SUMMARY The histone lysine demethylase KDM5B regulates gene transcription and cell differentiation. It contains three PHD fingers, the biological roles of which remain elusive. Here, we show that the first PHD1 finger of KDM5B binds unmodified histone H3, whereas the third PHD3 finger prefers the trimethylated mark, H3K4me3. RNA-seq analysis indicates that KDM5B functions as a transcriptional repressor for a set of genes. Biochemical analysis reveals that KDM5B associates with components of the nucleosome remodeling and deacetylase (NuRD) complex and may cooperate with HDAC1 in gene repression. Compared with the estrogen receptor positive breast cancers, KDM5B is downregulated in the triple-negative breast cancer. Overexpression of KDM5B in the MDA-MB 231 breast cancer cells suppresses cell migration and invasion ability, and the PHD1-H3K4me0 interaction is important for inhibition of migration. These findings highlight tumor-suppressive functions of KDM5B in triple-negative breast cancer cells and suggest a novel multivalent mechanism for KDM5B-mediated transcriptional regulation.

Eighty-four multiparous, nonlactating, pregnant Angus × Hereford cows were ranked by pregnancy type (56 AI and 28 natural service), BW, and BCS and allocated to 21 drylot pens at the end of their second trimester of gestation (d 0). Pens were assigned to receive forage-based diets containing 1) sulfate sources of Cu, Co, Mn, and Zn (INR); 2) an organic complexed source of Cu, Mn, Co, and Zn (AAC; Availa 4; Zinpro Corporation, Eden Prairie, MN); or 3) no supplemental Cu, Co, Mn, and Zn (CON). Diets were offered from d 0 until calving and formulated to meet requirements for energy, protein, macrominerals, Se, I, and vitamins. The INR and AAC diets provided the same daily amount of Cu, Co, Mn, and Zn. Cow BW and BCS were recorded and liver samples were collected on d -10 and 2 wk (d 75) before the calving season. Within 3 h after calving, calf BW was recorded, liver samples were collected, and the expelled placenta was retrieved ( = 47 placentas). Calves were weaned on d 283 of the experiment, preconditioned for 45 d (d 283 to 328), transferred to a growing lot on d 328, and moved to a finishing lot on d 440 where they remained until slaughter. Liver Co, Cu, and Zn concentrations on d 75 were greater ( ≤ 0.05) for INR and AAC cows compared with CON cows, whereas INR cows had reduced ( = 0.04) liver Co but greater ( = 0.03) liver Cu compared with AAC cows. In placental cotyledons, Co concentrations were greater ( ≤ 0.05) in AAC and INR cows compared with CON cows, whereas Cu concentrations were increased ( = 0.05) only in AAC cows compared with CON cows. Calves from INR and AAC cows had greater ( < 0.01) liver Co concentrations at birth compared with calves from CON cows. Liver Cu and Zn concentrations at birth were greater ( ≤ 0.05) in calves from AAC cows compared with cohorts from CON cows. Weaning BW was greater ( ≤ 0.05) in calves from AAC cows compared with cohorts from CON cows, and this difference was maintained until slaughter. In the growing lot, calves from AAC cows had reduced ( < 0.01) incidence of bovine respiratory disease compared with CON and INR cohorts. Collectively, these results suggest that feeding the AAC diet to late-gestating beef cows stimulated programming effects on postnatal offspring growth and health compared with the CON diet. Therefore, supplementing late-gestating beef cows with an organic complexed source of Co, Cu, Zn, and Mn instead of no supplementation appears to optimize offspring productivity in beef production systems.

This study was conducted to determine the effect of Se supplementation and source on the Se status of horses. Eighteen 18-mo-old nonexercised horses were randomly assigned within sex to 1 of 3 treatments: 1) control (CTRL, no supplemental Se, 0.15 mg of Se/kg of total diet DM); 2) inorganic Se (INORG, CTRL + 0.45 mg of Se/kg of total diet DM from NaSeO 3); or organic Se [ORG, CTRL + 0.45 mg of Se/kg of total diet DM from zinc-L-selenomethionine (Availa Se, Zinpro, Corp., Eden Prairie, MN)]. Horses were acclimated to the CTRL diet (7.1 kg of DM alfalfa hay and 1.2 kg of DM concentrate per horse daily) for 28 d. After the acclimation period, the appropriate treatment was topdressed on the individually fed concentrate for 56 d. Jugular venous blood samples were collected on d 0, 28, and 56. Middle gluteal muscle biopsies were collected on d 0 and 56. Muscle and plasma were analyzed for Se concentrations. Glutathione peroxidase activity was measured in muscle (M GPx-1), plasma (P GPx-3), and red blood cells (RBC GPx-1). Data were analyzed as a repeated measures design. Mean plasma Se concentra

OBJECTIVE To describe the incidence of specific causes of lameness and the associations of cause and severity of lameness on the outcome for cattle on commercial feedlots. DESIGN Dynamic population longitudinal study. ANIMALS Cattle on 6 commercial feedlots in Kansas and Nebraska during a 12-month period (mean daily population, 243,602 cattle; range, 223,544 to 252,825 cattle). PROCEDURES Feedlot personnel were trained to use a standardized diagnostic algorithm and locomotion score (LMS) system to identify and classify cattle by cause and severity of lameness. Information regarding lameness cause, severity, and treatments was recorded for individual cattle. Cattle were monitored until they left the feedlot (ie, outcome; shipped with pen mates [shipped], culled prematurely because of lameness [realized], or euthanized or died [died]). Incidence rates for various causes of lameness, LMSs, and outcomes were calculated. The respective associations of cause of lameness and LMS with outcome were evaluated. RESULTS Lameness was identified in 2,532 cattle, resulting in an overall lameness incidence rate of 1.04 cases/100 animal-years. Realized and mortality rates were 0.096 cattle/100 animal-years and 0.397 deaths/100 animal-years, respectively. Injury to the proximal portion of a limb was the most frequently identified cause of lameness followed by undefined lameness, septic joint or deep digital sepsis, and interdigital phlegmon (foot rot). As the LMS (lameness severity) at lameness detection increased, the percentage of cattle that died but not the percentage of cattle that were realized increased. CONCLUSIONS AND CLINICAL RELEVANCE Results provided clinically useful prognostic guidelines for management of lame feedlot cattle.

Summary Gastric ulcers are common in horses and equine gastric ulcer syndrome describes ulcers in the distal oesophagus, nonglandular and glandular stomach as well as the proximal duodenum. Ulcers in the distal oesophagus and nonglandular region of the stomach are probably caused by hydrochloric acid, whereas ulcers in the glandular stomach and proximal duodenum are likely to be caused by a breakdown in the mucosal defence mechanisms. Regardless of the location of ulcers, initial treatment with pharmacological agents is necessary to suppress hydrochloric acid; however, nutrition and management changes are required to maintain ulcer healing and help prevent recurrence. In addition, many dietary supplements have been marketed to help maintain stomach health and some scientific data on their effects on gastric ulcer scores and gastric juice pH are presented.