Associations between CXCR1 polymorphisms and pathogen-specific incidence rate of clinical mastitis, test-day somatic cell count, and test-day milk yield

The CXCR1 gene plays an important role in the innate immunity of the bovine mammary gland. Associations between single nucleotide polymorphisms (SNP) CXCR1c.735C>G and c.980A>G and udder health have been identified before in small populations. A fluorescent multiprobe PCR assay was designed specifically and validated to genotype both SNP simultaneously in a reliable and cost-effective manner. In total, 3,106 cows from 50 commercial Flemish dairy herds were genotyped using this assay. Associations between genotype and detailed phenotypic data, including pathogen-specific incidence rate of clinical mastitis (IRCM), test-day somatic cell count, and test-day milk yield (MY) were analyzed. Staphylococcus aureus IRCM tended to associate with SNP c.735C>G. Cows with genotype c.735GG had lower Staph. aureus IRCM compared with cows with genotype c.735CC (rate ratio = 0.35, 95% confidence interval = 0.14-0.90). Additionally, a parity-specific association between Staph. aureus IRCM and SNP c.980A>G was detected. Heifers with genotype c.980GG had a lower Staph. aureus IRCM compared with heifers with genotype c.980AG (rate ratio = 0.15, 95% confidence interval = 0.04-0.56). Differences were less pronounced in multiparous cows. Associations between CXCR1 genotype and somatic cell count were not detected. However, MY was associated with SNP c.735C>G. Cows with genotype c.735GG out-produced cows with genotype c.735CC by 0.8 kg of milk/d. Results provide a basis for further research on the relation between CXCR1 polymorphism and pathogen-specific mastitis resistance and MY

Pathogen-specific incidence rate of clinical mastitis in Flemish dairy herds, severity, and association with herd hygiene

A one-year survey on clinical mastitis was conducted on 50 randomly selected commercial Flemish dairy herds to estimate the pathogen-specific incidence rate of clinical mastitis (IRCM). The severity of the cases and the potential associations with herd hygiene were studied. Participating producers sampled 845 cases and 692 dairy cows. The mean and median IRCM was estimated at 7.4 and 5.3 quarter cases per 10,000 cow-days at risk, respectively. A large between-herd variation was observed (range of 0-21.3). In general, the IRCM was lower in heifers compared with multiparous cows (2.9 vs. 11.0 quarter cases per 10,000 cow-days at risk). However, the overall IRCM in the first week after calving was higher in heifers compared with cows (43.4 vs. 31.6 quarter cases per 10,000 cow-days at risk). Streptococcus uberis (18.2% of the cases) and Escherichia coli (15.5%) were the most frequently isolated pathogens and no growth was observed in 19.9% of the cases. The majority of the cases (63.1%) were mild (only clots in milk). Moderate (hard quarter without general signs) and severe symptoms (systemic illness) were observed in 29.9 and 7.0% of the cases, respectively. Isolation of E. coli (vs. any other culture result) was more likely in moderate and severe cases compared with mild cases. Overall IRCM and E. coli IRCM were higher in dirty compared with clean herds based on udder hygiene scores (9.0 and 1.7 vs. 6.0 and 0.6 quarter cases per 10,000 cow-days at risk, respectively). This study broadens the knowledge on clinical mastitis in Flemish dairy herds and underlines the high risk of CM in early-lactation heifers, the role of the so-called environmental pathogens, and herd hygiene

Quorumpeps database : chemical space, microbial origin and functionality of quorum sensing peptides

Quorum-sensing (QS) peptides are biologically attractive molecules, with a wide diversity of structures and prone to modifications altering or presenting new functionalities. Therefore, the Quorumpeps database (http://quorumpeps.ugent.be) is developed to give a structured overview of the QS oligopeptides, describing their microbial origin (species), functionality (method, result and receptor), peptide links and chemical characteristics (3D-structure-derived physicochemical properties). The chemical diversity observed within this group of QS signalling molecules can be used to develop new synthetic bio-active compounds

A phase I/II trial of fixed-dose stereotactic body radiotherapy with sequential or concurrent pembrolizumab in metastatic urothelial carcinoma : evaluation of safety and clinical and immunologic response

Background: Current first-line standard of therapy for metastatic urothelial carcinoma is platinum-based combination chemotherapy. Pembrolizumab in phase III has demonstrated a promising overall response rate of 21.1% in patients with progression or recurrence after platinum-based chemotherapy. Preclinical and clinical evidence suggests that radiotherapy has a systemic anti-cancer immune effect and can increase the level of PD-L1 and tumor infiltrating lymphocytes in the tumor microenvironment. These findings gave rise to the hypothesis that the combination of radiotherapy with anti-PD1 treatment could lead to a synergistic effect, hereby enhancing response rates. Methods: The phase I part will assess the dose limiting toxicity of the combination treatment of stereotactic body radiotherapy (SBRT) with four cycles of pembrolizumab (200 mg intravenously, every 3 weeks) in patients with metastatic urothelial carcinoma. The dose of both pembrolizumab and SBRT will be fixed, yet the patients will be randomized to receive SBRT either before the first cycle of pembrolizumab or before the third cycle of pembrolizumab. SBRT will be delivered (24 Gy in 3 fractions every other day) to the largest metastatic lesion. Secondary objectives include response rate according to RECIST v1.1 and immune related response criteria, progression-free survival and overall survival. The systemic immune effect triggered by the combination therapy will be monitored on various time points during the trial. The PD-L1/TIL status of the tumors will be analyzed via immunohistochemistry and response rates in the subgroups will be analyzed separately. A Simon's two-stage optimum design is used to select the treatment arm associated with the best response rate and with acceptable toxicity to proceed to the phase II trial. In this phase, 13 additional patients will be accrued to receive study treatment. Discussion: The progress made in the field of immunotherapy has lead to promising breakthroughs in various solid malignancies. Unfortunately, the majority of patients do not respond. The current trial will shed light on the toxicity and potential anti-tumor activity of the combination of radiotherapy with anti-PD1 treatment and may identify potential new markers for response and resistance to therapy

Quorum sensing peptides selectively penetrate the blood-brain barrier

Bacteria communicate with each other by the use of signaling molecules, a process called 'quorum sensing'. One group of quorum sensing molecules includes the oligopeptides, which are mainly produced by Gram-positive bacteria. Recently, these quorum sensing peptides were found to biologically influence mammalian cells, promoting i.a. metastasis of cancer cells. Moreover, it was found that bacteria can influence different central nervous system related disorders as well, e.g. anxiety, depression and autism. Research currently focuses on the role of bacterial metabolites in this bacteria-brain interaction, with the role of the quorum sensing peptides not yet known. Here, three chemically diverse quorum sensing peptides were investigated for their brain influx (multiple time regression technique) and efflux properties in an in vivo mouse model (ICR-CD-1) to determine blood-brain transfer properties: PhrCACET1 demonstrated comparatively a very high initial influx into the mouse brain (Kin = 20.87 μl/(g×min)), while brain penetrabilities of BIP-2 and PhrANTH2 were found to be low (Kin = 2.68 μl/(g×min)) and very low (Kin = 0.18 μl/(g×min)), respectively. All three quorum sensing peptides were metabolically stable in plasma (in vitro) during the experimental time frame and no significant brain efflux was observed. Initial tissue distribution data showed remarkably high liver accumulation of BIP-2 as well. Our results thus support the potential role of some quorum sensing peptides in different neurological disorders, thereby enlarging our knowledge about the microbiome-brain axis

M & L Jaargang 28/3

Sofie De Leeuw De Sint-Leonarduskerk van Zoutleeuw: kunstschrijn van Brabant.Dat de indrukwekkende sacramentstoren van Zoutleeuw maar één van de vele kunstschatten is van de rijke Sint-Leonarduskerk, wordt door Sofie De Leeuw kort geschetst.Dieter Nuytten De inventie van de sacramentstoren van Zoutleeuw: het oeuvre van Cornelis Floris en de artistieke Nederlanden tijdens de renaissance in de 16de eeuw. [The invention of the Zoutleeuw sacrament tower and the works of Cornelis Floris in the Low Countries art history of 16th century renaissance.]Dieter Nuytten situeert de sacramentstoren van Cornelis Floris binnen de noordelijke renaissance van de 16de eeuw en in het artistieke oeuvre van deze kunstenaar. Cornelis Floris als echte duivel-doet-al, toen uomo universalis genoemd, overschreed met ogenschijnlijk gemak de grenzen van de tot dan toe nauw omschreven ambachten en waagde zich zonder schroom zowel aan architectuur als aan tekeningen, drukwerken en beeldhouwwerken.Valérie Herremans De sacramentstoren als blikvanger in het historische kerkinterieur. [The sacraments tower as an eye-catcher in the historical church interior.]De merkwaardige ontwikkeling van de kleine pyxis, een bescheiden eucharistiedoosje, tot de overweldigende creatie van de Leeuwse sacramentstoren wordt door Valérie Herremans niet alleen vanuit zijn specifieke functie, maar ook vanuit een contextuele invalshoek belicht.Christina Ceulemans De iconografie van de sacramentstoren van Zoutleeuw: een grootse hulde aan het Heilig Sacrament. [The Zoutleeuw sacrament towers iconography: a magnificent hymn to the blessed sacraments.]Niet minder dan 180 beelden gaven, soms node, hun identiteit prijs aan Christina Ceulemans, die de voorstellingen beschrijft als een huldeprocessie aan de eucharistie. Dat een dergelijk ingewikkeld programma werd opgesteld door erudiete kerkgeleerden staat voor haar buiten kijf.Jan Verbeke en Jacques Vereecke Bouwtechniek van de toren. [Building technique of the sacraments tower.]Het gedetailleerde contract tussen Cornelis Floris en de mecenas Maarten Van Wilre levert precieze gegevens op over bouwtechniek en materialen. Toch kon het ervaren oog van de restaurateurs Jacques Vereecke en Jan Verbeke tal van andere bouwspecifieke technieken ontdekken, waarbij het spaarzaam omgaan met het dure materiaal en het onmiskenbare vakmanschap van dit goed georganiseerd atelier de leidraad bleken.Het petrografisch onderzoek van Francis Tourneur bevestigt Cornelis Floris aandacht voor de juiste materiaalkeuze.Summar