Use of on-farm data to guide treatment and control mastitis caused by Streptococcus uberis

Treatment of mastitis is the most common reason for use of antimicrobial agents in dairy cattle. The responsible use of antimicrobials could be strengthened by knowledge of predictors for cure, which would help to tailor treatment decisions. Ideally, to allow for widespread uptake, this would be achieved using data that are routinely available. To assess whether this is feasible in practice, farmers were invited to submit milk samples from mastitis cases to their veterinary practice for bacteriological culture. Among 624 culture-positive samples, 251 were positive for Streptococcus uberis. Using cow-level data, cases were classified as severe, first nonsevere, repeat, or subclinical. Additional data were collected at the cow level [somatic cell count (SCC), parity, lactation stage, milk yield, fat and protein contents, treatment] and at the herd level (housing, bedding, premilking teat disinfection, postmilking teat disinfection). Severe cases were overrepresented among heifers and animals in early lactation, and repeat cases were overrepresented in cows with 3 or more lactations. The probability of cure was higher among first- and second-parity animals than among older cows, and was higher in animals with a single elevated cow-level SCC than in animals with multiple high SCC records. Results obtained in the current study are similar to those previously described for Staphylococcus aureus mastitis. Thus, routinely available cow-level information can help to predict the outcome of antimicrobial treatment of the most common causes of gram-positive mastitis

Biology of the immunomodulatory molecule HLA-G in human liver diseases.

International audienceThe non-classical human leukocyte antigen-G, HLA-G, plays an important role in inducing tolerance, through its immunosuppressive effects on all types of immune cells. Immune tolerance is a key issue in the liver, both in liver homeostasis and in the response to liver injury or cancer. It would therefore appear likely that HLA-G plays an important role in liver diseases. Indeed, this molecule was recently shown to be produced by mast cells in the livers of patients infected with hepatitis C virus (HCV). Furthermore, the number of HLA-G-positive mast cells was significantly associated with fibrosis progression. The generation of immune tolerance is a role common to both HLA-G, as a molecule, and the liver, as an organ. This review provides a summary of the evidence implicating HLA-G in liver diseases. In the normal liver, HLA-G transcripts can be detected, but there is no HLA-G protein. However, HLA-G protein is detectable in the liver tissues and/or plasma of patients suffering from hepatocellular carcinoma, hepatitis B or C, or visceral leishmaniasis and in liver transplant recipients. The cells responsible for producing HLA-G differ between diseases. HLA-G expression is probably induced by microenvironmental factors, such as cytokines. The expression of HLA-G receptors, such as ILT2, ILT4, and KIRD2L4, on liver cells has yet to be investigated, but these receptors have been detected on all types of immune cells, and such cells are present in liver. The tolerogenic properties of HLA-G explain its deleterious effects in cancers and its beneficial effects in transplantation. Given the key role of HLA-G in immune tolerance, new therapeutic agents targeting HLA-G could be tested for the treatment of these diseases in the future

Increased acetylcholinesterase expression in bumble bees during neonicotinoid-coated corn sowing

While honey bee exposure to systemic insecticides has received much attention, impacts on wild pollinators have not been as widely studied. Neonicotinoids have been shown to increase acetylcholinesterase (AChE) activity in honey bees at sublethal doses. High AChE levels may therefore act as a biomarker of exposure to neonicotinoids. This two-year study focused on establishing whether bumble bees living and foraging in agricultural areas using neonicotinoid crop protection show early biochemical signs of intoxication. Bumble bee colonies (Bombus impatiens) were placed in two different agricultural cropping areas: 1) control (≥3 km from fields planted with neonicotinoid-treated seeds) or 2) exposed (within 500 m of fields planted with neonicotinoid-treated seeds) and maintained for the duration of corn sowing. As determined by Real Time qPCR, AChE mRNA expression was initially significantly higher in bumble bees from exposed sites, then decreased throughout the planting season to reach a similar endpoint to that of bumble bees from control sites. These findings suggest that exposure to neonicotinoid seed coating particles during the planting season can alter bumble bee neuronal activity. To our knowledge, this is the first study to report in situ that bumble bees living in agricultural areas exhibit signs of neonicotinoid intoxication

Testing mirror symmetry in the Universe with LIGO-Virgo black-hole mergers

Precessing black-hole mergers can produce gravitational waves with net circular polarization, understood as an imbalance between right- and left-handed amplitudes. According to the Cosmological Principle, such emission must average to zero across all binary mergers in our Universe to preserve mirror-reflection symmetry at very large scales. We present a new, independent gravitational-wave test of this hypothesis. Using a novel observable based on the Chern-Pontryagin pseudo-scalar, we measure the emission of net circular polarization across 47 black-hole mergers recently analyzed by Islam. et. al. with a state-of-the art model for precessing black-hole mergers. The average value obtained is consistent with zero. Remarkably, however, we find that at least $82\%$ of the analysed sources must have produced net circular polarization, which requires orbital precession. Of these, GW200129 shows strong evidence for mirror asymmetry, with a Bayes Factor of 12.6 or, equivalently, $93.1\%$ probability. We obtain consistent (although stronger) results of $97.5\%$ and $94.3\%$ respectively using public results on this event from Hannam et. al. and performing our own parameter inference. This finding further implies indirect evidence for spontaneous emission of circularly polarized photons out of the quantum vacuum. Forthcoming black-hole merger detections will enable stronger constraints on large-scale mirror asymmetry and the Cosmological Principle.Comment: 9 pages, 6 Figures, 3 Appendixe

Goal-seeking compresses neural codes for space in the human hippocampus and orbitofrontal cortex

Humans can navigate flexibly to meet their goals. Here, we asked how the neural representation of allocentric space is distorted by goal-directed behavior. Participants navigated an agent to two successive goal locations in a grid world environment comprising four interlinked rooms, with a contextual cue indicating the conditional dependence of one goal location on another. Examining the neural geometry by which room and context were encoded in fMRI signals, we found that map-like representations of the environment emerged in both hippocampus and neocortex. Cognitive maps in hippocampus and orbitofrontal cortices were compressed so that locations cued as goals were coded together in neural state space, and these distortions predicted successful learning. This effect was captured by a computational model in which current and prospective locations are jointly encoded in a place code, providing a theory of how goals warp the neural representation of space in macroscopic neural signals.</p

Expression of HLA-G by mast cells is associated with hepatitis C virus-induced liver fibrosis.

International audienceBACKGROUND AND AIMS: Infection by hepatitis C virus is a worldwide health problem. An inadequate Th2 cytokine response promotes the fibrosis-cirrhosis fate. Immune-modulating molecules favoring a Th2 profile, such as HLA-G molecules of the HLA class Ib family, may play a role in chronic hepatitis. HLA-G contributes to the escape of tumors, and their involvement in viral infections has been increasingly described. The aim of this work was to study the expression of HLA-G in the liver, its cellular source and its regulation in cases of chronic C hepatitis. METHODS: HLA-G cells in blocks of liver derived from patients infected with HCV were labeled by immunohistochemistry and enumerated. Double immunofluorescence allowed the identification of the cellular source. HLA-G secretion by a human mast cell line was quantified by ELISA after various stimulations. After treatment with IFN-α real-time PCR was performed to determine the kinetics of cytokine expression profiles, followed by heat map clustering analysis. RESULTS: The number of HLA-G + cells was significantly associated with the area of fibrosis. For the first time, we identify the HLA-G+ cells as being mast cells. HLA-G secretion was significantly induced in human mast cells stimulated by IL-10 or interferons of class I. The transcriptome of the secretome of this cell line stimulated by IFN-α revealed that i) the HLA-G gene is upregulated late, ii) T lymphocytes and NK cells are recruited. CONCLUSIONS: These findings suggest an autocrine loop in the genesis of HCV liver fibrosis, based on mast cells expressing HLA-G

Goal-seeking compresses neural codes for space in the human hippocampus and orbitofrontal cortex

Humans can navigate flexibly to meet their goals. Here, we asked how the neural representation of allocentric space is distorted by goal-directed behavior. Participants navigated an agent to two successive goal locations in a grid world environment comprising four interlinked rooms, with a contextual cue indicating the conditional dependence of one goal location on another. Examining the neural geometry by which room and context were encoded in fMRI signals, we found that map-like representations of the environment emerged in both hippocampus and neocortex. Cognitive maps in hippocampus and orbitofrontal cortices were compressed so that locations cued as goals were coded together in neural state space, and these distortions predicted successful learning. This effect was captured by a computational model in which current and prospective locations are jointly encoded in a place code, providing a theory of how goals warp the neural representation of space in macroscopic neural signals

Impact of the wavelike nature of Proca stars on their gravitational-wave emission

We present a systematic study of the dynamics and gravitational-wave emission of head-on collisions of spinning vector boson stars, known as Proca stars. To this aim we build a catalogue of about 800 numerical-relativity simulations of such systems. We find that the wave-like nature of bosonic stars has a large impact on the gravitational-wave emission. In particular, we show that the initial relative phase $\Delta \epsilon =\epsilon_1-\epsilon_2$ of the two complex fields forming the stars (or equivalently, the relative phase at merger) strongly impacts both the emitted gravitational-wave energy and the corresponding mode structure. This leads to a non-monotonic dependence of the emission on the frequency of the secondary star $\omega_2$, for fixed frequency $\omega_1$ of the primary. This phenomenology, which has not been found for the case of black-hole mergers, reflects the distinct ability of the Proca field to interact with itself in both constructive and destructive manners. We postulate this may serve as a smoking gun to shed light on the possible existence of these objects.This work was supported by the Center for Research and Development in Mathematics and Applications (CIDMA) through the Portuguese Foundation for Science and Technology (FCT—Fundação para a Ciência e a Tecnologia), references UIDB/04106/2020 and UIDP/ 04106/2020, by national funds (OE), through FCT, I. P., in the scope of the framework contract foreseen in the numbers 4, 5 and 6 of the article 23, of the Decree-Law 57/ 2016, changed by Law 57/2017, and by Projects No. PTDC/FIS-OUT/28407/2017, No. CERN/FIS-PAR/ 0027/2019, No. PTDC/FIS-AST/3041/2020, and No. CERN/FIS-PAR/0024/2021. This work has further been supported by the Spanish Agencia Estatal de Investigación (PGC2018-095984-B-I00 and PID2021- 125485NB-C21), by the Generalitat Valenciana (PROMETEO/2019/071), and by the European Union’s Horizon 2020 research and innovation (RISE) program H2020-MSCA-RISE-2017 Grant No. FunFiCO-777740. N. S.-G. acknowledges financial support by the Spanish Ministerio de Universidades, through a María Zambrano grant (ZA21-031) with reference UP2021-044, within the European Union-Next Generation EU. J. C. B. is supported by a fellowship from “la Caixa” Foundation (ID No. 100010434) and from the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie Grant Agreement No. 847648. The fellowship code is LCF/BQ/PI20/11760016. J. C. B. is also supported by the research Grant No. PID2020–118635GBI00 from the Spain-Ministerio de Ciencia e Innovación.publishe