Follicular thyroid carcinoma in an inbred family of mongrel dogs in Trinidad & Tobago.

Thyroid tumors occur in many domestic species, but are most common in the dog, in which they are classified as follicular or medullary. During 2012-2016, we received tissue specimens or whole carcasses of 4 dogs with variable enlargement of the thyroid glands. The 2 males and 2 females were of mixed (mongrel) inbreeding, 3-4.

Epigenetic tuning of PD-1 expression improves exhausted T cell function and viral control.

PD-1 is a key negative regulator of CD8 T cell activation and is highly expressed by exhausted T cells in cancer and chronic viral infection. Although PD-1 blockade can improve viral and tumor control, physiological PD-1 expression prevents immunopathology and improves memory formation. The mechanisms driving high PD-1 expression in exhaustion are not well understood and could be critical to disentangling its beneficial and detrimental effects.

Chronic viral infection alters PD-1 locus subnuclear localization in cytotoxic CD8 T cells.

During chronic infection, virus-specific CD8 cytotoxic T lymphocytes (CTLs) progressively lose their ability to mount effective antiviral responses. This "exhaustion" is coupled to persistent upregulation of inhibitory receptor programmed death-1 (PD-1) (Pdcd1)-key in suppressing antiviral CTL responses. Here, we investigate allelic Pdcd1 subnuclear localization and transcription during acute and chronic lymphocytic choriomeningitis virus (LCMV) infection in mice.

Coral reef fish larvae show no evidence for map-based navigation after physical displacement.

Millions of minute, newly hatched coral reef fish larvae get carried into the open ocean by highly complex and variable currents. To survive, they must return to a suitable reef habitat within a species-specific time. Strikingly, previous studies have demonstrated that return to home reefs is much more frequent than would be expected by chance.

IL-6/STAT3 Signaling Axis Enhances and Prolongs Pdcd1 Expression in Murine CD8 T Cells.

CD8 cytotoxic T cells are a potent line of defense against invading pathogens. To aid in curtailing aberrant immune responses, the activation status of CD8 T cells is highly regulated. One mechanism in which CD8 T cell responses are dampened is via signaling through the immune-inhibitory receptor Programmed Cell Death Protein-1, encoded by Pdcd1.

PD-1 blockade and vaccination provide therapeutic benefit against SIV by inducing broad and functional CD8 T cells in lymphoid tissue.

During antiretroviral therapy (ART), most of the human immunodeficiency virus (HIV) reservoirs persist in the B cell follicles (BCFs) of lymphoid tissue. Thus, for HIV cure strategies, it is critical to generate cytolytic CD8 T cells that home to BCF, reduce the reservoir burden, and maintain strong antiviral responses in the absence of ART. Here, using a chronic simian immunodeficiency virus (SIV)/rhesus macaque model, we showed that therapeutic vaccination under ART using a CD40L plus TLR7 agonist–adjuvanted DNA/modified vaccinia Ankara vaccine regimen induced robust and highly functional, SIV-specific CD4 and CD8 T cell responses.

The Prevalence of Gastrointestinal Parasites and Seroprevalence of in Captive Ocelots ( in Trinidad, West Indies.

This study was conducted from November 2010 to June 2011 to determine the prevalence of gastrointestinal parasites and the seroprevalence of in captive ocelots () in Trinidad. Faecal samples were collected and analyzed using faecal flotation to identify helminth ova and protozoan cysts and oocysts. Serum samples from captive ocelots were screened for using a latex agglutination test kit.

The Murine MHC Class II Super Enhancer Contains a Functionally Redundant CTCF-Binding Component and a Novel Element Critical for Maximal Expression.

In both humans and mice, CTCF-binding elements form a series of interacting loops across the MHC class II (MHC-II) locus, and CTCF is required for maximal MHC-II gene expression. In humans, a CTCF-bound chromatin insulator termed and a super enhancer (SE) situated in the intergenic region between and play critical roles in regulating MHC-II expression. In this study, we identify a similar SE, termed located between and of the mouse that contains a CTCF site () and a novel region of high histone H3K27 acetylation.

Neutrino Self-Interactions and XENON1T Electron Recoil Excess.

The XENON1T collaboration recently reported an excess in electron recoil events in the energy range between 1-7 keV. This excess could be understood to originate from the known solar neutrino flux if neutrinos couple to a light vector mediator with strength g_{νN} that kinetically mixes with the photon with strength χ and g_{νN}χ∼10^{-13}. Here, we show that such coupling values can naturally arise in a renormalizable model of long-range vector-mediated neutrino self-interactions.

PD-1 Expression during Acute Infection Is Repressed through an LSD1-Blimp-1 Axis.

During prolonged exposure to Ags, such as chronic viral infections, sustained TCR signaling can result in T cell exhaustion mediated in part by expression of programmed cell death-1 (PD-1) encoded by the gene. In this study, dynamic changes in histone H3K4 modifications at the locus during ex vivo and in vivo activation of CD8 T cells suggested a potential role for the histone H3 lysine 4 demethylase LSD1 in regulating PD-1 expression. CD8 T cells lacking LSD1 expressed higher levels of mRNA following ex vivo stimulation as well as increased surface levels of PD-1 during acute, but not chronic, infection with lymphocytic choriomeningitis virus (LCMV).

B cell activation and plasma cell differentiation are inhibited by de novo DNA methylation.

B cells provide humoral immunity by differentiating into antibody-secreting plasma cells, a process that requires cellular division and is linked to DNA hypomethylation. Conversely, little is known about how de novo deposition of DNA methylation affects B cell fate and function. Here we show that genetic deletion of the de novo DNA methyltransferases Dnmt3a and Dnmt3b (Dnmt3-deficient) in mouse B cells results in normal B cell development and maturation, but increased cell activation and expansion of the germinal center B cell and plasma cell populations upon immunization.

Plasma cell differentiation is controlled by multiple cell division-coupled epigenetic programs.

The genomic loci associated with B cell differentiation that are subject to transcriptional and epigenetic regulation in vivo are not well defined, leaving a gap in our understanding of the development of humoral immune responses. Here, using an in vivo T cell independent B cell differentiation model, we define a cellular division-dependent cis-regulatory element road map using ATAC-seq. Chromatin accessibility changes correlate with gene expression and reveal the reprogramming of transcriptional networks and the genes they regulate at specific cell divisions.

A Multicentric T-Cell Lymphoma with a Plasmacytoid Morphology in a Dog.

An 8-year-old male (neutered) Labrador with a history of erythematous skin lesions and exercise intolerance for a prolonged period was suddenly found dead. Necropsy findings revealed an infiltrative, focally extensive mass which occupied 25% of the cardiac interventricular septum. Severe endocardiosis was also found on the bicuspid and tricuspid valves.

A Case Report of Disseminated Canine Histiocytic Sarcoma in Trinidad and Tobago.

Ocular histiocytic sarcomas (as a presenting part of disseminated histiocytic sarcoma) are not commonly diagnosed. A 10-year-old female intact Rottweiler presented to the School of Veterinary Medicine, Trinidad with buphthalmia and pain in the left eye. The cornea of the left eye appeared diffusely opaque with a conjunctival mucopurulent ocular discharge.

Oral Plasmacytoma in a Dog.

A 6-year-old male Pit bull mix dog presented for bleeding from the mouth persisting for five days. A clinical evaluation revealed a 2 × 3 cm soft tissue mandibular mass at the crown of the first premolar, as well as a non-regenerative anemia and hyperproteinemia. Cytologic and histopathologic evaluations of the mass were compatible with an oral plasmacytoma.

Cutting Edge: Chromatin Accessibility Programs CD8 T Cell Memory.

CD8 T cell memory is characterized by rapid recall of effector function, increased proliferation, and reduced activation requirements. Despite the extensive functional characterization, the molecular mechanisms that facilitate these enhanced properties are not well characterized. In this study, the assay for transposase-accessible chromatin sequencing was employed to map the -regulatory elements in CD8 T cells responding to acute and chronic lymphocytic choriomeningitis virus infections.

A magnetic compass that might help coral reef fish larvae return to their natal reef.

Many coral reef fish larvae spend days to months in the open ocean before settlement on coral reefs [1]. Early in development, larvae have limited swimming capabilities and will therefore be greatly affected by currents. This can potentially result in dispersal distances of tens of kilometers [2].

Conserved Region C Functions To Regulate PD-1 Expression and Subsequent CD8 T Cell Memory.

Expression of programmed death 1 (PD-1) on CD8 T cells promotes T cell exhaustion during chronic Ag exposure. During acute infections, PD-1 is transiently expressed and has the potential to modulate CD8 T cell memory formation. Conserved region C (CR-C), a promoter proximal cis-regulatory element that is critical to PD-1 expression in vitro, responds to NFATc1, FoxO1, and/or NF-κB signaling pathways.

Plasma cell differentiation is coupled to division-dependent DNA hypomethylation and gene regulation.

The epigenetic processes that regulate antibody-secreting plasma cells are not well understood. Here, analysis of plasma cell differentiation revealed DNA hypomethylation of 10% of CpG loci that were overrepresented at enhancers. Inhibition of DNA methylation enhanced plasma cell commitment in a cell-division-dependent manner.

Genetic and Epigenetic Regulation of PD-1 Expression.

The inhibitory immune receptor programmed cell death-1 (PD-1) is intricately regulated. In T cells, PD-1 is expressed in response to most immune challenges, but it is rapidly downregulated in acute settings, allowing for normal immune responses. On chronically stimulated Ag-specific T cells, PD-1 expression remains high, leading to an impaired response to stimuli.

NF-κB regulates PD-1 expression in macrophages.

Programmed cell death-1 (PD-1) is responsible for T cell exhaustion during chronic viral infections and is expressed on a variety of immune cells following activation. Despite its importance, the mechanisms that regulate PD-1 in cell types other than CD8 T cells are poorly defined. In this study, the molecular mechanisms for inducing PD-1 expression in CD4 T cells, macrophages, and B cells were explored.

Stringent response activates quorum sensing and modulates cell density-dependent gene expression in Pseudomonas aeruginosa.

During nutrient starvation, Escherichia coli elicits a stringent response involving the ribosome-associated protein RelA. Activation of RelA results in a global change in the cellular metabolism including enhanced expression of the stationary-phase sigma factor RpoS. In the human pathogen Pseudomonas aeruginosa, a complex quorum-sensing circuitry, linked to RpoS expression, is required for cell density-dependent production of many secreted virulence factors, including LasB elastase.

A dynamic analysis of knee ligament injuries in alpine skiing.

The aim of this study is to understand better the dynamic mechanisms of anterior cruciate ligament (ACL) rupture in alpine skiing. As a result of these findings, improvements in the boot-binding release systems are proposed. Six patients who sustained ACL rupture, aged 19 to 43 years, were studied.