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The Ophiuchus stream is a short arc-like stellar feature of uncertain origin located $\sim 5$ kpc North of the Galactic centre. New proper motions from the second $Gaia$ data release reconcile the direction of motion of stream members with the stream arc, resolving a puzzling mismatch reported in earlier work. We use N-body simulations to show that the stream is likely only on its second pericentric passage, and thus was formed recently. The simulations suggest that the entire disrupted progenitor is visible in the observed stream today, and that little further tidal debris lies beyond the ends of the stream. The luminosity, length, width, and velocity dispersion of the stream suggest a globular cluster (GC) progenitor substantially fainter and of lower surface brightness than estimated in previous work, and unlike any other known globulars in the Galaxy. This result suggests the existence of clusters that would extend the known GC population to fainter and more weakly bound systems than hitherto known. How such a weakly-bound cluster of old stars survived until it was disrupted so recently, however, remains a mystery. Integrating backwards in time, we find that the orbits of Sagittarius and Ophiuchus passed within $\sim 5$ kpc of each other about $\sim 100$ Myrs ago, an interaction that might help resolve this puzzle. Comment: 11 pages, 7 figures, submitted to MNRAS

We have derived values of the Ultraviolet Index (UVI) at solar noon using the Tropospheric Ultraviolet Model (TUV) driven by ozone, temperature and aerosol fields from climate simulations of the first phase of the Chemistry-Climate Model Initiative (CCMI-1). Since clouds remain one of the largest uncertainties in climate projections, we simulated only the clear-sky UVI. We compared the modelled UVI climatologies against present-day climatological values of UVI derived from both satellite data (the OMI-Aura OMUVBd product) and ground-based measurements (from the NDACC network). Depending on the region, relative differences between the UVI obtained from CCMI/TUV calculations and the ground-based measurements ranged between −5.9% and 10.6%. We then calculated the UVI evolution throughout the 21st century for the four Representative Concentration Pathways (RCPs 2.6, 4.5, 6.0 and 8.5). Compared to 1960s values, we found an average increase in the UVI in 2100 (of 2–4%) in the tropical belt (30°N-30°S). For the mid-latitudes, we observed a 1.8 to 3.4 % increase in the Southern Hemisphere for RCP 2.6, 4.5 and 6.0, and found a 2.3% decrease in RCP 8.5. Higher increases in UVI are projected in the Northern Hemisphere except for RCP 8.5. At high latitudes, ozone recovery is well identified and induces a complete return of mean UVI levels to 1960 values for RCP 8.5 in the Southern Hemisphere. In the Northern Hemisphere, UVI levels in 2100 are higher by 0.5 to 5.5% for RCP 2.6, 4.5 and 6.0 and they are lower by 7.9% for RCP 8.5. We analysed the impacts of greenhouse gases (GHGs) and ozone-depleting substances (ODSs) on UVI from 1960 by comparing CCMI sensitivity simulations (1960–2100) with fixed GHGs or ODSs at their respective 1960 levels. As expected with ODS fixed at their 1960 levels, there is no large decrease in ozone levels and consequently no sudden increase in UVI levels. With fixed GHG, we observed a delayed return of ozone to 1960 values, with a corresponding pattern of change observed on UVI, and looking at the UVI difference between 2090s values and 1960s values, we found an 8 % increase in the tropical belt during the summer of each hemisphere. Finally we show that, while in the Southern Hemisphere the UVI is mainly driven by total ozone column, in the Northern Hemisphere both total ozone column and aerosol optical depth drive UVI levels, with aerosol optical depth having twice as much influence on the UVI as total ozone column does.

Frontiers in immunology 12, 701275 (2021). doi:10.3389/fimmu.2021.701275 Published by Frontiers Media, Lausanne

A conserved feature of the midblastula transition (MBT) is a requirement for a functional DNA replication checkpoint to coordinate cell cycle remodeling and zygotic genome activation (ZGA). We have investigated what triggers this checkpoint during Drosophila embryogenesis. We find that the magnitude of the checkpoint scales with the quantity of transcriptionally engaged DNA. Measuring RNA Polymerase II (Pol II) binding at 20-minute intervals over the course of ZGA reveals that the checkpoint coincides with widespread de novo recruitment of Pol II that precedes and does not require a functional checkpoint. This recruitment drives slowing or stalling of DNA replication at transcriptionally engaged loci. Reducing Pol II recruitment in zelda mutants both reduces replication stalling and bypasses the requirement for a functional checkpoint. This suggests a model where the checkpoint functions as a feedback mechanism to remodel the cell cycle in response to nascent ZGA.

Under the trend of antibiotic resistance of H. pylori leading to the decrease of eradication rate, the development of a vaccine is the best choice to fight against H. pylori. In this study, we attempted to reduce the amounts of required antigens by using three different parenteral routes of immunization and an adjuvant cGAMP (cyclic guanosine monophosphate-adenosine monophosphate) to enhance the immunogenicity of the vaccine candidate. The immune protection and post-challenge immune responses were assessed and compared in mice immunized with recombinant Helicobacter pylori urease A, urease B, and neutrophil-activating protein adjuvanted with cGAMP. The gastric mucosal colonization by H. pylori was significantly reduced in mice immunized by intranasal and, to a less degree, subcutaneous route, but not by intramuscular route. All immunized mice, regardless of the route of immunization, displayed significant, but comparable, increases in antigen-specific serum IgG and mucosal IgA responses 5 weeks post-challenge. The magnitude of the vaccine-induced protection appeared to be associated with the level of antigen-specific Th1 and particularly Th17 responses, as IL-17 responses were only detected in intranasally immunized mice. Taken together, we explored and confirmed the possibility of using a novel adjuvant (cGAMP) to induce significant protective immunity with 10% of oral vaccine antigen dosage through parenteral immunization, especially intranasal immunization. This may provide an alternative approach to oral immunization for the development of effective H. pylori vaccines.

Objective: This study examines whether depression is associated with the development of physical illness and multimorbidity, after controlling for socioeconomic, behavioral, and other potential confounders. Methods: This is a retrospective cohort study in which adult respondents to three nationally representative population health surveys were linked to health administrative databases in Ontario, Canada, and followed for 10 years from survey index. Respondents with any of the study outcome conditions at baseline were excluded to create a final cohort of 29,838 participants. The main exposure of interest was depression, measured using the Composite International Diagnostic Interview–Short Form for Major Depression. We controlled for age, body mass index, marital status, immigrant status, annual household income, smoking, alcohol consumption, physical activity, health status, and having a regular doctor. The outcome measure was the development of physical illness over 10 years of follow-up, defined as 1 of 15 common chronic conditions using administrative data. Results: Among the 29,838 participants (15,259 [51%] female), 8% of females and 4% of males had depression at baseline. In this cohort with no comorbidities at baseline, even in the fully adjusted model, depression increased the risk of developing a first physical illness for females (hazard ratio [HR] 1.16; 95% CI, 1.07 to 1.26) and males (HR 1.20; 95% CI, 1.07 to 1.36) and increased the risk of developing a second physical illness for females (HR 1.16; 95% CI, 1.02 to 1.33) over 10 years of follow-up. Conclusions: For individuals with no prior comorbidities, depression is associated with a greater risk of developing subsequent physical illness and multimorbidity over time. Thus, depression identifies a population of people who may benefit from early identification, additional screening, and intervention. Further study needs to be done to determine whether interventions to manage and support people with depression can prevent or delay the increased risk of multimorbidity.

The collection of patient reported outcomes (pros) is a standard of care in many cancer organizations. In Alberta, pros have been integrated into routine clinical practice since 2012. This longitudinal collection of pros provides a wealth of data and a unique research opportunity to improve cancer care. The goal of this pro data initiative is to establish a robust repository of information for ongoing clinical care and research focused on pros. In this paper, we describe the rationale, scope, and design of this initiative. The initiative consists of pros and other administrative health data from the province of Alberta. Retrieval of health data from a variety of provincially governed sources will create a platform of information on pros, health outcomes, cancer data, other health conditions, and demographics. The aims of the initiative are to use the data to inform best practices at the point of care and to evaluate a variety of pro-related outcomes. Because this effort represents our first to integrate routinely collected pros with other administrative health data, a unique and robust data repository will be created. The ability to integrate various types of data will provide a comprehensive mechanism to evaluate a variety of outcomes. Because cancer care in Alberta is governed by a single health care system, the data linkages will include population health and psychosocial cancer data. We anticipate that research related to this initiative will ultimately help to inform more patient-centred care. to conduct health services research, particularly clinical epidemiology studies