Monitoring cow comfort and rumen health indices in a cubicle-housed herd with an automatic milking system: a repeated measures approach

[This corrects the article DOI: 10.1186/s13620-015-0040-7.]

A Search for Non-Perturbative Dualities of Local N=2N=2 Yang--Mills Theories from Calabi--Yau Threefolds

The generalisation of the rigid special geometry of the vector multiplet quantum moduli space to the case of supergravity is discussed through the notion of a dynamical Calabi--Yau threefold. Duality symmetries of this manifold are connected with the analogous dualities associated with the dynamical Riemann surface of the rigid theory. N=2 rigid gauge theories are reviewed in a framework ready for comparison with the local case. As a byproduct we give in general the full duality group (quantum monodromy) for an arbitrary rigid $SU(r+1)$ gauge theory, extending previous explicit constructions for the $r=1,2$ cases. In the coupling to gravity, R--symmetry and monodromy groups of the dynamical Riemann surface, whose structure we discuss in detail, are embedded into the symplectic duality group $\Gamma_D$ associated with the moduli space of the dynamical Calabi--Yau threefold.Comment: Latex. Version of previous paper with enlarged and revised appendix 35 pages, plain LaTe

Glycogen synthase kinase-3 mediates acetaminophen-induced apoptosis in human hepatoma cells

ABSTRACT The mild analgesic drug acetaminophen (AAP) induces severe hepatic injury when taken at excessive doses. Recent evidence shows that the initial form of damage is through apoptosis, but this fails to go to completion and degenerates into necrosis. The aim of this study was to elucidate the mechanism through which AAP induces apoptosis using human HuH7 hepatoma cells as an in vitro model system to investigate the initial phase of AAP-induced hepatic injury. AAP-induced apoptosis in HuH7 cells as evidenced by chromatin condensation was preceded by the translocation of Bax to mitochondria and the cytoplasmic release of the proapoptotic factors cytochrome c and Smac/DIABLO. A concomitant loss of mitochondrial membrane potential occurred. Activation of the mitochondrial pathway of apoptosis led to the activation of execution caspases-3 and -7. AAP-induced apoptosis and cell death was blocked by inhibitors of caspases but not by inhibitors of calpains, cathepsins, and serine proteases. Apoptosis was unaffected by inhibitors of the mitochondrial permeability transition pore and by inhibitors of Jun NH 2 -terminal kinases, p38 mitogen-activated protein kinase, or mitogen-activated protein kinase kinase 1/2. However, pharmacological inhibition of glycogen synthase kinase-3 (GSK-3) delayed and decreased the extent of AAP-induced apoptosis. In comparison, endoplasmic reticulum stress-induced but not prooxidant-induced apoptosis of HuH7 cells was sensitive to GSK-3 inhibition. It is concluded that AAP-induced apoptosis involves the mitochondrial pathway of apoptosis that is mediated by GSK-3 and most likely initiated through an endoplasmic reticulum stress response. The mild analgesic acetaminophen (paracetamol, AAP) remains the commonest cause of acute liver failure in the United States and other parts of the world as a result of accidental or deliberate overdose Many of the histochemical and biochemical features of the late stages of AAP toxicity, particularly after high doses, support the conclusion that AAP induces hepatocellular necrosi

Glycogen synthase kinase-3 mediates acetaminophen-induced apoptosis in human hepatoma cells

Abstract: 232 Introduction: 61

Behavioural changes in dairy cows with lameness in an automatic milking system

There is a tendency worldwide for the automation of farms; this has included the introduction of automatic milking systems (AMS) in the dairy industry. Lameness in dairy cows is highly prevalent and painful. These impacts potentially affect not only animal welfare, but also farm economies. Three independent observational studies were carried out to assess the impact of lameness on the behaviour of zero grazed high yielding Holstein cows managed in an AMS. The aim of the first study was to examine the impact of lameness on rumination time, the second study investigated differences between lame and sound dairy cows in total eating time and the third study assessed the impact of lameness on milking behaviour (frequency and time of visits to the AMS). In the first study data from 150 cows were used to analyse rumination (collected using rumination collars) for the 48hr following locomotion scoring. A multilevel linear regression demonstrated that lameness had a small but significant negative association (coefficient: -7.88 (SE: 3.93)) with rumination. In the second study the behaviour of eleven matched lame and sound pairs of cows at the feed face was analysed for 24 hours after locomotion scoring. Each feeding behaviour variable (total duration time, frequency of feeding bouts and length of bouts) was analysed using individual single level regression models. There was a significant negative association between total feeding time and lameness (coefficient: -73.65 (SE: 25.47)) and the frequency of feeding bouts and lameness (-9.93 (2.49)). Finally, the third observational study used 38 matched pairs of lame and sound cows. Data on the number and timings of visits to the AMS were collected for 24 hours after each locomotion score and analysed using a binomial logistic regression model. There was a significant difference in AMS visits between groups; lame animals visiting the robot less frequently than sound cows (median difference 0.50 milking visits; T = 256.0; N = 25; p = 0.01) and lame cows were 0.33 times less likely to visit the AMS between 24:01 and 06:00. Results from these studies reveal that lameness in an AMS affected feeding behaviour, rumination and AMS visits. All of these impacts are likely to have negative consequences for farm profitability, but also implications for the health and welfare of the animals

Use of phosphorus fertilization and mycorrhization as strategies for reducingcopper toxicity in young grapevines.

Established vineyard soils may have high copper (Cu) contents due to the ongoing foliar applications of copper-based fungicides. In viticulture, the replacement of old vineyards with new vines is common practice, however,limited by Cu excess in soil and its toxicity to young grapevines. The application of phosphorus (P) and ar-buscular mycorrhizal fungi (AMF) inoculation are potential strategies to reduce Cu toxicity to young grapevines.This study aimed to assess the effects of phosphorus fertilization and AMF (Rhizophagus clarus) inoculation ongrowth and physiological parameters of young grapevines grown in soil with high Cu content. The experimentwas conducted in a greenhouse, where natural grassland soil was artificially contaminated by the addition of60 mg kg−1Cu. The soils were treated with and without AMF inoculation, combined with additions of 0, 40 and100 mg P kg−1. After 90 days of cultivation, grapevine plants were assessed for chlorophyllafluorescence,photosynthetic pigment contents, superoxide dismutase (SOD) activity, plant height, plant biomass, and con-centrations of Cu and P in roots and shoots. Phosphorus fertilization promoted increases in seedling growth(related to the increase of total P concentration in roots and shoots), soluble Pi concentration in leaves, and thequantum yield of the PSII (YII) (associated with a reduction in shoot Cu concentration). The AMF inoculationincreased the concentration of P in roots and shoots, soluble Pi in leaves and electron transport rate (ETR).Phosphorus fertilization and inoculation of grapevines with AMF are strategies capable of reducing Cu toxicity inyoung grapevines

GZMKhigh CD8+ T effector memory cells are associated with CD15high neutrophil abundance in non-metastatic colorectal tumors and predict poor clinical outcome.

CD8(+) T cells are a major prognostic determinant in solid tumors, including colorectal cancer (CRC). However, understanding how the interplay between different immune cells impacts on clinical outcome is still in its infancy. Here, we describe that the interaction of tumor infiltrating neutrophils expressing high levels of CD15 with CD8(+) T effector memory cells (T(EM)) correlates with tumor progression. Mechanistically, stromal cell-derived factor-1 (CXCL12/SDF-1) promotes the retention of neutrophils within tumors, increasing the crosstalk with CD8(+) T cells. As a consequence of the contact-mediated interaction with neutrophils, CD8(+) T cells are skewed to produce high levels of GZMK, which in turn decreases E-cadherin on the intestinal epithelium and favors tumor progression. Overall, our results highlight the emergence of GZMK(high) CD8(+) T(EM) in non-metastatic CRC tumors as a hallmark driven by the interaction with neutrophils, which could implement current patient stratification and be targeted by novel therapeutics

Functional Characterization of an Aspergillus fumigatus Calcium Transporter (PmcA) that Is Essential for Fungal Infection

Aspergillus fumigatus is a primary and opportunistic pathogen, as well as a major allergen, of mammals. The Ca+2-calcineurin pathway affects virulence, morphogenesis and antifungal drug action in A. fumigatus. Here, we investigated three components of the A. fumigatus Ca+2-calcineurin pathway, pmcA,-B, and -C, which encode calcium transporters. We demonstrated that CrzA can directly control the mRNA accumulation of the pmcA-C genes by binding to their promoter regions. CrzA-binding experiments suggested that the 5′-CACAGCCAC-3′ and 5′-CCCTGCCCC-3′ sequences upstream of pmcA and pmcC genes, respectively, are possible calcineurin-dependent response elements (CDREs)-like consensus motifs. Null mutants were constructed for pmcA and -B and a conditional mutant for pmcC demonstrating pmcC is an essential gene. The ΔpmcA and ΔpmcB mutants were more sensitive to calcium and resistant to manganese and cyclosporin was able to modulate the sensitivity or resistance of these mutants to these salts, supporting the interaction between calcineurin and the function of these transporters. The pmcA-C genes have decreased mRNA abundance into the alveoli in the ΔcalA and ΔcrzA mutant strains. However, only the A. fumigatus ΔpmcA was avirulent in the murine model of invasive pulmonary aspergillosis

Combining ChIP-chip and Expression Profiling to Model the MoCRZ1 Mediated Circuit for Ca2+/Calcineurin Signaling in the Rice Blast Fungus

Significant progress has been made in defining the central signaling networks in many organisms, but collectively we know little about the downstream targets of these networks and the genes they regulate. To reconstruct the regulatory circuit of calcineurin signal transduction via MoCRZ1, a Magnaporthe oryzae C2H2 transcription factor activated by calcineurin dephosphorylation, we used a combined approach of chromatin immunoprecipitation - chip (ChIP-chip), coupled with microarray expression studies. One hundred forty genes were identified as being both a direct target of MoCRZ1 and having expression concurrently differentially regulated in a calcium/calcineurin/MoCRZ1 dependent manner. Highly represented were genes involved in calcium signaling, small molecule transport, ion homeostasis, cell wall synthesis/maintenance, and fungal virulence. Of particular note, genes involved in vesicle mediated secretion necessary for establishing host associations, were also found. MoCRZ1 itself was a target, suggesting a previously unreported autoregulation control point. The data also implicated a previously unreported feedback regulation mechanism of calcineurin activity. We propose that calcium/calcineurin regulated signal transduction circuits controlling development and pathogenicity manifest through multiple layers of regulation. We present results from the ChIP-chip and expression analysis along with a refined model of calcium/calcineurin signaling in this important plant pathogen