Bioactivity and circulation time of PEGylated NELL-1 in mice and the potential for osteoporosis therapy.

Osteoporosis is a progressive bone disease due to low osteoblast activity and/or high osteoclast activity. NELL-1 is a potential therapy for osteoporosis because it specifically increases osteoblast differentiation. However, similar to other protein drugs, the bioavailability of NELL-1 may be limited by its in vivo half-life and rapid clearance from body.

Learning sparse kernel classifiers for multi-instance classification.

We propose a direct approach to learning sparse kernel classifiers for multi-instance (MI) classification to improve efficiency while maintaining predictive accuracy. The proposed method builds on a convex formulation for MI classification by considering the average score of individual instances for bag-level prediction. In contrast, existing formulations used the maximum score of individual instances in each bag, which leads to nonconvex optimization problems.

Lentiviral delivery of PPARγ shRNA alters the balance of osteogenesis and adipogenesis, improving bone microarchitecture.

Introduction: Skeletal aging is associated not only with alterations in osteoblast (OB) and osteoclast (OC) number and activity within the basic metabolic unit, but also with increased marrow adiposity. Peroxisome proliferator-activated receptor gamma (PPARγ) is commonly considered the master transcriptional regulator of adipogenesis, however, it has known roles in osteoblast and osteoclast function as well. Here, we designed a lentiviral delivery system for PPARγ shRNA, and examined its effects in vitro on bone marrow stromal cells (BMSC) and in a mouse intramedullary injection model.

Fibromodulin-deficiency alters temporospatial expression patterns of transforming growth factor-β ligands and receptors during adult mouse skin wound healing.

Fibromodulin (FMOD) is a small leucine-rich proteoglycan required for scarless fetal cutaneous wound repair. Interestingly, increased FMOD levels have been correlated with decreased transforming growth factor (TGF)-β1 expression in multiple fetal and adult rodent models. Our previous studies demonstrated that FMOD-deficiency in adult animals results in delayed wound closure and increased scar size accompanied by loose package collagen fiber networks with increased fibril diameter.

Oligomerization-induced conformational change in the C-terminal region of Nel-like molecule 1 (NELL1) protein is necessary for the efficient mediation of murine MC3T3-E1 cell adhesion and spreading.

NELL1 is a large oligomeric secretory glycoprotein that functions as an osteoinductive factor. NELL1 contains several conserved domains, has structural similarities to thrombospondin 1, and supports osteoblastic cell adhesion through integrins. To define the structural requirements for NELL1-mediated cell adhesion, we prepared a series of recombinant NELL1 proteins (intact, deleted, and cysteine-mutant) from a mammalian expression system and tested their activities.

Omnidirectional antireflection polymer films nanoimprinted by density-graded nanoporous silicon and image improvement in display panel.

We present a low-cost method to fabricate large-area polycarbonate AR nanostructures to improve the luminous intensity and image clarity of a commercial 2.0-inch display panel in bright condition. The polycarbonate AR nanostructures were nanoimprinted by the graded-density nanoporous silicon template with nanoparticle-catalyzed etching.

Integrated strategic and tactical biomass-biofuel supply chain optimization.

To ensure effective biomass feedstock provision for large-scale biofuel production, an integrated biomass supply chain optimization model was developed to minimize annual biomass-ethanol production costs by optimizing both strategic and tactical planning decisions simultaneously. The mixed integer linear programming model optimizes the activities range from biomass harvesting, packing, in-field transportation, stacking, transportation, preprocessing, and storage, to ethanol production and distribution. The numbers, locations, and capacities of facilities as well as biomass and ethanol distribution patterns are key strategic decisions; while biomass production, delivery, and operating schedules and inventory monitoring are key tactical decisions.

The antimalarial drug quinine interferes with serotonin biosynthesis and action.

The major antimalarial drug quinine perturbs uptake of the essential amino acid tryptophan, and patients with low plasma tryptophan are predisposed to adverse quinine reactions; symptoms of which are similar to indications of tryptophan depletion. As tryptophan is a precursor of the neurotransmitter serotonin (5-HT), here we test the hypothesis that quinine disrupts serotonin function. Quinine inhibited serotonin-induced proliferation of yeast as well as human (SHSY5Y) cells.

Age-related effects on perceptual and semantic encoding in memory.

This study examined the age-related subsequent memory effect (SME) in perceptual and semantic encoding using event-related potentials (ERPs). Seventeen younger adults and 17 older adults studied a series of Chinese characters either perceptually (by inspecting orthographic components) or semantically (by determining whether the depicted object makes sounds). The two tasks had similar levels of difficulty.

How does experience modulate auditory spatial processing in individuals with blindness?

Comparing early- and late-onset blindness in individuals offers a unique model for studying the influence of visual experience on neural processing. This study investigated how prior visual experience would modulate auditory spatial processing among blind individuals. BOLD responses of early- and late-onset blind participants were captured while performing a sound localization task.

Evaluating the quality and readability of thyroplasty information on the Internet.

Objectives/hypothesis: To assess the quality and readability of thyroplasty information available on the Internet.

Study Design: Cross-sectional study.

Methods: We conducted a Google search for "thyroplasty treatment" and analyzed the first 50 Web sites using the DISCERN instrument, the Flesch Reading Ease Score (FRES), and the Flesch-Kincaid Grade Level (FKGL) score.

Regulation of vascular leak and recovery from ischemic injury by general and VE-cadherin-restricted miRNA antagonists of miR-27.

Cellular junctions are essential to the normal functioning of the endothelium and control angiogenesis, tissue leak, and inflammation. From a screen of micro RNAs (miRNAs) altered in in vitro angiogenesis, we selected a subset predicted to target junctional molecules. MiR-27a was rapidly downregulated upon stimulation of in vitro angiogenesis, and its level of expression is reduced in neovessels in vivo.

Fibromodulin promoted in vitro and in vivo angiogenesis.

Fibromodulin (FMOD) is an extracellular matrix (ECM) small leucine-rich proteoglycan (SLRP) that plays an important role in cell fate determination. Previous studies revealed that not only is FMOD critical in fetal-type scarless wound healing, but it also promotes adult wound closure and reduces scar formation. In addition, FMOD-deficient mice exhibit significantly reduced blood vessel regeneration in granulation tissues during wound healing.

BMP2-induced inflammation can be suppressed by the osteoinductive growth factor NELL-1.

Bone-morphogenetic protein 2 (BMP2) is currently the only Food and Drug Administration-approved osteoinductive growth factor used in clinical settings for bone regeneration and repair. However, the use of BMP2 is encumbered by numerous clinical complications, including postoperative inflammation and life-threatening cervical swelling. Thus, methods to prevent BMP2-induced inflammation would have far-reaching clinical implications toward improving current BMP2-based methods for bone regeneration.

Cell wall perturbation sensitizes fungi to the antimalarial drug chloroquine.

Chloroquine (CQ) has been a mainstay of antimalarial drug treatment for several decades. Additional therapeutic actions of CQ have been described, including some reports of fungal inhibition. Here we investigated the action of CQ in fungi, including the yeast model Saccharomyces cerevisiae.

NF-κB inhibits osteogenic differentiation of mesenchymal stem cells by promoting β-catenin degradation.

Mesenchymal stem cell (MSC)-based transplantation is a promising therapeutic approach for bone regeneration and repair. In the realm of therapeutic bone regeneration, the defect or injured tissues are frequently inflamed with an abnormal expression of inflammatory mediators. Growing evidence suggests that proinflammatory cytokines inhibit osteogenic differentiation and bone formation.

Human perivascular stem cells show enhanced osteogenesis and vasculogenesis with Nel-like molecule I protein.

An ideal mesenchymal stem cell (MSC) source for bone tissue engineering has yet to be identified. Such an MSC population would be easily harvested in abundance, with minimal morbidity and with high purity. Our laboratories have identified perivascular stem cells (PSCs) as a candidate cell source.

High Correlation of 2,2-diphenyl-1-picrylhydrazyl (DPPH) Radical Scavenging, Ferric Reducing Activity Potential and Total Phenolics Content Indicates Redundancy in Use of All Three Assays to Screen for Antioxidant Activity of Extracts of Plants from the Malaysian Rainforest.

Extracts of plants from the Malaysian rainforest and other fragile habitats are being researched intensively for identification of beneficial biological actions, with assessment of antioxidant behavior being a common component of such assessments. A number of tests for antioxidant behavior are used, with the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reduction activity potential (FRAP) assays often being used in parallel, and also with measurement of total phenolics content (TPC) as a surrogate marker for antioxidant capacity. The present study investigated the possible redundancy in using all three assays to determine antioxidant capacity in 92 extracts obtained from 27 plants from the Malaysian rainforest.

An abundant perivascular source of stem cells for bone tissue engineering.

Adipose tissue is an ideal mesenchymal stem cell (MSC) source, as it is dispensable and accessible with minimal morbidity. However, the stromal vascular fraction (SVF) of adipose tissue is a heterogeneous cell population, which has disadvantages for tissue regeneration. In the present study, we prospectively purified human perivascular stem cells (PSCs) from n = 60 samples of human lipoaspirate and documented their frequency, viability, and variation with patient demographics.

Perivascular stem cells: a prospectively purified mesenchymal stem cell population for bone tissue engineering.

Adipose tissue is an ideal source of mesenchymal stem cells for bone tissue engineering: it is largely dispensable and readily accessible with minimal morbidity. However, the stromal vascular fraction (SVF) of adipose tissue is a heterogeneous cell population, which leads to unreliable bone formation. In the present study, we prospectively purified human perivascular stem cells (PSCs) from adipose tissue and compared their bone-forming capacity with that of traditionally derived SVF.

NELL-1 injection maintains long-bone quantity and quality in an ovariectomy-induced osteoporotic senile rat model.

Over 10 million Americans have osteoporosis, and is the predominant cause of fractures in the elderly. Treatment of fractures in the setting of osteoporosis is complicated by a suboptimal bone regenerative response due to a decline in the number of osteoblasts, their function, and survival. Consequently, an osteogenic therapeutic to prevent and treat fractures in patients with osteoporosis is needed.

Differentiation of perceptual and semantic subsequent memory effects using an orthographic paradigm.

This study aimed to differentiate perceptual and semantic encoding processes using subsequent memory effects (SMEs) elicited by the recognition of orthographs of single Chinese characters. Participants studied a series of Chinese characters perceptually (by inspecting orthographic components) or semantically (by determining the object making sounds), and then made studied or unstudied judgments during the recognition phase. Recognition performance in terms of d-prime measure in the semantic condition was higher, though not significant, than that of the perceptual condition.

The antimicrobial and osteoinductive properties of silver nanoparticle/poly (DL-lactic-co-glycolic acid)-coated stainless steel.

Implant-associated bacterial infections are one of the most serious complications in orthopedic surgery. Treatment of these infections often requires multiple operations, device removal, long-term systemic antibiotics, and extended rehabilitation, and is frequently ineffective, leading to worse clinical outcomes and increased financial costs. In this study, we evaluated silver nanoparticle/poly(DL-lactic-co-glycolic acid) (PLGA)-coated stainless steel alloy(SNPSA) as a potential antimicrobial implant material.