Luteolysis and pregnancy outcomes after change in dose delivery of prostaglandin F2α in a 5-day timed artificial insemination program in dairy cows

Dairy Research, 2014 is known as Dairy Day, 2014Three experiments were conducted to determine if a larger dose of prostaglandin F2α (PG) administered on day 6 of a 5-day Ovsynch timed artificial insemination (AI) program would induce regression of the corpus luteum to facilitate AI and pregnancy outcomes similar to a traditional 5-day program with two doses of PG. When applying a 5-day program, cows that ovulate in response to the first GnRH injection have a new corpus luteum (CL) that is 2 days younger when PG is administered in a 5- versus 7-day program. To regress successfully the younger CL, a second injection of PG must be given 24 hours after the first PG injection to prevent reduced pregnancy rate after the timed AI. These experiments demonstrated that administering 50 mg PG (10 mL Lutalyse) on day 6 produced luteolysis as efficiently as 25 mg PG (5 mL Lutalyse) administered on days 5 and 6 when the cut point for progesterone was 1 ng/mL 72 hours after the first PG injection or 48 hours after the larger PG dose. In contrast, when the cut point was 0.5 ng/mL, the larger dose of PG was less effective. Pregnancy outcomes in cows did not differ between treatment doses except in one herd (Exp. 3). Although pregnancy outcomes were reduced only in one herd with the larger PG dose, this difference may be confounded with the earlier injection of the second GnRH injection 16 hours before timed AI, rather than failure of luteolysis in response to the larger dose of PG. Delaying the timing of AI, injection of the second GnRH, or both may be warranted to allow sufficient time for progesterone to decrease to basal concentrations in response to a larger dose of PG on day 6 to prevent a reduction in fertility

Simulations of Oligomeric Intermediates in Prion Diseases

We extend our previous stochastic cellular automata based model for areal aggregation of prion proteins on neuronal surfaces. The new anisotropic model allow us to simulate both strong beta-sheet and weaker attachment bonds between proteins. Constraining binding directions allows us to generate aggregate structures with the hexagonal lattice symmetry found in recently observed in vitro experiments. We argue that these constraints on rules may correspond to underlying steric constraints on the aggregation process. We find that monomer dominated growth of the areal aggregate is too slow to account for some observed doubling time-to-incubation time ratios inferred from data, and so consider aggregation dominated by relatively stable but non-infectious oligomeric intermediates. We compare a kinetic theory analysis of oligomeric aggregation to spatially explicit simulations of the process. We find that with suitable rules for misfolding of oligomers, possibly due to water exclusion by the surrounding aggregate, the resulting oligomeric aggregation model maps onto our previous monomer aggregation model. Therefore it can produce some of the same attractive features for the description of prion incubation time data. We propose experiments to test the oligomeric aggregation model.Comment: 8 pages, 10 figures For larger versions of several figures, see http://asaph.ucdavis.edu/~dmobley and click on the prion paper lin

Presynchronizing PGF2α and GnRH injections before timed artificial insemination CO-Synch + CIDR program

Fixed-time artificial insemination is an effective management tool that reduces the labor associated with more conventional artificial insemination programs requiring detection of estrus. The 7-day CO-Synch + controlled internal drug release (CIDR) insert protocol has been shown to effectively initiate estrus and ovulation in cycling and non-cycling suckled beef cows, producing pregnancy rates at or greater than 50% in beef cows. The gonadotropin-releasing hormone (GnRH) injection that begins the CO-Synch + CIDR program initiates ovulation in a large proportion of cows, particularly anestrous cows. The CIDR, which releases progesterone intravaginally, prevents short estrous cycles that usually follow the first postpartum ovulation in beef cows. Our hypothesis was that inducing estrus with a prostaglandin injection followed 3 days later with a GnRH injection, 7 days before applying the 7-day CO-Synch + CIDR protocol, might increase the percentage of cycling cows that would exhibit synchronous follicular waves after the onset of the CO-Synch + CIDR protocol. We also hypothesized that the additional GnRH injection would increase the percentage of anestrous cows that would ovulate, thereby increasing pregnancy outcomes

Serum and plasma metabolites and insemination timing associated with greater pregnancy risk in suckled beef cows subjected to artificial insemination programs

Doctor of PhilosophyDepartment of Animal Sciences and IndustryJeffrey S. StevensonFour experiments were conducted in beef cows to determine factors that increased the probability of pregnancy per AI when cows are inseminated by appointment. Cows in all experiments were inseminated after a 7-d CO-Synch + CIDR program (100 μg GnRH [2 mL Factrel, Pfizer Animal Health, Whitehouse Station, NJ] 7 d before 25 mg PGF₂[subscript]α [d 0; 5 mL Lutalyse; Pfizer Animal Health]). Experiment 1 compared 1 vs. 2 inseminations and GnRH injection times at 60 and 75 h after the CO-Synch + CIDR program. Delaying AI until 75 h, according to interpretation of estrus-detection patches, for cows not in estrus by 60 h after CIDR insert removal increased (P < 0.05) pregnancy risk (PR) compared with cows not in estrus and inseminated at 60 h (51.4 vs. 41.7%), respectively. The necessity of GnRH injection concurrent with AI was tested in experiment 2. Cows displaying estrus by 65 h that were injected with GnRH had similar PR to cows in estrus and not treated with GnRH (61.9 vs. 60.4%), respectively. Cows in experiment 2 that did not display estrus, but were treated with a GnRH injection at 65 h and then inseminated at 84 h after CIDR insert removal had increased PR compared with similar cows not treated with GnRH (33.4 vs. 15.0%; P < 0.01), respectively. Experiments 3 and 4 were observational studies conducted to determine if blood metabolites glucose and beta-hydroxy butyrate (BHB experiment 3), or physical body and blood metabolites, (glucose, BHB, non-esterified fatty acids [NEFA], blood urea nitrogen [BUN], body weight, rump fat [RF], or BCS; experiment 4) were indicative of future reproductive success in suckled beef cows enrolled in a timed AI program. In experiment 3, plasma glucose concentration 10 d before AI was lesser (P = 0.01; 52.2 vs. 56.9 mg/dL) and serum BHB concentration was lesser (P < 0.01) in cows that became pregnant 35 d after timed AI than for cows that did not become pregnant (600 vs. 690 μM), respectively. Experiment 4 identified relationships between indicators and reproductive success including the finding that serum NEFA concentration 2 to 4 wk before AI is negatively correlated (P < 0.05) with PR to AI

Saddles in the energy landscape: extensivity and thermodynamic formalism

We formally extend the energy landscape approach for the thermodynamics of liquids to account for saddle points. By considering the extensive nature of macroscopic potential energies, we derive the scaling behavior of saddles with system size, as well as several approximations for the properties of low-order saddles (i.e., those with only a few unstable directions). We then cast the canonical partition function in a saddle-explicit form and develop, for the first time, a rigorous energy landscape approach capable of reproducing trends observed in simulations, in particular the temperature dependence of the energy and fractional order of sampled saddles.Comment: 4 pages, 1 figur

What have we already learned from the CMB?

The COBE satellite, and the DMR experiment in particular, was extraordinarily successful. However, the DMR results were announced about 7 years ago, during which time a great deal more has been learned about anisotropies in the Cosmic Microwave Background (CMB). The CMB experiments currently being designed and built, including long-duration balloons, interferometers, and two space missions, promise to address several fundamental cosmological issues. We present our evaluation of what we already know, what we are beginning to learn now, and what the future may bring.Comment: 20 pages, 3 figures. Changes to match version accepted by PAS

RNA interference in marine and freshwater sponges

Background: The marine sponge Tethya wilhelma and the freshwater sponge Ephydatia muelleri are emerging model organisms to study evolution, gene regulation, development, and physiology in non-bilaterian animal systems. Thus far, functional methods (i.e., loss or gain of function) for these organisms have not been available. Results: We show that soaking developing freshwater sponges in double-stranded RNA and/or feeding marine and freshwater sponges bacteria expressing double-stranded RNA can lead to RNA interference and reduction of targeted transcript levels. These methods, first utilized in C. elegans, have been adapted for the development and feeding style of easily cultured marine and freshwater poriferans. We demonstrate phenotypic changes result from ‘knocking down’ expression of the actin gene. Conclusion: This technique provides an easy, efficient loss-of-function manipulation for developmental and gene regulatory studies in these important non-bilaterian animals

Innate Immunity and the Evolution of Resistance to an Emerging Infectious Disease in a Wild Bird

Innate immunity is expected to play a primary role in conferring resistance to novel infectious diseases, but few studies have attempted to examine its role in the evolution of resistance to emerging pathogens in wild vertebrate populations. Here, we used experimental infections and cDNA microarrays to examine whether changes in the innate and/or acquired immune responses likely accompanied the emergence of resistance in house finches (Carpodacus mexicanus) in the eastern United States subject to a recent outbreak of conjunctivitis-causing bacterium (Mycoplasma gallisepticum—MG). Three days following experimental infection with MG, we observed differences in the splenic transcriptional responses between house finches from eastern U.S. populations, with a 12-year history of MG exposure, versus western U.S. populations, with no history of exposure to MG. In particular, western birds down-regulated gene expression, while eastern finches showed no expression change relative to controls. Studies involving poultry have shown that MG can manipulate host immunity, and our observations suggest that pathogen manipulation occurred only in finches from the western populations, outside the range of MG. Fourteen days after infection, eastern finches, but not western finches, up-regulated genes associated with acquired immunity (cell-mediated immunity) relative to controls. These observations suggest population differences in the temporal course of the response to infection with MG and imply that innate immune processes were targets of selection in response to MG in the eastern U.S. population.Organismic and Evolutionary Biolog