Functionalisation of PLLA nanofiber scaffolds using a possible cooperative effect between collagen type I and BMP-2: impact on growth and osteogenic differentiation of human mesenchymal stem cells

Mesenchymal stem cell differentiation of osteoblasts is triggered by a series of signaling processes including integrin and bone morphogenetic protein (BMP), which therefore act in a cooperative manner. The aim of this study was to analyze whether these processes can be remodeled in an artificial poly-(l)-lactide acid (PLLA) based nanofiber scaffold. Matrices composed of PLLA-collagen type I or BMP-2 incorporated PLLA-collagen type I were seeded with human mesenchymal stem cells (hMSC) and cultivated over a period of 22 days, either under growth or osteoinductive conditions. During the course of culture, gene expression of alkaline phosphatase (ALP), osteocalcin (OC) and collagen I (COL-I) as well as Smad5 and focal adhesion kinase (FAK), two signal transduction molecules involved in BMP-2 or integrin signaling were analyzed. Furthermore, calcium and collagen I deposition, as well as cell densities and proliferation, were determined using fluorescence microscopy. The incorporation of BMP-2 into PLLA-collagen type I nanofibers resulted in a decrease in diameter as well as pore sizes of the scaffold. Mesenchymal stem cells showed better adherence and a reduced proliferation on BMP-containing scaffolds. This was accompanied by an increase in gene expression of ALP, OC and COL-I. Furthermore the presence of BMP-2 resulted in an upregulation of FAK, while collagen had an impact on the gene expression of Smad5. Therefore these different strategies can be combined in order to enhance the osteoblast differentiation of hMSC on PLLA based nanofiber scaffold. By doing this, different signal transduction pathways seem to be up regulated

A NORTHERN SKY SURVEY FOR POINT-LIKE SOURCES OF EeV NEUTRAL PARTICLES WITH THE TELESCOPE ARRAY EXPERIMENT

We report on the search for steady point-like sources of neutral particles around 10(18) eV between 2008 and 2013 May with the scintillator SD of the Telescope Array experiment. We found overall no significant point-like excess above 0.5 EeV in the northern sky. Subsequently, we also searched for coincidence with the Fermi bright Galactic sources. No significant coincidence was found within the statistical uncertainty. Hence, we set an upper limit on the neutron flux that corresponds to an averaged flux of 0.07 km(-2) yr(-1) for E > 1 EeV in the northern sky at the 95% confidence level. This is the most stringent flux upper limit in a northern sky survey assuming point-like sources. The upper limit at the 95% confidence level on the neutron flux from Cygnus X-3 is also set to 0.2 km(-2) yr(-1) for E > 0.5 EeV. This is an order of magnitude lower than previous flux measurementsopen0

Measurement of the proton-air cross section with Telescope Array's Middle Drum detector and surface array in hybrid mode

In this work we are reporting on the measurement of the proton-air inelastic cross section sigma(inel)(p-air) using the Telescope Array detector. Based on the measurement of the sigma(inel)(p-air), the proton-proton cross section sigma(p-p) value is also determined at root s = 95(-8)(+5) TeV. Detecting cosmic ray events at ultrahigh energies with the Telescope Array enables us to study this fundamental parameter that we are otherwise unable to access with particle accelerators. The data used in this report are the hybrid events observed by the Middle Drum fluorescence detector together with the surface array detector collected over five years. The value of the sigma(inel)(p-air) is found to be equal to 567.0 +/- 70.5[Stat](-25)(+29)[Sys] mb. The total proton-proton cross section is subsequently inferred from Glauber formalism and the Block, Halzen and Stanev QCD inspired fit and is found to be equal to 170(-44)(+48)[Stat](-17)(+19)[Sys] mb.open20

Indications of intermediate-scale anisotropy of cosmic rays with energy greater than 57 EeV in the northern sky measured with the surface detector of the Telescope Array experiment

We have searched for intermediate-scale anisotropy in the arrival directions of ultrahigh-energy cosmic rays with energies above 57 EeV in the northern sky using data collected over a 5 yr period by the surface detector of the Telescope Array experiment. We report on a cluster of events that we call the hotspot, found by oversampling using 20?? radius circles. The hotspot has a Li-Ma statistical significance of 5.1??, and is centered at R.A. = 146.??7, decl. = 43.??2. The position of the hotspot is about 19?? off of the supergalactic plane. The probability of a cluster of events of 5.1?? significance, appearing by chance in an isotropic cosmic-ray sky, is estimated to be 3.7 ?? 10-4 (3.4??).open2

The Herbicide Atrazine Activates Endocrine Gene Networks via Non-Steroidal NR5A Nuclear Receptors in Fish and Mammalian Cells

Atrazine (ATR) remains a widely used broadleaf herbicide in the United States despite the fact that this s-chlorotriazine has been linked to reproductive abnormalities in fish and amphibians. Here, using zebrafish we report that environmentally relevant ATR concentrations elevated zcyp19a1 expression encoding aromatase (2.2 µg/L), and increased the ratio of female to male fish (22 µg/L). ATR selectively increased zcyp19a1, a known gene target of the nuclear receptor SF-1 (NR5A1), whereas zcyp19a2, which is estrogen responsive, remained unchanged. Remarkably, in mammalian cells ATR functions in a cell-specific manner to upregulate SF-1 targets and other genes critical for steroid synthesis and reproduction, including Cyp19A1, StAR, Cyp11A1, hCG, FSTL3, LHß, INHα, αGSU, and 11ß-HSD2. Our data appear to eliminate the possibility that ATR directly affects SF-1 DNA- or ligand-binding. Instead, we suggest that the stimulatory effects of ATR on the NR5A receptor subfamily (SF-1, LRH-1, and zff1d) are likely mediated by receptor phosphorylation, amplification of cAMP and PI3K signaling, and possibly an increase in the cAMP-responsive cellular kinase SGK-1, which is known to be upregulated in infertile women. Taken together, we propose that this pervasive and persistent environmental chemical alters hormone networks via convergence of NR5A activity and cAMP signaling, to potentially disrupt normal endocrine development and function in lower and higher vertebrates