Stiffening and unfolding of early deposited-fibronectin increase proangiogenic factor secretion by breast cancer-associated stromal cells.

Fibronectin (Fn) forms a fibrillar network that controls cell behavior in both physiological and diseased conditions including cancer. Indeed, breast cancer-associated stromal cells not only increase the quantity of deposited Fn but also modify its conformation. However, (i) the interplay between mechanical and conformational properties of early tumor-associated Fn networks and (ii) its effect on tumor vascularization remain unclear. Here, we first used the Surface Forces Apparatus to reveal that 3T3-L1 preadipocytes exposed to tumor-secreted factors generate a stiffer Fn matrix relative to control cells. We then show that this early matrix stiffening correlates with increased molecular unfolding in Fn fibers, as determined by Förster Resonance Energy Transfer. Finally, we assessed the resulting changes in adhesion and proangiogenic factor (VEGF) secretion of newly seeded 3T3-L1s, and we examined altered integrin specificity as a potential mechanism of modified cell-matrix interactions through integrin blockers. Our data indicate that tumor-conditioned Fn decreases adhesion while enhancing VEGF secretion by preadipocytes, and that an integrin switch is responsible for such changes. Collectively, our findings suggest that simultaneous stiffening and unfolding of initially deposited tumor-conditioned Fn alters both adhesion and proangiogenic behavior of surrounding stromal cells, likely promoting vascularization and growth of the breast tumor. This work enhances our knowledge of cell - Fn matrix interactions that may be exploited for other biomaterials-based applications, including advanced tissue engineering approaches

Study on the Mutation Sites of CSF3R Responsible for the Clonal Advantage of Chronic Neutrophilic Leukemia

Objectives: Chronic neutrophilic leukemia (CNL) is a rare, but distinct, entity within myeloproliferative neoplasms, characterized by splenomegaly, sustained mature neutrophilia, and absence of the Philadelphia chromosome. In 2013, oncogenic mutations in colony stimulation factor 3 receptor (CSF3R) were identified in a majority of patients with CNL and it was demonstrated that their downstream signaling was sensitive to known kinase inhibitors. This discovery was then validated with the demonstration of 100% CSF3R mutational frequency (predominately CSF3R-T618I) in strictly CNL as defined by the World Health Organization (WHO). In September 2012, a 67-year-old Chinese man was admitted to the First Central Clinical College of Tianjin Medical University (Tianjin, China) and presented as a case who had fulfilled the WHO diagnostic criteria for CNL with a oncogenic mutation in CSF3R-T618I and also an unreported novel mutation site of CSF3R-H54A Thus, we sought to determine if CSF3R-FL, CSF3R-T618I, CSF3R-H54A mutations have some significance on the molecular pathogenesis of CNL. Methods: In this study, three main experiments were used including plasmid construction, lentiviral packaging system, and Mouse Colony-Forming Unit Assays Using MethoCult™. Results: The establishment of these three experiments was completed successfully. We confirmed the transformation capacity of the CSF3R mutations, especially that CSF3R-T618I was higher than CSF3R-FL Conclusion: This result demonstrates that T618I mutation of CSF3R conferred the clonal advantage of CNL leukemia cells

Collapses and revivals of exciton emission in a semiconductor microcavity: detuning and phase-space filling effects

We investigate exciton emission of quantum well embedded in a semiconductor microcavity. The analytical expressions of the light intensity for the cases of excitonic number state and coherent state are presented by using secular approximation. Our results show that the effective exciton-exciton interaction leads to the appearance of collapse and revival of the light intensity. The revival time is twice compared the coherent state case with that of the number state. The dissipation of the exciton-polariton lowers the revival amplitude but does not alter the revival time. The influences of the detuning and the phase-space filling are studied. We find that the effect of the higher-order exciton-photon interaction may be removed by adjusting the detuning.Comment: 7 pages, 3 figure

Pressure-induced one-dimensional oxygen ion diffusion channel in lead-apatite

Recently, Lee et al. claimed that the experimental observation of room-temperature ambient-pressure superconductivity in a Cu-doped lead-apatite (Pb10-xCux(PO4)6O). The study revealed the Cu doping induces a chemical pressure, resulting in a structural contraction of one-dimensional Cu-O-Cu atomic column. This unique structure promotes a one-dimensional electronic conduction channel along the c-axis mediated by the O atoms, which may be related to superconductivity. These O atoms occupy 1/4 of the equivalent positions along the c-axis and exhibit a low diffusion activation energy of 0.8 eV, indicating the possibility of diffusion between these equivalent positions. Here, using machine-learning based deep potential, we predict the pressure-induced fast diffusion of 1/4-occupied O atoms along the one-dimensional channel in Pb10(PO4)6O at 500 K, while the frameworks of Pb triangles and PO4 tetrahedrons remain stable. The calculation results also indicate Cu doping can provide appropriate effective chemical pressure, indicating the one-dimensional ion diffusion channel may appear in Pb9Cu(PO4)6O, even at ambient pressure. Our finding shows that the one-dimensional ions diffusion channel may be an important factor to affects the fabrication and electrical measurement of doped lead-apatite.Comment: 15 pages, 7 figure