TIAF1 self-aggregation in peritumor capsule formation, spontaneous activation of SMAD-responsive promoter in p53-deficient environment, and cell death

Self-aggregation of transforming growth factor β (TGF-β)1-induced antiapoptotic factor (TIAF1) is known in the nondemented human hippocampus, and the aggregating process may lead to generation of amyloid β (Aβ) for causing neurodegeneration. Here, we determined that overexpressed TIAF1 exhibits as aggregates together with Smad4 and Aβ in the cancer stroma and peritumor capsules of solid tumors. Also, TIAF1/Aβ aggregates are shown on the interface between brain neural cells and the metastatic cancer cell mass. TIAF1 is upregulated in developing tumors, but may disappear in established metastatic cancer cells. Growing neuroblastoma cells on the extracellular matrices from other cancer cell types induced production of aggregated TIAF1 and Aβ. In vitro induction of TIAF1 self-association upregulated the expression of tumor suppressors Smad4 and WW domain-containing oxidoreductase (WOX1 or WWOX), and WOX1 in turn increased the TIAF1 expression. TIAF1/Smad4 interaction further enhanced Aβ formation. TIAF1 is known to suppress SMAD-regulated promoter activation. Intriguingly, without p53, self-aggregating TIAF1 spontaneously activated the SMAD-regulated promoter. TIAF1 was essential for p53-, WOX1- and dominant-negative JNK1-induced cell death. TIAF1, p53 and WOX1 acted synergistically in suppressing anchorage-independent growth, blocking cell migration and causing apoptosis. Together, TIAF1 shows an aggregation-dependent control of tumor progression and metastasis, and regulation of cell death

T-Bet and Eomes Regulate the Balance between the Effector/Central Memory T Cells versus Memory Stem Like T Cells

Memory T cells are composed of effector, central, and memory stem cells. Previous studies have implicated that both T-bet and Eomes are involved in the generation of effector and central memory CD8 T cells. The exact role of these transcription factors in shaping the memory T cell pool is not well understood, particularly with memory stem T cells. Here, we demonstrate that both T-bet or Eomes are required for elimination of established tumors by adoptively transferred CD8 T cells. We also examined the role of T-bet and Eomes in the generation of tumor-specific memory T cell subsets upon adoptive transfer. We showed that combined T-bet and Eomes deficiency resulted in a severe reduction in the number of effector/central memory T cells but an increase in the percentage of CD62LhighCD44low Sca-1+ T cells which were similar to the phenotype of memory stem T cells. Despite preserving large numbers of phenotypic memory stem T cells, the lack of both of T-bet and Eomes resulted in a profound defect in antitumor memory responses, suggesting T-bet and Eomes are crucial for the antitumor function of these memory T cells. Our study establishes that T-bet and Eomes cooperate to promote the phenotype of effector/central memory CD8 T cell versus that of memory stem like T cells. © 2013 Li et al

Natural history of spontaneous aortic intramural hematoma progression: Six years follow-up with cardiovascular magnetic resonance

We described a 6 years follow-up of a spontaneous aortic intramural hematoma (IMH) with cardiovascular magnetic resonance (CMR) examination. Since multiple factors may play roles in the natural history of IMH, the patient experienced the course of progression, which included hematoma absorption, ulcer-like lesion, aneurysm and limited dissection. The initial and follow-up CMR examination included 3D CE MRA and non-enhanced "bright blood" pulse sequence. The inherent advantage of outstanding contrast with plain scan, which shorten the scan time and avoid potential risk of contrast agent, might make the fast gradient echo sequence as an alternative method when following stable IMH

Real-time evaluation of longitudinal peak systolic strain (speckle tracking measurement) in left and right ventricles of athletes

<p>Abstract</p> <p>Background</p> <p>Strain, and particularly Longitudinal Peak Systolic Strain (LPSS), plays a role in investigating the segmental and overall contractility of the heart which is a particularly interesting feature in athletes in whom regular training determines several morphological and functional modifications in both the ventricles, that normally work at different loads. Speckle tracking techniques assess the LPSS of LV and RV from B-mode imaging in real time, with uniform accuracy in all segments, and can verify the possible dissimilar segmental contributions of the two chambers to overall myocardial contraction. The aim of the study is to quantify the LPSS in real time in both the ventricles in order to estimate any possible different deformation properties in them during a systolic period.</p> <p>Methods</p> <p>32 subjects (20 athletes and 18 controls) were submitted to a standard echocardiographic examination at rest and after a Hand Grip (HG) stress. From a four-chamber-view image, the LPSS parameter was measured with Speckle Tracking analysis in the basal and medium-apical segments of the two ventricles, at rest and after HG.</p> <p>Results</p> <p>In both athletes and controls, LPSS values were significantly higher in the RV of athletes (RV LPSS ^{medium-apical}-23.87 ± 4.94; ^{basalfreewall}-25.04 ± 4.12 at rest) and controls (RV LPSS^{medium-apical}-25.21 ± 4.97; ^{basalfreewall}-28.69 ± 4.62 at rest) than in the LV of both (athletes LV LPSS ^{medium-apical}-18.14 ± 4.16; ^{basallateralwall}-16.05 ± 12.32; controls ^{medium-apical}-18.81 ± 2.64; ^{basallateralwall}-19.74 ± 3.84) With the HG test a significant enhancement of the LPSS(with P < .05) in the medium-apical segments of LV and RV was evident, but only in athletes; there was no modification of the standard echo-parameters in either group.</p> <p>Conclusion</p> <p>ST analysis is an easy method for investigating the contractility of the RV through deformation parameters, showing greater involvement of the RV than LV at rest. In athletes only, after isometric stress the two ventricles show particular myocardial deformation properties of the regions around the apex where the curvature of the wall is more marked. The clinical application of this new approach in athletes and normal subjects requires further investigation.</p

A qualitative investigation of the impact of peer to peer online support for women living with Polycystic Ovary Syndrome

Background: Polycystic Ovary Syndrome is a common, chronic condition which affects women living with the condition both physically and psychologically. Social support may be beneficial to sufferers in coping with chronic conditions and the Internet is becoming a common place for accessing social support and information. The aim of this study was to consider the experiences of women living with Polycystic Ovary Syndrome who access and participate in an online support group discussion forum dedicated to issues surrounding this condition. Methods: Fifty participants responded to a series of open-ended questions via an online survey. Results: Thematic analysis revealed a number of empowering and disempowering experiences associated with online support group participation. The empowering processes reported by members of the group included: Connecting with others who understand; Access to information and advice; Interaction with healthcare professionals; Treatment-related decision making; Improved adjustment and management. In terms disempowering processes, only two were described by group participants: Reading about the negative experiences of others and Feeling like an outsider. Conclusions: For women living with Polycystic Ovary Syndrome, participation within an online support group may help to empower them in a range of important ways however, there may be some disempowering consequences

Thermal and Sedimentation Stress Are Unlikely Causes of Brown Spot Syndrome in the Coral Reef Sponge, Ianthella basta

Background: Marine diseases are being increasingly linked to anthropogenic factors including global and local stressors. On the Great Barrier Reef, up to 66% of the Ianthella basta population was recently found to be afflicted by a syndrome characterized by brown spot lesions and necrotic tissue.\ud \ud Methodology/Principal Findings: Manipulative experiments were undertaken to ascertain the role of environmental stressors in this syndrome. Specifically, the effects of elevated temperature and sedimentation on sponge health and symbiont stability in I. basta were examined. Neither elevated temperature nor increased sedimentation were responsible for the brown spot lesions, but sponges exposed to 32°C developed substantial discoloration and deterioration of their tissues, resulting in death after eight days and a higher microbial diversity in those samples. No shifts in the microbial community of I. basta were observed across a latitudinal gradient or with increased sedimentation, with three previously described symbionts dominating the community of all sponges (Alphaproteobacteria, Gammaproteobacteria and Thaumarchaea).\ud \ud Conclusions/Significance: Results from this study highlight the stable microbial community of I. basta and indicate that thermal and sedimentation stress are not responsible for the brown spot lesions currently affecting this abundant and ecologically important sponge species