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.
The Human Cell Atlas is a large international collaborative effort to map all cell types of the human body. Single-cell RNA sequencing can generate high-quality data for the delivery of such an ...atlas. However, delays between fresh sample collection and processing may lead to poor data and difficulties in experimental design.
This study assesses the effect of cold storage on fresh healthy spleen, esophagus, and lung from ≥ 5 donors over 72 h. We collect 240,000 high-quality single-cell transcriptomes with detailed cell type annotations and whole genome sequences of donors, enabling future eQTL studies. Our data provide a valuable resource for the study of these 3 organs and will allow cross-organ comparison of cell types. We see little effect of cold ischemic time on cell yield, total number of reads per cell, and other quality control metrics in any of the tissues within the first 24 h. However, we observe a decrease in the proportions of lung T cells at 72 h, higher percentage of mitochondrial reads, and increased contamination by background ambient RNA reads in the 72-h samples in the spleen, which is cell type specific.
In conclusion, we present robust protocols for tissue preservation for up to 24 h prior to scRNA-seq analysis. This greatly facilitates the logistics of sample collection for Human Cell Atlas or clinical studies since it increases the time frames for sample processing.
Metal organic frameworks (MOFs) have recently debuted as participants and solid supports in catalytic water splitting. Their porosity and structural versatility offer a tantalising consolidation of ...the components needed for solar light harvesting and water splitting. Herein, we describe a selection of relevant contemporary investigations that employ electrocatalysis, chemically introduced redox partners, and photo-catalysts to generate dioxygen and dihydrogen from water. The role of semiconducting MOFs in these systems is addressed, in tandem with band gap control by linker functionalisation and doping. Considered holistically, MOFs offer an impressive physical, spatial and chemical versatility with which to support and sustain water splitting reactions. Major challenges toward practical implementation do remain, but opportunities for development are evidently numerous.
We present artificially motorized sperm cellsa novel type of hybrid micromotor, where customized microhelices serve as motors for transporting sperm cells with motion deficiencies to help them carry ...out their natural function. Our results indicate that metal-coated polymer microhelices are suitable for this task due to potent, controllable, and nonharmful 3D motion behavior. We manage to capture, transport, and release single immotile live sperm cells in fluidic channels that allow mimicking physiological conditions. Important steps toward fertilization are addressed by employing proper means of sperm selection and oocyte culturing. Despite the fact that there still remain some challenges on the way to achieve successful fertilization with artificially motorized sperms, we believe that the potential of this novel approach toward assisted reproduction can be already put into perspective with the present work.
A computationally efficient preconditioned conjugate gradient algorithm with a symmetric successive over-relaxation (SSOR) preconditioner for the iterative solution of set mixed model equations is ...described. The potential computational savings of this approach are examined for an example of single-step genomic evaluation of Australian sheep. Results show that the SSOR preconditioner can substantially reduce the number of iterates required for solutions to converge compared with simpler preconditioners with marked reductions in overall computing time.
We explore the estimation of uncertainty in evolutionary parameters using a recently devised approach for resampling entire additive genetic variance–covariance matrices (G). Large‐sample theory ...shows that maximum‐likelihood estimates (including restricted maximum likelihood, REML) asymptotically have a multivariate normal distribution, with covariance matrix derived from the inverse of the information matrix, and mean equal to the estimated G. This suggests that sampling estimates of G from this distribution can be used to assess the variability of estimates of G, and of functions of G. We refer to this as the REML‐MVN method. This has been implemented in the mixed‐model program WOMBAT. Estimates of sampling variances from REML‐MVN were compared to those from the parametric bootstrap and from a Bayesian Markov chain Monte Carlo (MCMC) approach (implemented in the R package MCMCglmm). We apply each approach to evolvability statistics previously estimated for a large, 20‐dimensional data set for Drosophila wings. REML‐MVN and MCMC sampling variances are close to those estimated with the parametric bootstrap. Both slightly underestimate the error in the best‐estimated aspects of the G matrix. REML analysis supports the previous conclusion that the G matrix for this population is full rank. REML‐MVN is computationally very efficient, making it an attractive alternative to both data resampling and MCMC approaches to assessing confidence in parameters of evolutionary interest.
Ferrocene and its decamethyl derivative Cp*₂Fe are the most common standards for nonaqueous electrochemical investigations because of their well-defined and only mildly solvent-dependent reversible ...Fe(II)/Fe(III) redox couple. Higher oxidation states have only rarely been studied. We report the isolation and crystallographic and spectroscopic characterization of surprisingly stable Fe(IV) salts of the Cp*₂Fe²⁺ dication, produced by oxidation of Cp*₂Fe with AsF₅, SbF₅, or ReF₆ in neat sulfur dioxide as well as XeF(Sb₂F₁₁) in neat hydrogen fluoride. The Sb₂F₁₁⁻ salt exhibits a metallocene with the expected mutually parallel arrangements of the Cp* rings, whereas the As₂F₁₁⁻, AsF₆⁻, SbF₆⁻, and ReF₆⁻ salts manifest tilt angles ranging from 4° to 17°. Both ⁵⁷Fe Mössbauer spectroscopy and superconducting quantum interference device magnetization studies reveal identical d-orbital splitting with an S = 1, ³E ground state based on the 3d electronic configuration ${\mathrm{e}}_{2\mathrm{g}}{^{3}{\mathrm{a}}_{1\mathrm{g}}}^{1}$ of all Cp*₂Fe²⁺ salts.
Coronal jets represent important manifestations of ubiquitous solar transients, which may be the source of significant mass and energy input to the upper solar atmosphere and the solar wind. While ...the energy involved in a jet-like event is smaller than that of "nominal" solar flares and coronal mass ejections (CMEs), jets share many common properties with these phenomena, in particular, the explosive magnetically driven dynamics. Studies of jets could, therefore, provide critical insight for understanding the larger, more complex drivers of the solar activity. On the other side of the size-spectrum, the study of jets could also supply important clues on the physics of transients close or at the limit of the current spatial resolution such as spicules. Furthermore, jet phenomena may hint to basic process for heating the corona and accelerating the solar wind; consequently their study gives us the opportunity to attack a broad range of solar-heliospheric problems.
Although the application of thoracic high-resolution computed tomography (HRCT) to clinical pulmonology has revolutionised the diagnostic approach to patients with suspected interstitial lung disease ...(ILD), additional testing is often needed to make a confident ILD diagnosis. Bronchoalveolar lavage (BAL) can play a significant role in making an accurate and confident diagnosis of specific forms of ILD. When BAL is used in conjunction with comprehensive clinical information and HRCT, BAL nucleated immune cell patterns can frequently provide useful information for diagnostic evaluation and lessen the need to proceed to more invasive procedures, such as surgical lung biopsy. Additionally, BAL can identify confounding conditions, such as infection or malignancy. However, BAL technique, and protocols for processing and analysing BAL fluid are critically important for providing useful information. This perspective reviews the current status of using BAL as a diagnostic tool for the diagnosis of ILD.
Pancreas allograft acceptance is markedly more selective than other solid organs. The number of pancreata recovered is insufficient to meet the demand for pancreas transplants (PTx), particularly for ...patients awaiting simultaneous kidney‐pancreas (SPK) transplant. Development of a pancreas donor risk index (PDRI) to identify factors associated with an increased risk of allograft failure in the context of SPK, pancreas after kidney (PAK) or pancreas transplant alone (PTA), and to assess variation in allograft utilization by geography and center volume was undertaken. Retrospective analysis of all PTx performed from 2000 to 2006 (n = 9401) was performed using Cox regression controlling for donor and recipient characteristics. Ten donor variables and one transplant factor (ischemia time) were subsequently combined into the PDRI. Increased PDRI was associated with a significant, graded reduction in 1‐year pancreas graft survival. Recipients of PTAs or PAKs whose organs came from donors with an elevated PDRI (1.57–2.11) experienced a lower rate of 1‐year graft survival (77%) compared with SPK transplant recipients (88%). Pancreas allograft acceptance varied significantly by region particularly for PAK/PTA transplants (p < 0.0001). This analysis demonstrates the potential value of the PDRI to inform organ acceptance and potentially improve the utilization of higher risk organs in appropriate clinical settings.
The Pancreas Donor Risk Index identifies factors associated with graft loss following transplantation which appear to differentially affect pancreas allograft survival in isolated transplants compared with simultaneous kidney‐pancreas transplant.
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