38 research outputs found
Novel Biodegradable Composite of Calcium Phosphate Cement and the Collagen I Mimetic P-15 for Pedicle Screw Augmentation in Osteoporotic Bone
Osteoporotic vertebral fractures often necessitate fusion surgery, with high rates of implant failure. We present a novel bioactive composite of calcium phosphate cement (CPC) and the collagen I mimetic P-15 for pedicle screw augmentation in osteoporotic bone. Methods involved expression analysis of osteogenesis-related genes during osteoblastic differentiation by RT-PCR and immunostaining of osteopontin and Ca2+ deposits. Untreated and decalcified sheep vertebrae were utilized for linear pullout testing of pedicle screws. Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry (DEXA). Expression of ALPI II (p p p p p p p p p = 0.04) with PMMA, and 1252 ± 131 N (p < 0.0078) with CPC-P-15. CPC-P-15 induces osteoblastic differentiation of human MES and improves pullout resistance of pedicle screws in osteoporotic and non-osteoporotic bone
A computationally inspired in-vivo approach identifies a link between amygdalar transcriptional heterogeneity, socialization and anxiety
Pharmaceutical breakthroughs for anxiety have been lackluster in the last half-century. Converging behavior and limbic
molecular heterogeneity has the potential to revolutionize biomarker-driven interventions. However, current in vivo models
too often deploy artificial systems including directed evolution, mutations and fear induction, which poorly mirror clinical
manifestations. Here, we explore transcriptional heterogeneity of the amygdala in isogenic mice using an unbiased multidimensional
computational approach that segregates intra-cohort reactions to moderate situational adversity and intersects
it with high content molecular profiling. We show that while the computational approach stratifies known features of
clinical anxiety including nitric oxide, opioid and corticotropin signaling, previously unrecognized druggable biomarkers
emerge, such as calpain11 and scand1. Through ingenuity pathway analyses, we further describe a role for neurosteroid
estradiol signaling, heat shock proteins, ubiquitin ligases and lipid metabolism. In addition, we report a remarkable
behavioral pattern that maps to molecular features of anxiety in mice through counterphobic social attitudes, which
manifest as increased, yet spatially distant socialization. These findings provide an unbiased approach for interrogating
anxiolytics, and hint toward biomarkers underpinning behavioral and social patterns that merit further exploration
Explicit solution for a Gaussian wave packet impinging on a square barrier
The collision of a quantum Gaussian wave packet with a square barrier is
solved explicitly in terms of known functions. The obtained formula is suitable
for performing fast calculations or asymptotic analysis. It also provides
physical insight since the description of different regimes and collision
phenomena typically requires only some of the terms.Comment: To be published in J. Phys.
A Systematic Proteomic Study of Irradiated DNA Repair Deficient Nbn-Mice
BACKGROUND: The NBN gene codes for the protein nibrin, which is involved in the detection and repair of DNA double strand breaks (DSBs). The NBN gene is essential in mammals. METHODOLOGY/PRINCIPAL FINDINGS: We have used a conditional null mutant mouse model in a proteomics approach to identify proteins with modified expression levels after 4 Gy ionizing irradiation in the absence of nibrin in vivo. Altogether, amongst approximately 8,000 resolved proteins, 209 were differentially expressed in homozygous null mutant mice in comparison to control animals. One group of proteins significantly altered in null mutant mice were those involved in oxidative stress and cellular redox homeostasis (p<0.0001). In substantiation of this finding, analysis of Nbn null mutant fibroblasts indicated an increased production of reactive oxygen species following induction of DSBs. CONCLUSIONS/SIGNIFICANCE: In humans, biallelic hypomorphic mutations in NBN lead to Nijmegen breakage syndrome (NBS), an autosomal recessive genetic disease characterised by extreme radiosensitivity coupled with growth retardation, immunoinsufficiency and a very high risk of malignancy. This particularly high cancer risk in NBS may be attributable to the compound effect of a DSB repair defect and oxidative stress