Assessment of the genetic basis of rosacea by genome-wide association study.

Rosacea is a common, chronic skin disease that is currently incurable. Although environmental factors influence rosacea, the genetic basis of rosacea is not established. In this genome-wide association study, a discovery group of 22,952 individuals (2,618 rosacea cases and 20,334 controls) was analyzed, leading to identification of two significant single-nucleotide polymorphisms (SNPs) associated with rosacea, one of which replicated in a new group of 29,481 individuals (3,205 rosacea cases and 26,262 controls). The confirmed SNP, rs763035 (P=8.0 × 10(-11) discovery group; P=0.00031 replication group), is intergenic between HLA-DRA and BTNL2. Exploratory immunohistochemical analysis of HLA-DRA and BTNL2 expression in papulopustular rosacea lesions from six individuals, including one with the rs763035 variant, revealed staining in the perifollicular inflammatory infiltrate of rosacea for both proteins. In addition, three HLA alleles, all MHC class II proteins, were significantly associated with rosacea in the discovery group and confirmed in the replication group: HLA-DRB1*03:01 (P=1.0 × 10(-8) discovery group; P=4.4 × 10(-6) replication group), HLA-DQB1*02:01 (P=1.3 × 10(-8) discovery group; P=7.2 × 10(-6) replication group), and HLA-DQA1*05:01 (P=1.4 × 10(-8) discovery group; P=7.6 × 10(-6) replication group). Collectively, the gene variants identified in this study support the concept of a genetic component for rosacea, and provide candidate targets for future studies to better understand and treat rosacea

Infrared Variability of Two Dusty White Dwarfs

The most heavily polluted white dwarfs often show excess infrared radiation from circumstellar dust disks, which are modeled as a result of tidal disruption of extrasolar minor planets. Interaction of dust, gas, and disintegrating objects can all contribute to the dynamical evolution of these dust disks. Here, we report on two infrared variable dusty white dwarfs, SDSS J1228+1040 and G29-38. For SDSS J1228+1040, compared to the first measurements in 2007, the IRAC [3.6] and [4.5] fluxes decreased by 20% by 2014 to a level also seen in the recent 2018 observations. For G29-38, the infrared flux of the 10 $\mu$m silicate emission feature became 10% stronger between 2004 and 2007, We explore several scenarios that could account for these changes, including tidal disruption events, perturbation from a companion, and runaway accretion. No satisfactory causes are found for the flux drop in SDSS J1228+1040 due to the limited time coverage. Continuous tidal disruption of small planetesimals could increase the mass of small grains and concurrently change the strength of the 10 $\mu$m feature of G29-38. Dust disks around white dwarfs are actively evolving and we speculate that there could be different mechanisms responsible for the temporal changes of these disks.Comment: ApJ, in pres

Near-infrared variability in dusty white dwarfs: tracing the accretion of planetary material

The inwards scattering of planetesimals towards white dwarfs is expected to be a stochastic process with variability on human time-scales. The planetesimals tidally disrupt at the Roche radius, producing dusty debris detectable as excess infrared emission. When sufficiently close to the white dwarf, this debris sublimates and accretes on to the white dwarf and pollutes its atmosphere. Studying this infrared emission around polluted white dwarfs can reveal how this planetary material arrives in their atmospheres. We report a near-infrared monitoring campaign of 34 white dwarfs with infrared excesses with the aim to search for variability in the dust emission. Time series photometry of these white dwarfs from the United Kingdom Infrared Telescope (Wide Field Camera) in the J, H and K bands were obtained over baselines of up to three years. We find no statistically significant variation in the dust emission in all three near-infrared bands. Specifically, we can rule out variability at ~1.3% for the 13 white dwarfs brighter than 16th mag in K band, and at ~10% for the 32 white dwarfs brighter than 18th mag over time-scales of three years. Although to date two white dwarfs, SDSS J095904.69-020047.6 and WD 1226+110, have shown K band variability, in our sample we see no evidence of new K band variability at these levels. One interpretation is that the tidal disruption events which lead to large variabilities are rare, occur on short time-scales, and after a few years the white dwarfs return to being stable in the near-infrared.Comment: 14 pages + supplementary figures, 9 figures, accepted for publication in MNRA

Shallow Ultraviolet Transits of WD 1145+017

WD 1145+017 is a unique white dwarf system that has a heavily polluted atmosphere, an infrared excess from a dust disk, numerous broad absorption lines from circumstellar gas, and changing transit features, likely from fragments of an actively disintegrating asteroid. Here, we present results from a large photometric and spectroscopic campaign with Hubble, Keck , VLT, Spitzer, and many other smaller telescopes from 2015 to 2018. Somewhat surprisingly, but consistent with previous observations in the u' band, the UV transit depths are always shallower than those in the optical. We develop a model that can quantitatively explain the observed "bluing" and the main findings are: I. the transiting objects, circumstellar gas, and white dwarf are all aligned along our line of sight; II. the transiting object is blocking a larger fraction of the circumstellar gas than of the white dwarf itself. Because most circumstellar lines are concentrated in the UV, the UV flux appears to be less blocked compared to the optical during a transit, leading to a shallower UV transit. This scenario is further supported by the strong anti-correlation between optical transit depth and circumstellar line strength. We have yet to detect any wavelength-dependent transits caused by the transiting material around WD 1145+017.Comment: 16 pages, 11 figures, 6 tables, ApJ, in pres

The VCAM1-ApoE pathway directs microglial chemotaxis and alleviates Alzheimer\u27s disease pathology

In Alzheimer\u27s disease (AD), sensome receptor dysfunction impairs microglial danger-associated molecular pattern (DAMP) clearance and exacerbates disease pathology. Although extrinsic signals, including interleukin-33 (IL-33), can restore microglial DAMP clearance, it remains largely unclear how the sensome receptor is regulated and interacts with DAMP during phagocytic clearance. Here, we show that IL-33 induces VCAM1 in microglia, which promotes microglial chemotaxis toward amyloid-beta (Aβ) plaque-associated ApoE, and leads to Aβ clearance. We show that IL-33 stimulates a chemotactic state in microglia, characterized by Aβ-directed migration. Functional screening identified that VCAM1 directs microglial Aβ chemotaxis by sensing Aβ plaque-associated ApoE. Moreover, we found that disrupting VCAM1-ApoE interaction abolishes microglial Aβ chemotaxis, resulting in decreased microglial clearance of Aβ. In patients with AD, higher cerebrospinal fluid levels of soluble VCAM1 were correlated with impaired microglial Aβ chemotaxis. Together, our findings demonstrate that promoting VCAM1-ApoE-dependent microglial functions ameliorates AD pathology

Fluctuation Study of the Specific Heat of MgB2

The specific heat of polycrystalline Mg$^{11}$B$_{2}$ has been measured with high resolution ac calorimetry from 5 to 45 K at constant magnetic fields. The excess specific heat above T$_{c}$ is discussed in terms of Gaussian fluctuations and suggests that Mg$^{11}$B$_{2}$ is a bulk superconductor with Ginzburg-Landau coherence length $\xi_{0}=26$ \AA . The transition-width broadening in field is treated in terms of lowest-Landau-level (LLL) fluctuations. That analysis requires that $\xi_{0}=20$ \AA . The underestimate of the coherence length in field, along with deviations from 3D LLL predictions, suggest that there is an influence from the anisotropy of B$_{c2}$ between the c-axis and the a-b plane.Comment: Phys. Rev. B 66, 134515 (2002

Spectroscopic and Mechanistic Studies of Heterodimetallic Forms of Metallo-β-lactamase NDM-1

In an effort to characterize the roles of each metal ion in metallo-β-lactamase NDM-1, heterodimetallic analogues (CoCo-, ZnCo-, and CoCd-) of the enzyme were generated and characterized. UV–vis, 1H NMR, EPR, and EXAFS spectroscopies were used to confirm the fidelity of the metal substitutions, including the presence of a homogeneous, heterodimetallic cluster, with a single-atom bridge. This marks the first preparation of a metallo-β-lactamase selectively substituted with a paramagnetic metal ion, Co(II), either in the Zn1 (CoCd-NDM-1) or in the Zn2 site (ZnCo-NDM-1), as well as both (CoCo-NDM-1). We then used these metal-substituted forms of the enzyme to probe the reaction mechanism, using steady-state and stopped-flow kinetics, stopped-flow fluorescence, and rapid-freeze-quench EPR. Both metal sites show significant effects on the kinetic constants, and both paramagnetic variants (CoCd- and ZnCo-NDM-1) showed significant structural changes on reaction with substrate. These changes are discussed in terms of a minimal kinetic mechanism that incorporates all of the data

Help-seeking behaviour for pelvic floor dysfunction in women over 55: drivers and barriers

Objective: Our aim was to identify drivers of and barriers to help-seeking behaviour of older women with pelvic floor dysfunction (PFD) living independently in Australia . Methods: Women aged =55 years were recruited to this cross-sectional study during July and August 2016. Bladder, bowel, pelvic organ prolapse (POP) and sexual dysfunction were assessed with the Australian Pelvic Floor Questionnaire (APFQ). Drivers and barriers were based on the Barriers to Incontinence Care Seeking Questionnaire. Univariate analyses were used to assess any significant relationships between PFD, age, education level, self-reported PFD, barriers and drivers. Results: Of the 376 study participants [mean, standard deviation (SD) age 68.6 (10.5) years], 67% reported symptoms of PFD and 98.7% scored > 0 on the APFQ. Women were more likely to seek help if they scored higher on the APFQ (p < 0.001). The main barrier to seeking help was the perception that PFD was a normal part of ageing (22.4%). Of those who did seek help (50%), the main factor was increased level of symptom bother (51.4%). There was no difference in age or education level between women who did and did not seek help. Conclusion: Women are more likely to seek help for PFD if scoring higher on the APFQ or symptoms are becoming more bothersome. They are less likely to seek help if they view their symptoms as normal. Future direction should be taken to raise awareness of normal pelvic floor function as well as the availability of help for PFD

Radio emission from Supernova Remnants

The explosion of a supernova releases almost instantaneously about 10^51 ergs of mechanic energy, changing irreversibly the physical and chemical properties of large regions in the galaxies. The stellar ejecta, the nebula resulting from the powerful shock waves, and sometimes a compact stellar remnant, constitute a supernova remnant (SNR). They can radiate their energy across the whole electromagnetic spectrum, but the great majority are radio sources. Almost 70 years after the first detection of radio emission coming from a SNR, great progress has been achieved in the comprehension of their physical characteristics and evolution. We review the present knowledge of different aspects of radio remnants, focusing on sources of the Milky Way and the Magellanic Clouds, where the SNRs can be spatially resolved. We present a brief overview of theoretical background, analyze morphology and polarization properties, and review and critical discuss different methods applied to determine the radio spectrum and distances. The consequences of the interaction between the SNR shocks and the surrounding medium are examined, including the question of whether SNRs can trigger the formation of new stars. Cases of multispectral comparison are presented. A section is devoted to reviewing recent results of radio SNRs in the Magellanic Clouds, with particular emphasis on the radio properties of SN 1987A, an ideal laboratory to investigate dynamical evolution of an SNR in near real time. The review concludes with a summary of issues on radio SNRs that deserve further study, and analyzing the prospects for future research with the latest generation radio telescopes.Comment: Revised version. 48 pages, 15 figure

Chromosomal-level assembly of the Asian Seabass genome using long sequence reads and multi-layered scaffolding

We report here the ~670 Mb genome assembly of the Asian seabass (Lates calcarifer), a tropical marine teleost. We used long-read sequencing augmented by transcriptomics, optical and genetic mapping along with shared synteny from closely related fish species to derive a chromosome-level assembly with a contig N50 size over 1 Mb and scaffold N50 size over 25 Mb that span ~90% of the genome. The population structure of L. calcarifer species complex was analyzed by re-sequencing 61 individuals representing various regions across the species' native range. SNP analyses identified high levels of genetic diversity and confirmed earlier indications of a population stratification comprising three clades with signs of admixture apparent in the South-East Asian population. The quality of the Asian seabass genome assembly far exceeds that of any other fish species, and will serve as a new standard for fish genomics