Anti-DKK1 Enhances the Early Osteogenic Differentiation of Human Adipose-Derived Stem/Stromal Cells

: Adipose-derived stem/stromal cells (ASCs) have been previously used for bone repair. However, significant cell heterogeneity exists within the ASC population, which has the potential to result in unreliable bone tissue formation and/or low efficacy. Although the use of cell sorting to lower cell heterogeneity is one method to improve bone formation, this is a technically sophisticated and costly process. In this study, we tried to find a simpler and more deployable solution-blocking antiosteogenic molecule Dickkopf-1 (DKK1) to improve osteogenic differentiation. Human adipose-derived stem cells were derived from = 5 samples of human lipoaspirate. In vitro, anti-DKK1 treatment, but not anti-sclerostin (SOST), promoted ASC osteogenic differentiation, assessed by alizarin red staining and real-time polymerase chain reaction (qPCR). Increased canonical Wnt signaling was confirmed after anti-DKK1 treatment. Expression levels of DKK1 peaked during early osteogenic differentiation (day 3). Concordantly, anti-DKK1 supplemented early (day 3 or before), but not later (day 7) during osteogenic differentiation positively regulated osteoblast formation. Finally, anti-DKK1 led to increased transcript abundance of the Wnt inhibitor SOST, potentially representing a compensatory cellular mechanism. In sum, DKK1 represents a targetable "molecular brake" on the osteogenic differentiation of human ASC. Moreover, release of this brake by neutralizing anti-DKK1 antibody treatment at least partially rescues the poor bone-forming efficacy of ASC

Finding TJREVERB: A Crowdsourced Effort to Find a High School CubeSat

This paper documents the team\u27s process for finding the Thomas Jefferson Research and Education Vehicle for Radio Broadcasts (TJREVERB) with the help of the Amateur Radio community. The team attempted contacting the primary Iridium radio on TJREVERB for one week after it was deployed from the International Space Station but failed. The satellite did switch to its secondary radio, a SATT 4 APRS. However, the team was inexperienced and unprepared to contact the satellite using the SATT 4 APRS. Since we do not have access to an APRS ground station, we leveraged the help of twenty amateur radio volunteers from all around the world to contact TJREVERB. Additionally, many more amateur radio operators contributed their expertise and recorded sightings of TJREVERB using resources such as SatNog\u27s satellite database. This global network of volunteers cooperated to position their respective stations for the best possible chance of contact. This paper discusses how the Amateur Radio community\u27s involvement is invaluable to the students\u27 small satellite education. It also discusses the training program developed due to this experience. The lessons learned about satellite contacts and operations are critically important for future educational satellite teams and will contribute to their success

The Violin Students of Shakeh Ghoukasian

Program listing performers and works performe

Human perivascular stem cells prevent bone graft resorption in osteoporotic contexts by inhibiting osteoclast formation

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Systemic DKK1 neutralization enhances human adipose-derived stem cell mediated bone repair

: Progenitor cells from adipose tissue are able to induce bone repair; however, inconsistent or unreliable efficacy has been reported across preclinical and clinical studies. Soluble inhibitory factors, such as the secreted Wnt signaling antagonists Dickkopf-1 (DKK1), are expressed to variable degrees in human adipose-derived stem cells (ASCs), and may represent a targetable "molecular brake" on ASC mediated bone repair. Here, anti-DKK1 neutralizing antibodies were observed to increase the osteogenic differentiation of human ASCs in vitro, accompanied by increased canonical Wnt signaling. Human ASCs were next engrafted into a femoral segmental bone defect in NOD-Scid mice, with animals subsequently treated with systemic anti-DKK1 or isotype control during the repair process. Human ASCs alone induced significant but modest bone repair. However, systemic anti-DKK1 induced an increase in human ASC engraftment and survival, an increase in vascular ingrowth, and ultimately improved bone repair outcomes. In summary, anti-DKK1 can be used as a method to augment cell-mediated bone regeneration, and could be particularly valuable in the contexts of impaired bone healing such as osteoporotic bone repair

Lysosomal protein surface expression discriminates fat- from bone-forming human mesenchymal precursor cells

Tissue resident mesenchymal stem/stromal cells (MSCs) occupy perivascular spaces. Profiling human adipose perivascular mesenchyme with antibody arrays identified 16 novel surface antigens, including endolysosomal protein CD107a. Surface CD107a expression segregates MSCs into functionally distinct subsets. In culture, CD107a(low) cells demonstrate high colony formation, osteoprogenitor cell frequency, and osteogenic potential. Conversely, CD107a(high) cells include almost exclusively adipocyte progenitor cells. Accordingly, human CD107a(low) cells drove dramatic bone formation after intramuscular transplantation in mice, and induced spine fusion in rats, whereas CD107a(high) cells did not. CD107a protein trafficking to the cell surface is associated with exocytosis during early adipogenic differentiation. RNA sequencing also suggested that CD107a(low) cells are precursors of CD107a(high) cells. These results document the molecular and functional diversity of perivascular regenerative cells, and show that relocation to cell surface of a lysosomal protein marks the transition from osteo- to adipogenic potential in native human MSCs, a population of substantial therapeutic interest

ProteomeScout: A repository and analysis resource for post-translational modifications and proteins

ProteomeScout (https://proteomescout.wustl.edu) is a resource for the study of proteins and their post-translational modifications (PTMs) consisting of a database of PTMs, a repository for experimental data, an analysis suite for PTM experiments, and a tool for visualizing the relationships between complex protein annotations. The PTM database is a compendium of public PTM data, coupled with user-uploaded experimental data. ProteomeScout provides analysis tools for experimental datasets, including summary views and subset selection, which can identify relationships within subsets of data by testing for statistically significant enrichment of protein annotations. Protein annotations are incorporated in the ProteomeScout database from external resources and include terms such as Gene Ontology annotations, domains, secondary structure and non-synonymous polymorphisms. These annotations are available in the database download, in the analysis tools and in the protein viewer. The protein viewer allows for the simultaneous visualization of annotations in an interactive web graphic, which can be exported in Scalable Vector Graphics (SVG) format. Finally, quantitative data measurements associated with public experiments are also easily viewable within protein records, allowing researchers to see how PTMs change across different contexts. ProteomeScout should prove useful for protein researchers and should benefit the proteomics community by providing a stable repository for PTM experiments

Gene content evolution in the arthropods

Arthropods comprise the largest and most diverse phylum on Earth and play vital roles in nearly every ecosystem. Their diversity stems in part from variations on a conserved body plan, resulting from and recorded in adaptive changes in the genome. Dissection of the genomic record of sequence change enables broad questions regarding genome evolution to be addressed, even across hyper-diverse taxa within arthropods. Using 76 whole genome sequences representing 21 orders spanning more than 500 million years of arthropod evolution, we document changes in gene and protein domain content and provide temporal and phylogenetic context for interpreting these innovations. We identify many novel gene families that arose early in the evolution of arthropods and during the diversification of insects into modern orders. We reveal unexpected variation in patterns of DNA methylation across arthropods and examples of gene family and protein domain evolution coincident with the appearance of notable phenotypic and physiological adaptations such as flight, metamorphosis, sociality, and chemoperception. These analyses demonstrate how large-scale comparative genomics can provide broad new insights into the genotype to phenotype map and generate testable hypotheses about the evolution of animal diversity

Community-Centered Responses to Ebola in Urban Liberia: The View from Below

The West African Ebola epidemic has demonstrated that the existing range of medical and epidemiological responses to emerging disease outbreaks is insufficient, especially in post-conflict contexts with exceedingly poor healthcare infrastructures. This study provides baseline information on community-based epidemic control priorities and identifies innovative local strategies for containing EVD in Liberia.In this study the authors analyzed data from the 2014 Ebola outbreak in Monrovia and Montserrado County, Liberia. The data were collected for the purposes of program design and evaluation by the World Health Organization (WHO) and the Government of Liberia (GOL), in order to identify: (1) local knowledge about EVD, (2) local responses to the outbreak, and (3) community based innovations to contain the virus. At the time of data collection, the international Ebola response had little insight into how much local Liberian communities knew about Ebola, and how communities managed the epidemic when they could not get access to care due to widespread hospital and clinic closures. Methods included 15 focus group discussions with community leaders from areas with active Ebola cases. Participants were asked about best practices and what they were currently doing to manage EVD in their respective communities, with the goal of developing conceptual models of local responses informed by local narratives. Findings reveal that communities responded to the outbreak in numerous ways that both supported and discouraged formal efforts to contain the spread of the disease. This research will inform global health policy for both this, and future, epidemic and pandemic responses