Hauliers’ perceptions and attitudes towards farm animal welfare could influence the operational and logistics practices in sheep transport

survey of Mexico-based sheep hauliers was conducted in order to investigate perceptions and attitudes toward farm animal welfare (FAW) and their influence on operational and logistic practices (OLPs) in sheep transportation. The statistical analysis consisted in the application of 2-factor analyses (OLP and animal welfare attitudes), additionally a cluster analysis; the latter allowed a segmentation of hauliers according to their attitudes and OLP. The factor analysis gave 3 OLP factors: logistic issues, economic losses, and welfare losses. In the case of factor analyses about animal welfare attitudes, we obtained 4 factors: training and regulations, animal needs, welfare improvement, and sensibility. The cluster analysis of this study showed the existence of 3 haulier profiles; these were “efficient and concerned,” “efficient and not concerned,” and “not efficient and concerned.” Our results showed that hauliers’ perceptions had a clear influence on the performance of their operative and logistic activities during the sheep transportation. This study highlights the individual hauliers’ risk factors which can be considered to improve not only animal welfare but also indicates the need to consider the transportation as a whole because of potential factor combinations and confusions. The attitudes of sheep hauliers toward FAWare a strategic component that requires being considered when hauliers are trained. If it can be shown that modifying hauliers’ attitudes leads to improved OLP, then there is an opportunity to develop specific training programs to modify certain haulier’s animal welfare attitudes, with a subsequent improvement of sheep welfar

The Cancer Genomics Resource List 2014

Context.— Genomic sequencing for cancer is offered by commercial for-profit laboratories, independent laboratory networks, and laboratories in academic medical centers and integrated health networks. The variability among the tests has created a complex, confusing environment. Objective.— To address the complexity, the Personalized Health Care (PHC) Committee of the College of American Pathologists proposed the development of a cancer genomics resource list (CGRL). The goal of this resource was to assist the laboratory pathology and clinical oncology communities. Design.— The PHC Committee established a working group in 2012 to address this goal. The group consisted of site-specific experts in cancer genetic sequencing. The group identified current next-generation sequencing (NGS)–based cancer tests and compiled them into a usable resource. The genes were annotated by the working group. The annotation process drew on published knowledge, including public databases and the medical literature. Results.— The compiled list includes NGS panels offered by 19 laboratories or vendors, accompanied by annotations. The list has 611 different genes for which NGS-based mutation testing is offered. Surprisingly, of these 611 genes, 0 genes were listed in every panel, 43 genes were listed in 4 panels, and 54 genes were listed in 3 panels. In addition, tests for 393 genes were offered by only 1 or 2 institutions. Table 1 provides an example of gene mutations offered for breast cancer genomic testing with the annotation as it appears in the CGRL 2014. Conclusions.— The final product, referred to as the Cancer Genomics Resource List 2014, is available as supplemental digital content

An Anti-Inflammatory Role for Carbon Monoxide and Heme Oxygenase-1 in Chronic Th2-Mediated Murine Colitis

Cigarette smoking is a significant environmental factor in the human inflammatory bowel diseases, remarkably, conferring protection in ulcerative colitis. We previously demonstrated that a prominent component of cigarette smoke, CO, suppresses Th17-mediated experimental colitis in IL-10−/− mice through a heme oxygenase (HO)-1–dependent pathway. In this study, homeostatic and therapeutic effects of CO and HO-1 were determined in chronic colonic inflammation in TCR-α–deficient (−/−) mice, in which colitis is mediated by Th2 cytokines, similar to the cytokine milieu described in human ulcerative colitis. TCRα−/− mice exposed to CO or treated with the pharmacologic HO-1 inducer cobalt protoporphyrin demonstrated amelioration of active colitis. CO and cobalt protoporphyrin suppressed colonic IL-1β, TNF, and IL-4 production, whereas IL-10 protein secretion was increased. CO induced IL-10 expression in macrophages and in vivo through an HO-1–dependent pathway. Bacterial products regulate HO-1 expression in macrophages through MyD88- and IL-10–dependent pathways. CO exposure and pharmacologic HO-1 induction in vivo resulted in increased expression of HO-1 and IL-10 in CD11b+ lamina propria mononuclear cells. Moreover, induction of the IL-10 family member IL-22 was demonstrated in CD11b− lamina propria mononuclear cells. In conclusion, CO and HO-1 induction ameliorated active colitis in TCRα−/− mice, and therapeutic effects correlated with induction of IL-10. This study provides further evidence that HO-1 mediates an important homeostatic pathway with pleiotropic anti-inflammatory effects in different experimental models of colitis and that targeting HO-1, therefore, is a potential therapeutic strategy in human inflammatory bowel diseases

CXCR4-expressing Mist1\u3csup\u3e+\u3c/sup\u3e progenitors in the gastric antrum contribute to gastric cancer development

Mist1 was recently shown to identify a discrete population of stem cells within the isthmus of the oxyntic gland within the gastric corpus. Chief cells at the base of the gastric corpus also express Mist1. The relevance of Mist1 expression as a marker of specific cell populations within the antral glands of the distal stomach, however, is unknown. Using Mist1-CreERT mice, we revealed that Mist1+ antral cells, distinct from the Mist1+ population in the corpus, comprise long-lived progenitors that reside within the antral isthmus above Lgr5+ or CCK2R+ cells. Mist1+ antral progenitors can serve as an origin of antral tumors induced by loss of Apc or MNU treatment. Mist1+ antral progenitors, as well as other antral stem/progenitor population, express Cxcr4, and are located in close proximity to Cxcl12 (the Cxcr4 ligand)-expressing endothelium. During antral carcinogenesis, there is an expansion of Cxcr4+ epithelial cells as well as the Cxcl12+ perivascular niche. Deletion of Cxcl12 in endothelial cells or pharmacological blockade of Cxcr4 inhibits antral tumor growth. Cxcl12/Cxcr4 signaling may be a potential therapeutic target

Altered Macrophage Function Contributes to Colitis in Mice Defective in the Phosphoinositide-3 Kinase Subunit p110δ

Innate immune responses are crucial for host defense against pathogens, but need to be tightly regulated to prevent chronic inflammation. Initial characterization of mice with a targeted inactivating mutation in the p110d subunit of phosphoinositide 3-kinase (PI3K p110δD910A/D910A) reveal defects in B- and T-cell signaling and chronic colitis. Here, we further characterize features of inflammatory bowel diseases (IBD) in these mice and investigate underlying innate immune defects

Molecular Biomarkers for the Evaluation of Colorectal Cancer: Guideline From the American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology, and American Society of Clinical Oncology

OBJECTIVES: - To develop evidence-based guideline recommendations through a systematic review of the literature to establish standard molecular biomarker testing of colorectal cancer (CRC) tissues to guide epidermal growth factor receptor (EGFR) therapies and conventional chemotherapy regimens. METHODS: - The American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology, and American Society of Clinical Oncology convened an expert panel to develop an evidence-based guideline to establish standard molecular biomarker testing and guide therapies for patients with CRC. A comprehensive literature search that included more than 4,000 articles was conducted. RESULTS: - Twenty-one guideline statements were established. CONCLUSIONS: - Evidence supports mutational testing for EGFR signaling pathway genes, since they provide clinically actionable information as negative predictors of benefit to anti-EGFR monoclonal antibody therapies for targeted therapy of CRC. Mutations in several of the biomarkers have clear prognostic value. Laboratory approaches to operationalize CRC molecular testing are presented

Molecular Biomarkers for the Evaluation of Colorectal Cancer

Objectives: To develop evidence-based guideline recommendations through a systematic review of the literature to establish standard molecular biomarker testing of colorectal cancer (CRC) tissues to guide epidermal growth factor receptor (EGFR) therapies and conventional chemotherapy regimens

Mist1 Expressing Gastric Stem Cells Maintain the Normal and Neoplastic Gastric Epithelium and Are Supported by a Perivascular Stem Cell Niche

The regulation and stem cell origin of normal and neoplastic gastric glands are uncertain. Here, we show that Mist1 expression marks quiescent stem cells in the gastric corpus isthmus. Mist1+ stem cells serve as a cell-of-origin for intestinal-type cancer with the combination of Kras and Apc mutation and for diffuse-type cancer with the loss of E-cadherin. Diffuse-type cancer development is dependent on inflammation mediated by Cxcl12+ endothelial cells and Cxcr4+ gastric innate lymphoid cells (ILCs). These cells form the perivascular gastric stem cell niche, and Wnt5a produced from ILCs activates RhoA to inhibit anoikis in the E-cadherin-depleted cells. Targeting Cxcr4, ILCs, or Wnt5a inhibits diffuse-type gastric carcinogenesis, providing targets within the neoplastic gastric stem cell niche

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN