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We present astrometric measurements for 13 cold brown dwarfs in the solar neighborhood (d < 20pc). By combining archival Spitzer data with our own Hubble Space Telescope (HST) observations, we achieve parallax uncertainties typically around 10%. Using Spitzer and HST photometry we compare our targets with other known late T and Y dwarfs in the Solar neighborhood, confirming that there is large intrinsic scatter in the near- and mid-infrared absolute magnitudes and colors of this population, further highlighting the diversity observed spectroscopically by several James Webb Space Telescope (JWST) programs. This scatter makes photometric distance estimates highly unreliable and, therefore, makes astrometric parallax measurements fundamental for a meaningful characterization of even the nearest cold brown dwarfs.

The unique binary AR Scorpii consists of an asynchronously rotating, magnetized white dwarf (WD) that interacts with its red-dwarf companion to produce a large-amplitude, highly coherent pulsation every 1.97 minutes. Over the course of two years, we obtained thirty-nine hours of time-resolved, optical photometry of AR Sco at a typical cadence of 5 seconds to study this pulsation. We find that it undergoes significant changes across the binary orbital period and that its amplitude, phase, and waveform all vary as a function of orbital phase. We show that these variations can be explained by constructive and destructive interference between two periodic, double-peaked signals: the spin-orbit beat pulse, and a weaker WD spin pulse. Modelling of the light curve indicates that in the optical, the amplitude of the primary spin pulse is 50% of the primary beat amplitude, while the secondary maxima of the beat and spin pulses have similar amplitudes. Finally, we use our timings of the beat pulses to confirm the presence of the disputed spin-down of the WD. We measure a beat-frequency derivative of -5.14(32) x 10^-17 Hz/s and show that this is attributable to the spin-down of the WD. This value is approximately twice as large as the estimate from Marsh et al. (2016) but is nevertheless consistent with the constraints established in Potter & Buckley (2018). Our precise measurement of the spin-down rate confirms that the decaying rotational energy of the magnetized white dwarf is sufficient to power the excess electromagnetic radiation emitted by the binary.

We have used the UKIRT Hemisphere Survey (UHS) combined with the UKIDSS Galactic Cluster Survey (GCS), the UKIDSS Galactic Plane Survey (GPS), and the CatWISE2020 catalog to search for new substellar members of the nearest open cluster to the Sun, the Hyades. Eight new substellar Hyades candidate members were identified and observed with the Gemini/GNIRS near-infrared spectrograph. All eight objects are confirmed as brown dwarfs with spectral types ranging from L6 to T5, with two objects showing signs of spectral binarity and/or variability. A kinematic analysis demonstrates that all eight new discoveries likely belong to the Hyades cluster, with future radial velocity and parallax measurements needed to confirm their membership. CWISE J042356.23\\(+\\)130414.3, with a spectral type of T5, would be the coldest ($T_{\\rm eff}$$\\approx\\(1100 K) and lowest-mass (\\)M$$\\approx\\(30 \\)M_{\\rm Jup}$) free-floating member of the Hyades yet discovered. We further find that high-probability substellar Hyades members from this work and previous studies have redder near-infrared colors than field-age brown dwarfs, potentially due to lower surface gravities and super-solar metallicities.

The intermediate polar FO Aquarii (FO Aqr) experienced its first-reported low-accretion states in 2016, 2017, and 2018, and using newly available photographic plates, we identify pre-discovery low states in 1965, 1966, and 1974. The primary focus of our analysis, however, is an extensive set of time-series photometry obtained between 2002 and 2018, with particularly intensive coverage of the 2016-2018 low states. After computing an updated spin ephemeris for the white dwarf (WD), we show that its spin period began to increase in 2014 after having spent 27 years decreasing; no other intermediate polar has experienced a sign change of its period derivative, but FO Aqr has now done so twice. Our central finding is that the recent low states all occurred shortly after the WD began to spin down, even though no low states were reported in the preceding quarter-century, when it was spinning up. Additionally, the system's mode of accretion is extremely sensitive to the mass-transfer rate, with accretion being almost exclusively disk-fed when FO Aqr is brighter than V~14 and substantially stream-fed when it is not. Even in the low states, a grazing eclipse remains detectable, confirming the presence of a disk-like structure (but not necessarily a Keplerian accretion disk). We relate these various observations to theoretical predictions that during the low state, the system's accretion disk dissipates into a non-Keplerian ring of diamagnetic blobs. Finally, a new XMM-Newton observation from a high state in 2017 reveals an anomalously soft X-ray spectrum and diminished X-ray luminosity compared to pre-2016 observations.

New genome assemblies have been arriving at a rapidly increasing pace, thanks to decreases in sequencing costs and improvements in third-generation sequencing technologies 1 – 3 . For example, the number of vertebrate genome assemblies currently in the NCBI (National Center for Biotechnology Information) database 4 increased by more than 50% to 1,485 assemblies in the year from July 2018 to July 2019. In addition to this influx of assemblies from different species, new human de novo assemblies 5 are being produced, which enable the analysis of not only small polymorphisms, but also complex, large-scale structural differences between human individuals and haplotypes. This coming era and its unprecedented amount of data offer the opportunity to uncover many insights into genome evolution but also present challenges in how to adapt current analysis methods to meet the increased scale. Cactus 6 , a reference-free multiple genome alignment program, has been shown to be highly accurate, but the existing implementation scales poorly with increasing numbers of genomes, and struggles in regions of highly duplicated sequences. Here we describe progressive extensions to Cactus to create Progressive Cactus, which enables the reference-free alignment of tens to thousands of large vertebrate genomes while maintaining high alignment quality. We describe results from an alignment of more than 600 amniote genomes, which is to our knowledge the largest multiple vertebrate genome alignment created so far. The Progressive Cactus program can create reference-free alignments of hundreds of large vertebrate genomes efficiently, and is used for the alignment of more than 600 amniote genomes.

The subnanometre-resolution electron cryomicroscopy structure of TmrAB, a heterodimeric ABC transport protein, in a nucleotide-free, inward-facing conformation, is determined. An ABC transporter at 8.2-Å resolution The ATP-binding cassette (ABC) transporter is implicated in a number of human diseases and is an important drug target. It is a small hetero-oligomeric protein presenting a challenge to structural biologists. Here Yifan Cheng and colleagues report the 8.2 Å resolution electron cryomicroscopy structure of TmrAB, a 135 kDa heterodimeric ABC transport protein, in a nucleotide-free, inward-facing conformation. The structure shows that the cytoplasmic nucleotide-binding domains of this ABC transporter are in contact with each other. Comparison with the structures of other ABC transporters in various states suggest that the cytoplasmic nucleotide-binding domains slide and rotate during the transition from the inward-facing to the outward-facing conformation. ATP-binding cassette (ABC) transporters translocate substrates across cell membranes, using energy harnessed from ATP binding and hydrolysis at their nucleotide-binding domains 1 , 2 . ABC exporters are present both in prokaryotes and eukaryotes, with examples implicated in multidrug resistance of pathogens and cancer cells, as well as in many human diseases 3 , 4 . TmrAB is a heterodimeric ABC exporter from the thermophilic Gram-negative eubacterium Thermus thermophilus ; it is homologous to various multidrug transporters and contains one degenerate site with a non-catalytic residue next to the Walker B motif 5 . Here we report a subnanometre-resolution structure of detergent-solubilized TmrAB in a nucleotide-free, inward-facing conformation by single-particle electron cryomicroscopy. The reconstructions clearly resolve characteristic features of ABC transporters, including helices in the transmembrane domain and nucleotide-binding domains. A cavity in the transmembrane domain is accessible laterally from the cytoplasmic side of the membrane as well as from the cytoplasm, indicating that the transporter lies in an inward-facing open conformation. The two nucleotide-binding domains remain in contact via their carboxy-terminal helices. Furthermore, comparison between our structure and the crystal structures of other ABC transporters suggests a possible trajectory of conformational changes that involves a sliding and rotating motion between the two nucleotide-binding domains during the transition from the inward-facing to outward-facing conformations.

Various organisations and experts have published numerous statements and recommendations regarding different aspects of sports-related concussion including definition, presentation, treatment, management and return to play guidelines. 1–7 To date, there have been no written consensus statements specific for combat sports regarding management of combatants who have suffered a concussion or for return to competition after a concussion. In combat sports, head contact is an objective of the sport itself. Accordingly, management and treatment of concussion in combat sports should, and must, be more stringent than for non-combat sports counterparts.The Association of Ringside Physicians (an international, non-profit organisation dedicated to the health and safety of the combat sports athlete) sets forth this consensus statement to establish management guidelines that ringside physicians, fighters, referees, trainers, promoters, sanctioning bodies and other healthcare professionals can use in the ringside setting. We also provide guidelines for the return of a combat sports athlete to competition after sustaining a concussion. This consensus statement does not address the management of moderate to severe forms of traumatic brain injury, such as intracranial bleeds, nor does it address the return to competition for combat sports athletes who have suffered such an injury. These more severe forms of brain injuries are beyond the scope of this statement. This consensus statement does not address neuroimaging guidelines in combat sports.

Neuroinflammatory processes are increasingly believed to participate in the pathophysiology of a number of major psychiatric diseases, including depression. Immune activation stimulates the conversion of the amino acid tryptophan to kynurenine, leading to the formation of neuroactive metabolites, such as quinolinic acid and kynurenic acid. These compounds affect glutamatergic neurotransmission, which plays a prominent role in depressive pathology. Increased tryptophan degradation along the kynurenine pathway (KP) has been proposed to contribute to disease etiology. We used postmortem brain tissue from the ventrolateral prefrontal cortex (VLPFC) to assess tissue levels of tryptophan and KP metabolites, the expression of several KP enzymes and a series of cytokines as well as tissue pathology, including microglial activation. Tissue samples came from nonpsychiatric controls (n = 36) and individuals with depressive disorder not otherwise specified (DD-NOS, n = 45) who died of natural causes, homicide, accident, or suicide. We found a reduction in the enzymatic conversion of tryptophan to kynurenine, determined using the kynurenine:tryptophan ratio, and reduced messenger RNA expression of the enzymes indoleamine-2,3-dioxygenase 1 and 2 and tryptophan-2,3-dioxygenase in depressed individuals irrespective of the cause of death. These findings correlated with reductions in the expression of several cytokines, including interferon-γ and tumour necrosis factor-α. Notably, quinolinic acid levels were also lower in depressed individuals than controls. Information on the use of antidepressants and other psychotropic medications was insufficient for statistical comparisons. Contrary to expectations, the present results indicate that depression, in the absence of medical illness or an overt inflammatory process, is associated with compromised, rather than increased, KP metabolism in the VLPFC.

Background Children with cancer are frequently immunocompromised. While children are generally thought to be at less risk of severe SARS-CoV-2 infection than adults, comprehensive population-based evidence for the risk in children with cancer is unavailable. We aimed to produce evidence of the incidence and outcomes from SARS-CoV-2 in children with cancer attending all hospitals treating this population across the UK. Methods Retrospective and prospective observational study of all children in the UK under 16 diagnosed with cancer through data collection from all hospitals providing cancer care to this population. Eligible patients tested positive for SARS-CoV-2 on reverse transcription polymerase chain reaction (RT-PCR). The primary end-point was death, discharge or end of active care for COVID-19 for those remaining in hospital. Results Between 12 March 2020 and 31 July 2020, 54 cases were identified: 15 (28%) were asymptomatic, 34 (63%) had mild infections and 5 (10%) moderate, severe or critical infections. No patients died and only three patients required intensive care support due to COVID-19. Estimated incidence of hospital identified SARS-CoV-2 infection in children with cancer under 16 was 3%. Conclusions Children with cancer with SARS-CoV-2 infection do not appear at increased risk of severe infection compared to the general paediatric population. This is reassuring and supports the continued delivery of standard treatment.

The Xerces Blue ( Glaucopsyche xerces ) is considered to be the first butterfly to become extinct in historical times. It was notable for its chalky lavender wings with conspicuous white spots on the ventral wings. The last individuals were collected in their restricted habitat, in the dunes near the Presidio military base in San Francisco, in 1941. We sequenced the genomes of four 80- to 100-year-old Xerces Blue, and seven historical and one modern specimens of its closest relative, the Silvery Blue ( Glaucopsyche lygdamus ). We compared these to a novel annotated genome of the Green-Underside Blue ( Glaucopsyche alexis ). Phylogenetic relationships inferred from complete mitochondrial genomes indicate that Xerces Blue was a distinct species that diverged from the Silvery Blue lineage at least 850,000 years ago. Using nuclear genomes, both species experienced population growth during the Eemian interglacial period, but the Xerces Blue decreased to a very low effective population size subsequently, a trend opposite to that observed in the Silvery Blue. Runs of homozygosity and deleterious load in the former were significantly greater than in the later, suggesting a higher incidence of inbreeding. These signals of population decline observed in Xerces Blue could be used to identify and monitor other insects threatened by human activities, whose extinction patterns are still not well known.