Translational Roadmap for the Organs-on-a-Chip Industry toward Broad Adoption

Organs-on-a-Chip (OOAC) is a disruptive technology with widely recognized potential to change the efficiency, effectiveness, and costs of the drug discovery process; to advance insights into human biology; to enable clinical research where human trials are not feasible. However, further development is needed for the successful adoption and acceptance of this technology. Areas for improvement include technological maturity, more robust validation of translational and predictive in vivo-like biology, and requirements of tighter quality standards for commercial viability. In this review, we reported on the consensus around existing challenges and necessary performance benchmarks that are required toward the broader adoption of OOACs in the next five years, and we defined a potential roadmap for future translational development of OOAC technology. We provided a clear snapshot of the current developmental stage of OOAC commercialization, including existing platforms, ancillary technologies, and tools required for the use of OOAC devices, and analyze their technology readiness levels. Using data gathered from OOAC developers and end-users, we identified prevalent challenges faced by the community, strategic trends and requirements driving OOAC technology development, and existing technological bottlenecks that could be outsourced or leveraged by active collaborations with academia

Metabolomic Analysis Evidences That Uterine Epithelial Cells Enhance Blastocyst Development in a Microfluidic Device

Here we report the use of a microfluidic system to assess the differential metabolomics of murine embryos cultured with endometrial cells-conditioned media (CM). Groups of 10, 1-cell murine B6C3F1 × B6D2F1 embryos were cultured in the microfluidic device. To produce CM, mouse uterine epithelial cells were cultured in potassium simplex optimized medium (KSOM) for 24 h. Media samples were collected from devices after 5 days of culture with KSOM (control) and CM, analyzed by reverse phase liquid chromatography and untargeted positive ion mode mass spectrometry analysis. Blastocyst rates were significantly higher (p < 0.05) in CM (71.8%) compared to control media (54.6%). We observed significant upregulation of 341 compounds and downregulation of 214 compounds in spent media from CM devices when compared to control. Out of these, 353 compounds were identified showing a significant increased abundance of metabolites involved in key metabolic pathways (e.g., arginine, proline and pyrimidine metabolism) in the CM group, suggesting a beneficial effect of CM on embryo development. The metabolomic study carried out in a microfluidic environment confirms our hypothesis on the potential of uterine epithelial cells to enhance blastocyst development. Further investigations are required to highlight specific pathways involved in embryo development and implantation

Screening of DUB activity and specificity by MALDI-TOF mass spectrometry

Deubiquitylases (DUBs) are key regulators of the ubiquitin system which cleave ubiquitin moieties from proteins and polyubiquitin chains. Several DUBs have been implicated in various diseases and are attractive drug targets. We have developed a sensitive and fast assay to quantify in vitro DUB enzyme activity using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. Unlike other current assays, this method uses unmodified substrates, such as diubiquitin topoisomers. By analyzing 42 human DUBs against all diubiquitin topoisomers we provide an extensive characterization of DUB activity and specificity. Our results confirm the high specificity of many members of the OTU and JAMM DUB families and highlight that all USPs tested display low linkage selectivity. We also demonstrate that this assay can be deployed to assess the potency and specificity of DUB inhibitors by profiling 11 compounds against a panel of 32 DUBs

Argumentation in school science : Breaking the tradition of authoritative exposition through a pedagogy that promotes discussion and reasoning

The value of argumentation in science education has become internationally recognised and has been the subject of many research studies in recent years. Successful introduction of argumentation activities in learning contexts involves extending teaching goals beyond the understanding of facts and concepts, to include an emphasis on cognitive and metacognitive processes, epistemic criteria and reasoning. The authors focus on the difficulties inherent in shifting a tradition of teaching from one dominated by authoritative exposition to one that is more dialogic, involving small-group discussion based on tasks that stimulate argumentation. The paper builds on previous research on enhancing the quality of argument in school science, to focus on how argumentation activities have been designed, with appropriate strategies, resources and modelling, for pedagogical purposes. The paper analyses design frameworks, their contexts and lesson plans, to evaluate their potential for enhancing reasoning through foregrounding the processes of argumentation. Examples of classroom dialogue where teachers adopt the frameworks/plans are analysed to show how argumentation processes are scaffolded. The analysis shows that several layers of interpretation are needed and these layers need to be aligned for successful implementation. The analysis serves to highlight the potential and limitations of the design frameworks

Motivational Interviewing as Evidence-Based Practice? An Example from Sexual Risk Reduction Interventions Targeting Adolescents and Young Adults

This paper critically examines sexual risk reduction interventions, more specifically how they are evaluated and the implications that this has for sexual health policy. The focus is on motivational interviewing (MI) interventions which aim to promote protective behaviors related to sexual risk on the part of young people. MI has become increasingly popular, largely due to it being a highly flexible counseling approach that may, with adequate staff training, and fidelity in implementation, be tailored to many different settings (e.g., health care, schools and in community work). Following a scoping review that comprised 34 papers, of which 29 were unique studies, the range and type of existing research were examined. The results show a wide range of study designs and evaluation procedures, MI conceptualizations, modes of MI delivery, and the particular sub-populations of youth and sexual risk behaviors targeted. While this makes it difficult to draw any generalized conclusions about “what works” in prevention, it provides important insights about the complexity of sexual risk behavior as well as complex behavioral treatment approaches like MI. We therefore problematize the political drive to implement evidence-based methods without adequate resource allocation and contextual adaptation

Youth–adult partnership: exploring contributions to empowerment, agency and community connections in Malaysian youth programs

Youth–adult partnership (Y–AP) has emerged as a key practice for enacting two features of effective developmental settings: supportive adult relationships and support for efficacy and mattering. Previous studies have shown that when youth, supported by adults, actively participate in organizational and community decision-making they are likely to show greater confidence and agency, empowerment and critical consciousness, and community connections. Most of the extant research on Y–AP is limited to qualitative studies and the identification of organizational best practices. Almost all research focuses on Western sociocultural settings. To address these gaps, 299 youth, age 15 to 24, were sampled from established afterschool and community programs in Malaysia to explore the contribution of Y–AP (operationalized as having two components: youth voice in decision-making and supportive adult relationships) to empowerment, agency and community connections. As hypothesized, hierarchical regressions indicated that program quality (Y–AP, safe environment and program engagement) contributed to agency, empowerment and community connections beyond the contribution of family, school and religion. Additionally, the Y–AP measures contributed substantially more variance than the other measures of program quality on each outcome. Interaction effects indicated differences by age for empowerment and agency but not for community connections. The primary findings in this inquiry replicate those found in previous interview and observational-oriented studies. The data suggests fertile ground for future research while demonstrating that Y–AP may be an effective practice for positive youth development outside of Western settings

Engagement Across Developmental Periods

The goal of this chapter is to provide a cohesive developmental framework and foundation for which to understand student engagement across early childhood, middle childhood, and adolescence. Guided by the bioecological theory of human development and the person-environment fit perspective, this chapter extends Finn\u27s participation-identification model of engagement by mapping student engagement within a larger developmental sequence. This chapter discusses student engagement within specific developmental periods that are tied to the developmental tasks, opportunities, and challenges unique to early childhood, middle childhood, and adolescence. Student engagement is found to be a nuanced developmental outcome, and the differences may be a result of the maturation of biological, cognitive, and socioemotional developmental tasks and the changing contextual landscape for the children and adolescents. Recommendations for future research as well as policy implications are also discussed

Probing morphological, genetic and metabolomic changes of in vitro embryo development in a microfluidic device

Assisted reproduction technologies for clinical and research purposes rely on a brief in vitro embryo culture which, despite decades of progress, remain suboptimal in comparison to the physiological environment. One promising tool to improve this technique is the development of bespoke microfluidic chambers. Here we present and validate a new microfluidic device in polydimethylsiloxane (PDMS) for the culture of early mouse embryos. Device material and design resulted embryo compatible and elicit minimal stress. Blastocyst formation, hatching, attachment and outgrowth formation on fibronectin-coated devices were similar to traditional microdrop methods. Total blastocyst cell number and allocation to the trophectoderm and inner cell mass lineages were unaffected. The devices were designed for culture of 10-12 embryos. Development rates, mitochondrial polarisation and metabolic turnover of key energy substrates glucose, pyruvate and lactate were consistent with groups of 10 embryos in microdrop controls. Increasing group size to 40 embryos per device was associated with increased variation in development rates and altered metabolism. Device culture did not perturb blastocyst gene expression but did elicit changes in embryo metabolome, which can be ascribed to substrate leaching from PDMS and warrant further investigation