Both physical and dynamical properties must be considered to constrain the origins of the dynamically excited distant solar system populations. We present high-precision (g-r) colors for 25 small (Hr ...> 5) dynamically excited trans-Neptunian objects (TNOs) and centaurs acquired as part of the Colours of the Outer Solar System Origins Survey. We combine our data set with previously published measurements and consider a set of 229 colors of outer solar system objects on dynamically excited orbits. The overall color distribution is bimodal and can be decomposed into two distinct classes, termed gray and red, that each has a normal color distribution. The two color classes have different inclination distributions: red objects have lower inclinations than the gray ones. This trend holds for all dynamically excited TNO populations. Even in the worst-case scenario, biases in the discovery surveys cannot account for this trend; it is intrinsic to the TNO population. Considering that TNOs are the precursors of centaurs, and that their inclinations are roughly preserved as they become centaurs, our finding solves the conundrum of centaurs being the only outer solar system population identified so far to exhibit this property. The different orbital distributions of the gray and red dynamically excited TNOs provide strong evidence that their colors are due to different formation locations in a disk of planetesimals with a compositional gradient.
The response to the coronavirus disease 2019 (COVID-19) pandemic has been hampered by lack of an effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antiviral therapy. Here we ...report the use of remdesivir in a patient with COVID-19 and the prototypic genetic antibody deficiency X-linked agammaglobulinaemia (XLA). Despite evidence of complement activation and a robust T cell response, the patient developed persistent SARS-CoV-2 pneumonitis, without progressing to multi-organ involvement. This unusual clinical course is consistent with a contribution of antibodies to both viral clearance and progression to severe disease. In the absence of these confounders, we take an experimental medicine approach to examine the in vivo utility of remdesivir. Over two independent courses of treatment, we observe a temporally correlated clinical and virological response, leading to clinical resolution and viral clearance, with no evidence of acquired drug resistance. We therefore provide evidence for the antiviral efficacy of remdesivir in vivo, and its potential benefit in selected patients.
Using 7 yr of MACHO survey data, we present a new determination of the optical depth to microlensing toward the Galactic bulge. We select the sample of 62 microlensing events (60 unique) on clump ...giant sources and perform a detailed efficiency analysis. We use only the clump giant sources because these are bright bulge stars and are not as strongly affected by blending as other events. Using a subsample of 42 clump events concentrated in an area of 4.5 deg super(2) with 739,000 clump giant stars, we find t = 2.17 super(+) sub(-) super(0) sub(0) super(.) sub(.) super(4) sub(3) super(7) sub(8) x 10 super(-6) at (l,b) = (1.50, - 2.68), somewhat smaller than found in most previous MACHO studies but in excellent agreement with recent theoretical predictions. We also present the optical depth in each of the 19 fields in which we detected events and find limits on optical depth for fields with no events. The errors in optical depth in individual fields are dominated by Poisson noise. We measure optical depth gradients of (1.06 c 0.71) x 10 super(-6) deg super(-1) and (0.29 c 0.43) x 10 super(-6) deg super(-1) in the Galactic latitude b and longitude l directions, respectively. Finally, we discuss the possibility of anomalous duration distribution of events in the field 104 centered on (l,b) = (3.11, - 3.01), as well as investigate spatial clustering of events in all fields.
Summary Background Findings from family and twin studies suggest that genetic contributions to psychiatric disorders do not in all cases map to present diagnostic categories. We aimed to identify ...specific variants underlying genetic effects shared between the five disorders in the Psychiatric Genomics Consortium: autism spectrum disorder, attention deficit-hyperactivity disorder, bipolar disorder, major depressive disorder, and schizophrenia. Methods We analysed genome-wide single-nucleotide polymorphism (SNP) data for the five disorders in 33 332 cases and 27 888 controls of European ancestory. To characterise allelic effects on each disorder, we applied a multinomial logistic regression procedure with model selection to identify the best-fitting model of relations between genotype and phenotype. We examined cross-disorder effects of genome-wide significant loci previously identified for bipolar disorder and schizophrenia, and used polygenic risk-score analysis to examine such effects from a broader set of common variants. We undertook pathway analyses to establish the biological associations underlying genetic overlap for the five disorders. We used enrichment analysis of expression quantitative trait loci (eQTL) data to assess whether SNPs with cross-disorder association were enriched for regulatory SNPs in post-mortem brain-tissue samples. Findings SNPs at four loci surpassed the cutoff for genome-wide significance (p<5×10−8 ) in the primary analysis: regions on chromosomes 3p21 and 10q24, and SNPs within two L-type voltage-gated calcium channel subunits, CACNA1C and CACNB2 . Model selection analysis supported effects of these loci for several disorders. Loci previously associated with bipolar disorder or schizophrenia had variable diagnostic specificity. Polygenic risk scores showed cross-disorder associations, notably between adult-onset disorders. Pathway analysis supported a role for calcium channel signalling genes for all five disorders. Finally, SNPs with evidence of cross-disorder association were enriched for brain eQTL markers. Interpretation Our findings show that specific SNPs are associated with a range of psychiatric disorders of childhood onset or adult onset. In particular, variation in calcium-channel activity genes seems to have pleiotropic effects on psychopathology. These results provide evidence relevant to the goal of moving beyond descriptive syndromes in psychiatry, and towards a nosology informed by disease cause. Funding National Institute of Mental Health.
The murine γ-herpesvirus-68 MK3 protein inhibits CD8
+ T cell recognition by ubiquitinating the cytoplasmic tails of classical MHC class I heavy chains. Here we show that MK3 also provides the first ...example of a protein that degrades tapasin and TAP. The degradation was MK3 RING finger dependent and primarily affected TAP. MK3 associated with TAP1 in the absence of tapasin or TAP2, suggesting that TAP1 was a primary binding partner in the peptide loading complex. TAP2 also played a major role in MK3 stability and function. By degrading TAP, therefore, MK3 limited its own expression. However, TAP degradation also broadened the MK3 inhibitory repertoire and achieved a remarkable resistance to MHC class I upregulation by interferon-γ, suggesting that it represents a specific adaptation to immune evasion in lymphoid tissue.
The nature of dark matter remains mysterious, with luminous material accounting for at most ∼25 per cent of the baryons in the Universe. We accordingly undertook a survey looking for the microlensing ...of stars in the Large Magellanic Cloud (LMC) to determine the fraction of Galactic dark matter contained in massive compact halo objects (MACHOs). The presence of the dark matter would be revealed by gravitational lensing of the light from an LMC star as the foreground dark matter moves across the line of sight. The duration of the lensing event is the key observable parameter, but gives non-unique solutions when attempting to estimate the mass, distance and transverse velocity of the lens. The survey results to date indicate that between 8 and 50 per cent of the baryonic mass of the Galactic halo is in the form of MACHOs (ref. 3), but removing the degeneracy by identifying a lensing object would tighten the constraints on the mass in MACHOs. Here we report a direct image of a microlens, revealing it to be a nearby low-mass star in the disk of the Milky Way. This is consistent with the expected frequency of nearby stars acting as lenses, and demonstrates a direct determination of a lens mass from a microlensing event. Complete solutions such as this for halo microlensing events will probe directly the nature of the MACHOs.
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