Dysregulated circulating dendritic cell function in ulcerative colitis is partially restored by probiotic strain Lactobacillus casei Shirota

BACKGROUND: Dendritic cells regulate immune responses to microbial products and play a key role in ulcerative colitis (UC) pathology. We determined the immunomodulatory effects of probiotic strain Lactobacillus casei Shirota (LcS) on human DC from healthy controls and active UC patients. METHODS: Human blood DC from healthy controls (control-DC) and UC patients (UC-DC) were conditioned with heat-killed LcS and used to stimulate allogeneic T cells in a 5-day mixed leucocyte reaction. RESULTS: UC-DC displayed a reduced stimulatory capacity for T cells (P < 0.05) and enhanced expression of skin-homing markers CLA and CCR4 on stimulated T cells (P < 0.05) that were negative for gut-homing marker β7. LcS treatment restored the stimulatory capacity of UC-DC, reflecting that of control-DC. LcS treatment conditioned control-DC to induce CLA on T cells in conjunction with β7, generating a multihoming profile, but had no effects on UC-DC. Finally, LcS treatment enhanced DC ability to induce TGFβ production by T cells in controls but not UC patients. CONCLUSIONS: We demonstrate a systemic, dysregulated DC function in UC that may account for the propensity of UC patients to develop cutaneous manifestations. LcS has multifunctional immunoregulatory activities depending on the inflammatory state; therapeutic effects reported in UC may be due to promotion of homeostasis.

Thomas Heywood: just in time

The scholarly study of the dramatic works and career of Thomas Heywood has increased significantly in the last fifty years but still lags far behind that of his contemporaries Shakespeare and Jonson. Labelled the ‘prose Shakespeare’ by Charles Lamb in the early nineteenth century, Heywood seems to have been considered by scholars and publishers to be a ghostly figure who haunted the early modern theatrical world. In fact, recent research using archival records shows the ways in which Heywood is at the centre of an extensive and highly networked professional industry.

Genomic signals of migration and continuity in Britain before the Anglo-Saxons

The purported migrations that have formed the peoples of Britain have been the focus of generations of scholarly controversy. However, this has not benefited from direct analyses of ancient genomes. Here we report nine ancient genomes (~1 x) of individuals from northern Britain: seven from a Roman era York cemetery, bookended by earlier Iron-Age and later Anglo-Saxon burials. Six of the Roman genomes show affinity with modern British Celtic populations, particularly Welsh, but significantly diverge from populations from Yorkshire and other eastern English samples. They also show similarity with the earlier Iron-Age genome, suggesting population continuity, but differ from the later Anglo-Saxon genome. This pattern concords with profound impact of migrations in the Anglo-Saxon period. Strikingly, one Roman skeleton shows a clear signal of exogenous origin, with affinities pointing towards the Middle East, confirming the cosmopolitan character of the Empire, even at its northernmost fringes.

What controls the vertical distribution of aerosol? Relationships between process sensitivity in HadGEM3–UKCA and inter-model variation from AeroCom Phase II

The vertical profile of aerosol is important for its radiative effects, but weakly constrained by observations on the global scale, and highly variable among different models. To investigate the controlling factors in one particular model, we investigate the effects of individual processes in HadGEM3–UKCA and compare the resulting diversity of aerosol vertical profiles with the inter-model diversity from the AeroCom Phase II control experiment. In this way we show that (in this model at least) the vertical profile is controlled by a relatively small number of processes, although these vary among aerosol components and particle sizes. We also show that sufficiently coarse variations in these processes can produce a similar diversity to that among different models in terms of the global-mean profile and, to a lesser extent, the zonal-mean vertical position. However, there are features of certain models' profiles that cannot be reproduced, suggesting the influence of further structural differences between models. In HadGEM3–UKCA, convective transport is found to be very important in controlling the vertical profile of all aerosol components by mass. In-cloud scavenging is very important for all except mineral dust. Growth by condensation is important for sulfate and carbonaceous aerosol (along with aqueous oxidation for the former and ageing by soluble material for the latter). The vertical extent of biomass-burning emissions into the free troposphere is also important for the profile of carbonaceous aerosol. Boundary-layer mixing plays a dominant role for sea salt and mineral dust, which are emitted only from the surface. Dry deposition and below-cloud scavenging are important for the profile of mineral dust only. In this model, the microphysical processes of nucleation, condensation and coagulation dominate the vertical profile of the smallest particles by number (e.g. total CN  >  3 nm), while the profiles of larger particles (e.g. CN  >  100 nm) are controlled by the same processes as the component mass profiles, plus the size distribution of primary emissions. We also show that the processes that affect the AOD-normalised radiative forcing in the model are predominantly those that affect the vertical mass distribution, in particular convective transport, in-cloud scavenging, aqueous oxidation, ageing and the vertical extent of biomass-burning emissions.

Observation in the MINOS far detector of the shadowing of cosmic rays by the sun and moon

The shadowing of cosmic ray primaries by the moon and sun was observed by the MINOS far detector at a depth of 2070 mwe using 83.54 million cosmic ray muons accumulated over 1857.91 live-days. The shadow of the moon was detected at the 5.6 sigma level and the shadow of the sun at the 3.8 sigma level using a log-likelihood search in celestial coordinates. The moon shadow was used to quantify the absolute astrophysical pointing of the detector to be 0.17 +/- 0.12 degrees. Hints of interplanetary magnetic field effects were observed in both the sun and moon shadow. Published by Elsevier B.V.