Dry eye disease in mice activates adaptive corneal epithelial regeneration distinct from constitutive renewal in homeostasis

Many epithelial compartments undergo constitutive renewal in homeostasis but activate unique regenerative responses following injury. The clear corneal epithelium is crucial for vision and is renewed from limbal stem cells (LSCs). Using single-cell RNA sequencing, we profiled the mouse corneal epithelium in homeostasis, aging, diabetes, and dry eye disease (DED), where tear deficiency predisposes the cornea to recurrent injury. In homeostasis, we capture the transcriptional states that accomplish continuous tissue turnover. We leverage our dataset to identify candidate genes and gene networks that characterize key stages across homeostatic renewal, including markers for LSCs. In aging and diabetes, there were only mild changes with \u3c15 dysregulated genes. The constitutive cell types that accomplish homeostatic renewal were conserved in DED but were associated with activation of cell states that comprise adaptive regeneration. We provide global markers that distinguish cell types in homeostatic renewal vs. adaptive regeneration and markers that specifically define DED-elicited proliferating and differentiating cell types. We validate that expression of SPARC, a marker of adaptive regeneration, is also induced in corneal epithelial wound healing and accelerates wound closure in a corneal epithelial cell scratch assay. Finally, we propose a classification system for LSC markers based on their expression fidelity in homeostasis and disease. This transcriptional dissection uncovers the dramatically altered transcriptional landscape of the corneal epithelium in DED, providing a framework and atlas for future study of these ocular surface stem cells in health and disease

Chemical abundances and ages of the bulge stars in APOGEE high-velocity peaks

A cold high-velocity (HV, $\sim$ 200 km/s) peak was first reported in several Galactic bulge fields based on the APOGEE commissioning observations. Both the existence and the nature of the high-velocity peak are still under debate. Here we revisit this feature with the latest APOGEE DR13 data. We find that most of the low latitude bulge fields display a skewed Gaussian distribution with a HV shoulder. However, only 3 out of 53 fields show distinct high-velocity peaks around 200 km/s. The velocity distribution can be well described by Gauss-Hermite polynomials, except the three fields showing clear HV peaks. We find that the correlation between the skewness parameter ($h_{3}$) and the mean velocity ($\bar{v}$), instead of a distinctive HV peak, is a strong indicator of the bar. It was recently suggested that the HV peak is composed of preferentially young stars. We choose three fields showing clear HV peaks to test this hypothesis using the metallicity, [$\alpha$/M] and [C/N] as age proxies. We find that both young and old stars show HV features. The similarity between the chemical abundances of stars in the HV peaks and the main component indicates that they are not systematically different in terms of chemical abundance or age. In contrast, there are clear differences in chemical space between stars in the Sagittarius dwarf and the bulge stars. The strong HV peaks off-plane are still to be explained properly, and could be different in nature.Comment: 13 pages, 10 figures, published in ApJ. Updated to match the final ApJ published version. Minor revisions to the text and Figure

Torus knots and mirror symmetry

We propose a spectral curve describing torus knots and links in the B-model. In particular, the application of the topological recursion to this curve generates all their colored HOMFLY invariants. The curve is obtained by exploiting the full Sl(2, Z) symmetry of the spectral curve of the resolved conifold, and should be regarded as the mirror of the topological D-brane associated to torus knots in the large N Gopakumar-Vafa duality. Moreover, we derive the curve as the large N limit of the matrix model computing torus knot invariants.Comment: 30 pages + appendix, 3 figure

Integrated approach to designing growth factor delivery systems

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154661/1/fsb2fj067873com-sup-0001.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154661/2/fsb2fj067873com.pd

New improved Moser-Trudinger inequalities and singular Liouville equations on compact surfaces

We consider a singular Liouville equation on a compact surface, arising from the study of Chern-Simons vortices in a self dual regime. Using new improved versions of the Moser-Trudinger inequalities (whose main feature is to be scaling invariant) and a variational scheme, we prove new existence results.Comment: to appear in GAF

Activation of the innate immune receptor Dectin-1 upon formation of a 'phagocytic synapse'.

Innate immune cells must be able to distinguish between direct binding to microbes and detection of components shed from the surface of microbes located at a distance. Dectin-1 (also known as CLEC7A) is a pattern-recognition receptor expressed by myeloid phagocytes (macrophages, dendritic cells and neutrophils) that detects β-glucans in fungal cell walls and triggers direct cellular antimicrobial activity, including phagocytosis and production of reactive oxygen species (ROS). In contrast to inflammatory responses stimulated upon detection of soluble ligands by other pattern-recognition receptors, such as Toll-like receptors (TLRs), these responses are only useful when a cell comes into direct contact with a microbe and must not be spuriously activated by soluble stimuli. In this study we show that, despite its ability to bind both soluble and particulate β-glucan polymers, Dectin-1 signalling is only activated by particulate β-glucans, which cluster the receptor in synapse-like structures from which regulatory tyrosine phosphatases CD45 and CD148 (also known as PTPRC and PTPRJ, respectively) are excluded (Supplementary Fig. 1). The 'phagocytic synapse' now provides a model mechanism by which innate immune receptors can distinguish direct microbial contact from detection of microbes at a distance, thereby initiating direct cellular antimicrobial responses only when they are required

Human RTEL1 associates with Poldip3 to facilitate responses to replication stress and R-loop resolution

International audienc

An improved geometric inequality via vanishing moments, with applications to singular Liouville equations

We consider a class of singular Liouville equations on compact surfaces motivated by the study of Electroweak and Self-Dual Chern-Simons theories, the Gaussian curvature prescription with conical singularities and Onsager's description of turbulence. We analyse the problem of existence variationally, and show how the angular distribution of the conformal volume near the singularities may lead to improvements in the Moser-Trudinger inequality, and in turn to lower bounds on the Euler-Lagrange functional. We then discuss existence and non-existence results.Comment: some references adde

Phenotypic redshifts with self-organizing maps: A novel method to characterize redshift distributions of source galaxies for weak lensing

Wide-field imaging surveys such as the Dark Energy Survey (DES) rely on coarse measurements of spectral energy distributions in a few filters to estimate the redshift distribution of source galaxies. In this regime, sample variance, shot noise, and selection effects limit the attainable accuracy of redshift calibration and thus of cosmological constraints. We present a new method to combine wide-field, few-filter measurements with catalogs from deep fields with additional filters and sufficiently low photometric noise to break degeneracies in photometric redshifts. The multi-band deep field is used as an intermediary between wide-field observations and accurate redshifts, greatly reducing sample variance, shot noise, and selection effects. Our implementation of the method uses self-organizing maps to group galaxies into phenotypes based on their observed fluxes, and is tested using a mock DES catalog created from N-body simulations. It yields a typical uncertainty on the mean redshift in each of five tomographic bins for an idealized simulation of the DES Year 3 weak-lensing tomographic analysis of $\sigma_{\Delta z} = 0.007$, which is a 60% improvement compared to the Year 1 analysis. Although the implementation of the method is tailored to DES, its formalism can be applied to other large photometric surveys with a similar observing strategy.Comment: 24 pages, 11 figures; matches version accepted to MNRA

SARS-CoV-2 infects human engineered heart tissues and models COVID-19 myocarditis

There is ongoing debate as to whether cardiac complications of coronavirus disease-2019 (COVID-19) result from myocardial viral infection or are secondary to systemic inflammation and/or thrombosis. We provide evidence that cardiomyocytes are infected in patients with COVID-19 myocarditis and are susceptible to severe acute respiratory syndrome coronavirus 2. We establish an engineered heart tissue model of COVID-19 myocardial pathology, define mechanisms of viral pathogenesis, and demonstrate that cardiomyocyte severe acute respiratory syndrome coronavirus 2 infection results in contractile deficits, cytokine production, sarcomere disassembly, and cell death. These findings implicate direct infection of cardiomyocytes in the pathogenesis of COVID-19 myocardial pathology and provides a model system to study this emerging disease