To comprehensively assess conventional vs. some alternative laying-hen housing systems under U.S. production conditions, a multi-institute and multi-disciplinary project, known as the Coalition for Sustainable Egg Supply (CSES) study, was carried out at a commercial egg production farm in the Midwestern United States over two single-cycle production flocks. The housing systems studied include a conventional cage house (200,000 hen capacity), an aviary house (50,000 hen capacity), and an enriched colony house (50,000 hen capacity). As an integral part of the CSES project, continual environmental monitoring over a 27-month period described in this paper quantifies indoor gaseous and particulate matter concentrations, thermal environment, and building ventilation rate of each house. Results showed that similar indoor thermal environments in all three houses were maintained through ventilation management and environmental control. Gaseous and particulate matter concentrations of the enriched colony house were comparable with those of the conventional cage house. In comparison, the aviary house had poorer indoor air quality, especially in wintertime, resulting from the presence of floor litter (higher ammonia levels) and hens’ activities (higher particulate matter levels) in it. Specifically, daily mean indoor ammonia concentrations had the 95% confidence interval values of 3.8 to 4.2 (overall mean of 4.0) ppm for the conventional cage house; 6.2 to 7.2 (overall mean of 6.7) ppm for the aviary house; and 2.7 to 3.0 (overall mean of 2.8) ppm for the enriched colony house. The 95% confidence interval (overall mean) values of daily mean indoor carbon dioxide concentrations were 1997 to 2170 (2083) ppm for the conventional cage house, 2367 to 2582 (2475) ppm for the aviary house, and 2124 to 2309 (2216) ppm for the enriched colony house. Daily mean indoor methane concentrations were similar for all three houses, with 95% confidence interval values of 11.1 to 11.9 (overall mean of 11.5) ppm. The 95% confidence interval values (overall mean) of daily mean PM10 and PM2.5 concentrations, in mg/m3, were, respectively, 0.57 to 0.61 (0.59) and 0.033 to 0.037 (0.035) for the conventional cage house, 3.61 to 4.29 (3.95) and 0.374 to 0.446 (0.410) for the aviary house, and 0.42 to 0.46 (0.44) and 0.054 to 0.059 (0.056) for the enriched colony house. Investigation of mitigation practices to improve indoor air quality of the litter-floor aviary housing system is warranted.

The use of selective estrogen receptor modulators for the treatment of estrogen-dependent diseases in premenopausal women has been hindered by undesirable ovarian stimulation and associated risks of ovarian cysts. We have identified a selective estrogen receptor modulator compound (LY2066948) that is a strong estrogen antagonist in the uterus yet has minimal effects on the ovaries of rats. LY2066948 binds with high affinity to both estrogen receptors and has potent estrogen antagonist activity in human uterine and breast cancer cells. Oral administration of LY2066948 to immature rats blocked uterine weight gain induced by ethynyl estradiol with an ED50 of 0.07 mg/kg. Studies in mature rats demonstrated that LY2066948 decreases uterine weight by 51% after 35 d treatment, confirming potent uterine antagonist activity over several estrous cycles. This strong uterine response contrasted with the minimal effects on the ovaries: serum estradiol levels remained within the normal range, whereas histologic evaluation showed granulosa cell hyperplasia in few of the rats. Bone studies demonstrated that LY2066948 prevented ovariectomy-induced bone loss and treatment of ovary-intact rats caused no bone loss, confirming estrogen receptor agonist skeletal effects. Collectively, these data show that LY2066948 exhibits a tissue-specific profile consistent with strong antagonist activity in the uterus, agonist activity in bone, and minimal effects in the ovaries.

As an integral part of the Coalition for Sustainable Egg Supply (CSES) Project, this study simultaneously monitored air emissions of 3 commercially operated egg production systems at the house level and associated manure storage over 2 single-cycle flocks (18 to 78 wk of age). The 3 housing systems were 1) a conventional cage house (CC) with a 200,000-hen capacity (6 hens in a cage at a stocking density of 516 cm2/hen), 2) an enriched colony house (EC) with a 50,000-hen capacity (60 hens per colony at a stocking density of 752 cm2/hen), and 3) an aviary house (AV) with a 50,000-hen capacity (at a stocking density of 1253 to 1257 cm2/hen). The 3 hen houses were located on the same farm and were populated with Lohmann white hens of the same age. Indoor environment and house-level gaseous (ammonia [NH3] and greenhouse gasses [GHG], including carbon dioxide [CO2], methane [CH4], and nitrous oxide [N2O]) and particulate matter (PM10, PM2.5) emissions were monitored continually. Gaseous emissions from the respective manure storage of each housing system were also monitored. Emission rates (ERs) are expressed as emission quantities per hen, per animal unit (AU, 500 kg live BW), and per kilogram of egg output. House-level NH3 ER (g/hen/d) of EC (0.054) was significantly lower than that of CC (0.082) or AV (0.112) (P < 0.05). The house-level CO2 ER (g/hen/d) was lower for CC (68.3) than for EC and AV (74.4 and 74.0, respectively), and the CH4 ER (g/hen/d) was similar for all 3 houses (0.07 to 0.08). The house-level PM ER (mg/hen/d), essentially representing the farm-level PM ER, was significantly higher for AV (PM10 100.3 and PM2.5 8.8) than for CC (PM10 15.7 and PM2.5 0.9) or EC (PM10 15.6 and PM2.5 1.7) (P < 0.05). The farm-level (house plus manure storage) NH3 ER (g/hen/d) was significantly lower for EC (0.16) than for CC (0.29) or AV (0.30) (P < 0.05). As expected, the magnitudes of GHG emissions were rather small for all 3 production systems. Data from this study enable comparative assessment of conventional vs. alternative hen housing systems regarding air emissions and enhance the U.S. national air emissions inventory for farm animal operations.

Human rhinovirus, the chief cause of the common cold, contains a positive-sense strand of RNA which is translated into a large polyprotein in infected cells. Cleavage of the latter to produce the mature viral proteins required for replication is catalyzed in large part by a virally encoded cysteine proteinase (3Cpro) which is highly selective for -Q approximately GP- cleavage sites. We synthesized peptidyl derivatives of vinylogous glutamine or methionine sulfone esters (e.g., Boc-Val-Leu-Phe-vGln-OR: R = Me, 1; R = Et, 2) and evaluated them as inhibitors of HRV-14 3C protease (3Cpro). Compounds 1 and 2 and several related tetra- and pentapeptide analogues rapidly inactivated 3Cpro with submicromolar IC50 values. Electrospray mass spectrometry confirmed the expected 1:1 stoichiometry of 3Cpro inactivation by 1, 2, and several other analogues. Compound 2 also proved to be useful for active site titration of 3Cpro, which has not been possible heretofore because of the lack of a suitable reagent. In contrast to 1, 2, and congeners, peptidyl Michael acceptors lacking a P4 residue have greatly reduced or negligible activity against 3Cpro, consistent with previously established structure-activity relationships for 3Cpro substrates. Hydrolysis of the P1 vinylogous glutamine ester to a carboxylic acid also decreased inhibitory activity considerably, consistent with the decreased reactivity of acrylic acids vs acrylic esters as Michael acceptors. Incorporating a vinylogous methionine sulfone ester in place of the corresponding glutamine derivative in 1 also reduced activity substantially. Compounds 1 and 2 and several of their analogues inhibited HRV replication in cell culture by 50% at low micromolar concentrations while showing little or no evidence of cytotoxicity at 10-fold higher concentrations. Peptidyl Michael acceptors and their analogues may prove useful as therapeutic agents for pathologies involving cysteine proteinase enzymes.