The impact of growth promoters on muscle growth and the potential consequences for meat quality

To meet the demands of increased global meat consumption, animal production systems will have to become more efficient, or at least maintain the current efficiency utilizing feed ingredients that are not also used for human consumption. Use of growth promoters is a potential option for increasing production animal feed efficiency and increased muscle growth. The objective of this manuscript is to describe the mechanisms by which the growth promoters, beta-adrenergic agonists and growth hormone, mediate their effects, with specific consideration of the aspects which have implications for meat quality.The work described in this manuscript was supported by a BBSRC LINK Zoetis grant, number BB/J005320/1, as well as a BBSRC CASE PhD studentship awarded to David Brown and Krystal Hemmings and a PhD scholarship awarded to Molebeledi HD Mareko by the Botswana College of Agricultur

Motivation and treatment engagement intervention trial (MotivaTe-IT): The effects of motivation feedback to clinicians on treatment engagement in patients with severe mental illness

Background: Treatment disengagement and non-completion poses a major problem for the successful treatment of patients with severe mental illness. Motivation for treatment has long been proposed as a major determinant of treatment engagement, but exact mechanisms remain unclear. This current study serves three purposes: 1) to determine whether a feedback intervention based on the patients' motivation for treatment is effective at improving treatment engagement (TE) of severe mentally ill patients in outpatient psychiatric treatment, 2) to gather insight into motivational processes and pos

Global diversity of enterococci and description of 18 novel species

Bacteria of the genus Enterococcus colonize the guts of diverse animals. Some species have acquired multiple antibiotic resistances on top of a high level of intrinsic resistance and have emerged as leading causes of hospital-associated infection. Although clinical isolates of enterococcal species E. faecalis and E. faecium have been studied with respect to their antibiotic resistances and infection pathogenesis, comparatively little is known about the biology of enterococci in their natural context of the guts of humans and other land animals, including arthropods and other invertebrates. Importantly, little is also known about the global pool of genes already optimized for expression in an enterococcal background with the potential to be readily acquired by hospital adapted strains of E. faecalis and E. faecium , known facile exchangers of mobile genetic elements. We therefore undertook a global study designed to reach into maximally diverse habitats, to establish a first approximation of the genetic diversity of enterococci on Earth. Presumptive enterococci from over 900 diverse specimens were initially screened by PCR using a specific reporter gene that we found to accurately reflect genomic diversity. The genomes of isolates exceeding an operationally set threshold for diversity were then sequenced in their entirety and analyzed. This provided us with data on the global occurrence of many known enterococcal species and their association with various hosts and ecologies and identified 18 novel species expanding the diversity of the genus Enterococcus by over 25%. The 18 novel enterococcal species harbor a diverse array of genes associated with toxins, detoxification, and resource acquisition that highlight the capacity of the enterococci to acquire and adapt novel functions from diverse gut environments. In addition to the discovery and characterization of new species, this expanded diversity permitted a higher resolution analysis of the phylogenetic structure of the Enterococcus genus, including identification of distinguishing features of its 4 deeply rooted clades and genes associated with range expansion such as B-vitamin biosynthesis and flagellar motility. Collectively, this work provides an unprecedentedly broad and deep view of the genus Enterococcus , along with new insights into their potential threat to human health

Global diversity of enterococci and description of 18 previously unknown species

Enterococci are gut microbes of most land animals. Likely appearing first in the guts of arthropods as they moved onto land, they diversified over hundreds of millions of years adapting to evolving hosts and host diets. Over 60 enterococcal species are now known. Two species, Enterococcus faecalis and Enterococcus faecium, are common constituents of the human microbiome. They are also now leading causes of multidrug-resistant hospital-associated infection. The basis for host association of enterococcal species is unknown. To begin identifying traits that drive host association, we collected 886 enterococcal strains from widely diverse hosts, ecologies, and geographies. This identified 18 previously undescribed species expanding genus diversity by >25%. These species harbor diverse genes including toxins and systems for detoxification and resource acquisition. Enterococcus faecalis and E. faecium were isolated from diverse hosts highlighting their generalist properties. Most other species showed a more restricted distribution indicative of specialized host association. The expanded species diversity permitted the Enterococcus genus phylogeny to be viewed with unprecedented resolution, allowing features to be identified that distinguish its four deeply rooted clades, and the entry of genes associated with range expansion such as B-vitamin biosynthesis and flagellar motility to be mapped to the phylogeny. This work provides an unprecedentedly broad and deep view of the genus Enterococcus, including insights into its evolution, potential new threats to human health, and where substantial additional enterococcal diversity is likely to be found

Mass cytometry detects H3.3K27M-specific vaccine responses in diffuse midline glioma

BACKGROUNDPatients with diffuse midline gliomas (DMGs), including diffuse intrinsic pontine glioma (DIPG), have dismal outcomes. We previously described the H3.3K27M mutation as a shared neoantigen in HLA-A*02.01+, H3.3K27M+ DMGs. Within the Pacific Pediatric Neuro-Oncology Consortium, we assessed the safety and efficacy of an H3.3K27M-targeted peptide vaccine.METHODSNewly diagnosed patients, aged 3-21 years, with HLA-A*02.01+ and H3.3K27M+ status were enrolled in stratum A (DIPG) or stratum B (nonpontine DMG). Vaccine was administered in combination with polyinosinic-polycytidylic acid-poly-I-lysine carboxymethylcellulose (poly-ICLC) every 3 weeks for 8 cycles, followed by once every 6 weeks. Immunomonitoring and imaging were performed every 3 months. Imaging was centrally reviewed. Immunological responses were assessed in PBMCs using mass cytometry.RESULTSA total of 19 patients were enrolled in stratum A (median age,11 years) and 10 in stratum B (median age, 13 years). There were no grade-4 treatment-related adverse events (TRAEs). Injection site reaction was the most commonly reported TRAE. Overall survival (OS) at 12 months was 40% (95% CI, 22%-73%) for patients in stratum A and 39% (95% CI, 16%-93%) for patients in stratum B. The median OS was 16.1 months for patients who had an expansion of H3.3K27M-reactive CD8+ T cells compared with 9.8 months for their counterparts (P = 0.05). Patients with DIPG with below-median baseline levels of myeloid-derived suppressor cells had prolonged OS compared with their counterparts (P < 0.01). Immediate pretreatment dexamethasone administration was inversely associated with H3.3K27M-reactive CD8+ T cell responses.CONCLUSIONAdministration of the H3.3K27M-specific vaccine was well tolerated. Patients with H3.3K27M-specific CD8+ immunological responses demonstrated prolonged OS compared with nonresponders.TRIAL REGISTRATIONClinicalTrials.gov NCT02960230.FUNDINGThe V Foundation, the Pacific Pediatric Neuro-Oncology Consortium Foundation, the Pediatric Brain Tumor Foundation, the Mithil Prasad Foundation, the MCJ Amelior Foundation, the Anne and Jason Farber Foundation, Will Power Research Fund Inc., the Isabella Kerr Molina Foundation, the Parker Institute for Cancer Immunotherapy, and the National Institute of Neurological Disorders and Stroke (NINDS), NIH (R35NS105068)