Common marmoset (Callithrix jacchus) personality, subjective well-being, hair cortisol level and AVPR1a, OPRM1, and DAT genotypes

We studied personality, subjective well-being, and hair cortisol level, in common marmosets Callithrix jacchus, a small, cooperatively breeding New World monkey, by examining their associations with one another and genotypes. Subjects were 68 males and 9 females that lived in the RIKEN Center for Life Science Technologies. Personality and subjective well-being were assessed by keeper ratings on two questionnaires, hair samples were obtained to assay cortisol level and buccal swabs were used to assess AVPR1a, OPRM1 and DAT genotypes. Three personality domains—Dominance, Sociability, and Neuroticism—were identified. Consistent with findings in other species, Sociability and Neuroticism were related to higher and lower subjective well-being, respectively. Sociability was also associated with higher hair cortisol levels. The personality domains and hair cortisol levels were heritable and associated with genotypes: the short form of AVPR1a was associated with lower Neuroticism and the AA genotype of the A111T SNP of OPRM1 was related to lower Dominance, lower Neuroticism, and higher hair cortisol level. Some genetic associations were not in directions that one would expect given findings in other species. These findings provide insights into the proximate and ultimate bases of personality in common marmosets, other primates and humans

NUDT2 Disruption Elevates Diadenosine Tetraphosphate (Ap4A) and Down-Regulates Immune Response and Cancer Promotion Genes.

Regulation of gene expression is one of several roles proposed for the stress-induced nucleotide diadenosine tetraphosphate (Ap4A). We have examined this directly by a comparative RNA-Seq analysis of KBM-7 chronic myelogenous leukemia cells and KBM-7 cells in which the NUDT2 Ap4A hydrolase gene had been disrupted (NuKO cells), causing a 175-fold increase in intracellular Ap4A. 6,288 differentially expressed genes were identified with P < 0.05. Of these, 980 were up-regulated and 705 down-regulated in NuKO cells with a fold-change ≥ 2. Ingenuity® Pathway Analysis (IPA®) was used to assign these genes to known canonical pathways and functional networks. Pathways associated with interferon responses, pattern recognition receptors and inflammation scored highly in the down-regulated set of genes while functions associated with MHC class II antigens were prominent among the up-regulated genes, which otherwise showed little organization into major functional gene sets. Tryptophan catabolism was also strongly down-regulated as were numerous genes known to be involved in tumor promotion in other systems, with roles in the epithelial-mesenchymal transition, proliferation, invasion and metastasis. Conversely, some pro-apoptotic genes were up-regulated. Major upstream factors predicted by IPA® for gene down-regulation included NFκB, STAT1/2, IRF3/4 and SP1 but no major factors controlling gene up-regulation were identified. Potential mechanisms for gene regulation mediated by Ap4A and/or NUDT2 disruption include binding of Ap4A to the HINT1 co-repressor, autocrine activation of purinoceptors by Ap4A, chromatin remodeling, effects of NUDT2 loss on transcript stability, and inhibition of ATP-dependent regulatory factors such as protein kinases by Ap4A. Existing evidence favors the last of these as the most probable mechanism. Regardless, our results suggest that the NUDT2 protein could be a novel cancer chemotherapeutic target, with its inhibition potentially exerting strong anti-tumor effects via multiple pathways involving metastasis, invasion, immunosuppression and apoptosis

Sclerosing mesenteritis affecting the small and the large intestine in a male patient with non-Hodgkin lymphoma: a case presentation and review of the literature

<p>Abstract</p> <p>Introduction</p> <p>Sclerosing mesenteritis is a rare disease resembling a mesenteric tumour. We present here a case of sclerosing mesenteritis that affected both the large and the small intestine of the patient. Therapeutic and diagnostic issues are discussed.</p> <p>Case presentation</p> <p>A 62-year-old man with a history of non-Hodgkin lymphoma presented with fatigue, a palpable tender abdominal mass and clinical signs of progressing intestinal obstruction. The preoperative evaluation failed to prove recurrence of the lymphoma or any other definite diagnosis. A laparotomy was performed through a midline incision. The mesentery resembled a tumour-like thickened and fibrotic mass. Abundant, rigid intestinal loop adhesions were observed. Diffuse fibrotic infiltration of the ileum and of the sigmoid colon, which obviously affected the intestinal vascular supply, were identified. A right colectomy and partial sigmoidectomy were performed. Pathological evaluation revealed extensive myofibroblastic reaction of the mesentery with accompanying loci of fat necrosis and areas of inflammation. A diffuse fibrotic infiltration that focally showed a ground-glass appearance was observed. The post-operative course was complicated by respiratory insufficiency and infections and the patient died 2 months after the operation.</p> <p>Conclusion</p> <p>Sclerosing mesenteritis that affects both the small and the large intestine is extremely rare. The disease is characterized by myofibroblastic reaction, fat necrosis and diffuse fibrosis of the mesentery. Pathological confirmation may be required for definite diagnosis. If the disease is characterized by severe and diffuse fibrosis, then the application of surgical therapy may be problematic.</p

Crosstalk of carcinoembryonic antigen and transforming growth factor-β via their receptors: comparing human and canine cancer

There is accumulating evidence that the transforming growth factor beta (TGF-β) and nuclear factor kappa-B (NFκB) pathways are tightly connected and play a key role in malignant transformation in cancer. Immune infiltration by regulatory T- and B-lymphocytes (Tregs, Bregs) has recently gained increased attention for being an important source of TGF-β. There is a plethora of studies examining the pro-tumorigenic functions of carcinoembryonic antigen (CEA), but its receptor CEAR is far less studied. So far, there is a single connecting report that TGF-β also may signal through CEAR. The crosstalk between cancer tissues is further complicated by the expression of CEAR and TGF-β receptors in stromal cells, and implications of TGF-β in epithelial–mesenchymal transition. Furthermore, tumor-infiltrating Tregs and Bregs may directly instruct cancer cells by secreting TGF-β binding to their CEAR. Therefore, both TGF-β and CEA may act synergistically in breast cancer and cause disease progression, and NFκB could be a common crossing point between their signaling. CEAR, TGF-β1–3, TGF-β-R types I–III and NFκB class I and II molecules have an outstanding human–canine sequence identity, and only a canine CEA homolog has not yet been identified. For these reasons, the dog may be a valid translational model patient for investigating the crosstalk of the interconnected CEA and TGF-β networks

Paclitaxel Resistance and Multicellular Spheroid Formation Are Induced by Kallikrein-Related Peptidase 4 in Serous Ovarian Cancer Cells in an Ascites Mimicking Microenvironment

<div><p>High tumor kallikrein-related-peptidase 4 (KLK4) levels are associated with a poor outcome for women with serous epithelial ovarian cancer (EOC), for which peritoneal dissemination and chemoresistance are key events. To determine the role of KLK4 in these events, we examined KLK4-transfected SKOV-3 and endogenous KLK4 expressing OVCA432 cells in 3-dimensional (3D) suspension culture to mimic the ascites microenvironment. KLK4-SKOV-3 cells formed multicellular aggregates (MCAs) as seen in ascites, as did SKOV-3 cells treated with active KLK4. MCA formation was reduced by treatment with a KLK4 blocking antibody or the selective active site KLK4 sunflower trypsin inhibitor (SFTI-FCQR). KLK4-MCAs formed larger cancer cell foci in mesothelial cell monolayers than those formed by vector and native SKOV-3 cells, suggesting KLK4-MCAs are highly invasive in the peritoneal microenvironment. A high level of KLK4 is expressed by ascitic EOC cells compared to matched primary tumor cells, further supporting its role in the ascitic microenvironment. Interestingly, KLK4 transfected SKOV-3 cells expressed high levels of the KLK4 substrate, urokinase plasminogen activator (uPA), particularly in 3D-suspension, and high levels of both KLK4 and uPA were observed in patient cells taken from ascites. Importantly, the KLK4-MCAs were paclitaxel resistant which was reversed by SFTI-FCQR and to a lesser degree by the general serine protease inhibitor, Aprotinin, suggesting that in addition to uPA, other as yet unidentified substrates of KLK4 must be involved. Nonetheless, these data suggest that KLK4 inhibition, in conjunction with paclitaxel, may improve the outcome for women with serous epithelial ovarian cancer and high KLK4 levels in their tumors.</p> </div

Teacher Burnout and Contextual and Compositional Elements of School Environment

BACKGROUND: Teachers report higher levels of stress than most occupational groups. Burnout is a specific psychological condition that results from chronic job stress characterized by emotional exhaustion, low personal accomplishment, and depersonalization. This study considers associations between aspects of the school environment and teacher burnout. METHODS: Exploratory analysis of baseline data from a cluster randomized controlled trial of 40 schools and 2278 teachers in the United Kingdom. Multilevel methods were used to consider the associations between different compositional and contextual aspects of the school environment and teacher burnout. RESULTS: There was evidence for school effects on teacher burnout, evidenced by ICCs and likelihood ratio tests, supporting the association between school environment and teacher burnout. The factors most consistently associated with teacher burnout in our study were teachers' perceptions of the school's safety and support and student attitudes to learning. CONCLUSIONS: The school environment does influence teacher burnout. More research is needed to develop and test causal pathways between the school environment and teacher burnout, and to understand ecological and individual predictors of teacher burnout and the interaction between the two