Accuracy of predicting milk yield from alternative milk recording schemes

peer-reviewedThe effect of reducing the frequency of official milk recording and the number of recorded samples per test-day on the accuracy of predicting daily yield and cumulative 305-day yield was investigated. A control data set consisting of 58 210 primiparous cows with milk test-day records every 4 weeks was used to investigate the influence of reduced milk recording frequencies. The accuracy of prediction of daily yield with one milk sample per test-day was investigated using 41 874 testday records from 683 cows. Results show that five or more test-day records taken at 8-weekly intervals (A8) predicted 305-day yield with a high level of accuracy. Correlations between 305-day yield predicted from 4-weekly recording intervals (A4) and from 8-weekly intervals were 0.99, 0.98 and 0.98 for milk, fat and protein, respectively. The mean error in estimating 305-day yield from the A8 scheme was 6.8 kg (s.d. 191 kg) for milk yield, 0.3 kg (s.d. 10 kg) for fat yield, and −0.3 kg (s.d. 7 kg) for protein yield, compared with the A4 scheme. Milk yield and composition taken during either morning (AM) or evening (PM) milking predicted 24-h yield with a high degree of accuracy. Alternating between AM and PM sampling every 4 weeks predicted 305-day yield with a higher degree of accuracy than either all AM or all PM sampling. Alternate AM-PM recording every 4 weeks and AM + PM recording every 8 weeks produced very similar accuracies in predicting 305-day yield compared with the official AM + PM recording every 4 weeks

T-cell recognition is shaped by epitope sequence conservation in the host proteome and microbiome

Several mechanisms exist to avoid or suppress inflammatory T-cell immune responses that could prove harmful to the host due to targeting self-antigens or commensal microbes. We hypothesized that these mechanisms could become evident when comparing the immunogenicity of a peptide from a pathogen or allergen with the conservation of its sequence in the human proteome or the healthy human microbiome. Indeed, performing such comparisons on large sets of validated T-cell epitopes, we found that epitopes that are similar with self-antigens above a certain threshold showed lower immunogenicity, presumably as a result of negative selection of T cells capable of recognizing such peptides. Moreover, we also found a reduced level of immune recognition for epitopes conserved in the commensal microbiome, presumably as a result of peripheral tolerance. These findings indicate that the existence (and potentially the polarization) of T-cell responses to a given epitope is influenced and to some extent predictable based on its similarity to self-antigens and commensal antigens.Fil: Bresciani, Anne Gøther. Technical University of Denmark; Dinamarca. La Jolla Institute for Allergy and Immunology; Estados UnidosFil: Paul, Sinu. La Jolla Institute for Allergy and Immunology; Estados UnidosFil: Schommer, Nina. La Jolla Institute for Allergy and Immunology; Estados UnidosFil: Dillon, Myles B.. La Jolla Institute for Allergy and Immunology; Estados UnidosFil: Bancroft, Tara. La Jolla Institute for Allergy and Immunology; Estados UnidosFil: Greenbaum, Jason. La Jolla Institute for Allergy and Immunology; Estados UnidosFil: Sette, Alessandro. La Jolla Institute for Allergy and Immunology; Estados UnidosFil: Nielsen, Morten. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas ; Argentina. Technical University of Denmark; DinamarcaFil: Peters, Bjoern. La Jolla Institute for Allergy and Immunology; Estados Unido

Deep Synoptic Array science I: discovery of the host galaxy of FRB 20220912A

We report the detection and interferometric localization of the repeating fast radio burst (FRB) source FRB 20220912A during commissioning observations with the Deep Synoptic Array (DSA-110). Two bursts were detected from FRB 20220912A, one each on 2022 October 18 and 2022 October 25. The best-fit position is (R.A. J2000, decl. J2000) = (23:09:04.9, +48:42:25.4), with a 90% confidence error ellipse of $\pm2$ arcsec and $\pm1$ arcsec in right ascension and declination respectively. The two bursts have disparate polarization properties and temporal profiles. We find a Faraday rotation measure that is consistent with the low value of $+0.6$ rad m$^{-2}$ reported by CHIME/FRB. The DSA-110 localization overlaps with the galaxy PSO J347.2702+48.7066 at a redshift $z=0.0771$, which we identify as the likely host. PSO J347.2702$+$48.7066 has a stellar mass of approximately $10^{10}M_{\odot}$, modest internal dust extinction, and a star-formation rate likely in excess of $0.1\,M_{\odot}$ yr$^{-1}$. The host-galaxy contribution to the dispersion measure is likely $\lesssim50$ pc cm$^{-3}$. The FRB 20220912A source is therefore likely viewed along a tenuous plasma column through the host galaxy.Comment: 10 pages, 7 figures, 2 tables, submitted to AAS Journal

A framework for highly multiplexed dextramer mapping and prediction of T cell receptor sequences to antigen specificity.

T cell receptor (TCR) antigen-specific recognition is essential for the adaptive immune system. However, building a TCR-antigen interaction map has been challenging due to the staggering diversity of TCRs and antigens. Accordingly, highly multiplexed dextramer-TCR binding assays have been recently developed, but the utility of the ensuing large datasets is limited by the lack of robust computational methods for normalization and interpretation. Here, we present a computational framework comprising a novel method, ICON (Integrative COntext-specific Normalization), for identifying reliable TCR-pMHC (peptide-major histocompatibility complex) interactions and a neural network-based classifier TCRAI that outperforms other state-of-the-art methods for TCR-antigen specificity prediction. We further demonstrated that by combining ICON and TCRAI, we are able to discover novel subgroups of TCRs that bind to a given pMHC via different mechanisms. Our framework facilitates the identification and understanding of TCR-antigen-specific interactions for basic immunological research and clinical immune monitoring

Response and resistance to BET bromodomain inhibitors in triple-negative breast cancer

Triple-negative breast cancer (TNBC) is a heterogeneous and clinically aggressive disease for which there is no targeted therapy. BET bromodomain inhibitors, which have shown efficacy in several models of cancer have not been evaluated in TNBC. These inhibitors displace BET bromodomain proteins such as BRD4 from chromatin by competing with their acetyl-lysine recognition modules, leading to inhibition of oncogenic transcriptional programs. Here we report the preferential sensitivity of TNBCs to BET bromodomain inhibition in vitro and in vivo, establishing a rationale for clinical investigation and further motivation to understand mechanisms of resistance. In paired cell lines selected for acquired resistance to BET inhibition from previously sensitive TNBCs, we failed to identify gatekeeper mutations, new driver events or drug pump activation. BET-resistant TNBC cells remain dependent on wild-type BRD4, which supports transcription and cell proliferation in a bromodomain-independent manner. Proteomic studies of resistant TNBC identify strong association with MED1 and hyper-phosphorylation of BRD4 attributable to decreased activity of PP2A, identified here as a principal BRD4 serine phosphatase. Together, these studies provide a rationale for BET inhibition in TNBC and present mechanism-based combination strategies to anticipate clinical drug resistance

Response and resistance to BET bromodomain inhibitors in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a heterogeneous and clinically aggressive disease for which there is no targeted therapy. BET bromodomain inhibitors, which have shown efficacy in several models of cancer, have not been evaluated in TNBC. These inhibitors displace BET bromodomain proteins such as BRD4 from chromatin by competing with their acetyl-lysine recognition modules, leading to inhibition of oncogenic transcriptional programs. Here we report the preferential sensitivity of TNBCs to BET bromodomain inhibition in vitro and in vivo, establishing a rationale for clinical investigation and further motivation to understand mechanisms of resistance. In paired cell lines selected for acquired resistance to BET inhibition from previously sensitive TNBCs, we failed to identify gatekeeper mutations, new driver events or drug pump activation. BET-resistant TNBC cells remain dependent on wild-type BRD4, which supports transcription and cell proliferation in a bromodomain-independent manner. Proteomic studies of resistant TNBC identify strong association with MED1 and hyper-phosphorylation of BRD4 attributable to decreased activity of PP2A, identified here as a principal BRD4 serine phosphatase. Together, these studies provide a rationale for BET inhibition in TNBC and present mechanism-based combination strategies to anticipate clinical drug resistance

Evolution of dispersal strategies and dispersal syndromes in fragmented landscapes

Funded by ERA-Net BiodivERsAPeer reviewedPostprin

Táin Bó Fraích

Byrne Mary E., Dillon Myles. Táin Bó Fraích. In: Etudes Celtiques, vol. 2, fascicule 3, 1937. pp. 1-27