Across-generation effects of maternal heat stress during late gestation on production, female fertility and longevity traits in dairy cows.

This research paper focuses on time-lagged heat stress (HS) effects from an across-generation perspective. Temperature × humidity indexes (THI) from the last 8 weeks of pregnancy were associated with subsequent female offspring performances. The offspring dataset considered 172 905 Holstein dairy cows from calving years 2002-2013 from 1,968 herds, located in the German federal state of Hesse. Production traits included milk yield (MKG), protein percentage (PRO%), fat percentage (FAT%), somatic cell score (SCS) and milk urea nitrogen (MUN) from the first official test-day in first lactation. Female fertility traits were the non-return-rate after 56 d (NRR56) in heifers and the interval from calving to first insemination (ICFI) in first parity cows. Longevity traits were the length of productive life (LPL), lifetime productivity in milk yield (LTP-MKG) and milk yield per day of life (MKG-DL). The association analyzes for 10 traits combined with meteorological data from 8 single weeks before calving implied in total 80 different runs. THI ≥50 from all single 8 weeks before calving had unfavorably significant effects on FAT%, ICFI and LPL. Heat stress in terms of THI ≥60 from the last 3 weeks before calving impaired MKG. NRR56 decreased with increasing THI, as observed for all 6 weeks before calving. LTP-MKG and MKG-DL decreased due to high THI in the last 4 weeks before calving. Heat stress (THI ≥60) during late pregnancy had no significantly unfavorable impact on PRO% and MUN. Interestingly, SCS in offspring declined with increasing THI during late pregnancy. In conclusion, for most of the primary and functional traits, unfavorable impact of HS from the dry period on time-lagged performances in offspring was identified, even on longevity. From a practical perspective, our data suggest to provide HS abatement to late gestation dams to avoid long-term adverse effects on the offspring.

Subclinical endometritis in dairy cattle is associated with distinct mRNA expression patterns in blood and endometrium.

Cattle with subclinical endometritis (SCE) are sub-fertile and diagnosing subclinical uterine disease remains a challenge. The hypothesis for this study was that endometrial inflammation is reflected in mRNA expression patterns of peripheral blood leucocytes. Transcriptome profiles were evaluated in healthy cows and in cows with SCE using circulating white blood cells (WBC) and endometrial biopsy samples collected from the same animals at 45-55 days postpartum. Bioinformatic analyses of microarray-based transcriptional data identified gene profiles associated with distinct biological functions in circulating WBC and endometrium. In circulating WBC, SCE promotes a pro-inflammatory environment, whereas functions related to tissue remodeling are also affected in the endometrium. Nineteen differentially expressed genes associated with SCE were common to both circulating WBC and the endometrium. Among these genes, transcript abundance of immune factors C3, C2, LTF, PF4 and TRAPPC13 were up-regulated in SCE cows at 45-55 days postpartum. Moreover, mRNA expression of C3, CXCL8, LTF, TLR2 and TRAPPC13 was temporally regulated during the postpartum period in circulating WBC of healthy cows compared with SCE cows. This observation might indicate an advantageous modulation of the immune system in healthy animals. The transcript abundance of these genes represents a potential source of indicators for postpartum uterine health.

Long-term use of yeast fermentation products in comparison to halofuginone for the control of cryptosporidiosis in neonatal calves.

The objective of this study was to compare the effect of non-GMO Saccharomyces cerevisiae fermentation products (SCFP) with that of a halofuginone treatment against Cryptosporidium parvum infection in pre-weaned calves on a commercial dairy farm. A total of 123 neonatal female calves, housed in individual hutches, were enrolled sequentially based on date of birth in 41 blocks of 3 animals each. Calves within each block were allocated to one of 3 treatments: remaining untreated, fed with SCFP (Diamond V SmartCare® at 1 g/d in milk and NutriTek® at 5 g/d in starter grain) for the first 63 days of life, or treated with halofuginone (0.1 mg/kg/d) for the first 7 days of life. Fecal samples collected on days 4-21 post-partum were examined for both Cryptosporidium oocysts and coproantigen. The presence and intensity of diarrhea were monitored by scoring daily for the first 4 weeks of life. Calves were weighed at 0, 21, 42 and 63 days of age. Almost all calves were Cryptosporidium-positive at least once during the study. Halofuginone significantly reduced the number of Cryptosporidium-positive fecal samples as compared to the two other groups. Based on the coproantigen scores, both halofuginone and SCFP feeding significantly reduced the intensity of Cryptosporidium infection as compared to the untreated group. Diarrhea was recorded in almost all calves at least once. Neither the proportion of diarrheic calves nor the intensity and duration of diarrhea differed among the 3 treatment groups significantly. The mean daily weight gain during the first 3 weeks of life was significantly lower in halofuginone treated calves than in both other groups; however, at the end of the study period the total weight gain did not significantly differ among the 3 treatment groups. In conclusion, the clinical results and weight gains of pre-weaning supplementation with the SCFP were neither better nor worse than the 7-day halofuginone treatment suggesting that the SCFP feeding may be from the clinical point of view a natural alternative measure, instead of halofuginone treatment, in bovine cryptosporidiosis.

Cold Collisions in a Molecular Synchrotron.

We study collisions between neutral, deuterated ammonia molecules (ND_{3}) stored in a 50 cm diameter synchrotron and argon atoms in copropagating supersonic beams. The advantages of using a synchrotron in collision studies are twofold: (i) By storing ammonia molecules many round-trips, the sensitivity to collisions is greatly enhanced; (ii) the collision partners move in the same direction as the stored molecules, resulting in low collision energies. We tune the collision energy in three different ways: by varying the velocity of the stored ammonia packets, by varying the temperature of the pulsed valve that releases the argon atoms, and by varying the timing between the supersonic argon beam and the stored ammonia packets. These give consistent results. We determine the relative, total, integrated cross section for ND_{3}+Ar collisions in the energy range of 40-140 cm^{-1}, with a resolution of 5-10 cm^{-1} and an uncertainty of 7%-15%. Our measurements are in good agreement with theoretical scattering calculations.

Peripheral blood leukocytes of cows with subclinical endometritis show an altered cellular composition and gene expression.

Subclinical endometritis (SCE) is an important postpartum disease in dairy cows, but conventional cytobrush diagnosis often gives imprecise results. The aim of this study was to analyze disease-associated changes in peripheral blood as potential diagnostic parameters. Cellular subpopulations of blood leukocytes from cows with or without SCE (45-55 days postpartum) were flow-cytometrically quantified. Gene expression of whole blood leukocytes was assessed by PAXgene analysis. Subclinical endometritis cows showed significantly higher number of blood mononuclear cells and neutrophils. Among mononuclear cells, numbers of B-cells, NK-cells, and CD172a-positive monocytes were significantly elevated. Compared with non-SCE cows, blood leukocytes of SCE cows significantly expressed higher copy numbers of CXCL8, TNF, and IL12. To test whether circulating plasma factors are responsible for these changes, leukocytes, polymorphonuclear cells, and monocyte subpopulations (classical, intermediate, nonclassical) of healthy cows were stimulated with plasma of SCE and non-SCE cows. Although gene expression of whole leukocytes and polymorphonuclear cells remained unaltered, plasma from SCE animals significantly elevated expressed messenger RNA copy numbers of CXCL8, CXCL1, and IL1B in intermediate monocytes. In conclusion, elevated number of selected mononuclear subpopulations in peripheral blood and enhanced expression of distinct genes encoding for inflammatory mediators in blood leukocytes reflect the subclinical uterine inflammatory process in cows. Whether the observed changes in the periphery of SCE cows are the consequence of the uterine inflammatory process, or whether they affect the pathogenesis of the disease is currently unknown.

Differential endometrial cell sensitivity to a cholesterol-dependent cytolysin links Trueperella pyogenes to uterine disease in cattle.

Purulent disease of the uterus develops in 40% of dairy cows after parturition, when the epithelium of the endometrium is disrupted to expose the underlying stroma to bacteria. The severity of endometrial pathology is associated with isolation of Trueperella pyogenes. In the present study, T. pyogenes alone caused uterine disease when infused into the uterus of cattle where the endometrial epithelium was disrupted. The bacterium secretes a cholesterol-dependent cytolysin, pyolysin (PLO), and the plo gene was identical and the plo gene promoter was highly similar amongst 12 clinical isolates of T. pyogenes. Bacteria-free filtrates of the T. pyogenes cultures caused hemolysis and endometrial cytolysis, and PLO was the main cytolytic agent, because addition of anti-PLO antibody prevented cytolysis. Similarly, a plo-deletion T. pyogenes mutant did not cause hemolysis or endometrial cytolysis. Endometrial stromal cells were notably more sensitive to PLO-mediated cytolysis than epithelial or immune cells. Stromal cells also contained more cholesterol than epithelial cells, and reducing stromal cell cholesterol content using cyclodextrins protected against PLO. Although T. pyogenes or plo-deletion T. pyogenes stimulated accumulation of inflammatory mediators, such as IL-1beta, IL-6, and IL-8, from endometrium, PLO did not stimulate inflammatory responses by endometrial or hematopoietic cells, or in vitro organ cultures of endometrium. The marked sensitivity of stromal cells to PLO-mediated cytolysis provides an explanation for how T. pyogenes acts as an opportunistic pathogen to cause pathology of the endometrium once the protective epithelium is lost after parturition.

Phenotypic and functional heterogeneity of bovine blood monocytes.

Murine and human peripheral blood monocytes are heterogeneous in size, granularity, nuclear morphology, phenotype and function. Whether and how bovine blood monocytes follow this pattern was analyzed in this study. Flow cytometrically, classical monocytes (cM) CD14⁺CD16⁻, intermediate monocytes (intM) CD14⁺ CD16⁺ and nonclassical monocytes (ncM) CD14⁺ CD16⁺ were identified, with cM being the predominant subset (89%). cM showed a significant lower expression of CD172a, intM expressed the highest level of MHC class II molecules, and ncM were low positive for CD163. Compared to cM and intM, ncM showed a significantly reduced phagocytosis capacity, a significantly reduced generation of reactive oxygen species, and reduced mRNA expression of CXCL8, CXCL1 and IL-1ß after LPS stimulation. Based on IL-1ß secretion after LPS/ATP stimulation, the inflammasome could be activated in cM and intM, but not in ncM. IFNγ increased the expression of CD16 selectively on cM and induced a shift from cM into intM in vitro. In summary, bovine CD172a-positive mononuclear cells define three monocyte subsets with distinct phenotypic and functional differences. Bovine cM and intM share homologies with their human counterparts, whereas bovine ncM are not inflammatory monocytes.

Multiple packets of neutral molecules revolving for over a mile.

The level of control that one has over neutral molecules in beams dictates their possible applications. Here we experimentally demonstrate that state-selected, neutral molecules can be kept together in a few mm long packet for a distance of over one mile. This is accomplished in a circular arrangement of 40 straight electrostatic hexapoles through which the molecules propagate over 1000 times. Up to 19 packets of molecules have simultaneously been stored in this ring structure. This brings the realization of a molecular low-energy collider within reach.