SCAR is a primary regulator of Arp2/3-dependent morphological events in Drosophila

The Arp2/3 complex and its activators, Scar/WAVE and Wiskott-Aldrich Syndrome protein (WASp), promote actin polymerization in vitro and have been proposed to influence cell shape and motility in vivo. We demonstrate that the Drosophila Scar homologue, SCAR, localizes to actin-rich structures and is required for normal cell morphology in multiple cell types throughout development. In particular, SCAR function is essential for cytoplasmic organization in the blastoderm, axon development in the central nervous system, egg chamber structure during oogenesis, and adult eye morphology. Highly similar developmental requirements are found for subunits of the Arp2/3 complex. In the blastoderm, SCAR and Arp2/3 mutations result in a reduction in the amount of cortical filamentous actin and the disruption of dynamically regulated actin structures. Remarkably, the single Drosophila WASp homologue, Wasp, is largely dispensable for these numerous Arp2/3-dependent functions, whereas SCAR does not contribute to cell fate decisions in which Wasp and Arp2/3 play an essential role. These results identify SCAR as a major component of Arp2/3-dependent cell morphology during Drosophila development and demonstrate that the Arp2/3 complex can govern distinct cell biological events in response to SCAR and Wasp regulation

Classifying Medulloblastoma Subgroups Based on Small, Clinically Achievable Gene Sets

As treatment protocols for medulloblastoma (MB) are becoming subgroup-specific, means for reliably distinguishing between its subgroups are a timely need. Currently available methods include immunohistochemical stains, which are subjective and often inconclusive, and molecular techniques—e.g., NanoString, microarrays, or DNA methylation assays—which are time-consuming, expensive and not widely available. Quantitative PCR (qPCR) provides a good alternative for these methods, but the current NanoString panel which includes 22 genes is impractical for qPCR. Here, we applied machine-learning–based classifiers to extract reliable, concise gene sets for distinguishing between the four MB subgroups, and we compared the accuracy of these gene sets to that of the known NanoString 22-gene set. We validated our results using an independent microarray-based dataset of 92 samples of all four subgroups. In addition, we performed a qPCR validation on a cohort of 18 patients diagnosed with SHH, Group 3 and Group 4 MB. We found that the 22-gene set can be reduced to only six genes (IMPG2, NPR3, KHDRBS2, RBM24, WIF1, and EMX2) without compromising accuracy. The identified gene set is sufficiently small to make a qPCR-based MB subgroup classification easily accessible to clinicians, even in developing, poorly equipped countries

TMPRSS2/ERG Promotes Epithelial to Mesenchymal Transition through the ZEB1/ZEB2 Axis in a Prostate Cancer Model

Prostate cancer is the most common non-dermatologic malignancy in men in the Western world. Recently, a frequent chromosomal aberration fusing androgen regulated TMPRSS2 promoter and the ERG gene (TMPRSS2/ERG) was discovered in prostate cancer. Several studies demonstrated cooperation between TMPRSS2/ERG and other defective pathways in cancer progression. However, the unveiling of more specific pathways in which TMPRSS2/ERG takes part, requires further investigation. Using immortalized prostate epithelial cells we were able to show that TMPRSS2/ERG over-expressing cells undergo an Epithelial to Mesenchymal Transition (EMT), manifested by acquisition of mesenchymal morphology and markers as well as migration and invasion capabilities. These findings were corroborated in vivo, where the control cells gave rise to discrete nodules while the TMPRSS2/ERG-expressing cells formed malignant tumors, which expressed EMT markers. To further investigate the general transcription scheme induced by TMPRSS2/ERG, cells were subjected to a microarray analysis that revealed a distinct EMT expression program, including up-regulation of the EMT facilitators, ZEB1 and ZEB2, and down-regulation of the epithelial marker CDH1(E-Cadherin). A chromatin immunoprecipitation assay revealed direct binding of TMPRSS2/ERG to the promoter of ZEB1 but not ZEB2. However, TMPRSS2/ERG was able to bind the promoters of the ZEB2 modulators, IL1R2 and SPINT1. This set of experiments further illuminates the mechanism by which the TMPRSS2/ERG fusion affects prostate cancer progression and might assist in targeting TMPRSS2/ERG and its downstream targets in future drug design efforts

The influence of the interpersonal dimension on mentors' perception of the effectiveness of mentoring

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PEDAGOGICAL PARTNERSHIP: A MINDFULNESS PERSPECTIVE

This case study is based on the phenomenological-qualitative paradigm. Its purpose is to examine how may mindfulness practices can help lead a Pedagogical Partnership in teacher training colleges. A Pedagogical Partnership is a partnership focusing on learning-teaching processes between faculty and students at academies. Mindfulness is a method of achieving conscious attention to the present, in a deliberately non-judgmental way. The participants in this research were three lecturers and three students, who were not involved in a teacher-student relationship. Our research tools included lesson observations written by students; reflective dialogue held between these lecturers and students at the end of each lesson; reflective diaries written by the lecturers; and semi-structured in-depth interviews at the end of the semester. The collected data was analyzed, using a qualitative content analysis method, based on open content analysis. The research findings indicate that lecturers described their Pedagogical Partnership experiences with the use of four concepts of mindfulness principles Compassion; Beginner’s Mind; Non-judgmental State and Delay of Response; Non-Attachment. The analysis of the students\u27 data revealed only two concepts of mindfulness Non-judgmental State and Delay of Response and Non-Attachment. Institutions of higher education that operate Pedagogical Partnership programs may consider incorporating mindfulness practices into their programs. They may greatly benefit for all partners both from the personal and the professional aspects

Improved ICU mortality prediction based on SOFA scores and gastrointestinal parameters.

BACKGROUND:The Sequential Organ Failure Assessment (SOFA) score is commonly used in ICUs around the world, designed to assess the severity of the patient's clinical state based on function/dysfunction of six major organ systems. The goal of this work is to build a computational model to predict mortality based on a series of SOFA scores. In addition, we examined the possibility of improving the prediction by incorporating a new component designed to measure the performance of the gastrointestinal system, added to the other six components. METHODS:In this retrospective study, we used patients' three latest SOFA scores recorded during an individual ICU stay as input to different machine learning models and ensemble learning models. We added three validated parameters representing gastrointestinal failure. Among others, we used classification models such as Support Vector Machines (SVMs), Neural Networks, Logistic Regression and a penalty function used to increase model robustness in regard to certain extreme cases, which may be found in ICU population. We used the Area under Curve (AUC) performance metric to examine performance. RESULTS:We found an ensemble model of linear and logistic regression achieves a higher AUC compared related works in past years. After incorporating the gastrointestinal failure score along with the penalty function, our best performing ensemble model resulted in an additional improvement in terms of AUC metrics. We implemented and compared 36 different models that were built using both the information from the SOFA score as well as that of the gastrointestinal system. All compared models have approximately similar and relatively large AUC (between 0.8645 and 0.9146) with the best results are achieved by incorporating the gastrointestinal parameters into the prediction models. CONCLUSIONS:Our findings indicate that gastrointestinal parameters carry significant information as a mortality predictor in addition to the conventional SOFA score. This information improves the predictive power of machine learning models by extending the SOFA to include information related to gastrointestinal organ system. The described method improves mortality prediction by considering the dynamics of the extended SOFA score. Although tested on a limited data set, the results' stability across different models suggests robustness in real-time use

One-Class FMRI-Inspired EEG Model for Self-Regulation Training.

Recent evidence suggests that learned self-regulation of localized brain activity in deep limbic areas such as the amygdala, may alleviate symptoms of affective disturbances. Thus far self-regulation of amygdala activity could be obtained only via fMRI guided neurofeedback, an expensive and immobile procedure. EEG on the other hand is relatively inexpensive and can be easily implemented in any location. However the clinical utility of EEG neurofeedback for affective disturbances remains limited due to low spatial resolution, which hampers the targeting of deep limbic areas such as the amygdala. We introduce an EEG prediction model of amygdala activity from a single electrode. The gold standard used for training is the fMRI-BOLD signal in the amygdala during simultaneous EEG/fMRI recording. The suggested model is based on a time/frequency representation of the EEG data with varying time-delay. Previous work has shown a strong inhomogeneity among subjects as is reflected by the models created to predict the amygdala BOLD response from EEG data. In that work, different models were constructed for different subjects. In this work, we carefully analyzed the inhomogeneity among subjects and were able to construct a single model for the majority of the subjects. We introduce a method for inhomogeneity assessment. This enables us to demonstrate a choice of subjects for which a single model could be derived. We further demonstrate the ability to modulate brain-activity in a neurofeedback setting using feedback generated by the model. We tested the effect of the neurofeedback training by showing that new subjects can learn to down-regulate the signal amplitude compared to a sham group, which received a feedback obtained by a different participant. This EEG based model can overcome substantial limitations of fMRI-NF. It can enable investigation of NF training using multiple sessions and large samples in various locations

OCT4 induces long-lived dedifferentiated kidney progenitors poised to redifferentiate in 3D kidney spheroids

Upscaling of kidney epithelial cells is crucial for renal regenerative medicine. Nonetheless, the adult kidney lacks a distinct stem cell hierarchy, limiting the ability to long-term propagate clonal populations of primary cells that retain renal identity. Toward this goal, we tested the paradigm of shifting the balance between differentiation and stemness in the kidney by introducing a single pluripotency factor, OCT4. Here we show that ectopic expression of OCT4 in human adult kidney epithelial cells (hKEpC) induces the cells to dedifferentiate, stably proliferate, and clonally emerge over many generations. Control hKEpC dedifferentiate, assume fibroblastic morphology, and completely lose clonogenic capacity. Analysis of gene expression and histone methylation patterns revealed that OCT4 represses the HNF1B gene module, which is critical for kidney epithelial differentiation, and concomitantly activates stemness-related pathways. OCT4-hKEpC can be long-term expanded in the dedifferentiated state that is primed for renal differentiation. Thus, when expanded OCT4-hKEpC are grown as kidney spheroids (OCT4-kSPH), they reactivate the HNF1B gene signature, redifferentiate, and efficiently generate renal structures in vivo. Hence, changes occurring in the cellular state of hKEpC following OCT4 induction, long-term propagation, and 3D aggregation afford rapid scale-up technology of primary renal tissue-forming cells