The Wae to repair: prostaglandin E2 (PGE2) triggers intestinal wound repair

Accurate wound repair is a crucial step to protect organisms from environmental damage, for example infection and toxin exposure. In this issue of The EMBO Journal, Miyoshi et al (2017) have elucidated a new mechanism underpinning this process within the intestine where mesenchymal prostaglandin E2 produced following damage drives intestinal regeneration

Study Of The Ability To Detect Humor In Visual Images By 2-5 Year Olds

Problem Understanding the impact that humor can have as a form of therapy has been studied mostly in relation to mental and spiritual healing. As a result, little focus has been given to understanding the types of humor and how one’s understanding of and appreciation for types of humor develop over time. Gaining an understanding of humor development is important due to discoveries that the use of humor is a great intervention tool when working with children. Nevertheless, the use of pictures (with humor) is often used within speech therapy sessions, but seldom used correctly due to the lack of understanding of humor development in children. Method This study was carried out by individually removing each participant from the classroom A total of 12 pictures were presented to each child (i.e. three groups of four pictures) via the iPad. When the first photo grid was presented, the experimenter directed the participant’s attention to the reference picture, and created a story line to explain the reference picture. Then the experimenter directed the participant’s attention to the other three pictures by saying, “…Point to the picture that makes you laugh the most.” The participant then selected from the three alternatives, with the expected selection to be the one of incongruency. Each participant was given a range of 0 to 90 seconds to observe each photo grid and select a response. Results A Pearson product-moment correlation coefficient showed that there was a positive correlation on all of the dependent variables (types of humor) and some independent variables (i.e. language and gender), as well as between gender and hyperbolic humor type. Repeated measures ANOVA resulted in significant difference in participants’ ability to correctly identify incongruent elements in types of humor based on gender, language and age. A multiple regression analysis was done and resulted in there being a high level of significance for the independent variables age grouping, gender and language skills to operate as successful predictors of overall correct identification of incongruence in the dependent variables. Conclusion It is important to take into consideration the age, gender and type of humor as well as the language skill level of each client, because these aspects could have a major impact on the success or failure of a session and overall work with a client

Application of a mixed variational higher order plate theory towards understanding the deformation behavior of hybrid laminates

Hybrid laminates containing an elastomer layer in addition to fiber reinforced polymer as well as metal layers have been found beneficial in compensating issues frequently found with traditional fiber metal laminates. Commonly used equivalent single-layer shell and plate theories, however, are unable to account for the strong heterogeneous stiffness distribution of the constituents within the laminate. Furthermore, the transverse shear and normal deformations in the elastomer layer are expected to significantly influence the deformation of the neighboring laminae. An accurate depiction of these transverse stresses requires a multi-layer shell theory as opposed to commonly used single-layer formulations. Hence, a higher order mixed variational plate theory is applied in order to study and predict the mechanical behavior of such laminates, especially on a structural level where the computational effort forbids the use of a three dimensional continuum formulation

Microsatellite instability, KRAS mutations and cellular distribution of TRAIL-receptors in early stage colorectal cancer.

Thus, we evaluated the immunofluorescence pattern of TRAIL-receptors and E-cadherin to assess the fraction of membrane-bound TRAIL-receptors in 231 selected patients with early-stage CRC undergoing surgical treatment only. Moreover, we investigated whether membrane staining for TRAIL-receptors as well as the presence of KRAS mutations or of microsatellite instability (MSI) had an effect on survival and thus a prognostic effect. The fact that the receptors for the TNF-related apoptosis inducing ligand (TRAIL) are almost invariably expressed in colorectal cancer (CRC) represents the rationale for the employment of TRAIL-receptors targeting compounds for the therapy of patients affected by this tumor. Yet, first reports on the use of these bioactive agents provided disappointing results. We therefore hypothesized that loss of membrane-bound TRAIL-R might be a feature of some CRC and that the evaluation of membrane staining rather than that of the overall expression of TRAIL-R might predict the response to TRAIL-R targeting compounds in this tumor. As expected, almost all CRC samples stained positive for TRAIL-R1 and 2. Instead, membrane staining for these receptors was positive in only 71% and 16% of samples respectively. No correlation between KRAS mutation status or MSI-phenotype and prognosis could be detected. TRAIL-R1 staining intensity correlated with survival in univariate analysis, but only membranous staining of TRAIL-R1 and TRAIL-R2 on cell membranes was an independent predictor of survival (cox multivariate analysis: TRAIL-R1: p = 0.019, RR 2.06[1.12-3.77]; TRAIL-R2: p = 0.033, RR 3.63[1.11-11.84]). In contrast to the current assumptions, loss of membrane staining for TRAIL-receptors is a common feature of early stage CRC which supersedes the prognostic significance of their staining intensity. Failure to achieve therapeutic effects in recent clinical trials using TRAIL-receptors targeting compounds might be due to insufficient selection of patients bearing tumors with membrane-bound TRAIL-receptors

A multidimensional metabolomics workflow to image biodistribution and evaluate pharmacodynamics in adult zebrafish

An integrated evaluation of the tissue distribution and pharmacodynamic properties of a therapeutic is essential for successful translation to the clinic. To date, however, cost-effective methods to measure these parameters at the systems level in model organisms are lacking. Here, we introduce a multidimensional workflow to evaluate drug activity that combines mass spectrometry-based imaging, absolute drug quantitation across different biological matrices, in vivo isotope tracing and global metabolome analysis in the adult zebrafish. As a proof of concept, we quantitatively determined the whole-body distribution of the anti-rheumatic agent hydroxychloroquine sulfate (HCQ) and measured the systemic metabolic impacts of drug treatment. We found that HCQ distributed to most organs in the adult zebrafish 24 h after addition of the drug to water, with the highest accumulation of both the drug and its metabolites being in the liver, intestine and kidney. Interestingly, HCQ treatment induced organ-specific alterations in metabolism. In the brain, for example, HCQ uniquely elevated pyruvate carboxylase activity to support increased synthesis of the neuronal metabolite, N-acetylaspartate. Taken together, this work validates a multidimensional metabolomics platform for evaluating the mode of action of a drug and its potential off-target effects in the adult zebrafish. This article has an associated First Person interview with the first author of the paper