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At least 505 records · Page 28

MiR-125a TNF receptor-associated factor 6 to inhibit osteoclastogenesis

MicroRNAs (miRNAs) play important roles in osteoclastogenesis and bone resorption. In the present study, we found that miR-125a was dramatically down-regulated during macrophage colony stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL) induced osteoclastogenesis of circulating CD14+ peripheral blood mononuclear cells (PBMCs). Overexpression of miR-125a in CD14+ PBMCs inhibited osteoclastogenesis, while inhibition of miR-125a promoted osteoclastogenesis. TNF receptor-associated factor 6 (TRAF6), a transduction factor for RANKL/RANK/NFATc1 signal, was confirmed to be a target of miR-125a. EMSA and ChIP assays confirmed that NFATc1 bound to the promoter of the miR-125a. Overexpression of NFATc1 inhibited miR-125a transcription, and block of NFATc1 expression attenuated RANKL-regulated miR-125a transcription. Here, we reported that miR-125a played a biological function in osteoclastogenesis through a novel TRAF6/ NFATc1/miR-125a regulatory feedback loop. It suggests that regulation of miR-125a expression may be a potential strategy for ameliorating metabolic disease. - Highlights: • MiR-125a was significantly down-regulated in osteoclastogenesis of CD14+ PBMCs. • MiR-125a inhibited osteoclast differentiation by targeting TRAF6. • NFATc1 inhibited miR-125a transciption by binding to the promoter of miR-125a. • TRAF6/NFATc1 and miR-125a form a regulatory feedback loop in osteoclastogenesis.

60 APPLIED LIFE SCIENCES↗

Cells from the adult corneal stroma can be reprogrammed to a neuron-like cell using exogenous growth factors

Cells thought to be stem cells isolated from the cornea of the eye have been shown to exhibit neurogenic potential. We set out to uncover the identity and location of these cells within the cornea and to elucidate their neuronal protein and gene expression profile during the process of switching to a neuron-like cell. Here we report that every cell of the adult human and rat corneal stroma is capable of differentiating into a neuron-like cell when treated with neurogenic differentiation specifying growth factors. Furthermore, the expression of genes regulating neurogenesis and mature neuronal structure and function was increased. The switch from a corneal stromal cell to a neuron-like cell was also shown to occur in vivo in intact corneas of living rats. Our results clearly indicate that lineage specifying growth factors can affect changes in the protein and gene expression profiles of adult cells, suggesting that possibly many adult cell populations can be made to switch into another type of mature cell by simply modifying the growth factor environment. - Highlights: • Adult corneal stromal cells can differentiated into neuron-like cells. • Neuronal specification of the adult stromal cell population is stochastic. • Neuronal specification in an adult cell population can be brought about by growth factors.

60 APPLIED LIFE SCIENCES↗

A synthetic mechano-growth factor E peptide promotes rat tenocyte migration by lessening cell stiffness and increasing F-actin formation via the FAK-ERK1/2 signaling pathway

Tendon injuries are common in sports and are frequent reasons for orthopedic consultations. The management of damaged tendons is one of the most challenging problems in orthopedics. Mechano-growth factor (MGF), a recently discovered growth repair factor, plays positive roles in tissue repair through the improvement of cell proliferation and migration and the protection of cells against injury-induced apoptosis. However, it remains unclear whether MGF has the potential to accelerate tendon repair. We used a scratch wound assay in this study to demonstrate that MGF-C25E (a synthetic mechano-growth factor E peptide) promotes the migration of rat tenocytes and that this promotion is accompanied by an elevation in the expression of the following signaling molecules: focal adhesion kinase (FAK) and extracellular signal regulated kinase1/2 (ERK1/2). Inhibitors of the FAK and ERK1/2 pathways inhibited the MGF-C25E-induced tenocyte migration, indicating that MGF-C25E promotes tenocyte migration through the FAK-ERK1/2 signaling pathway. The analysis of the mechanical properties showed that the Young's modulus of tenocytes was decreased through treatment of MGF-C25E, and an obvious formation of pseudopodia and F-actin was observed in MGF-C25E-treated tenocytes. The inhibition of the FAK or ERK1/2 signals restored the decrease in Young's modulus and inhibited the formation of pseudopodia and F-actin. Overall, our study demonstrated that MGF-C25E promotes rat tenocyte migration by lessening cell stiffness and increasing pseudopodia formation via the FAK-ERK1/2 signaling pathway. - Highlights: • Mechano-growth factor E peptide (MGF-C25E) promotes migration of rat tenocytes. • MGF-C25E activates the FAK-ERK1/2 pathway in rat tenocytes. • MGF-C25E induces the actin remodeling and the formation of pseudopodia, and decreases the stiffness in rat tenocytes. • MGF-C25E promotes tenocyte migration via altering stiffness and forming pseudopodia by the activation of the FAK-ERK1/2 pathway.

60 APPLIED LIFE SCIENCES↗

Differential transcription factor expression by human epithelial cells of buccal and urothelial derivation

Identification of transcription factors expressed by differentiated cells is informative not only of tissue-specific pathways, but to help identify master regulators for cellular reprogramming. If applied, such an approach could generate healthy autologous tissue-specific cells for clinical use where cells from the homologous tissue are unavailable due to disease. Normal human epithelial cells of buccal and urothelial derivation maintained in identical culture conditions that lacked significant instructive or permissive signaling cues were found to display inherent similarities and differences of phenotype. Investigation of transcription factors implicated in driving urothelial-type differentiation revealed buccal epithelial cells to have minimal or absent expression of PPARG, GATA3 and FOXA1 genes. Retroviral overexpression of protein coding sequences for GATA3 or PPARy1 in buccal epithelial cells resulted in nuclear immunolocalisation of the respective proteins, with both transductions also inducing expression of the urothelial differentiation-associated claudin 3 tight junction protein. PPARG1 overexpression alone entrained expression of nuclear FOXA1 and GATA3 proteins, providing objective evidence of its upstream positioning in a transcription factor network and identifying it as a candidate factor for urothelial-type transdifferentiation or reprogramming.

60 APPLIED LIFE SCIENCES↗

Buried Hydrogen Bond Interactions Contribute to the High Potency of Complement Factor D Inhibitors

Aberrant activation of the complement system is associated with diseases, including paroxysmal nocturnal hemoglobinuria and age-related macular degeneration. Complement factor D is the rate-limiting enzyme for activating the alternative pathway in the complement system. Recent development led to a class of potent amide containing pyrrolidine derived factor D inhibitors. Here, we used biochemical enzymatic and biolayer interferometry assays to demonstrate that the amide group improves the inhibitor potency by more than 80-fold. Our crystal structures revealed buried hydrogen bond interactions are important. Molecular orbital analysis from quantum chemistry calculations dissects the chemical groups participating in these interactions. Free energy calculation supports the differential contributions of the amide group to the binding affinities of these inhibitors. Cell-based hemolysis assay confirmed these compounds inhibit factor D mediated complement activation via the alternative pathway. Our study highlights the important interactions contributing to the high potency of factor D inhibitors reported recently.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Rhodopseudomonas palustris CGA010 Proteome Implicates Extracytoplasmic Function Sigma Factor in Stress Response

Rhodopseudomonas palustris encodes 16 extracytoplasmic function (ECF) σ factors. In this paper, to begin to investigate the regulatory network of one of these ECF σ factors, the whole proteome of R. palustris CGA010 was quantitatively analyzed by tandem mass spectrometry from cultures episomally expressing the ECF σ RPA4225 (ecfT) versus a WT control. Among the proteins with the greatest increase in abundance were catalase KatE, trehalose synthase, a DPS-like protein, and several regulatory proteins. Alignment of the cognate promoter regions driving expression of several upregulated proteins suggested a conserved binding motif in the -35 and -10 regions with the consensus sequence GGAAC-18N-TT. Additionally, the putative anti-σ factor RPA4224, whose gene is contained in the same predicted operon as RPA4225, was identified as interacting directly with the predicted response regulator RPA4223 by mass spectrometry of affinity-isolated protein complexes. Furthermore, another gene (RPA4226) coding for a protein that contains a cytoplasmic histidine kinase domain is located immediately upstream of RPA4225. The genomic organization of orthologs for these four genes is conserved in several other strains of R. palustris as well as in closely related α-Proteobacteria. Finally, taken together, these data suggest that ECF σ RPA4225 and the three additional genes make up a sigma factor mimicry system in R. palustris.

59 BASIC BIOLOGICAL SCIENCES↗

Measuring the axial form factor of {sup 3}He using weak capture of polarized electrons

A low energy, high intensity polarized electron beam could enable the extraction of the A=3 weak axial form factors F{sub A} using the reaction →e+{sup 3}He→{sup 3}H+ν. These form factors have never been measured before. We discuss the feasibility of such an experiment using a small toroidal magnet and a radial low energy recoil detector to tag the recoil tritons. A moderately high intensity polarized electron beam (>500 μA) with beam energies between 50 - 150 MeV is necessary for the cross section measurement and to provides a free clean measurement of the background. Moreover, in addition to the cross section, by measuring the electron spin and recoil triton correlation coefficient it may be possible to search for second class currents and to extract the ratio of the axial to the vector form factor of the nucleon. Such novel electron scattering based measurements would have a completely different set of systematic uncertainties compared to polarized neutron beta decay, neutrino scattering and muon capture experiments which are typically used to extract the weak form-factors.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

Influence of graphene on quality factor variation in a silicon ring resonator

Selectively patterned graphene is integrated onto a silicon ring resonator to investigate the quality factor (Q factor) variation. The Q factor sharply decreases from 7900 to 1200 as the patterned graphene length increases from 0 to 20 μm. A numerical estimation, which takes into account optical absorption by graphene, shows an exponential damping of the Q factor with increasing graphene length and is consistent with the experimental result. We expect these fundamental characterizations to be helpful in developing graphene-integrated silicon photonics applications.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Gated Si nanowires for large thermoelectric power factors

We investigate the effect of electrostatic gating on the thermoelectric power factor of p-type Si nanowires (NWs) of up to 20 nm in diameter in the [100], [110], and [111] crystallographic transport orientations. We use atomistic tight-binding simulations for the calculation of the NW electronic structure, coupled to linearized Boltzmann transport equation for the calculation of the thermoelectric coefficients. We show that gated NW structures can provide ∼5× larger thermoelectric power factor compared to doped channels, attributed to their high hole phonon-limited mobility, as well as gating induced bandstructure modifications which further improve mobility. Despite the fact that gating shifts the charge carriers near the NW surface, surface roughness scattering is not strong enough to degrade the transport properties of the accumulated hole layer. The highest power factor is achieved for the [111] NW, followed by the [110], and finally by the [100] NW. As the NW diameter increases, the advantage of the gated channel is reduced. We show, however, that even at 20 nm diameters (the largest ones that we were able to simulate), a ∼3× higher power factor for gated channels is observed. Our simulations suggest that the advantage of gating could still be present in NWs with diameters of up to ∼40 nm.

77 NANOSCIENCE AND NANOTECHNOLOGY↗

A small-form-factor piezoelectric vibration energy harvester using a resonant frequency-down conversion

While environmental vibrations are usually in the range of a few hundred Hertz, small-form-factor piezoelectric vibration energy harvesters will have higher resonant frequencies due to the structural size effect. To address this issue, we propose a resonant frequency-down conversion based on the theory of dynamic vibration absorber for the design of a small-form-factor piezoelectric vibration energy harvester. The proposed energy harvester consists of two frequency-tuned elastic components for lowering the first resonant frequency of an integrated system but is so configured that an energy harvesting beam component is inverted with respect to the other supporting beam component for a small form factor. Furthermore, in order to change the unwanted modal characteristic of small separation of resonant frequencies, as is the case with an inverted configuration, a proof mass on the supporting beam component is slightly shifted toward a second proof mass on the tip of the energy harvesting beam component. The proposed small-form-factor design capability was experimentally verified using a fabricated prototype with an occupation volume of 20 × 39 × 6.9 mm{sup 3}, which was designed for a target frequency of as low as 100 Hz.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Analytical evaluation of atomic form factors: Application to Rayleigh scattering

Atomic form factors are widely used for the characterization of targets and specimens, from crystallography to biology. By using recent mathematical results, here we derive an analytical expression for the atomic form factor within the independent particle model constructed from nonrelativistic screened hydrogenic wave functions. The range of validity of this analytical expression is checked by comparing the analytically obtained form factors with the ones obtained within the Hartee-Fock method. As an example, we apply our analytical expression for the atomic form factor to evaluate the differential cross section for Rayleigh scattering off neutral atoms.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Effective g-factors of carriers in inverted InAs/GaSb bilayers

We perform tilt-field transport experiment on inverted InAs/GaSb, which hosts quantum spin Hall insulator. By means of coincidence method, Landau level (LL) spectra of electron and hole carriers are systematically studied at different carrier densities tuned by gate voltages. When Fermi level stays in the conduction band, we observe LL crossing and anti-crossing behaviors at odd and even filling factors, respectively, with a corresponding g-factor of 11.5. It remains nearly constant for varying filling factors and electron densities. On the contrary, for GaSb holes, only a small Zeeman splitting is observed even at large tilt angles, indicating a g-factor of less than 3.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Microcrystalline diamond cylindrical resonators with quality-factor up to 0.5 million

We demonstrate high quality-factor 1.5 mm diameter batch-fabricated microcrystalline diamond cylindrical resonators (CR) with quality-factors limited by thermoelastic damping (TED) and surface loss. Resonators were fabricated 2.6 and 5.3 μm thick in-situ boron-doped microcrystalline diamond films deposited using hot filament chemical vapor deposition. The quality-factor (Q) of as-fabricated CR's was found to increase with the resonator diameter and diamond thickness. Annealing the CRs at 700 °C in a nitrogen atmosphere led to a three-fold increase in Q, a result we attribute to thinning of the diamond layer via reaction with residual O{sub 2} in the annealing furnace. Post-anneal Q exceeding 0.5 million (528 000) was measured at the 19 kHz elliptical wineglass modes, producing a ring-down time of 8.9 s. A model for Q versus diamond thickness and resonance frequency is developed including the effects of TED and surface loss. Measured quality factors are shown to agree with the predictions of this model.

36 MATERIALS SCIENCE↗

Dispersion of the electron g factor anisotropy in InAs/InP self-assembled quantum dots

The electron g factor in an ensemble of InAs/InP quantum dots with emission wavelengths around 1.4 μm is measured using time-resolved pump-probe Faraday rotation spectroscopy in different magnetic field orientations. Thereby, we can extend recent single dot photoluminescence measurements significantly towards lower optical transition energies through 0.86 eV. This allows us to obtain detailed insight into the dispersion of the recently discovered g factor anisotropy in these infrared emitting quantum dots. We find with decreasing transition energy over a range of 50 meV a strong enhancement of the g factor difference between magnetic field normal and along the dot growth axis, namely, from 1 to 1.7. We argue that the g factor cannot be solely determined by the confinement energy, but the dot asymmetry underlying this anisotropy therefore has to increase with increasing dot size.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Extending the limits of powder diffraction analysis: diffraction parameter space, occupancy defects, and atomic form factors

Although the determination of site occupancies is often a major goal in Rietveld refinement studies, the accurate refinement of site occupancies is exceptionally challenging due to the many correlations and systematic errors that have a hidden impact on the final refined occupancy parameters. Through the comparison of results independently obtained from neutron and synchrotron powder diffraction, improved approaches capable of detecting occupancy defects with an exceptional sensitivity of 0.1% (absolute) in the class of layered NMC Li-ion battery cathode materials have been developed. A new method of visualizing the diffraction parameter space associated with crystallographic site scattering power through the use of f* diagrams is described and this method is broadly applicable to ternary compounds. The f* diagrams allow the global minimum fit to be easily identified and also permit a robust determination of the number and type of occupancy defects within a structure. Through a comparison of neutron and X-ray diffraction results, a systematic error in the synchrotron results was identified using f* diagrams for a series of NMC compounds. Using neutron diffraction data as a reference, this error was shown to specifically result from problems associated with the neutral oxygen X-ray atomic form factor and could be eliminated by using the ionic O 2- form factor for this anion while retaining the neutral form factors for cationic species. The f* diagram method offers a new opportunity to experimentally assess the quality of atomic form factors through powder diffraction studies on chemically related multi-component compounds.

25 ENERGY STORAGE↗

Extracellular Matrix-Inspired Growth Factor Delivery Systems for Skin Wound Healing

Blood vessel growth plays a key role in regenerative medicine, both to restore blood supply to ischemic tissues and to ensure rapid vascularization of clinical-size tissue-engineered grafts. For example, vascular endothelial growth factor (VEGF) is the master regulator of physiological blood vessel growth and is one of the main molecular targets of therapeutic angiogenesis approaches. However, angiogenesis is a complex process and there is a need to develop rational therapeutic strategies based on a firm understanding of basic vascular biology principles, as evidenced by the disappointing results of initial clinical trials of angiogenic factor delivery. In particular, the spatial localization of angiogenic signals in the extracellular matrix (ECM) is crucial to ensure the proper assembly and maturation of new vascular structures. Here, we discuss the therapeutic implications of matrix interactions of angiogenic factors, with a special emphasis on VEGF, as well as provide an overview of current approaches, based on protein and biomaterial engineering that mimic the regulatory functions of ECM to optimize the signaling microenvironment of vascular growth factors.

59 BASIC BIOLOGICAL SCIENCES↗

Spectroscopic factors in dripline nuclei

Single-nucleon knockout reaction studies of the proton-dripline nuclei 9 C and 13 O suggest an appreciable suppression of spectroscopic factors. In this work, we calculate the one-neutron and one-proton spectroscopic factors for the mirror pair 9 C – 9 Li and 13 O using two variants of the continuum shell model: the complex-energy Gamow shell model and the real-energy shell model embedded in the continuum. Furthermore, our results indicate that the continuum effects strongly suppress the spectroscopic factors of well-bound orbits in the dripline systems but have less impact on the spectroscopic factors of weakly bound states.

6 ≤ A ≤ 19↗

Gravitational form factors of nuclei in the Skyrme model

Here, we compute the gravitational form factor D(t) of various nuclei in the generalized Skyrme model where nuclei are described as solitonic field configurations each with a definite baryon number B. We separately discuss the cases B = 1 (nucleons), B = 2 (deuteron), B = 3 (helium-3 and tritium), and extrapolate to larger B-values. Configurations with B > 1 are in general not spherically symmetric, and we demonstrate how group theory helps to extract the form factor. Numerical results are presented for the configurations with B = 1, 2, 3, 4, 5, 6, 7, 8, 32, 108. We find that the B-dependence is consistent with a power-law D(0) ∝ B β with β = 1.7–1.8. Other gravitational form factors can be calculated in the same framework, and we show the result for the J(t) form factor associated with the angular momentum for the B = 3 solution.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗