Sister chromatids are tethered together by the cohesin complex from the time they are made until their separation at anaphase. The ability of cohesin to tether sister chromatids together depends on acetylation of its Smc3 subunit by members of the Eco1 family of cohesin acetyltransferases. Vertebrates express two orthologs of Eco1, called Esco1 and Esco2, both of which are capable of modifying Smc3, but their relative contributions to sister chromatid cohesion are unknown. We therefore set out to determine the precise contributions of Esco1 and Esco2 to cohesion in vertebrate cells. Here we show that cohesion establishment is critically dependent upon Esco2. Although most Smc3 acetylation is Esco1 dependent, inactivation of the gene has little effect on mitotic cohesion. The unique ability of Esco2 to promote cohesion is mediated by sequences in the N terminus of the protein. We propose that Esco1-dependent modification of Smc3 regulates almost exclusively the noncohesive activities of cohesin, such as DNA repair, transcriptional control, chromosome loop formation, and/or stabilization. Collectively, our data indicate that Esco1 and Esco2 contribute to distinct and separable activities of cohesin in vertebrate cells.

Background: Comprehensive endoscopic scoring of the upper and lower airways for inflammation has not been critically assessed among a large population of horses. The relationship between upper and lower airways described in humans by the "one airway, one disease" concept might also apply to horses.Hypothesis/Objectives: To evaluate if an association exists between endoscopic inflammatory scores and mucus scores of upper and lower airways and to investigate if endoscopic findings correlate with the lower airway inflammation measured by bronchoalveolar lavage (BAL) cytology.Methods: Prospective field study. Pharyngitis, pharyngeal mucus, tracheal mucus, tracheal septum thickness, and bronchial mucus were scored using new and previously described scoring systems on a convenience sample of 128 horses with and without lung inflammation. Based on BAL fluid cytology, horses were categorized as having normal, moderate, or severe inflammation of the lower airways.Results: All 5 endoscopy scores showed excellent interobserver agreement. Tracheal mucus (P < .001), tracheal septum thickness (P = .036), and bronchial mucus (P = .037) were significantly increased in horses with severe inflammation BALs and were correlated among themselves but not with upper airways scores. BAL neutrophils percentage was correlated with tracheal mucus (r s = 0.41, P < .001), bronchial mucus (r s = 0.27, P = .003), and had a weak negative correlation with pharyngitis (r s = À0.25, P = .004).Conclusions and Clinical Importance: Lower airway endoscopy scores are reflective of lower airway inflammation; however, upper and lower airways are independent in terms of severity of inflammation. Therefore, observing upper airway inflammation is not an indication to test for lower airway inflammation.

BackgroundAirway hyperresponsiveness (AWHR), expressed as hypersensitivity (PC 75 RL) or hyperreactivity (slope of the histamine dose‐response curve), is a feature of inflammatory airway disease (IAD) or mild equine asthma in horses. Glucocorticoids are used empirically to treat IAD.ObjectivesTo determine whether dexamethasone (DEX) (0.05 mg/kg IM q24h) and inhaled fluticasone (FLUT) (3,000 μg q12h) administered by inhalation are effective in decreasing AWHR, lung inflammation, and clinical signs in horses with IAD.MethodsA randomized crossover study design was used. Eight horses with IAD were assigned to a treatment group with either DEX or FLUT. Measured outcomes included lung mechanics during bronchoprovocative challenges, bronchoalveolar lavage fluid (BALF) cytology, and scoring of clinical signs during exercise.ResultsDexamethasone and FLUT abolished the increase in RL by 75% at any histamine bronchoprovocative dose in all horses after the first week of treatment. However, after 2 weeks of FLUT treatment, 1 horse redeveloped hypersensitivity. There was a significant decrease in the number of lymphocytes after treatment with both DEX and FLUT (P = .039 for both) but no significant differences in other BALF cell types or total cell counts (P > .05). There was no difference in the scoring of the clinical signs during each treatment and washout period (P > .05).Conclusions and Clinical ImportanceBoth DEX and FLUT treatments significantly inhibit airway hypersensitivity and hyperreactivity in horses with IAD. There are no significant effects on the clinical signs or the number of inflammatory cells (except lymphocytes) in BALF. The treatments have no residual effect 3 weeks after discontinuation.

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