Breed associations for canine exocrine pancreatic insufficiency

BACKGROUND: Knowledge of breed associations is valuable to clinicians and researchers investigating diseases with a genetic basis. HYPOTHESIS: Among symptomatic dogs tested for exocrine pancreatic insufficiency (EPI) by canine trypsin-like immunoreactivity (cTLI) assay, EPI is common in certain breeds and rare in others. Some breeds may be overrepresented or underrepresented in the population of dogs with EPI. Pathogenesis of EPI may be different among breeds. ANIMALS: Client-owned dogs with clinical signs, tested for EPI by radioimmunoassay of serum cTLI, were used. METHODS: In this retrospective study, results of 13,069 cTLI assays were reviewed. RESULTS: An association with EPI was found in Chows, Cavalier King Charles Spaniels (CKCS), Rough-Coated Collies (RCC), and German Shepherd Dogs (GSD) (all P < .001). Chows (median, 16 months) were younger at diagnosis than CKCS (median, 72 months, P < .001), but not significantly different from GSD (median, 36 months, P = .10) or RCC (median, 36 months, P = .16). GSD (P < .001) and RCC (P = .015) were younger at diagnosis than CKCS. Boxers (P < .001), Golden Retrievers (P < .001), Labrador Retrievers (P < .001), Rottweilers (P = .022), and Weimaraners (P = .002) were underrepresented in the population with EPI. CONCLUSIONS AND CLINICAL IMPLICATIONS: An association with EPI in Chows has not previously been reported. In breeds with early-onset EPI, immune-mediated mechanisms are possible or the disease may be congenital. When EPI manifests later, as in CKCS, pathogenesis is likely different (eg, secondary to chronic pancreatitis). Underrepresentation of certain breeds among dogs with EPI has not previously been recognized and may imply the existence of breed-specific mechanisms that protect pancreatic tissue from injury.     

Prey‐type‐dependent foraging of young‐of‐the‐year fish in turbid and humic environments

Abstract – Fish, which are generally visual foragers, experiences reduced reaction distance in visually degraded environments, which has consequences for encounter rates with prey. Small prey is detected at shorter distances than larger prey, and piscivores are therefore predicted to be more strongly affected by visual degradation. In experiments, roach (Rutilus rutilus) were fed two plankton prey types and pike (Esox lucius) were fed Daphnia and larval roach, in clear water, algal turbid water and water coloured brown by dissolved organic matter (DOM). Planktivorous foraging in roach was not affected by visual degradation, while pike foraging on both Daphnia and larval roach was. Pike showed increased reaction distance to Daphnia in visually degraded water, while it was severely reduced with roach as prey even if the visual range was not reduced below pike reaction distances in clear water. Pike foraging on Daphnia was not affected, but when foraging on roach, the reduced search efficiency was counteracted by increased attack rates. However, there was no increase in movement and no difference between turbid and DOM treatments. Effects on piscivores will likely become more pronounced at later life stages as prey size and the reliance on long‐distance detection increases at the same time as changing climatic conditions may further deteriorate the visual conditions in future.     

Temporal bone preservation in a 2600-year-old Egyptian mummy

Perforated eardrums in the preserved temporal bones of a mummified Egyptian male in otherwise normal middle ears offer new evidence of acute otitis media and probable defective hearing among ancient Egyptians.     

Structural basis of type II topoisomerase inhibition by the anticancer drug etoposide

Type II topoisomerases (TOP2s) resolve the topological problems of DNA by transiently cleaving both strands of a DNA duplex to form a cleavage complex through which another DNA segment can be transported. Several widely prescribed anticancer drugs increase the population of TOP2 cleavage complex, which leads to TOP2-mediated chromosome DNA breakage and death of cancer cells. We present the crystal structure of a large fragment of human TOP2β complexed to DNA and to the anticancer drug etoposide to reveal structural details of drug-induced stabilization of a cleavage complex. The interplay between the protein, the DNA, and the drug explains the structure-activity relations of etoposide derivatives and the molecular basis of drug-resistant mutations. The analysis of protein-drug interactions provides information applicable for developing an isoform-specific TOP2-targeting strategy.     

Tandem regions of yeast DNA topoisomerase II share homology with different subunits of bacterial gyrase

The nucleotide sequence for the Saccharomyces cerevisiae gene TOP2, which encodes DNA topoisomerase II, was compared with the sequence for bacterial DNA gyrase. The amino and carboxyl terminal halves of the single-subunit yeast enzyme showed homologies with the B and A subunits of bacterial gyrase, respectively, at corresponding positions along the polypeptide chains. Although the two enzymes differ in both quaternary structure and activity, the homology between the two proteins indicates mechanistic as well as structural similarities, and a probable evolutionary relationship.     

The involvement of the anterior cingulate cortex in remote contextual fear memory

Although the molecular, cellular, and systems mechanisms required for initial memory processing have been intensively investigated, those underlying permanent memory storage remain elusive. We present neuroanatomical, pharmacological, and genetic results demonstrating that the anterior cingulate cortex plays a critical role in remote memory for contextual fear conditioning. Imaging of activity-dependent genes shows that the anterior cingulate is activated by remote memory and that this activation is impaired by a null alpha-CaMKII mutation that blocks remote memory. Accordingly, reversible inactivation of this structure in normal mice disrupts remote memory without affecting recent memory.