The University of Illinois College of Veterinary Medicine opened a clinical skills laboratory in August 2009, making it one of the earliest North American veterinary schools to do so. The Clinical Skills Learning Center has been an integral component of the Illinois veterinary professional curriculum since its inception. However, its role in the curriculum has changed over time, which has had an impact on its size, scope, and staffing. In this article, we describe the development and growth of the Clinical Skills Learning Center, with an emphasis on its evolving curricular role and the lessons we have learned over nine years.

The 8-week dairy production medicine course at the National Center of Excellence in Dairy Production Medicine Education for Veterinarians is designed to equip senior veterinary students with the knowledge and skills needed to serve the dairy industry. Course developers identified 59 topics of importance for dairy production medicine veterinarians. Students (N = 50) were surveyed before and after the course to determine their perceptions of (a) the importance of the 59 topics for their intended positions and (b) their knowledge and skill in those areas. We expected the course to affirm or strengthen perceptions of importance and increase confidence. Students rated 57 of the topics as moderately or very important before the course. Ratings were unchanged (56 topics) or increased (3 topics) after the course. Before the course, students believed they had a lot of knowledge and skill in just one area: animal behavior and handling. At the end of the course, students believed they had a lot of knowledge and skill in 21 areas; confidence ratings were higher for 47 of the 59 topics. Alumni were surveyed 1-2 years after graduation to determine the importance of the 59 topics to their positions, their impressions about how well the course prepared them in those areas, and whether they referred back to course materials. Feedback was used to adjust the course. The topics alumni rated as most important were similar to those students predicted would be most important. Seventy-five percent of alumni used the course website as a resource in practice.

Predictions of drug residues in milk are critical in food protection and are a major consideration in the economics of treatment of mastitis in dairy cows. Nonlinear mixed-effects modeling (NLME) has been advocated as a suitable pharmaco-statistical method for the study of drug residues in milk. Recent developments in physiologically based pharmacokinetic (PBPK) modeling of intramammary drugs allow the combination of a mechanistic description of milk pharmacokinetics with NLME methods. The PBPK model was applied to NLME analysis of a data set consisting of milk drug concentrations from 78 healthy cows and 117 with clinical mastitis. Pirlimycin milk pharmacokinetics were adequately described by the model across the range of observed concentrations. Mastitis was characterized by increased variance in milk production volume. Udder residual volume was larger in cows with 1, or 2 or greater diseased mammary glands than in the healthy cows. Low-producing cows had a greater risk of prolonged milk residues. With the exclusion of the low-production cows, the model predicted that healthy cows required a milk discard time 12 h longer than that indicated by the label, and the diseased cows 36 h longer than indicated by the label. More pirlimycin was systemically absorbed in the gram-positive infected compared with the gram-negative infected or healthy cows, suggesting a greater risk of violative meat residues in gram-positive infected cows. Using NLME and PBPK models, we identified factors associated with changes in pirlimycin milk residues that may affect food safety. This model extends the verification of a simple physiologically based framework for the study of intramammary drugs.

Three cohorts of senior veterinary students (n = 50) from seven United States (US) colleges of veterinary medicine took an 8-week dairy production medicine course at the Dairy Center of Excellence in Production Medicine Education for Veterinarians (DCE) between 2012 and 2014. Participants completed a questionnaire before and after the course and 1 to 2 years after graduation. Objectives were to determine the prior academic training and livestock experience of course participants, to compare students' career aspirations before and after taking the course, and to identify factors associated with post-graduate position. Response rates were 58%-96%. Most students had taken undergraduate animal science courses (83%), worked (76%) and/or lived (52%) on a livestock operation, participated in youth livestock activities (63%), worked at a mixed practice (71%), taken production medicine-related elective courses (65%), taken other food animal rotations (91%), and/or done dairy externships (65%) before taking the DCE course. Students who were very likely to pursue a dairy-focused position before taking the course (36%) remained committed after the course, whereas students who were not likely initially (39%) were not further motivated by the course. Students who had worked with a dairy veterinarian were more likely to pursue a dairy-focused position than those who had not. Most course alumni accepted positions in mixed practice, with a >= 50% (54%) or < 50% (23%) dairy component, and post-graduate positions were consistent with students' predictions. Students who held an undergraduate degree or had worked for a dairy veterinarian were more likely to accept a dairy-focused practice position than those who did not.

The need for consortial programs to provide advanced education in food animal veterinary production medicine has been recognized and lauded for nearly three decades. This article describes one effort to create a dairy production medicine curriculum funded by a United States Department of Agriculture (USDA) Higher Education Challenge Grant. This National Center of Excellence in Dairy Production Medicine Education for Veterinarians is housed at the Dairy Education Center of the University of Minnesota and the project was a collaboration of the University of Minnesota, the University of Illinois, the University of Georgia, and Kansas State University. The article reviews the need for innovative ways to educate students who will optimally serve the dairy industry, provides a broad overview of the process of developing and delivering the eight-week dairy production medicine curriculum, and describes the challenges faced and lessons learned as a result of offering such a program.

Between 2012 and 2014, three cohorts of senior veterinary students participated in an 8-week dairy production medicine course created by the National Center of Excellence in Dairy Production Medicine Education for Veterinarians. One goal of this course is to better prepare veterinary students to serve the increasingly complex needs of the dairy industry. In this article, we describe the assessment methods and student performance outcomes of those first three cohorts. A combination of assessment methods was used, including pre- and post-testing; instructor observations and scores on individual and group projects, including a final integrative project; and peer evaluation. Student feedback, collected via anonymous survey, provided insight into students' perceptions about the course and their learning. Performance and feedback suggest that the course was successful in preparing students for careers using skills in dairy production medicine. Pre- and post-testing was conducted for most topic modules in the course. The mean (median) pre- and post-test scores were 47% (50% ) and 83% (88%), respectively. The mean improvement in score was significant (p < .002) for all modules and cohorts. Students indicated a moderate or high degree of confidence in performing dairy production medicine skills after each module. Of students in cohorts 1, 2, and 3, respectively, 55%, 75%, and 82% felt they could provide dairy production medicine services (e.g., records analysis, problem investigation, protocol and standard operating procedure design) either alone or with some mentoring, immediately after graduation. In addition, assessment results and student feedback enabled timely course modifications during these first three cohorts.

BackgroundSubclinical mastitis is of concern in veterinary hospitals because contagious mastitis pathogens might be unknowingly transmitted to susceptible cows and then back to their farm of origin.ObjectivesTo evaluate the California mastitis test (CMT) as an indicator of intramammary infection (IMI) in lactating dairy cows admitted to a veterinary hospital.AnimalsA total of 139 admissions of 128 lactating dairy cows admitted to the University of Illinois Veterinary Teaching Hospital over a 2‐year period.MethodsA retrospective study with a convenience sample was conducted. Medical records of cows with CMT results and milk culture results for the day of admission were reviewed. Breed, age, season, maximum CMT score for the 4 quarters, maximum CMT score difference, and clinical diagnosis were evaluated as predictors of IMI by the chi‐square test and stepwise logistic regression.ResultsAn IMI was identified in 51% of quarters. For cows admitted without evidence of clinical mastitis, the sensitivity of a CMT score ≥trace in predicting an IMI on a quarter or cow basis was 0.45 and 0.68, respectively. The distributions of maximal quarter CMT score and the maximum difference in quarter CMT score for cows without evidence of clinical mastitis did not differ (P = 0.28,P = 0.84, respectively) for cows with and without IMI. Stepwise logistic regression did not identify significant predictors of IMI in cows without clinical mastitis.ConclusionsLactating dairy cattle admitted to a veterinary hospital should be managed as if they have an IMI, even in the absence of clinical mastitis.

The organization and delivery of a curriculum is the responsibility of the faculty in educational institutions. Curricular revision is often a hotly debated topic in any college faculty. At the University of Illinois, a 2006 mandate for curriculum modernization from the American Veterinary Medical Association Council on Education provided impetus for a long-discussed curricular revision. After two iterations and a lengthy development process, a new curriculum was gradually implemented at Illinois with the August 2009 matriculation of the Class of 2013. The goals of the revision included earlier clinical exposure for veterinary students through introductions to clinical rotations in years 1 to 3 and an integrated body systems approach in lecture/laboratory courses. A new Clinical Skills Learning Center facilitates development of clinical skills earlier in the curriculum and promotes the development of those skills throughout all 4 years of the curriculum. New outcomes assessments include comprehensive written examinations and Objective Structured Clinical Examinations (OSCEs) in years 2 and 3. Curriculum management, including grading of clinical rotations in all 4 years, is achieved through a commercially available software package. For the past 5 years, when candidates were asked why they chose to apply to Illinois, the new curriculum (27.4%) was the most common answer given during interviews. The Illinois revision has resulted in measurably increased veterinary student self-confidence (p<.001) at graduation.

Objective —To identify cow and management factors associated with colostral IgG concentration in dairy cows. Design —Prospective observational study. Animals —81 multiparous Holstein-Friesian cows from a single herd. Procedures —Serum was obtained at the start of the nonlactating period, and cows were assigned to 1 of 4 photoperiod groups: natural day length (n = 22 cows), long days (16 h of light/d [21]) or short days (8 h of light/d [20]) for the entire nonlactating period, or natural day length followed by short days for the last 21 days of the nonlactating period (18). Serum and colostrum were collected at the first milking after calving. Regression analysis was used to investigate associations between colostral IgG concentration and the interval between calving and first milking, colostral volume, photoperiod, length of the nonlactating period, and season of calving. Results —Colostral IgG concentration decreased by 3.7% during each subsequent hour after calving because of postparturient secretion by the mammary glands. The interval between calving and first milking and the colostral volume were significantly and negatively associated with colostral IgG concentration, with the former effect predominating. Photoperiod had no effect on colostral IgG concentration or volume. Serum protein concentration at calving correlated poorly with colostral IgG concentration. Conclusions and Clinical Relevance —Dairy producers should harvest colostrum as soon as possible after calving to optimize transfer of passive immunity in neonatal calves. Photoperiod can be manipulated without adversely affecting colostral IgG concentration.

Our objective was to compare mammary tissue gene expression profiles during a Streptococcus uberis (S. uberis) mastitis challenge between lactating cows subjected to dietary-induced negative energy balance (NEB; n = 5) and cows fed ad libitum to maintain positive energy balance (PEB; n = 5) to better understand the mechanisms associated with NEB and risk of mastitis during the transition period. The NEB cows were feed-restricted to 60% of calculated net energy for lactation requirements for 7 days, and cows assigned to PEB were fed the same diet for ad libitum intake. Five days after feed restriction, one rear mammary quarter of each cow was inoculated with 5,000 cfu of S. uberis (O140J). At 20 h postinoculation, S. uberis-infected mammary quarters from all cows were biopsied for RNA extraction. Negative energy balance resulted in 287 differentially expressed genes (DEG; false discovery rate ≤ 0.05), with 86 DEG upregulated and 201 DEG downregulated in NEB vs. PEB. Canonical pathways most affected by NEB were IL-8 signaling (10 genes), glucocorticoid receptor signaling (13), and NRF2-mediated oxidative stress response (10). Among the genes differentially expressed by NEB, cell growth and proliferation (48) and cellular development (36) were the most enriched functions. Regarding immune response, HLA-A was upregulated due to NEB, whereas the majority of genes involved in immune response were downregulated (e.g., AKT1, IRAK1, MAPK9, and TRAF6). This study provided new avenues for investigation into the mechanisms relating NEB and susceptibility to mastitis in lactating dairy cows.

Cows experiencing severe postpartal negative energy balance (NEB) are at greater risk of developing mastitis than cows in positive energy balance (PEB). Our objectives were to compare mammary tissue gene expression profiles between lactating cows (n = 5/treatment) subjected to feed restriction to induce NEB and cows fed ad libitum to maintain PEB in order to identify genes involved in immune response and cellular metabolism that may predispose cows to an intramammary infection in non-infected mammary gland. The NEB cows were feed-restricted to 60% of calculated net energy for lactation requirements, and cows fed PEB cows were fed the same diet ad libitum. At 5 days after feed restriction, one rear mammary gland from all cows was biopsied for RNA extraction and transcript profiling using microarray and quantitative PCR. Energy balance (NEB vs. PEB) resulted in 278 differentially expressed genes (DEG). Among up-regulated DEG (n = 180), Ingenuity Pathway Analysis® identified lipid metabolism (8) and molecular transport (14) as some of the most enriched molecular functions. Genes down-regulated by NEB (98) were associated with cell growth and proliferation (21) and cell death (18). Results indicate that DEG due to NEB in mid-lactation were associated with numerous biological functions but we did not identify genes that could, a priori, be associated with risk of intramammary infection in non-infected mammary glands. Further studies with early postpartal cows are required.

Our objectives were to compare gene expression profiles in blood polymorphonuclear cells (PMN) during a Streptococcus uberis intramammary challenge between lactating cows subjected to feed restriction to induce negative energy balance (NEB; n=5) and cows fed ad libitum to maintain positive energy balance (PEB; n=5). After 5 days of feed restriction, one rear mammary quarter of each cow was inoculated with 5,000 cfu of S. uberis. Blood PMN were isolated at 24 h post-inoculation from all cows for mRNA expression via quantitative polymerase chain reaction for 20 genes associated with immune response and metabolism. A total of 12 genes were differentially expressed in blood PMN in NEB versus PEB cows. Upregulated genes by NEB were ALOX5AP, CPNE3, IL1R2, IL6, TLR2, TLR4, and THY1, and downregulated genes were HLA-DRA, HLA-A, IRAK1, SOD1, and TNF. Network analysis revealed that TNF was associated with several of the affected genes in NEB cows compared with PEB cows. Results showed that 24 h after intramammary challenge with S. uberis, cows in NEB had altered PMN expression of genes involved with immune response. Our data provide new information on transcriptomic mechanisms associated with NEB and the corresponding inhibition of immune response in lactating dairy cows.

Ten multiparous Holstein cows were used to determine the effects of negative energy balance (NEB) on the immune response to a Streptococcus uberis (strain O140J) mastitis challenge during midlactation. Before the study, milk from all quarters of each cow was bacteriologically negative, with a composite somatic cell count of <200,000 cells/mL. Cows were paired based on parity, days in milk, and milk yield. At approximately 77 d in milk, half the cows (n = 5) were feed-restricted to 60% of calculated net energy for lactation requirements to induce NEB. Feed restriction lasted 7 d. Control cows (n = 5) were fed the same diet ad libitum (i.e., positive energy balance; PEB). After 5 d, one rear quarter in all cows was inoculated with 5,000 cfu of Strep. uberis. Jugular blood and aseptic quarter milk samples were collected daily until inoculation and every 6 h postinoculation for 36 h. Blood was analyzed for nonesterified fatty acids, beta-hydroxybutyrate, insulin, cortisol, albumin, serum amyloid A (SAA), and haptoglobin (Hp). Periodically throughout the trial period, blood neutrophils were isolated for determination of cell morphology, chemotaxis, and phagocytosis capability in vitro. Quarter milk samples were analyzed for concentrations of SAA, Hp, cytokines (tumor necrosis factor-alpha, IL-10 and IL-1beta), and activity of respiratory burst enzymes (superoxide dismutase and glutathione peroxidase). All cows developed local and systemic signs of mastitis and calculated NEB was similar to that of cows experiencing postpartal NEB. Serum glucose and insulin concentrations increased in both groups after challenge, most likely because of enhanced glycogenolysis and gluconeogenesis; results indicate that immune cell function may be glucose dependent. Serum cortisol concentration was higher in NEB than PEB cows during feed restriction only (before inoculation), and serum albumin concentration was higher in NEB than PEB cows during the infection period. Compared with PEB, cows in NEB had lower SAA concentrations in serum after 5 d of feed restriction but higher SAA concentrations in milk after Strep. uberis challenge. Serum Hp concentration was higher by 36 h postchallenge in NEB than in PEB cows. Phagocytic capability of neutrophils was lower in NEB than in PEB cows at 0 h of infection but decreased in both PEB and NEB cows through 36 h postinfection. Our results indicate that cows subjected to dietary-induced NEB during midlactation had relatively minimal alterations in immune function.

Hepatic lipidosis and hypophosphatemia are frequently observed in high-yielding periparturient dairy cows. Objectives of this study were to investigate the association of the liver P content with the degree of liver fat accumulation and serum P concentration and to characterize the change in liver P content throughout the transition period. In a cross-sectional study, liver biopsies obtained from 33 Holstein-Friesian cows 14 d postpartum (p.p.) were assayed for total lipid (TLip), triacylglycerol, DNA, P, Mg, K, Na, and Ca content. Serum samples obtained at the time of biopsy were analyzed for indices of liver function and injury and the serum P concentration was determined. From this cross-sectional study, 6 cows were selected for a longitudinal study and liver tissue obtained from the 6 cows on d -65, -30, -14, 1, 14, 28, and 49 relative to calving was assayed. The amounts of P, K, Mg, Na, and Ca were expressed as amount in dry weight (DW), wet weight (WW), nonfat wet weight (NFWW), and indexed to DNA. In the cross-sectional study, P(DW) and P(WW) decreased with increasing TLip, whereas P(NFWW) and P(DNA) were independent of TLip. Values for P(DNA) varied widely, whereas P(NFWW) varied within a narrow range. Stepwise regression analysis revealed the strongest associations between P(DW) and the amount of tissue water (partial R2 = 0.74) and the log to the base 10 of triacylglycerol (partial R2 = 0.05). The P(WW) was associated with the log to the base 10 of triacylglycerol (partial R2 = 0.20), but no associations were found for P(NFWW). These findings indicate that decreased electrolyte content in dry and wet liver tissue with increased liver lipid content is predominantly due to the decrease in tissue water and therefore the distribution volume of electrolytes. In the longitudinal study, P(DW), P(WW), and P(NFWW) were decreased on d 14 p.p. Similar directional decreases were found for K, Mg, and Na, but P was the only electrolyte that was significantly decreased in liver tissue at d 14 p.p. This finding indicates that the P content of liver tissue decreases in early lactation due to a reduction in hepatocellular cytosol volume as well as a decrease in cytosolic P concentration, with the latter having biological relevance. The clinical significance of decreased cytosolic P concentration in the hepatocytes of dairy cows in early lactation remains to be determined.

Background Information generated via microarrays might uncover interactions between the mammary gland and Streptococcus uberis ( S. uberis ) that could help identify control measures for the prevention and spread of S. uberis mastitis, as well as improve overall animal health and welfare, and decrease economic losses to dairy farmers. The main objective of this study was to determine the most affected gene networks and pathways in mammary tissue in response to an intramammary infection ( IMI ) with S. uberis and relate these with other physiological measurements associated with immune and/or metabolic responses to mastitis challenge with S. uberis O140J. Results Streptococcus uberis IMI resulted in 2,102 (1,939 annotated) differentially expressed genes ( DEG ). Within this set of DEG, we uncovered 20 significantly enriched canonical pathways (with 20 to 61 genes each), the majority of which were signaling pathways. Among the most inhibited were LXR/RXR Signaling and PPARα/RXRα Signaling . Pathways activated by IMI were IL-10 Signaling and IL-6 Signaling which likely reflected counter mechanisms of mammary tissue to respond to infection. Of the 2,102 DEG, 1,082 were up-regulated during IMI and were primarily involved with the immune response, e.g., IL6 , TNF , IL8, IL10, SELL, LYZ , and SAA3 . Genes down-regulated (1,020) included those associated with milk fat synthesis, e.g., LPIN1, LPL, CD36 , and BTN1A1 . Network analysis of DEG indicated that TNF had positive relationships with genes involved with immune system function (e.g., CD14, IL8, IL1B , and TLR2 ) and negative relationships with genes involved with lipid metabolism (e.g., GPAM , SCD , FABP4 , CD36 , and LPL ) and antioxidant activity ( SOD1 ). Conclusion Results provided novel information into the early signaling and metabolic pathways in mammary tissue that are associated with the innate immune response to S. uberis infection. Our study indicated that IMI challenge with S. uberis (strain O140J) elicited a strong transcriptomic response, leading to potent activation of pro-inflammatory pathways that were associated with a marked inhibition of lipid synthesis, stress-activated kinase signaling cascades, and PPAR signaling (most likely PPARγ). This latter effect may provide a mechanistic explanation for the inverse relationship between immune response and milk fat synthesis.

The objective was to determine the effect of milking frequency and dosing interval on pharmacokinetics of cephapirin after intramammary infusion. Six healthy Holstein cows were administered cephapirin (200 mg) into 1 rear mammary gland after each of 2 milkings. Cows were milked twice daily (2x) and dosed at a 12-h interval or 3 times daily (3x) and dosed at an 8- or 16-h interval. A duplicated Latin square design allowed each cow to receive all 3 frequency-dose treatments, with intervening washout periods. Concentrations of cephapirin (CEPH) and desacetylcephapirin (DAC) in milk from the treated glands were determined at each milking after infusion using liquid chromatography-mass spectrometry. Data were fitted using 1- and 2-compartment pharmacokinetic models, as well as a noncompartmental model. Cephapirin was rapidly metabolized to DAC in the mammary gland, with DAC being the predominant agent in milk until 48 h after infusion. Pharmacokinetics of CEPH and DAC were similar for all treatment groups, with a 1-compartment model providing a better fit than a 2-compartment model in most instances. Milking frequency did not affect the length of time that milk CEPH concentration exceeded MIC(50) or MIC(90) values (the minimum inhibitory antimicrobial concentration needed to inhibit 50 or 90% of microbial activity, respectively) for common mastitis pathogens, except that cows milked 3x and dosed at a 16-h interval maintained inhibitory concentrations approximately 8 h longer than those dosed at an 8-h interval. Time for milk CEPH concentration to reach the FDA tolerance did not differ among treatment groups [mean +/- SD; 68 +/- 20, 66 +/- 22, and 57 +/- 18 h after last treatment for cows treated at 12, 16, and 8 h, respectively]. Mean residence time for CEPH in the mammary gland was linearly and negatively associated with the volume of milk produced. Calculated CEPH concentration in composite milk from all 4 mammary glands was below the FDA tolerance in all cows by 96 h after the last infusion, which is the labeled withholding time for the preparation used. Our findings suggest that this CEPH preparation, which is labeled for 2 doses 12 h apart, could be administered at a 16-h interval in herds milking 3x, with no significant effect on inhibitory concentrations in milk or withdrawal time; extended withdrawal times would be prudent for cows with very low milk production. Further investigation is needed to determine if milking frequency affects CEPH pharmacokinetics in cows with clinical mastitis.

Clinical mastitis in dairy cows is commonly treated with intramammary (IMM) antimicrobial agents. Pharmacokinetic data are used to design treatment regimens and determine withholding times. In some pharmacokinetic studies, investigators measure antimicrobial concentrations in foremilk, whereas in others, they use bucket milk or do not specify the milk fraction sampled. Our objective was to compare antimicrobial concentrations in foremilk, bucket milk, and strippings after IMM treatment of six healthy Holsteins. One mammary gland/cow was infused with 200 mg of cephapirin (CEPH) after each of the two milkings, using different milking frequencies and treatment intervals in a randomized crossover design. Treated glands were sampled at the first milking following each infusion. Antimicrobial concentrations in milk were measured using HPLC/MS/MS. CEPH concentration was higher in foremilk (geometric mean 44.2 microg/mL) than in bucket milk (15.7 microg/mL) or strippings (18.5 microg/mL), as it was true for desacetylcephapirin (DAC) (59.5, 23.0, and 30.2 microg/mL, respectively). This finding, which was based on milk samples collected at the first milking after IMM infusion, suggests that pharmacokinetic data based on drug concentrations in foremilk may be misleading. Strippings were more representative of bucket milk than foremilk. The relationship between milk fraction and antimicrobial concentration should be investigated for other IMM antimicrobial agents. Meanwhile, it is essential that pharmacokinetic and residue studies report the fraction of milk that was analyzed.

Objectives were to compare mammary tissue gene expression profiles between lactating cows subjected to dietary‐induced negative energy balance (NEB; n = 5/treatment) and cows fed ad libitum (AL) to maintain positive energy balance. NEB cows were feed restricted (FR) to 60% of calculated net energy for lactation requirements for 5 d. After 5 d of FR, both rear mammary quarters of all cows were biopsied for RNA extraction. A 13,257 oligonucleotide (70‐mers) array and qPCR were used for transcript profiling. Annotation was based on similarity searches using BLASTN against human, mouse and bovine RefSeq, human, mouse, and bovine UniGene, and bovine TIGR. Cy3‐ and Cy5‐labelled cDNA from mammary tissue and a reference standard were used for hybridizations. NEB resulted in 299 differentially expressed genes (P < 0.01). Among genes downregulated with NEB (156 genes total), Ingenuity Pathway Analysis® identified cell cycle (5), cell morphology (12), and cellular development (18) as some of the most enriched molecular functions. Genes upregulated by NEB (141 genes total) were associated with amino acid metabolism (11), small molecule biochemistry (18), gene expression (10) and lipid metabolism (8). Results indicate that NEB alters mammary gene expression. Project was funded by Section 1433 Animal Health and Disease, University of Illinois #ILLU‐538‐981, and NRI‐USDA #2007‐35204‐17758.

Dairy cows are highly susceptible after parturition to developing liver lipidosis and ketosis, which are costly diseases to farmers. A bovine microarray platform consisting of 13,257-annotated oligonucleotides was used to study hepatic gene networks underlying nutrition-induced ketosis. On day 5 postpartum, 14 Holstein cows were randomly assigned to ketosis-induction (n = 7) or control (n = 7) groups. Cows in the ketosis-induction group were fed at 50% of day 4 intake until they developed signs of clinical ketosis, and cows in the control group were fed ad libitum throughout the treatment period. Liver was biopsied at 10-14 (ketosis) or 14 days postpartum (controls). Feed restriction increased blood concentrations of nonesterified fatty acids and beta-hydroxybutyrate, but decreased glucose. Liver triacylglycerol concentration also increased. A total of 2,415 genes were altered by ketosis (false discovery rate = 0.05). Ingenuity Pathway Analysis revealed downregulation of genes associated with oxidative phosphorylation, protein ubiquitination, and ubiquinone biosynthesis with ketosis. Other molecular adaptations included upregulation of genes and nuclear receptors associated with cytokine signaling, fatty acid uptake/transport, and fatty acid oxidation. Genes downregulated during ketosis included several associated with cholesterol metabolism, growth hormone signaling, proton transport, and fatty acid desaturation. Feed restriction and ketosis resulted in previously unrecognized alterations in gene network expression underlying key cellular functions and discrete metabolic events. These responses might help explain well-documented physiological adaptations to reduced feed intake in early postpartum cows and, thus, provide molecular targets that might be useful in prevention and treatment of liver lipidosis and ketosis.