Despite their crucial role in health and disease, our knowledge of immune cells within human tissues remains limited. We surveyed the immune compartment of 16 tissues from 12 adult donors by ...single-cell RNA sequencing and VDJ sequencing generating a dataset of ~360,000 cells. To systematically resolve immune cell heterogeneity across tissues, we developed CellTypist, a machine learning tool for rapid and precise cell type annotation. Using this approach, combined with detailed curation, we determined the tissue distribution of finely phenotyped immune cell types, revealing hitherto unappreciated tissue-specific features and clonal architecture of T and B cells. Our multitissue approach lays the foundation for identifying highly resolved immune cell types by leveraging a common reference dataset, tissue-integrated expression analysis, and antigen receptor sequencing.
A synthetic procedure to access 2-unsubstituted pyrrolidines and piperidines is presented. In the presence of MgI2 as Lewis acid, donor–acceptor cyclopropanes or corresponding cyclobutanes were ...treated with 1,3,5-triazinanes, leading to the five- or six-membered ring systems under mild conditions in yields up to 93%. This protocol tolerates a great variety of functional groups and thus provides an efficient entry to this class of pyrrolidines and piperidines.
The first ring‐opening reaction of donor–acceptor cyclopropanes to give diamines is reported. For this reaction, a 1,3‐bisfunctionalization was developed using cyclopropanes, triazinanes, and ...Sc(OTf)3 as the catalyst, followed by treatment with acid. The reaction proceeds under very mild conditions and tolerates many functional groups. Moreover, a library of various 1,3‐diazepanes, which arise as intermediates of the first formal aza‐4+3‐cycloaddition reaction with donor–acceptor cyclopropanes, was synthesized.
Double Amination: Donor–acceptor cyclopropanes can be selectively opened with triazinanes to give diamines under scandium catalysis and mild acidic conditions. Moreover, a library of various 1,3‐diazepanes, which arise as intermediates of these formal aza‐4+3‐cycloaddition reactions, was synthesized.
Donor–acceptor cyclopropanes with two geminal carboxylic esters are reacted with chalcogenyl chlorides and bromides to afford ring-opened products bearing the halogen atoms in the 1-position, ...adjacent to the donor, and the chalcogenyl residue in the 3-position next to the two acceptor groups. A variety of different donors (e.g., aryl, N, and O) are used. The stereospecificity of the reaction is demonstrated by using a chiral starting material.
Donor–acceptor cyclopropanes are reacted with iodobenzene dichloride to afford ring-opened products bearing chlorine atoms in the 1- and 3-positions, adjacent to the donor and acceptor groups. A ...variety of different donors (e.g., alkyl, aryl, N, and O) and acceptor moieties (e.g., ketones, diesters, and dinitriles) are used.
At the watershed scale, soil moisture is the major control for rainfall-runoff response, especially where saturation excess runoff processes dominate. From the ecological point of view, the pools of ...soil moisture are fundamental ecosystem resources providing the transpirable water for plants. In drylands particularly, soil moisture is one of the major controls on the structure, function, and diversity in ecosystems. In terms of the global hydrological cycle, the overall quantity of soil moisture is small, approximately 0.05%; however, its importance to the global energy balance and the distribution of precipitation far outweighs its physical amount. In soils it governs microbial activity that affects important biogeochemical processes such as nitrification and CO2 production via respiration. During the past 20 years, technology has advanced considerably, with the development of different electrical sensors for determining soil moisture at a point. However, modeling of watersheds requires areal averages. As a result, point measurements and modeling grid cell data requirements are generally incommensurate. We review advances in sensor technology, particularly emerging geophysical methods and distributed sensors, aimed at bridging this gap. We consider some of the data analysis methods for upscaling from a point to give an areal average. Finally, we conclude by offering a vision for future research, listing many of the current scientific and technical challenges.
Understanding the patterns of wild meat consumption from tropical forests is important for designing approaches to address this major threat to biodiversity and mitigate potential pathways for ...transmission of emerging diseases. Bushmeat consumption has been particularly poorly studied in Madagascar, one of the world's hottest biodiversity hotspots. Studying bushmeat consumption is challenging as many species are protected and researchers must consider the incentives faced by informants. Using interviews with 1154 households in 12 communes in eastern Madagascar, as well as local monitoring data, we investigated the importance of socio-economic variables, taste preference and traditional taboos on consumption of 50 wild and domestic species. The majority of meals contain no animal protein. However, respondents consume a wide range of wild species and 95% of respondents have eaten at least one protected species (and nearly 45% have eaten more than 10). The rural/urban divide and wealth are important predictors of bushmeat consumption, but the magnitude and direction of the effect varies between species. Bushmeat species are not preferred and are considered inferior to fish and domestic animals. Taboos have provided protection to some species, particularly the Endangered Indri, but we present evidence that this taboo is rapidly eroding. By considering a variety of potential influences on consumption in a single study we have improved understanding of who is eating bushmeat and why. Evidence that bushmeat species are not generally preferred meats suggest that projects which increase the availability of domestic meat and fish may have success at reducing demand. We also suggest that enforcement of existing wildlife and firearm laws should be a priority, particularly in areas undergoing rapid social change. The issue of hunting as an important threat to biodiversity in Madagascar is only now being fully recognised. Urgent action is required to ensure that heavily hunted species are adequately protected.
There are no epidemiological studies from the British Isles of chronic granulomatous disease, characterized by recurrent, life-threatening bacterial and fungal infections and inflammatory sequelae. ...Patients were enrolled in a national registry and medical records were analysed. Of 94 subjects, 69 had X-linked disease, 16 had autosomal recessive disease and nine were unknown. Prevalence was 7·5/million for 1990-99 and 8·5/million for 1980-89. Suppurative adenitis, abscesses and pneumonia presented commonly. Twenty-three of 30 patients who underwent high resolution computerized tomography had chronic respiratory disease. Inflammatory sequelae included bowel stricture and urogenital tract granulomata. Growth failure was common; 75% of those measured were below the population mean. All patients received prophylactic antibiotics and 93% anti-fungal prophylaxis. Interferon gamma was used to treat infection, but rarely as prophylaxis. Despite prophylaxis, estimated survival was 88% at 10 years but 55% at age 30 years. Morbidity remains significant, severe infectious complications common. Curative treatments including stem cell transplantation should be considered for patients with frequent or serious complications.
ABSTRACT We give an overview of the Grism Lens Amplified Survey from Space (GLASS), a large Hubble Space Telescope program aimed at obtaining grism spectroscopy of the fields of 10 massive clusters ...of galaxies at redshift z = 0.308-0.686, including the Hubble Frontier Fields (HFF). The Wide Field Camera 3 (WFC3) yields near-infrared spectra of the cluster cores covering the wavelength range 0.81-1.69 m through grisms G102 and G141, while the Advanced Camera for Surveys in parallel mode provides G800L spectra of the infall regions of the clusters. The WFC3 spectra are taken at two almost orthogonal position angles in order to minimize the effects of confusion. After summarizing the scientific drivers of GLASS, we describe the sample selection as well as the observing strategy and data processing pipeline. We then utilize MACS J0717.5+3745, a HFF cluster and the first one observed by GLASS, to illustrate the data quality and the high-level data products. Each spectrum brighter than is visually inspected by at least two co-authors and a redshift is measured when sufficient information is present in the spectra. Furthermore, we conducted a thorough search for emission lines through all of the GLASS WFC3 spectra with the aim of measuring redshifts for sources with continuum fainter than We provide a catalog of 139 emission-line-based spectroscopic redshifts for extragalactic sources, including three new redshifts of multiple image systems (one probable, two tentative). In addition to the data itself, we also release software tools that are helpful to navigate the data.
Major depressive disorder (MDD) is a common and disabling condition with well-established heritability and environmental risk factors. Gene-environment interaction studies in MDD have typically ...investigated candidate genes, though the disorder is known to be highly polygenic. This study aims to test for interaction between polygenic risk and stressful life events (SLEs) or childhood trauma (CT) in the aetiology of MDD.
The RADIANT UK sample consists of 1605 MDD cases and 1064 controls with SLE data, and a subset of 240 cases and 272 controls with CT data. Polygenic risk scores (PRS) were constructed using results from a mega-analysis on MDD by the Psychiatric Genomics Consortium. PRS and environmental factors were tested for association with case/control status and for interaction between them.
PRS significantly predicted depression, explaining 1.1% of variance in phenotype (p = 1.9 × 10(-6)). SLEs and CT were also associated with MDD status (p = 2.19 × 10(-4) and p = 5.12 × 10(-20), respectively). No interactions were found between PRS and SLEs. Significant PRSxCT interactions were found (p = 0.002), but showed an inverse association with MDD status, as cases who experienced more severe CT tended to have a lower PRS than other cases or controls. This relationship between PRS and CT was not observed in independent replication samples.
CT is a strong risk factor for MDD but may have greater effect in individuals with lower genetic liability for the disorder. Including environmental risk along with genetics is important in studying the aetiology of MDD and PRS provide a useful approach to investigating gene-environment interactions in complex traits.
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