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.
Infection of dogs with SARS-CoV-2 Sit, Thomas H C; Brackman, Christopher J; Ip, Sin Ming ...
Nature (London),
10/2020, Letnik:
586, Številka:
7831
Journal Article
Recenzirano
Odprti dostop
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first detected in Wuhan in December 2019 and caused coronavirus disease 2019 (COVID-19)
. In 2003, the closely related SARS-CoV had ...been detected in domestic cats and a dog
. However, little is known about the susceptibility of domestic pet mammals to SARS-CoV-2. Here, using PCR with reverse transcription, serology, sequencing the viral genome and virus isolation, we show that 2 out of 15 dogs from households with confirmed human cases of COVID-19 in Hong Kong were found to be infected with SARS-CoV-2. SARS-CoV-2 RNA was detected in five nasal swabs collected over a 13-day period from a 17-year-old neutered male Pomeranian. A 2.5-year-old male German shepherd was positive for SARS-CoV-2 RNA on two occasions and virus was isolated from nasal and oral swabs. Antibody responses were detected in both dogs using plaque-reduction-neutralization assays. Viral genetic sequences of viruses from the two dogs were identical to the virus detected in the respective human cases. The dogs remained asymptomatic during quarantine. The evidence suggests that these are instances of human-to-animal transmission of SARS-CoV-2. It is unclear whether infected dogs can transmit the virus to other animals or back to humans.
Trials are at risk of contamination bias which can occur when participants in the control group are inadvertently exposed to the intervention. This is a particular risk in rehabilitation studies ...where it is easy for trial interventions to be either intentionally or inadvertently adopted in control settings. The Falls in Care Homes (FinCH) trial is used in this paper as an example of a large randomised controlled trial of a complex intervention to explore the potential risks of contamination bias. We outline the FinCH trial design, present the potential risks from contamination bias, and the strategies used in the design of the trial to minimise or mitigate against this. The FinCH trial was a multi-centre randomised controlled trial, with embedded process evaluation, which evaluated whether systematic training in the use of the Guide to Action Tool for Care Homes reduced falls in care home residents. Data were collected from a number of sources to explore contamination in the FinCH trial. Where specific procedures were adopted to reduce risk of, or mitigate against, contamination, this was recorded. Data were collected from study e-mails, meetings with clinicians, research assistant and clinician network communications, and an embedded process evaluation in six intervention care homes. During the FinCH trial, there were six new falls prevention initiatives implemented outside the study which could have contaminated our intervention and findings. Methods used to minimise contamination were: cluster randomisation at the level of care home; engagement with the clinical community to highlight the risks of early adoption; establishing local collaborators in each site familiar with the local context; signing agreements with NHS falls specialists that they would maintain confidentiality regarding details of the intervention; opening additional research sites; and by raising awareness about the importance of contamination in research among participants.
Complex rehabilitation trials are at risk of contamination bias. The potential for contamination bias in studies can be minimized by strengthening collaboration and dialogue with the clinical community. Researchers should recognise that clinicians may contaminate a study through lack of research expertise.
Surface enhanced Raman scattering (SERS) spectra of bacteria were obtained using citrate (capped) and borohydride (uncapped) generated silver nanoparticles (Ag NPs).The observed differences in SERS ...spectra are attributed to the manner in which these Ag NPs interact with bacteria. Capped Ag NPs are able to partition through the surface polysaccharides of the bacterial cell to bind to the inner and outer cell membranes, as well as the periplasmic space between them. The resultant spectra show contributions due to the components of the cell envelope and cellular secretions. Uncapped Ag NPs are unable to partition through the polysaccharide outer structures of the cells. Spectral features observed for these uncapped Ag NPs are secretions primarily due to the metabolites of purine degradation.
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•SERS spectra of bacteria were obtained using capped and uncapped Ag NPs.•Capped Ag NPs partition through the cell envelope of a bacterium while uncapped cannot.•Partitioning of uncapped Ag NPs can be monitored by varying the colloid: bacteria ratio.•Uncapped Ag NPs can only detect purine metabolites secreted outside the cells.•Capped Ag NPs detect purine metabolites and constituents making up the cell envelope.
Varicella-zoster virus (VZV) is the etiologic agent of varicella (chickenpox) and herpes zoster (shingles) infections commonly involving skin, mucous membranes, and less frequently the central ...nervous system. Traditional methods for the laboratory diagnosis of these infections are time-consuming, labor-intensive, and often insensitive. As such, these tests are being replaced by more sensitive and rapid molecular methods. This study evaluated the performance of two different molecular assays, the Simplexa VZV Direct and Simplexa VZV Swab Direct, to detect VZV DNA in cerebrospinal fluid (CSF) and lesion-swab specimens, respectively. The Simplexa VZV Direct and Simplexa VZV Swab Direct assays were compared against individual composite reference methods that varied depending on the sample cohort examined. A total of 883 CSF and 452 cutaneous and mucocutaneous prospective, retrospective, and contrived specimens were evaluated in this multicenter study. The results of this study showed that the Simplexa assays demonstrated near perfect agreement (k = 0.98) compared to the composite reference methods for the detection of VZV in CSF and lesion swab specimens. A further comparison between the standard of care molecular assays employed at the site of specimen collection and the Simplexa assays demonstrated excellent agreement (k = 1.0). The Simplexa assays offer rapid and reliable alternatives for the detection of VZV in certain clinical specimens without the need for nucleic acid extraction.
The Salvador/Warts/Hippo (Hippo) signaling pathway defines a novel signaling cascade regulating cell contact inhibition, organ size control, cell growth, proliferation, apoptosis and cancer ...development in mammals. The upstream regulation of this pathway has been less well defined than the core kinase cassette. KIBRA has been shown to function as an upstream member of the Hippo pathway by influencing the phosphorylation of LATS and YAP, but functional consequences of these biochemical changes have not been previously addressed. We show that in MCF10A cells, loss of KIBRA expression displays epithelial-to-mesenchymal transition (EMT) features, which are concomitant with decreased LATS and YAP phosphorylation, but not MST1/2. In addition, ectopic KIBRA expression antagonizes YAP via the serine 127 phosphorylation site and we show that KIBRA, Willin and Merlin differentially regulate genes controlled by YAP. Finally, reduced KIBRA expression in primary breast cancer specimens correlates with the recently described claudin-low subtype, an aggressive sub-group with EMT features and a poor prognosis.
Several rare earth elements are considered by-products to rare earth mining efforts. By using one of these by-product elements in a high-volume application such as aluminum casting alloys, the supply ...of more valuable rare earths can be globally stabilized. Stabilizing the global rare earth market will decrease the long-term criticality of other rare earth elements. The low demand for Ce, the most abundant rare earth, contributes to the instability of rare earth extraction. In this article, we discuss a series of intermetallic-strengthened Al alloys that exhibit the potential for new high-volume use of Ce. The castability, structure, and mechanical properties of binary, ternary, and quaternary Al-Ce based alloys are discussed. We have determined Al-Ce based alloys to be highly castable across a broad range of compositions. Nanoscale intermetallics dominate the microstructure and are the theorized source of the high ductility. In addition, room-temperature physical properties appear to be competitive with existing aluminum alloys with extended high-temperature stability of the nanostructured intermetallic.
Surface supported, low dimensional gold nanostructures are of interest for plasmonic applications. Low dimensional nanostructures are readily accessible by solution-phase growth, where shape control ...through the addition of growth-directing surfactants is well established. Yet, shape control in chemical vapor deposition (CVD) has not been well explored, and metallic gold films are typically limited to nanoparticulate or thin film morphologies. This article describes the self-seeded growth of high aspect ratio gold plates and wires by CVD. A directed growth mechanism is proposed, where growth is directed by the coordinating N-heterocyclic carbene (NHC) and phosphine ligands originating from the thermal decomposition of the two gas-phase precursors, Au(HMDS) (NHC) (HMDS = hexamethyldisilazide, NHC = 1,3-diisopropyl-imidazolidin-2-ylidene) and Au(HMDS) (PMe3). These ligands acted as transient surfactants for plate growth between 370 and 460 °C and at high precursor flux. Energy dispersive X-ray spectroscopy (EDS) and X-ray photoelectron spectroscopy (XPS) evidence indicates that hydroxyl terminated substrate surfaces are passivated with trimethylsilyl (TMS) moieties originating from the HMDS ligand in both precursors, which promoted island type growth and directed precursor decomposition to occur on gold surfaces. Secondary nucleation is observed on all gold structures and is a crucial component to gas-phase surfactant-mediated CVD growth. This work identifies the potential to use precursor-bound coordinative ligands or gas-phase surfactants to direct growth of metal nanocrystals by CVD.
This study was designed to determine if the maturation stage of engineered cartilage implanted in a goat model of cartilage injury influences the repair outcome. Goat engineered cartilage was ...generated from autologous chondrocytes cultured in hyaluronic acid scaffolds using 2 d, 2 weeks or 6 weeks of pre-culture and implanted above hydroxyapatite/hyaluronic acid sponges into osteochondral defects. Control defects were left untreated or treated with cell-free scaffolds. The quality of repair tissues was assessed 8 weeks or 8 months post implantation by histological staining, modified O'Driscoll scoring and biochemical analyses. Increasing pre-culture time resulted in progressive maturation of the grafts in vitro. After 8 weeks in vivo, the quality of the repair was not improved by any treatment. After 8 months, O'Driscoll histology scores indicated poor cartilage architecture for untreated (29.7 ± 1.6) and cell-free treated groups (24.3 ± 5.8). The histology score was improved when cellular grafts were implanted, with best scores observed for grafts pre-cultured for 2 weeks (16.3 ± 5.8). As compared to shorter pre-culture times, grafts cultured for 6 weeks (histology score: 22.3 ± 6.4) displayed highest type II/I collagen ratios but also inferior architecture of the surface and within the defect, as well as lower integration with native cartilage. Thus, pre-culture of engineered cartilage for 2 weeks achieved a suitable compromise between tissue maturity and structural/integrative properties of the repair tissue. The data demonstrate that the stage of development of engineered cartilage is an important parameter to be considered in designing cartilage repair strategies.
Over the past 4 decades there has been a growing concern for the conservation status of elasmobranchs (sharks and rays). In 2002, the first elasmobranch species were added to Appendix II of the ...Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES). Less than 20 yr later, there were 39 species on Appendix II and 5 on Appendix I. Despite growing concern, effective conservation and management remain challenged by a lack of data on population status for many species, human−wildlife interactions, threats to population viability, and the efficacy of conservation approaches. We surveyed 100 of the most frequently published and cited experts on elasmobranchs and, based on ranked responses, prioritized 20 research questions on elasmobranch conservation. To address these questions, we then convened a group of 47 experts from 35 institutions and 12 countries. The 20 questions were organized into the following broad categories: (1) status and threats, (2) population and ecology, and (3) conservation and management. For each section, we sought to synthesize existing knowledge, describe consensus or diverging views, identify gaps, and suggest promising future directions and research priorities. The resulting synthesis aggregates an array of perspectives on emergent research and priority directions for elasmobranch conservation.
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