Single-cell multi-omic analysis of fibrolamellar carcinoma reveals rewired cell-to-cell communication patterns and unique vulnerabilities.

Fibrolamellar carcinoma (FLC) is a rare malignancy disproportionately affecting adolescents and young adults with no standard of care. FLC is characterized by thick stroma, which has long suggested an important role of the tumor microenvironment. Over the past decade, several studies have revealed aberrant markers and pathways in FLC.

Transcriptional reprogramming primes CD8+ T cells toward exhaustion in Myalgic encephalomyelitis/chronic fatigue syndrome.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME) is a severe, debilitating disease, with substantial evidence pointing to immune dysregulation as a key contributor to pathophysiology. To characterize the gene regulatory state underlying T cell dysregulation in ME, we performed multiomic analysis across T cell subsets by integrating single-cell RNA-seq, RNA-seq, and ATAC-seq and further analyzed CD8+ T cell subpopulations following symptom provocation. Specific subsets of CD8+ T cells, as well as certain innate T cells, displayed the most pronounced dysregulation in ME.

Positive selection, genetic recombination, and intra-host evolution in novel equine coronavirus genomes and other members of the subgenus.

There are several examples of coronaviruses in the Betacoronavirus subgenus that have jumped from an animal to the human host. Studying how evolutionary factors shape coronaviruses in non-human hosts may provide insight into the coronavirus host-switching potential. Equids, such as horses and donkeys, are susceptible to equine coronaviruses (ECoVs).

The gene regulatory basis of bystander activation in CD8 T cells.

CD8 T cells are classically recognized as adaptive lymphocytes based on their ability to recognize specific foreign antigens and mount memory responses. However, recent studies indicate that some antigen-inexperienced CD8 T cells can respond to innate cytokines alone in the absence of cognate T cell receptor stimulation, a phenomenon referred to as bystander activation. Here, we demonstrate that neonatal CD8 T cells undergo a robust and diverse program of bystander activation, which corresponds to enhanced innate-like protection against unrelated pathogens.

Single-cell transcriptomics of the immune system in ME/CFS at baseline and following symptom provocation.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a serious and poorly understood disease. To understand immune dysregulation in ME/CFS, we use single-cell RNA sequencing (scRNA-seq) to examine immune cells in patient and control cohorts. Postexertional malaise (PEM), an exacerbation of symptoms following strenuous exercise, is a characteristic symptom of ME/CFS.

Neonatal CD8+ T Cells Resist Exhaustion during Chronic Infection.

Chronic viral infections, such as HIV and hepatitis C virus, represent a major public health problem. Although it is well understood that neonates and adults respond differently to chronic viral infections, the underlying mechanisms remain unknown. In this study, we transferred neonatal and adult CD8+ T cells into a mouse model of chronic infection (lymphocytic choriomeningitis virus clone 13) and dissected out the key cell-intrinsic differences that alter their ability to protect the host.

Polyomavirus-associated Disseminated T-cell Lymphoma in a Colony of Zebra Finches ().

Four zebra finches in a closed research colony presented with variable clinical signs, including masses, skin lesions, shivering, and/or ruffled feathers. These birds were not responsive to treatment efforts; 3 died and one was euthanized. All 4 were submitted for necropsy to determine the cause of the clinical signs.

HIV-1 active and latent infections induce disparate chromatin reorganization and transcriptional regulation of mRNAs and lncRNAs in SupT1 cells.

HIV-1 infection of T-lymphocytes depends on co-opting cellular transcriptional and translational machineries for viral replication. This requires significant changes in the cellular microenvironment. We have characterized and compared the changes in cellular chromatin structures as well as gene expression landscapes in T cells that are either actively or latently infected with HIV-1.

Genomic landscape and gene expression profiles of feline oral squamous cell carcinoma.

Feline oral squamous cell carcinoma (FOSCC) is a cancer of the squamous cell lining in the oral cavity and represents up to 80% of all oral cancers in cats, with a poor prognosis. We have used whole exome sequencing (WES) and RNA sequencing of the tumor to discover somatic mutations and gene expression changes that may be associated with FOSCC occurrence. FOSCC offers a potential comparative model to study human head and neck squamous cell carcinoma (HNSCC) due to its similar spontaneous formation, and morphological and histological features.

Delay modulates the immune response to nerve repair.

Effective regeneration after peripheral nerve injury requires macrophage recruitment. We investigated the activation of remodeling pathways within the macrophage population when repair is delayed and identified alteration of key upstream regulators of the inflammatory response. We then targeted one of these regulators, using exogenous IL10 to manipulate the response to injury at the repair site.

Postnatal oogenesis leads to an exceptionally large ovarian reserve in naked mole-rats.

In the long-lived naked mole-rat (NMR), the entire process of oogenesis occurs postnatally. Germ cell numbers increase significantly in NMRs between postnatal days 5 (P5) and P8, and germs cells positive for proliferation markers (Ki-67, pHH3) are present at least until P90. Using pluripotency markers (SOX2 and OCT4) and the primordial germ cell (PGC) marker BLIMP1, we show that PGCs persist up to P90 alongside germ cells in all stages of female differentiation and undergo mitosis both in vivo and in vitro.

Delayed puberty, gonadotropin abnormalities and subfertility in male Padi2/Padi4 double knockout mice.

Background: Peptidylarginine deiminase enzymes (PADs) convert arginine residues to citrulline in a process called citrullination or deimination. Recently, two PADs, PAD2 and PAD4, have been linked to hormone signaling in vitro and the goal of this study was to test for links between PAD2/PAD4 and hormone signaling in vivo.

Methods: Preliminary analysis of Padi2 and Padi4 single knockout (SKO) mice did not find any overt reproductive defects and we predicted that this was likely due to genetic compensation.

Comparative transcriptional profiling of canine acanthomatous ameloblastoma and homology with human ameloblastoma.

Ameloblastomas are odontogenic tumors that are rare in people but have a relatively high prevalence in dogs. Because canine acanthomatous ameloblastomas (CAA) have clinicopathologic and molecular features in common with human ameloblastomas (AM), spontaneous CAA can serve as a useful translational model of disease. However, the molecular basis of CAA and how it compares to AM are incompletely understood.

Dual RNA-Sequencing of -Infected Cells from a Murine Infection Model.

Dual RNA-sequencing is a powerful technique to assess both bacterial and host transcriptomes in an unbiased way. We developed a protocol to perform Dual RNA-seq on -derived macrophage populations infected with . Here, we provide a practical step-by-step guide to execute the protocol on Mtb-infected cells from a murine infection model.

Evaluation of a Bed Reaggregation Initiative at an Urban Academic Medical Center.

Background: Hospital flow disruptions have been linked to treatment delays, longer length of stay (LOS), poor patient outcomes, and overburdened staff leading to disengagement.

Objective: This project was designed to evaluate and determine if the bed reaggregation was successful at meeting its goals.

Methods: Donabedian's framework guided the following evaluation points: 1) patient placement accuracy, 2) LOS variance, 3) emergency department (ED) boarding times, 4) hospital bypass hours, 5) operational declination rates, 6) patient satisfaction, and 7) RN engagement.

Implementing a Food is Medicine Program to Address Food Insecurity in an Academic Medical Center.

Background: Food insecurity is a public, social, and health concern.

Local Problem: A Food is Medicine Program was developed to address food insecurity.

Methods: A quality improvement initiative was piloted on 3 acute care units.

Multisite Evaluation of Next-Generation Methods for Small RNA Quantification.

Small RNAs (smRNAs) are important regulators of many biologic processes and are now most frequently characterized using Illumina sequencing. However, although standard RNA sequencing library preparation has become routine in most sequencing facilities, smRNA sequencing library preparation has historically been challenging because of high input requirements, laborious protocols involving gel purifications, inability to automate, and a lack of benchmarking standards. Additionally, studies have suggested that many of these methods are nonlinear and do not accurately reflect the amounts of smRNAs .