RNA encodes physical information.

Most amino acids are encoded by multiple codons, making the genetic code degenerate. Synonymous mutations affect protein translation and folding, but their impact on RNA itself is often neglected. We developed a genetic algorithm that introduces synonymous mutations to control the diversity of structures sampled by an mRNA.

A gene duplication of a septin reveals a developmentally regulated filament length control mechanism.

Septins are a family of conserved filament-forming proteins that function in multiple cellular processes. The number of septin genes within an organism varies, and higher eukaryotes express many septin isoforms due to alternative splicing. It is unclear if different combinations of septin proteins in complex alter the polymers' biophysical properties.

Double-stranded RNA drives SARS-CoV-2 nucleocapsid protein to undergo phase separation at specific temperatures.

Nucleocapsid protein (N-protein) is required for multiple steps in betacoronaviruses replication. SARS-CoV-2-N-protein condenses with specific viral RNAs at particular temperatures making it a powerful model for deciphering RNA sequence specificity in condensates. We identify two separate and distinct double-stranded, RNA motifs (dsRNA stickers) that promote N-protein condensation.

Double-stranded RNA drives SARS-CoV-2 nucleocapsid protein to undergo phase separation at specific temperatures.

Betacoronavirus SARS-CoV-2 infections caused the global Covid-19 pandemic. The nucleocapsid protein (N-protein) is required for multiple steps in the betacoronavirus replication cycle. SARS-CoV-2-N-protein is known to undergo liquid-liquid phase separation (LLPS) with specific RNAs at particular temperatures to form condensates.

Genomic RNA Elements Drive Phase Separation of the SARS-CoV-2 Nucleocapsid.

We report that the SARS-CoV-2 nucleocapsid protein (N-protein) undergoes liquid-liquid phase separation (LLPS) with viral RNA. N-protein condenses with specific RNA genomic elements under physiological buffer conditions and condensation is enhanced at human body temperatures (33°C and 37°C) and reduced at room temperature (22°C). RNA sequence and structure in specific genomic regions regulate N-protein condensation while other genomic regions promote condensate dissolution, potentially preventing aggregation of the large genome.

Genetic and environmental risk for lymphoma in boxer dogs.

Background: Non-Hodgkin lymphoma in humans is associated with environmental chemical exposures, and risk is enhanced by genetic variants in glutathione S-transferases (GST) enzymes.

Objective: We hypothesized that boxer dogs, a breed at risk for lymphoma, would have a higher prevalence of GST variants with predicted low activity, and greater accumulated DNA damage, compared to other breeds. We also hypothesized that lymphoma in boxers would be associated with specific environmental exposures and a higher prevalence of canine GST variants.

Antioxidant supplementation during illness in dogs: effect on oxidative stress and outcome, an exploratory study.

Objectives: To assess whether combination antioxidant supplementation for 30 days in systemically ill dogs alters antioxidant status, degree of lipid peroxidation, clinical score and survival.

Materials And Methods: Forty client-owned systemically-ill hospitalised dogs were eligible for inclusion. Dogs were randomised to no supplementation (NS; n=19) or supplementation with N-acetylcysteine/S-adenosylmethionine/silybin and vitamin E (AS; n=20) for 30 days.

Glutathione S-transferase theta genotypes and environmental exposures in the risk of canine transitional cell carcinoma.

Introduction: Transitional cell carcinoma (TCC) in humans is associated with environmental exposures and variants in glutathione S-transferase (GST) genes. Scottish Terriers have a high breed risk for TCC, but the relationship between genetic and environmental risk in dogs is not fully understood.

Hypotheses: Scottish Terriers have a higher frequency of GST-theta variants compared to lower risk breeds.

Biomarkers of oxidative stress as an assessment of the redox status of the liver in dogs.

Background: Oxidative stress is associated with a diverse group of liver disorders across species.

Objectives: Determine whether glutathione (GSH) concentration in plasma and red blood cells correlates with liver GSH concentration in dogs and evaluate whether other markers of systemic oxidative stress, plasma vitamin E and urine 8-isoprostanes/creatinine (F -IsoPs/Cr) concentrations, correlate with liver GSH.

Animals: Thirty-four client-owned dogs undergoing clinically indicated liver biopsy and 15 healthy control dogs.

Glutathione-S-transferase-theta genotypes and the risk of cyclophosphamide toxicity in dogs.

The antineoplastic agent cyclophosphamide (CP) has dose-limiting side effects including sterile haemorrhagic cystitis (SHC), bone marrow (BM) suppression and gastrointestinal (GI) toxicity in dogs. The metabolites acrolein and phosphoramide that mediate these toxicities are glutathione-S-transferase (GST) substrates, and low functioning GST alleles are associated with CP toxicity in humans. The aim of this study was to determine whether variants in 2 canine GST genes, GSTT1 and GSTT5, were over-represented in dogs that developed CP toxicity.

Evaluation of potential serum biomarkers of hepatic fibrosis and necroinflammatory activity in dogs with liver disease.

Background: Serum interleukin 6 (IL-6), chemokine ligand 2 (CCL2), C-reactive protein (CRP), and the ratio of aspartate transaminase to alanine transaminase (AST:ALT) have been correlated with fibrosis and necroinflammatory activity in humans with various hepatopathies.

Hypothesis/objectives: To determine whether increases in serum IL-6, CCL2, CRP, or AST:ALT were associated with moderate to severe fibrosis or necroinflammatory activity in dogs with various hepatopathies.

Animals: Forty-four client-owned dogs with clinical evidence of liver disease and 10 healthy purpose-bred dogs, all undergoing liver biopsies by laparoscopy or laparotomy.

A single-nucleotide polymorphism in the canine cytochrome b reductase (CYB5R3) gene is associated with sulfonamide hypersensitivity and is overrepresented in Doberman Pinschers.

Canine sulfonamide hypersensitivity (HS) has been associated with a variant in the cytochrome b reductase gene (CYB5R3 729A>G), which encodes a drug-detoxifying enzyme. Study objectives were to determine variant allele frequency in Doberman Pinschers (DOBE), a breed which may be predisposed to sulfonamide HS, and to characterize the effects of CYB5R3 729G on gene expression and function. CYB5R3 729A>G allele frequencies were compared between DOBE (n = 24) vs.

A 6-bp Deletion Variant in a Novel Canine Glutathione-S-Transferase Gene (GSTT5) Leads to Loss of Enzyme Function.

Objectives: Glutathione-S-transferases (GSTs) detoxify reactive xenobiotics, and defective GST gene polymorphisms increase cancer risk in humans. A low activity GST-theta variant was previously found in research beagles. The purpose of our study was to determine the molecular basis for this phenotype and its allele frequency in pet dogs.

Characterization of a low expression haplotype in canine glutathione S-transferase (GSTT1) and its prevalence in golden retrievers.

Glutathione S-transferase-theta (GSTT1) is a carcinogen detoxification enzyme, and low activity variants are associated with lymphoma in humans. We recently found a variant in the 3' untranslated region (UTR) of canine GSTT1, *101_102insT, which was predicted to change miRNA binding and was found in 5 of 17 golden retriever (GR) dogs with lymphoma but none of 14 healthy GRs. The aim of this study was to determine whether this variant led to decreased GSTT1 expression and was a discernible risk factor for lymphoma within the GR breed.

Sexual development in Cryptococcus neoformans requires CLP1, a target of the homeodomain transcription factors Sxi1alpha and Sxi2a.

Sexual development in the human fungal pathogen Cryptococcus neoformans is a multistep process that results in the formation of spores, the likely infectious particles. A critical step in this developmental process is the transition from bud-form growth to filamentous growth. This transition is controlled by the homeodomain transcription factors Sxi1alpha and Sxi2a, whose targets are largely unknown.

HMR-I is an origin of replication and a silencer in Saccharomyces cerevisiae.

There appear to be fundamental differences between the properties of the silencers at HML and HMR, with some being origins of replication and others not. Moreover, past studies have suggested that HMR-I's role in silencing may be restricted to plasmid contexts. This study established that HMR-I, like HMR-E and unlike either HML silencer, is an origin of replication.