Nuclear Localization of COX-2 in relation to the Expression of Stemness Markers in Urinary Bladder Cancer

Inflammation may activate stem cells via prostaglandin E2 (PGE2) production mediated by cyclooxygenase-2 (COX-2) expression. We performed an immunohistochemical analysis of the expression of stemness markers (Oct3/4 and CD44v6) and COX-2 in urinary bladder tissues obtained from cystitis and cancer patients with and without Schistosoma haematobium infections. Immunoreactivity to Oct3/4 was significantly higher in S. haematobium-associated cystitis and cancer tissues than in normal tissues. CD44v6 expression was significantly higher in bladder cancer without S. haematobium than in normal tissues. COX-2 was located in the cytoplasmic membrane, cytoplasm, and nucleus of the cancer cells. Interestingly, the nuclear localization of COX-2, which was reported to function as a transcription factor, was significantly associated with the upregulation of Oct3/4 and CD44v6 in bladder cancer tissues with and without S. haematobium infection, respectively. COX-2 activation may be involved in inflammation-mediated stem cell proliferation/differentiation in urinary bladder carcinogenesis

Noncanonical binding of BiP ATPase domain to Ire1 and Perk is dissociated by unfolded protein CH1 to initiate ER stress signaling

The unfolded protein response (UPR) is an essential cell signaling system that detects the accumulation of misfolded proteins within the endoplasmic reticulum (ER) and initiates a cellular response in order to maintain homeostasis. How cells detect the accumulation of misfolded proteins remains unclear. In this study, we identify a noncanonical interaction between the ATPase domain of the ER chaperone BiP and the luminal domains of the UPR sensors Ire1 and Perk that dissociates when authentic ER unfolded protein CH1 binds to the canonical substrate binding domain of BiP. Unlike the interaction between chaperone and substrates, we found that the interaction between BiP and UPR sensors was unaffected by nucleotides. Thus, we discover that BiP is dual functional UPR sensor, sensing unfolded proteins by canonical binding to substrates and transducing this event to noncanonical, signaling interaction to Ire1 and Perk. Our observations implicate BiP as the key component for detecting ER stress and suggest an allosteric mechanism for UPR induction.</jats:p

UPR Signal Activation by Luminal Sensor Domains

The unfolded protein response (UPR) is a cell-signaling system that detects the accumulation of unfolded protein within the endoplasmic reticulum (ER) and initiates a number of cellular responses to restore ER homeostasis. The presence of unfolded protein is detected by the ER-luminal sensor domains of the three UPR-transducer proteins IRE1, PERK, and ATF6, which then propagate the signal to the cytosol. In this review, we discuss the various mechanisms of action that have been proposed on how the sensor domains detect the presence of unfolded protein to activate downstream UPR signaling. © 2013 by the authors; licensee MDPI, Basel, Switzerland

Two types of martensitic phase transformations in magnetic shape memory alloys by in-situ nanoindentation studies

Ni based magnetic shape memory alloys (MSMAs) have broad applications in actuators and MEMS devices. Two-stage stress induced martensitic phase transformation, a widely observed phenomenon in these alloys, is described conventionally as a first stage L21 (austenite)-to-10M/14M (M: modulated martensite) transition, followed by a second stage 14M-to-L10 (tetragonal martensite) transformation at higher stresses. Here we show, for the first time via in-situ nanoindentation on single crystalline Ni54Fe19Ga27 alloy, that a reversible L21-to-10M/14M transformations took place at lower stress. However at higher stress, an irreversible transition from residual L21 to L10 martensite (a second type of phase transformation) occurred. Furthermore phase fronts propagate gradually during the L21-to-10M/14M transformation, whereas L10 is abruptly emitted in a jerky style during the 14M-to-L10 transformation. Detailed examination of crystal structure suggests that a direct transition from 14M to observed L10 is crystallographically forbidden in the current loading condition. This study provides new perspective for understanding of stress induced various types of phase transformations in MSMAs. This research is funded by NSF-CMMI under grant no. 1129065

Orientation dependence of the elastocaloric effect in Ni54Fe19Ga27 ferromagnetic shape memory alloy

The crystallographic anisotropy of elastocaloric effect (ECE) and relative cooling power (RCP) in Ni54Fe19Ga27 shape memory alloy single crystals are studied via compression tests. Single crystals are studied along the [001], [123], and [011] austenite directions and yield different ECE behaviors and maximum RCPs for various strain levels. A thermodynamic framework using the Helmholtz free energy is employed to analyze the total entropy change as a function of strain. Thermodynamic losses are computed from the mechanical hysteresis of superelasticity experiments to quantify the strain dependent RCP. It is found that the [001] orientation generates the highest maximal RCP of 738 J kg−1 when unloaded from 200 MPa. This is attributed mainly to the large superelastic temperature window of 45 K. However, loading the crystals to stresses higher than 200 MPa causes a multistep transformation in the [011] direction, thus reducing the alloy's overall RCP by 135 J kg−1. This is a consequence of the negative entropy change and large transformation hysteresis generated by the second‐stage transformation in the [011] direction. Interestingly, if only the first‐stage transformation in [011] is employed for the ECE, the [011] direction yields the highest RCP compared to [001] and [123] for any strain up to 3.5%

Pontine extension of a tentorial schwannoma without cranial nerve involvement: a case report

<p>Abstract</p> <p>Introduction</p> <p>Intracranial schwannomas unrelated to the cranial nerves are uncommon. We report a new case of tentorial schwannoma unrelated to the cranial nerves, with extension into the pons. A literature review with discussion of the most relevant pathogenetic aspects is also performed.</p> <p>Case presentation</p> <p>A 42-year-old Caucasian man was admitted with right-sided paresthesias and weakness of his upper and lower extremities. The neurological examination revealed right hemiparesis and hemi-hypoesthesia. A brain magnetic resonance imaging scan revealed a cerebellopontine lesion, arising from the left free edge of the tentorium, and extending into his pons. A piecemeal removal was performed through a retrosigmoid approach. The lesion was not found to be associated with any cranial nerves. The histological examination revealed a schwannoma Antoni type A. His postoperative course was uneventful. At one year follow-up, the patient was neurologically intact and the magnetic resonance imaging of his brain performed at that time showed complete removal without signs of recurrence.</p> <p>Conclusion</p> <p>Tentorial schwannomas are rare clinical entities. Knowledge of their clinical, radiological and anatomical characteristics is very important for the correct diagnosis and management.</p

BiP Binding to the ER-Stress Sensor Ire1 Tunes the Homeostatic Behavior of the Unfolded Protein Response

Computational modeling and experimentation in the unfolded protein response reveals a role for the ER-resident chaperone protein BiP in fine-tuning the system's response dynamics