A single-nucleus and spatial transcriptomic atlas of the COVID-19 liver reveals topological, functional, and regenerative organ disruption in patients.

Background: The molecular underpinnings of organ dysfunction in severe COVID-19 and its potential long-term sequelae are under intense investigation. To shed light on these in the context of liver function, we perform single-nucleus RNA-seq and spatial transcriptomic profiling of livers from 17 COVID-19 decedents.

Results: We identify hepatocytes positive for SARS-CoV-2 RNA with an expression phenotype resembling infected lung epithelial cells, and a central role in a pro-fibrotic TGFβ signaling cell-cell communications network.

A single-nucleus and spatial transcriptomic atlas of the COVID-19 liver reveals topological, functional, and regenerative organ disruption in patients.

The molecular underpinnings of organ dysfunction in acute COVID-19 and its potential long-term sequelae are under intense investigation. To shed light on these in the context of liver function, we performed single-nucleus RNA-seq and spatial transcriptomic profiling of livers from 17 COVID-19 decedents. We identified hepatocytes positive for SARS-CoV-2 RNA with an expression phenotype resembling infected lung epithelial cells.

SARS-CoV-2 infection produces chronic pulmonary epithelial and immune cell dysfunction with fibrosis in mice.

A subset of individuals who recover from coronavirus disease 2019 (COVID-19) develop post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (PASC), but the mechanistic basis of PASC-associated lung abnormalities suffers from a lack of longitudinal tissue samples. The mouse-adapted SARS-CoV-2 strain MA10 produces an acute respiratory distress syndrome in mice similar to humans. To investigate PASC pathogenesis, studies of MA10-infected mice were extended from acute to clinical recovery phases.

PSMA-targeting TGFβ-insensitive armored CAR T cells in metastatic castration-resistant prostate cancer: a phase 1 trial.

Chimeric antigen receptor (CAR) T cells have demonstrated promising efficacy, particularly in hematologic malignancies. One challenge regarding CAR T cells in solid tumors is the immunosuppressive tumor microenvironment (TME), characterized by high levels of multiple inhibitory factors, including transforming growth factor (TGF)-β. We report results from an in-human phase 1 trial of castration-resistant, prostate cancer-directed CAR T cells armored with a dominant-negative TGF-β receptor (NCT03089203).

System-wide transcriptome damage and tissue identity loss in COVID-19 patients.

The molecular mechanisms underlying the clinical manifestations of coronavirus disease 2019 (COVID-19), and what distinguishes them from common seasonal influenza virus and other lung injury states such as acute respiratory distress syndrome, remain poorly understood. To address these challenges, we combine transcriptional profiling of 646 clinical nasopharyngeal swabs and 39 patient autopsy tissues to define body-wide transcriptome changes in response to COVID-19. We then match these data with spatial protein and expression profiling across 357 tissue sections from 16 representative patient lung samples and identify tissue-compartment-specific damage wrought by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, evident as a function of varying viral loads during the clinical course of infection and tissue-type-specific expression states.

A model of persistent post SARS-CoV-2 induced lung disease for target identification and testing of therapeutic strategies.

COVID-19 survivors develop post-acute sequelae of SARS-CoV-2 (PASC), but the mechanistic basis of PASC-associated lung abnormalities suffers from a lack of longitudinal samples. Mouse-adapted SARS-CoV-2 MA10 produces an acute respiratory distress syndrome (ARDS) in mice similar to humans. To investigate PASC pathogenesis, studies of MA10-infected mice were extended from acute disease through clinical recovery.

The tumor immune microenvironment of primary and metastatic HER2- positive breast cancers utilizing gene expression and spatial proteomic profiling.

Background: The characterization of the immune component of the tumor microenvironment (TME) of human epidermal growth factor receptor 2 positive (HER2+) breast cancer has been limited. Molecular and spatial characterization of HER2+ TME of primary, recurrent, and metastatic breast tumors has the potential to identify immune mediated mechanisms and biomarker targets that could be used to guide selection of therapies.

Methods: We examined 15 specimens from eight patients with HER2+ breast cancer: 10 primary breast tumors (PBT), two soft tissue, one lung, and two brain metastases (BM).

Visualizing in deceased COVID-19 patients how SARS-CoV-2 attacks the respiratory and olfactory mucosae but spares the olfactory bulb.

Anosmia, the loss of smell, is a common and often the sole symptom of COVID-19. The onset of the sequence of pathobiological events leading to olfactory dysfunction remains obscure. Here, we have developed a postmortem bedside surgical procedure to harvest endoscopically samples of respiratory and olfactory mucosae and whole olfactory bulbs.

The spatial landscape of lung pathology during COVID-19 progression.

Recent studies have provided insights into the pathology of and immune response to COVID-19. However, a thorough investigation of the interplay between infected cells and the immune system at sites of infection has been lacking. Here we use high-parameter imaging mass cytometry that targets the expression of 36 proteins to investigate the cellular composition and spatial architecture of acute lung injury in humans (including injuries derived from SARS-CoV-2 infection) at single-cell resolution.

Systemic Tissue and Cellular Disruption from SARS-CoV-2 Infection revealed in COVID-19 Autopsies and Spatial Omics Tissue Maps.

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus has infected over 115 million people and caused over 2.5 million deaths worldwide. Yet, the molecular mechanisms underlying the clinical manifestations of COVID-19, as well as what distinguishes them from common seasonal influenza virus and other lung injury states such as Acute Respiratory Distress Syndrome (ARDS), remains poorly understood.

Shotgun transcriptome, spatial omics, and isothermal profiling of SARS-CoV-2 infection reveals unique host responses, viral diversification, and drug interactions.

In less than nine months, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) killed over a million people, including >25,000 in New York City (NYC) alone. The COVID-19 pandemic caused by SARS-CoV-2 highlights clinical needs to detect infection, track strain evolution, and identify biomarkers of disease course. To address these challenges, we designed a fast (30-minute) colorimetric test (LAMP) for SARS-CoV-2 infection from naso/oropharyngeal swabs and a large-scale shotgun metatranscriptomics platform (total-RNA-seq) for host, viral, and microbial profiling.

Minimal residual disease undetectable by next-generation sequencing predicts improved outcome in CLL after chemoimmunotherapy.

Patients with chronic lymphocytic leukemia (CLL) who achieve blood or bone marrow (BM) undetectable minimal residual disease (U-MRD) status after first-line fludarabine, cyclophosphamide, and rituximab (FCR) have prolonged progression-free survival (PFS), when assessed by an assay with sensitivity 10-4 (MRD4). Despite reaching U-MRD4, many patients, especially those with unmutated IGHV, subsequently relapse, suggesting residual disease <10-4 threshold and the need for more sensitive MRD evaluation. MRD evaluation by next-generation sequencing (NGS) has a sensitivity of 10-6 (MRD6).

Correction: Cryptic chytridiomycosis linked to climate and genetic variation in amphibian populations of the southeastern United States.

[This corrects the article DOI: 10.1371/journal.pone.

Cryptic chytridiomycosis linked to climate and genetic variation in amphibian populations of the southeastern United States.

North American amphibians have recently been impacted by two major emerging pathogens, the fungus Batrachochytrium dendrobatidis (Bd) and iridoviruses in the genus Ranavirus (Rv). Environmental factors and host genetics may play important roles in disease dynamics, but few studies incorporate both of these components into their analyses. Here, we investigated the role of environmental and genetic factors in driving Bd and Rv infection prevalence and severity in a biodiversity hot spot, the southeastern United States.

Genetic regulatory network motifs constrain adaptation through curvature in the landscape of mutational (co)variance.

Systems biology is accumulating a wealth of understanding about the structure of genetic regulatory networks, leading to a more complete picture of the complex genotype-phenotype relationship. However, models of multivariate phenotypic evolution based on quantitative genetics have largely not incorporated a network-based view of genetic variation. Here we model a set of two-node, two-phenotype genetic network motifs, covering a full range of regulatory interactions.

Goldilocks Meets Santa Rosalia: An Ephemeral Speciation Model Explains Patterns of Diversification Across Time Scales.

Understanding the rate at which new species form is a key question in studying the evolution of life on earth. Here we review our current understanding of speciation rates, focusing on studies based on the fossil record, phylogenies, and mathematical models. We find that speciation rates estimated from these different studies can be dramatically different: some studies find that new species form quickly and often, while others find that new species form much less frequently.

Fat frogs, mobile genes: unexpected phylogeographic patterns for the ornate chorus frog (Pseudacris ornata).

The southeastern coastal plain of the United States is a region marked by extraordinary phylogeographic congruence that is frequently attributed to the changing sea levels that occurred during the glacial-interglacial cycles of the Pleistocene epoch. A phylogeographic break corresponding to the Apalachicola River has been suggested for many species studied to date that are endemic to this region. Here, we used this pattern of phylogeographic congruence to develop and test explicit hypotheses about the genetic structure in the ornate chorus frog (Pseudacris ornata).

Permanent Genetic Resources added to Molecular Ecology Resources Database 1 August 2009-30 September 2009.

This article documents the addition of 238 microsatellite marker loci and 72 pairs of Single Nucleotide Polymorphism (SNP) sequencing primers to the Molecular Ecology Resources Database. Loci were developed for the following species: Adelges tsugae, Artemisia tridentata, Astroides calycularis, Azorella selago, Botryllus schlosseri, Botrylloides violaceus, Cardiocrinum cordatum var. glehnii, Campylopterus curvipennis, Colocasia esculenta, Cynomys ludovicianus, Cynomys leucurus, Cynomys gunnisoni, Epinephelus coioides, Eunicella singularis, Gammarus pulex, Homoeosoma nebulella, Hyla squirella, Lateolabrax japonicus, Mastomys erythroleucus, Pararge aegeria, Pardosa sierra, Phoenicopterus ruber ruber and Silene latifolia.

Eight novel tetranucleotide and five cross-species dinucleotide microsatellite loci for the ornate chorus frog (Pseudacris ornata).

We describe the cloning and characterization of eight novel tetranucleotide microsatellite loci in the ornate chorus frog (Pseudacris ornata). We also screened 26 loci from GenBank that were isolated from other Pseudacris species and obtained consistent product from five of these dinucleotide loci. All loci are polymorphic.