Investigating the Effects of Tissue-Specific Extracellular Matrix on the Adipogenic and Osteogenic Differentiation of Human Adipose-Derived Stromal Cells Within Composite Hydrogel Scaffolds

© Copyright © 2019 Shridhar, Amsden, Gillies and Flynn. While it has been postulated that tissue-specific bioscaffolds derived from the extracellular matrix (ECM) can direct stem cell differentiation, systematic comparisons of multiple ECM sources are needed to more fully assess the benefits of incorporating tissue-specific ECM in stem cell culture and delivery platforms. To probe the effects of ECM sourced from decellularized adipose tissue (DAT) or decellularized trabecular bone (DTB) on the adipogenic and osteogenic differentiation of human adipose-derived stem/stromal cells (ASCs), a novel detergent-free decellularization protocol was developed for bovine trabecular bone that complemented our established detergent-free decellularization protocol for human adipose tissue and did not require specialized equipment or prolonged incubation times. Immunohistochemical and biochemical characterization revealed enhanced sulphated glycosaminoglycan content in the DTB, while the DAT contained higher levels of collagen IV, collagen VI and laminin. To generate platforms with similar structural and biomechanical properties to enable assessment of the compositional effects of the ECM on ASC differentiation, micronized DAT and DTB were encapsulated with human ASCs within methacrylated chondroitin sulfate (MCS) hydrogels through UV-initiated crosslinking. High ASC viability (\u3e90%) was observed over 14 days in culture. Adipogenic differentiation was enhanced in the MCS+DAT composites relative to the MCS+DTB composites and MCS controls after 14 days of culture in adipogenic medium. Osteogenic differentiation studies revealed a peak in alkaline phosphatase (ALP) enzyme activity at 7 days in the MCS+DTB group cultured in osteogenic medium, suggesting that the DTB had bioactive effects on osteogenic protein expression. Overall, the current study suggests that tissue-specific ECM sourced from DAT or DTB can act synergistically with soluble differentiation factors to enhance the lineage-specific differentiation of human ASCs within 3-D hydrogel systems

A Statistical Analysis of STEVE

There has been an exciting recent development in auroral research associated with the discovery of a new subauroral phenomenon called STEVE (Strong Thermal Emission Velocity Enhancement). Although STEVE has been documented by amateur night sky watchers for decades, it is as yet an unidentified upper atmosphere phenomenon. Observed first by amateur auroral photographers, STEVE appears as a narrow luminous structure across the night sky over thousands of kilometers in the east‐west direction. In this paper, we present the first statistical analysis of the properties of 28 STEVE events identified using Time History of Events and Macroscale Interactions during Substorms (THEMIS) all‐sky imager and the Redline Emission Geospace Observatory (REGO) database. We find that STEVE occurs about 1 hr after substorm onset at the end of a prolonged expansion phase. On average, the AL index magnitude is larger and the expansion phase has a longer duration for STEVE events compared to subauroral ion drifts or substorms. The average duration for STEVE is about 1 hr, and its latitudinal width is ~20 km, which corresponds to ~¼ of the width of narrow auroral structures like streamers. STEVE typically has an equatorward displacement from its initial location of about 50 km and a longitudinal extent of 2,145 km

Precise Measurement of Gravity Variations During a Total Solar Eclipse

The variations of gravity were measured with a high precision LaCoste-Romberg D gravimeter during a total solar eclipse to investigate the effect of solar eclipse on the gravitational field. The observed anomaly $(7.0 \pm 2.7) \times 10^{-8}$ m/s$^2$ during the eclipse implies that there may be a shielding property of gravitation

λϕ4\lambda\phi^4 model and Higgs mass in standard model calculated by Gaussian effective potential approach with a new regularization-renormalization method

Basing on new regularization-renormalization method, the $\lambda\phi^4$ model used in standard model is studied both perturbatively and nonperturbatively (by Gaussian effective potential). The invariant property of two mass scales is stressed and the existence of a (Landau) pole is emphasized. Then after coupling with the SU(2)$\times$U(1) gauge fields, the Higgs mass in standard model (SM) can be calculated as $m_H\approx$138GeV. The critical temperature ($T_c$) for restoration of symmetry of Higgs field, the critical energy scale ($\mu_c$, the maximum energy scale under which the lower excitation sector of the GEP is valid) and the maximum energy scale ($\mu_{max}$, at which the symmetry of the Higgs field is restored) in the standard model are $T_c\approx$476 GeV, $\mu_c\approx 0.547\times 10^{15}$GeV and $\mu_{\max}\approx 0.873 \times 10^{15}$ GeVv respectively.Comment: 12 pages, LaTex, no figur

Comparison of spinal cord stimulation profiles from intra- and extradural electrode arrangements by finite element modelling

Spinal cord stimulation currently relies on extradural electrode arrays that are separated from the spinal cord surface by a highly conducting layer of cerebrospinal fluid. It has recently been suggested that intradural placement of the electrodes in direct contact with the pial surface could greatly enhance the specificity and efficiency of stimulation. The present computational study aims at quantifying and comparing the electrical current distributions as well as the spatial recruitment profiles resulting from extra- and intra-dural electrode arrangements. The electrical potential distribution is calculated using a 3D finite element model of the human thoracic spinal canal. The likely recruitment areas are then obtained using the potential as input to an equivalent circuit model of the pre-threshold axonal response. The results show that the current threshold to recruitment of axons in the dorsal column is more than an order of magnitude smaller for intradural than extradural stimulation. Intradural placement of the electrodes also leads to much higher contrast between the stimulation thresholds for the dorsal root entry zone and the dorsal column, allowing better focusing of the stimulus

Predicting the safety and efficacy of butter therapy to raise tumour pHe: an integrative modelling study

Background: Clinical positron emission tomography imaging has demonstrated the vast majority of human cancers exhibit significantly increased glucose metabolism when compared with adjacent normal tissue, resulting in an acidic tumour microenvironment. Recent studies demonstrated reducing this acidity through systemic buffers significantly inhibits development and growth of metastases in mouse xenografts.\ud \ud Methods: We apply and extend a previously developed mathematical model of blood and tumour buffering to examine the impact of oral administration of bicarbonate buffer in mice, and the potential impact in humans. We recapitulate the experimentally observed tumour pHe effect of buffer therapy, testing a model prediction in vivo in mice. We parameterise the model to humans to determine the translational safety and efficacy, and predict patient subgroups who could have enhanced treatment response, and the most promising combination or alternative buffer therapies.\ud \ud Results: The model predicts a previously unseen potentially dangerous elevation in blood pHe resulting from bicarbonate therapy in mice, which is confirmed by our in vivo experiments. Simulations predict limited efficacy of bicarbonate, especially in humans with more aggressive cancers. We predict buffer therapy would be most effectual: in elderly patients or individuals with renal impairments; in combination with proton production inhibitors (such as dichloroacetate), renal glomular filtration rate inhibitors (such as non-steroidal anti-inflammatory drugs and angiotensin-converting enzyme inhibitors), or with an alternative buffer reagent possessing an optimal pK of 7.1–7.2.\ud \ud Conclusion: Our mathematical model confirms bicarbonate acts as an effective agent to raise tumour pHe, but potentially induces metabolic alkalosis at the high doses necessary for tumour pHe normalisation. We predict use in elderly patients or in combination with proton production inhibitors or buffers with a pK of 7.1–7.2 is most promising

Choroidal structural changes correlate with neovascular activity in neovascular age related macular degeneration

PURPOSE. To correlate changes in choroidal thickness and vascularity index with disease activity in patients with neovascular age-related macular degeneration (nAMD). METHODS. Eyes diagnosed with AMD that had two sequential visits within 12 months and that had no choroidal neovascularization (CNV) or had inactive CNV at the first visit were included. Those that had active CNV at follow-up were enrolled as cases. Eyes that did not developed a CNV or that were still inactive at the second visit were enrolled as controls. Disease activity was based on optical coherence tomography (OCT) and fluorescein angiography findings. Subfoveal choroidal thickness (SCT), mean choroidal thickness (MCT), and choroidal vascularity index (CVI) were assessed on enhanced depth imaging OCT and compared between the baseline and follow-up visit. Subgroup analysis accounting for lesion type and previous treatment, if any, were performed. RESULTS. Sixty-five eyes from 60 patients (35 females) and 50 age-and sex-matched controls were included. At the active visit, cases had an increase from 164 +/- 67 mu m to 175 +/- 70 mu m in mean +/- SD SCT and from 144 +/- 45 mu m to 152 +/- 45 mu m in MCT (both P < 0.0001). The mean CVI also increased at from 54.5% +/- 3.3% to 55.4% +/- 3.8% (P = 0.04). Controls did not show significant changes in choroidal measurements between the two visits. Mean SCT, MCT, and CVI values were similar for previously treated and treatment-naive eyes. CONCLUSIONS. Choroidal thickness and CVI significantly increased with active disease in nAMD eyes. Changes in choroidal thickness may predict CNV development or recurrence before they are otherwise evident clinically

Heterozygous mutations in HSD17B4 cause juvenile peroxisomal D-bifunctional protein deficiency

Objective: To determine the genetic cause of slowly progressive cerebellar ataxia, sensorineural deafness, and hypergonadotropic hypogonadism in 5 patients from 3 different families. Methods: The patients comprised 2 sib pairs and 1 sporadic patient. Clinical assessment included history, physical examination, and brain MRI. Linkage analysis was performed separately on the 2 sets of sib pairs using single nucleotide polymorphism microarrays, followed by analysis of the intersection of the regions. Exome sequencing was performed on 1 affected patient with variant filtering and prioritization undertaken using these intersected regions. Results: Using a combination of sequencing technologies, we identified compound heterozygous mutations in HSD17B4 in all 5 affected patients. In all 3 families, peroxisomal D-bifunctional protein (DBP) deficiency was caused by compound heterozygosity for 1 nonsense/deletion mutation and 1 missense mutation. Conclusions: We describe 5 patients with juvenile DBP deficiency from 3 different families, bringing the total number of reported patients to 14, from 8 families. This report broadens and consolidates the phenotype associated with juvenile DBP deficiency

Quintessence, the Gravitational Constant, and Gravity

Dynamical vacuum energy or quintessence, a slowly varying and spatially inhomogeneous component of the energy density with negative pressure, is currently consistent with the observational data. One potential difficulty with the idea of quintessence is that couplings to ordinary matter should be strongly suppressed so as not to lead to observable time variations of the constants of nature. We further explore the possibility of an explicit coupling between the quintessence field and the curvature. Since such a scalar field gives rise to another gravity force of long range (\simg H^{-1}_0), the solar system experiments put a constraint on the non-minimal coupling: |\xi| \siml 10^{-2}.Comment: 9 pages, a version to be published in Phys.Rev.