are exposed to an increasing number of security threats. With new types of attacks appearing continually, developing flexible and adaptive security oriented ...approaches is a severe challenge. In this context, anomaly-based network intrusion detection techniques are a valuable technology to protect target systems and networks against malicious activities. However, despite the variety of such methods described in the literature in recent years, security tools incorporating anomaly detection functionalities are just starting to appear, and several important problems remain to be solved. This paper begins with a review of the most well-known anomaly-based intrusion detection techniques. Then, available platforms, systems under development and research projects in the area are presented. Finally, we outline the main challenges to be dealt with for the wide scale deployment of anomaly-based intrusion detectors, with special emphasis on assessment issues.
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