Hypoxia promotes redifferentiation and suppresses markers of hypertrophy and degeneration in both healthy and osteoarthritic chondrocytes

INTRODUCTION: Hypoxia is considered to be a positive influence on the healthy chondrocyte phenotype and cartilage matrix formation. However, hypoxia-inducible factors (HIFs) have been implicated in the pathogenesis of osteoarthritis (OA). Thus, we assessed whether healthy and OA chondrocytes have distinct responses to oxygen, particularly with regard to hypertrophy and degradation during redifferentiation. METHODS: Monolayer-expanded healthy and OA chondrocytes were redifferentiated for 14 days in pellet cultures under standard (20% oxygen) or hypoxic (2% oxygen) conditions. Cartilage matrix gene expression, matrix quality and quantity, degradative enzyme expression and HIF expression were measured. RESULTS: In hypoxia, both healthy and OA chondrocytes had higher human collagen type II, α1 gene (COL2A1), and aggrecan (ACAN) expression and sulfated glycosaminoglycan (sGAG) accumulation, concomitant with lower human collagen type X, α1 gene (COL10A1), and human collagen type I, α1 gene (COL1A1), expression and collagen I extracellular accumulation. OA chondrocytes had significantly lower sGAGs/DNA than healthy chondrocytes, but only in high oxygen conditions. Hypoxia also caused significantly greater sGAG retention and hyaluronic acid synthase 2 (HAS2) expression by OA chondrocytes. Both healthy and OA chondrocytes had significantly lower expression of matrix metalloproteinases (MMPs) MMP1, MMP2, MMP3 and MMP13 in hypoxia and less active MMP2 enzyme, consistent with lower MMP14 expression. However, aggrecanase (ADAMTS4 and ADAMTS5) expression was significantly lowered by hypoxia only in healthy cells, and COL10A1 and MMP13 remained significantly higher in OA chondrocytes than in healthy chondrocytes in hypoxic conditions. HIF-1α and HIF-2α had similar expression profiles in healthy and OA cells, increasing to maximal levels early in hypoxia and decreasing over time. CONCLUSIONS: Hypoxic culture of human chondrocytes has long been acknowledged to result in increased matrix accumulation, but still little is known of its effects on catabolism. We show herein that the increased expression of matrix proteins, combined with decreased expression of numerous degradative enzymes by hypoxia, minimizes but does not abolish differences between redifferentiated healthy and OA chondrocytes. Hypoxia-induced HIF expression is associated with hypertrophic marker and degradative enzyme downregulation and increased measures of redifferentiation in both healthy and OA chondrocytes. Therefore, though HIFs may be involved in the pathogenesis of OA, conditions that promote HIF expression in vitro promote matrix accumulation and decrease degradation and hypertrophy, even in cells from OA joints

Understanding faculty and student perceptions about reward and advancement : survey of four STEM departments at research intensive universities

This report summarizes the results of a survey exploring four STEM departments that have engaged in meaningful reforms in academic systems of reward and advancement including promotion and tenure (P&T). The survey was administered as part of a study seeking to expose the strengths and challenges of reform efforts by understanding the lived experiences of faculty and graduate trainees. The four departments are relatively large (>40 faculty), and are situated in public, very high research activity (Carnegie R1) institutions located in relatively small, suburban or rurally-situated college towns in the Northwest and Midwest United States. It aims to provide insights into faculty and student perceptions of and experiences with departmental level practices. University leaders and those working on national-scale initiatives to improve reward and advancement in higher education may find these results useful

What nonpharmacological treatments are effective against common nongenital warts?

Cryotherapy has similar cure rates to topical salicylate (a pharmacologic therapy) for non-genital common warts (strength of recommendation [SOR]: B, based on systemic review of variable quality randomized trials). Duct tape may be equivalent to cryotherapy (SOR: B, based on a single randomized trial). CO2 laser, photodynamic therapy, pulsed dye laser (PDL), and Er:Yag laser therapies may also be effective for recalcitrant warts (SOR: C, based on observational cohort studies)

Bacteria isolated from Bengal cat (Felis catus × Prionailurus bengalensis) anal sac secretions produce volatile compounds potentially associated with animal signaling.

In social animals, scent secretions and marking behaviors play critical roles in communication, including intraspecific signals, such as identifying individuals and group membership, as well as interspecific signaling. Anal sacs are an important odor producing organ found across the carnivorans (species in the mammalian Order Carnivora). Secretions from the anal sac may be used as chemical signals by animals for behaviors ranging from defense to species recognition to signaling reproductive status. In addition, a recent study suggests that domestic cats utilize short-chain free fatty acids in anal sac secretions for individual recognition. The fermentation hypothesis is the idea that symbiotic microorganisms living in association with animals contribute to odor profiles used in chemical communication and that variation in these chemical signals reflects variation in the microbial community. Here we examine the fermentation hypothesis by characterizing volatile organic compounds (VOC) and bacteria isolated from anal sac secretions collected from a male Bengal cat (Felis catus × Prionailurus bengalensis), a cross between the domestic cat and the leopard cat. Both left and right anal sacs of a male Bengal cat were manually expressed (emptied) and collected. Half of the material was used to culture bacteria or to extract bacterial DNA and the other half was used for VOC analysis. DNA was extracted from the anal sac secretions and used for a 16S rRNA gene PCR amplification and sequencing based characterization of the microbial community. Additionally, some of the material was plated out in order to isolate bacterial colonies. Three taxa (Bacteroides fragilis, Tessaracoccus, and Finegoldia magna) were relatively abundant in the 16S rRNA gene sequence data and also isolated by culturing. Using Solid Phase Microextraction (SPME) gas chromatography-mass spectrometry (GC-MS), we tentatively identified 52 compounds from the Bengal cat anal sac secretions and 67 compounds from cultures of the three bacterial isolates chosen for further analysis. Among 67 compounds tentatively identified from bacterial isolates, 51 were also found in the anal sac secretion. We show that the bacterial community in the anal sac consists primarily of only a few abundant taxa and that isolates of these taxa produce numerous volatiles that are found in the combined anal sac volatile profile. Several of these volatiles are found in anal sac secretions from other carnivorans, and are also associated with known bacterial biosynthesis pathways. This is consistent with the fermentation hypothesis and the possibility that the anal sac is maintained at least in part to house bacteria that produce volatiles for the host

Going Beyond Hooked Participants: The Nibble-and-Drop Framework for Classifying Citizen Science Participation

Many citizen science (CS) programs aim to grow and sustain a pool of enthusiastic participants who consistently contribute their efforts to a specific scientific endeavor. Consequently, much research has explored CS participants’ motivations and their relationship to participant recruitment and retention. However, much of this research has focused on actively participating citizen scientists. If researchers want to elucidate the relationship between participant factors (such as demographics and motivations) and participant retention, it is necessary to develop a more comprehensive picture of the different degrees of participation in CS. This paper presents a framework for classifying participation throughout the participant’s engagement in a CS project/program. We suggest a CS participation model that captures the dynamic nature of participation across an arc of volunteering. Called the Nibble-and-Drop Framework, the model describes multiple exit points and stages of contribution typical of participation in a CS program. Applying the framework to the NASA GLOBE Observer (GO) CS program, we found that it captured the dynamics of participation in a global-scale, mobile, app-based, contributory-style CS project. The framework guided our analysis of how different participant factors correlate with degrees of participation. We found that participants were motivated to initially participate because they wanted to contribute to NASA research and science. Participants who dropped out of the program at various points often initially engaged through specific collection events and did not feel the need to continue contributing beyond the event; other drop-outs doubted whether their contributions were meaningful, showing again the need to ensure that participants understand the value of their engagement in a CS project.Keywords: Retention, Recruitment, Participation, Evaluatio

Reflections on the Cost of Low-Cost Whole Genome Sequencing: Framing the Health Policy Debate

The cost of whole genome sequencing is dropping rapidly. There has been a great deal of enthusiasm about the potential for this technological advance to transform clinical care. Given the interest and significant investment in genomics, this seems an ideal time to consider what the evidence tells us about potential benefits and harms, particularly in the context of health care policy. The scale and pace of adoption of this powerful new technology should be driven by clinical need, clinical evidence, and a commitment to put patients at the centre of health care policy

Inclusively Recognizing Faculty Innovation and Entrepreneurship Impact Within Promotion and Tenure Considerations

Faculty research has led to a plethora of innovations and entrepreneurial resources (I&E), allowing for enhancements to the greater social good including, but not limited to, technological and economic advancements. Faculty I&E also enhances faculty competitiveness for funding, institutional image and fundraising, and supports students’ workforce preparation. Over time institutions of higher education have recognized the value of faculty I&E in their mission statements and strategic plans. Yet commensurate promotion and tenure processes and policies are not a given, within and across institutions, and many faculties may be in the position of weighing their own interests in I&E activity against a lack of its explicit value in academia. Admittedly, though, an empirical basis regarding these suspicions is limited. Herein, we describe our work: 1) mapping the otherwise unknown terrain of factors relevant to the evaluation of tenure-line faculty members’ I&E in promotion considerations in the US, via a survey of 99 unique institutions across the academic spectrum and, from this, 2) advancing recommendations to inform a non-binding alliance of over 67 US institutions that share a common commitment to pursuing best practices for inclusively recognizing faculty I&E impact through university reward structures.Keywords: Faculty Innovation, Entrepreneurship, Promotion, Tenure, Higher Educatio

Supplementary Material from Nationwide Survey to Gain Understanding of the Current Evaluation of Tenure-line Faculty Members’ I&E in P&T Considerations

This document provides supplementary material from nationwide survey sent to 377 institutions to gain an understanding of the current evaluation of tenure-line faculty members’ innovation and entrepreneurial impact in promotion and tenure considerations. This work was support by the National Science Foundation (Grant # CNS-1936073) and it part of the Promotion & Tenure Innovation & Entrepreneurship (PTIE) effort (PTIE.org)