Inheritance of equine sarcoid disease in Franches-Montagnes horses

The mode of inheritance for susceptibility to equine sarcoid disease (ES) remains unknown. The objectives of this study were to analyse a large sample of the Franches-Montagnes (FM) horse population and investigate the heritability and mode of inheritance for susceptibility to ES. Horses were clinically examined for the presence of sarcoid tumours. A standardized examination protocol and client questionnaire were used and a pedigree- and subsequent segregation-analysis for the ES trait performed. To investigate the mode of inheritance, five models were evaluated and compared in a hierarchical way.The analyses reveal that variation in susceptibility to ES is best explained by a model incorporating polygenic variation. The possible effect of a major gene, such as specific equine leukocyte antigen alleles, is unlikely, but cannot be ruled-out entirely. The heritability of the phenotype on the observation scale for the trait ‘affected with ES’ was estimated to be 8%. A corrected value for the heritability on a liability scale was estimated at 21% and it is therefore possible to estimate breeding values for ES. The arguments against the practical implementation of an estimated breeding value in a multifactorial condition like ES are discussed.     

Stimulation of airway neutrophils following dexamethasone administration and equid herpesvirus-2 challenge in horses

The aim of this study was to investigate neutrophil stimulation following experimentally-induced airway inflammation in healthy horses. Six horses received dexamethasone and four were then inoculated with equid herpesvirus-2 (EHV-2). Significant neutrophilia was detected in tracheal wash and bronchoalveolar lavage fluid for up to 6 days. Concentrations of neutrophil elastase (NE) and myeloperoxidase (MPO) were significantly increased compared to baseline for up to 14 days in tracheal washes and both markers were significantly correlated with neutrophil counts. Serum levels of surfactant protein D were not significantly modified throughout the study. These results suggest that dexamethasone administration with or without EHV-2 inoculation is associated with a sustainable activation and degranulation of neutrophils in the trachea along with moderate modifications detectable in the lower airways.     

Relative timing of deglacial climate events in Antarctica and Greenland

The last deglaciation was marked by large, hemispheric, millennial-scale climate variations: the B?lling-Aller?d and Younger Dryas periods in the north, and the Antarctic Cold Reversal in the south. A chronology from the high-accumulation Law Dome East Antarctic ice core constrains the relative timing of these two events and provides strong evidence that the cooling at the start of the Antarctic Cold Reversal did not follow the abrupt warming during the northern B?lling transition around 14,500 years ago. This result suggests that southern changes are not a direct response to abrupt changes in North Atlantic thermohaline circulation, as is assumed in the conventional picture of a hemispheric temperature seesaw.     

The Near Eastern origin of cat domestication

The world's domestic cats carry patterns of sequence variation in their genome that reflect a history of domestication and breed development. A genetic assessment of 979 domestic cats and their wild progenitors-Felis silvestris silvestris (European wildcat), F. s. lybica (Near Eastern wildcat), F. s. ornata (central Asian wildcat), F. s. cafra (southern African wildcat), and F. s. bieti (Chinese desert cat)-indicated that each wild group represents a distinctive subspecies of Felis silvestris. Further analysis revealed that cats were domesticated in the Near East, probably coincident with agricultural village development in the Fertile Crescent. Domestic cats derive from at least five founders from across this region, whose descendants were transported across the world by human assistance.     

Intramembrane cleavage of AMA1 triggers Toxoplasma to switch from an invasive to a replicative mode

Apicomplexan parasites invade host cells and immediately initiate cell division. The extracellular parasite discharges transmembrane proteins onto its surface to mediate motility and invasion. These are shed by intramembrane cleavage, a process associated with invasion but otherwise poorly understood. Functional analysis of Toxoplasma rhomboid 4, a surface intramembrane protease, by conditional overexpression of a catalytically inactive form produced a profound block in replication. This was completely rescued by expression of the cleaved cytoplasmic tail of Toxoplasma or Plasmodium apical membrane antigen 1 (AMA1). These results reveal an unexpected function for AMA1 in parasite replication and suggest that invasion proteins help to promote parasite switch from an invasive to a replicative mode.     

Expression and function of junctional adhesion molecule-C in myelinated peripheral nerves

JAM-C is an adhesion molecule that is expressed on cells within the vascular compartment and epithelial cells and, to date, has been largely studied in the context of inflammatory events. Using immunolabeling procedures in conjunction with confocal and electron microscopy, we show here that JAM-C is also expressed in peripheral nerves and that this expression is localized to Schwann cells at junctions between adjoining myelin end loops. Sciatic nerves from JAM-C-deficient [having the JAM-C gene knocked out (KO)] mice exhibited loss of integrity of the myelin sheath and defective nerve conduction as indicated by morphological and electrophysiological studies, respectively. In addition, behavioral tests showed motor abnormalities in the KO animals. JAM-C was also expressed in human sural nerves with an expression profile similar to that seen in mice. These results demonstrate that JAM-C is a component of the autotypic junctional attachments of Schwann cells and plays an important role in maintaining the integrity and function of myelinated peripheral nerves.     

Negative epistasis between beneficial mutations in an evolving bacterial population

Epistatic interactions between mutations play a prominent role in evolutionary theories. Many studies have found that epistasis is widespread, but they have rarely considered beneficial mutations. We analyzed the effects of epistasis on fitness for the first five mutations to fix in an experimental population of Escherichia coli. Epistasis depended on the effects of the combined mutations--the larger the expected benefit, the more negative the epistatic effect. Epistasis thus tended to produce diminishing returns with genotype fitness, although interactions involving one particular mutation had the opposite effect. These data support models in which negative epistasis contributes to declining rates of adaptation over time. Sign epistasis was rare in this genome-wide study, in contrast to its prevalence in an earlier study of mutations in a single gene.     

Pyogranulomatous panniculitis in a domestic cat associated with Pseudomonas luteola infection

Pseudomonas luteola, a pathogen causing disease in humans, has in animals been reported only in rainbow trout and ferrets. This case report describes pyogranulomatous panniculitis in a cat associated with P. luteola infection. Organisms were seen histologically and identified with PCR and sequencing. Lesions resolved after treatment with marbofloxacin.     

Prognostic value of pretreatment plasma D‐dimer level in dogs with intermediate to high‐grade non‐Hodgkin lymphoma

Pretreatment D‐dimer levels have been reported to predict survival in several types of malignancies in human patients. The objective of this study was to evaluate the prognostic value of pretreatment D‐dimer level in dogs with intermediate to high‐grade non‐Hodgkin lymphoma (NHL). In a prospective, randomized, double‐blind study of F14512 vs etoposide phosphate, we assessed the prognostic value of pretreatment plasma D‐dimer level in 48 client‐owned dogs diagnosed with intermediate to high‐grade NHL. The correlation between pretreatment plasma D‐dimer level and various clinical features, progression‐free survival (PFS) and overall survival (OS) was analysed. The median value of pretreatment plasma D‐dimer level was 0.4 μg/mL (range: 0.1‐14.3 μg/mL). High pretreatment plasma D‐dimer level (>0.5 μg/mL) was detected in 44% (21/48) of dogs. High D‐dimer levels were not correlated with naive vs relapsed lymphoma, clinical stage, substage, immunophenotype or treatment group. D‐dimer levels >0.5 μg/mL were significantly associated with inferior median PFS (54 vs 104 days, P = .011) and OS (93 vs 169 days, P = .003). In the multivariate analysis, high D‐dimer levels remained an independent predictor for worse PFS (HR: 3.21, 95% CI: 1.57‐6.56, P = .001) and OS (HR: 3.87, 95% CI: 1.88‐7.98; P < .001). This study suggests that pretreatment plasma D‐dimer level can serve as a predictor of prognosis in dogs with intermediate to high‐grade NHL. Further studies are warranted to confirm these findings.