Bilingual, Digital, Audio-Visual Training Modules Improve Technical Knowledge of Feedlot and Dairy Workers
In: Online journal of rural research & policy, Band 5, Heft 7
ISSN: 1936-0487
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In: Online journal of rural research & policy, Band 5, Heft 7
ISSN: 1936-0487
Many human foodborne illnesses are caused by pathogens commonly harbored by food animals. Escherichia coli O157 is one of these pathogens commonly isolated from beef cattle feces and can enter the food chain at harvest. In addition to the human health concerns, this pathogen has important economic implications. Costly recalls of beef products and loss of consumer confidence associated with outbreaks of foodborne illness can affect profitability on many levels of production. In the past 10 years, E. coli O157 has cost the beef industry an estimated $2.67 billion. A portion of this expense is allocated to government and industry research. Methods to intervene and reduce the opportunity of these pathogens to enter the food chain have been tested and implemented both pre- and postharvest. The focus of this experiment was to evaluate the effectiveness of a novel vaccine technology to reduce E. coli O157 shedding in feeder cattle prior to harvest. A relatively new vaccine technology developed by Epitopix (Wilmar, MN) targets pathogenic bacteria based on their inherent requirement for iron. Vaccines developed with this technology target siderophore receptor and porin proteins (SRP) of specific bacteria and disrupt their iron transport systems, which ultimately causes death of the organisms. Preliminary experiments have shown that SRP vaccines reduce fecal shedding of Salmonella Newport and E. coli O157 in experimentally infected mice. In two experiments involving experimentally infected cattle, an SRP vaccine for E. coli O157 reduced fecal shedding of the experimental strain of E. coli O157. Given the success of this vaccine in cattle challenged with E. coli O157, the objective of the current experiment was to test the efficacy of the E.coli O157 SRP vaccine in feedlot cattle naturally infected with E. coli O157.
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Funding Information: Conflict of interest SM has received honoraria and research funding from Novartis, Pfizer and Bristol-Myers Squibb (not related to this study). SAA has received research funding from Incyte. SB is a member of Member of the advisory board of Qiagen, Novartis, and Cepheid and has received research funding from Novartis, honoraria from Novartis, Qiagen, Cepheid, and Bristol-Myers Squibb and support from the National Health and Medical Research Council of Australia APP1117718 and APP1104425, the Ray and Shirl Norman Cancer Research Trust, and the Royal Adelaide Hospital Research Foundation. The other authors declare that they have no conflict of interest. Funding Information: Funding This work was supported by Academy of Finland (Grant No. 292605 and 287224), the Finnish Funding Agency for Innovation (Dnro 6113/31/2016), Finnish special governmental subsidy for health sciences, research and training, Signe and Ane Gyllenberg Foundation, Finnish Cultural Foundation, Nordic Cancer Union, Helsinki Institute of Life Science, Cancer Foundation Finland, Relander Foundation, Incyte Nordic Hematology grant, and Finnish Cancer Institute. Publisher Copyright: © 2020, The Author(s). ; Blast-phase chronic myeloid leukemia (BP-CML) is associated with additional chromosomal aberrations, RUNX1 mutations being one of the most common. Tyrosine kinase inhibitor therapy has only limited efficacy in BP-CML, and characterization of more defined molecular subtypes is warranted in order to design better treatment modalities for this poor prognosis patient group. Using whole-exome and RNA sequencing we demonstrate that PHF6 and BCORL1 mutations, IKZF1 deletions, and AID/RAG-mediated rearrangements are enriched in RUNX1mut BP-CML leading to typical mutational signature. On transcriptional level interferon and TNF signaling were deregulated in primary RUNX1mut CML cells and stem cell and B-lymphoid factors upregulated giving a rise to distinct phenotype. This was accompanied with the sensitivity of RUNX1mut blasts to CD19-CAR T cells in ex vivo assays. High-throughput drug sensitivity and resistance testing revealed leukemia cells from RUNX1mut patients to be highly responsive for mTOR-, BCL2-, and VEGFRinhibitors and glucocorticoids. These findings were further investigated and confirmed in CRISPR/Cas9-edited homozygous RUNX1−/− and heterozygous RUNX1−/mut BCR-ABL positive cell lines. Overall, our study provides insights into the pathogenic role of RUNX1 mutations and highlights personalized targeted therapy and CAR T-cell immunotherapy as potentially promising strategies for treating RUNX1mut BP-CML patients. ; Peer reviewed
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