A Pilot Study Investigating the Effect of the Supervision-Questioning-Feedback Model of Supervision on Stimulating Critical Thinking in Speech-Language Pathology Graduate Students

Purpose The purpose of this study was to investigate the effect of the supervision-questioning-feedback (SQF) model of supervision on critical thinking in graduate students studying speech-language pathology. The researchers hypothesized that students who were provided with the SQF model of supervision would score higher than students who received the non-SQF (NSQF) style of supervision on the selected critical thinking measures. Method Seventeen out of 24 first semester graduate students in speech-language pathology completing their on-site university-based clinical practicum experience consented to participate in the study. Of the 17 participating first semester students, 9 were randomly assigned to 1 of 3 SQF trained supervisors, and the other 8 were randomly assigned to 1 of 2 NSQF trained supervisors for the duration of 1 semester. Additionally, 3 out of 24 fourth semester graduate students completing their off-site externship experience and their supervisors consented to participate in the study. Four additional study participants served as independent SQF-trained raters charged with the task of analyzing video recorded student-supervisor conferences to determine whether the SQF model of supervision was being implemented. Prior to and at the conclusion of the clinical experience, all participating students completed two measures of critical thinking: (1) California Critical Thinking Skills Test (CCTST) and (2) two Simucase® clinical simulations. At the conclusion of the clinical experience, seventeen out of 20 participating students (11/12 SQF students and 6/8 NSQF students) completed a post-survey rating their supervisory experience . Results For participating first semester students, there were no overall statistically significant differences between SQF and NSQF groups as measured by pre to post completion of (1) CCTST (p=.544) and (2) two Simucase® clinical simulations (p=.781). The 3 participating fourth semester students who received the SQF model of supervision also showed no statistically significant differences on pre to post completion of the (1) CCTST (p=.827) and (2) two Simucase® virtual cases (p=.879). Results from SQF ratings revealed variability in the implementation of the SQF model across supervisors with a moderate level of inter-rater agreement. Results from post surveys completed by students showed that students preferred the SQF model of supervision over the NSQF model (p=.044). Conclusion Results from this preliminary study indicated that the SQF model did not influence the overall outcomes on the selected critical thinking measures. Student preference for the SQF model may support existing evidence that learning clinicians want to be actively engaged in the supervisory process. There were several limitations to this study including the small sample size, variability in the implementation of the SQF model across supervisors, sensitivity of the selected critical thinking measures, and timing of post-intervention procedures. Further investigation of the effects of SQF on students’ critical thinking is warranted

Chaperones rescue the energetic landscape of mutant CFTR at single molecule and in cell

Molecular chaperones are pivotal in folding and degradation of the cellular proteome but their impact on the conformational dynamics of near-native membrane proteins with disease relevance remains unknown. Here we report the effect of chaperone activity on the functional conformation of the temperature-sensitive mutant cystic fibrosis channel (Delta F508-CFTR) at the plasma membrane and after reconstitution into phospholipid bilayer. Thermally induced unfolding at 37 degrees C and concomitant functional inactivation of Delta F508-CFTR are partially suppressed by constitutive activity of Hsc70 and Hsp90 chaperone/co-chaperone at the plasma membrane and post-endoplasmic reticulum compartments in vivo, and at singlemolecule level in vitro, indicated by kinetic and thermodynamic remodeling of the mutant gating energetics toward its wild-type counterpart. Thus, molecular chaperones can contribute to functional maintenance of Delta F508-CFTR by reshaping the conformational energetics of its final fold, a mechanism with implication in the regulation of metastable ABC transporters and other plasma membrane proteins activity in health and diseases

Thermal induced structural and magnetic transformations in Fe_{73.5−x}Ce_{x=0,3,5,7}Si_{13.5}B_9Nb_3Cu_1 amorphous alloy

Structural and magnetic properties of amorphous and partly crystallized Fe_{73.5−x}Ce_{x=0,3,5,7}Si_{13.5}B_9Nb_3Cu_1 alloys, were analysed in the temperature ranging from RT to 800 °C with scanning calorimetry and magnetometry. The Fe(Si) and Fe(B) structures were identified and characterised with set of crystallization temperatures and activation energies. Also, Curie temperatures for amorphous and for crystalline structures were determined and analysed as functions of Ce content

NF-κB, stem cells and breast cancer: the links get stronger

Self-renewing breast cancer stem cells are key actors in perpetuating tumour existence and in treatment resistance and relapse. The molecular pathways required for their maintenance are starting to be elucidated. Among them is the transcription factor NF-κB, which is known to play critical roles in cell survival, inflammation and immunity. Recent studies indicate that mammary epithelial NF-κB regulates the self-renewal of breast cancer stem cells in a model of Her2-dependent tumourigenesis. We will describe here the NF-κB-activating pathways that are involved in this process and in which progenitor cells this transcription factor is actually activated

Identification of a Novel Calotropis procera Protein That Can Suppress Tumor Growth in Breast Cancer through the Suppression of NF-κB Pathway

10.1371/journal.pone.0048514PLoS ONE712

Withanolides-Induced Breast Cancer Cell Death Is Correlated with Their Ability to Inhibit Heat Protein 90

Withanolides are a large group of steroidal lactones found in Solanaceae plants that exhibit potential anticancer activities. We have previously demonstrated that a withanolide, tubocapsenolide A, induced cycle arrest and apoptosis in human breast cancer cells, which was associated with the inhibition of heat shock protein 90 (Hsp90). To investigate whether other withanolides are also capable of inhibiting Hsp90 and to analyze the structure-activity relationships, nine withanolides with different structural properties were tested in human breast cancer cells MDA-MB-231 and MCF-7 in the present study. Our data show that the 2,3-unsaturated double bond-containing withanolides inhibited Hsp90 function, as evidenced by selective depletion of Hsp90 client proteins and induction of Hsp70. The inhibitory effect of the withanolides on Hsp90 chaperone activity was further confirmed using in vivo heat shock luciferase activity recovery assays. Importantly, Hsp90 inhibition by the withanolides was correlated with their ability to induce cancer cell death. In addition, the withanolides reduced constitutive NF-κB activation by depleting IκB kinase complex (IKK) through inhibition of Hsp90. In estrogen receptor (ER)-positive MCF-7 cells, the withanolides also reduced the expression of ER, and this may be partly due to Hsp90 inhibition. Taken together, our results suggest that Hsp90 inhibition is a general feature of cytotoxic withanolides and plays an important role in their anticancer activity

Identification of a potent herbal molecule for the treatment of breast cancer

<p>Abstract</p> <p>Background</p> <p>Breast cancer (BCa)-related mortality still remains the second leading cause of cancer-related deaths worldwide. Patients with BCa have increasingly shown resistance and high toxicity to current chemotherapeutic drugs for which identification of novel targeted therapies are required.</p> <p>Methods</p> <p>To determine the effect of PDBD on BCa cells, estrogen-receptor positive (ER⁺)-MCF-7 and estrogen-receptor negative (ER^-)-MDA 231 cells were treated with PDBD and the cell viability, apoptotic, cell cycle, Western blot and Promoter assays were performed.</p> <p>Results</p> <p>PDBD inhibits cell viability of ER⁺and ER^-BCa cells by inducing apoptosis without causing significant toxicity in normal breast epithelial cells. While dissecting the mechanism of action of PDBD on BCa, we found that PDBD inhibits Akt signaling and its downstream targets such as NF-κB activation, IAP proteins and Bcl-2 expression. On the other hand, activation of JNK/p38 MAPK-mediated pro-apoptotic signaling was observed in both ER⁺and ER^-BCa cells.</p> <p>Conclusion</p> <p>These findings suggest that PDBD may have wide therapeutic application in the treatment of BCa.</p

Similar NF-κB Gene Signatures in TNF-α Treated Human Endothelial Cells and Breast Tumor Biopsies

BACKGROUND: Endothelial dysfunction has been implicated in the pathogenesis of diverse pathologies ranging from vascular and immune diseases to cancer. TNF-α is one of the mediators of endothelial dysfunction through the activation of transcription factors, including NF-κB. While HUVEC (macrovascular cells) have been largely used in the past, here, we documented an NF-κB gene signature in TNFα-stimulated microvascular endothelial cells HMEC often used in tumor angiogenesis studies. METHODOLOGY/PRINCIPAL FINDINGS: We measured mRNA expression of 55 NF-κB related genes using quantitative RT-PCR in HUVEC and HMEC. Our study identified twenty genes markedly up-regulated in response to TNFα, including adhesion molecules, cytokines, chemokines, and apoptosis regulators, some of them being identified as TNF-α-inducible genes for the first time in endothelial cells (two apoptosis regulators, TNFAIP3 and TNFRSF10B/Trail R2 (DR5), the chemokines GM-CSF/CSF2 and MCF/CSF1, and CD40 and TNF-α itself, as well as NF-κB components (RELB, NFKB1 or 50/p105 and NFKB2 or p52/p100). For eight genes, the fold induction was much higher in HMEC, as compared to HUVEC. Most importantly, our study described for the first time a connection between NF-κB activation and the induction of most, if not all, of these genes in HMEC as evaluated by pharmacological inhibition and RelA expression knock-down by RNA interference. Moreover, since TNF-α is highly expressed in tumors, we further applied the NF-κB gene signature documented in TNFα-stimulated endothelial cells to human breast tumors. We found a significant positive correlation between TNF and the majority (85 %) of the identified endothelial TNF-induced genes in a well-defined series of 96 (48 ERα positive and 48 ERα negative) breast tumors. CONCLUSION/SIGNIFICANCE: Taken together these data suggest the potential use of this NF-κB gene signature in analyzing the role of TNF-α in the endothelial dysfunction, as well as in breast tumors independently of the presence of ERα

Inhibition of Specific NF-κB Activity Contributes to the Tumor Suppressor Function of 14-3-3σ in Breast Cancer

14-3-3σ is frequently lost in human breast cancers by genetic deletion or promoter methylation. We have now investigated the involvement of 14-3-3σ in the termination of NF-κB signal in mammary cells and its putative role in cancer relapse and metastasis. Our results show that 14-3-3σ regulates nuclear export of p65-NF-κB following chronic TNFα stimulation. Restoration of 14-3-3σ in breast cancer cells reduces migration capacity and metastatic abilities in vivo. By microarray analysis, we have identified a genetic signature that responds to TNFα in a 14-3-3σ-dependent manner and significantly associates with different breast and other types of cancer. By interrogating public databases, we have found that over-expression of this signature correlates with poor relapse-free survival in breast cancer patients. Finally, screening of 96 human breast tumors showed that NF-κB activation strictly correlates with the absence of 14-3-3σ and it is significantly associated with worse prognosis in the multivariate analysis. Our findings identify a genetic signature that is important for breast cancer prognosis and for future personalized treatments based on NF-κB targeting