Regulations and Ethical Considerations for Astronomy Education Research II: Resources and Worked Examples

This article discusses the legal and ethical requirements of human subjects research proposals in astronomy education research. We present an overview of the relevant laws, regulations, and guidelines that inform an Institutional Review Board evaluation of proposed research. We also present examples of potential research projects in astronomy education research and discuss their ethical issues

Hedgehog Pathway Activation Alters Ciliary Signaling in Primary Hypothalamic Cultures

Primary cilia dysfunction has been associated with hyperphagia and obesity in both ciliopathy patients and mouse models of cilia perturbation. Neurons throughout the brain possess these solitary cellular appendages, including in the feeding centers of the hypothalamus. Several cell biology questions associated with primary neuronal cilia signaling are challenging to address in vivo. Here we utilize primary hypothalamic neuronal cultures to study ciliary signaling in relevant cell types. Importantly, these cultures contain neuronal populations critical for appetite and satiety such as pro-opiomelanocortin (POMC) and agouti related peptide (AgRP) expressing neurons and are thus useful for studying signaling involved in feeding behavior. Correspondingly, these cultured neurons also display electrophysiological activity and respond to both local and peripheral signals that act on the hypothalamus to influence feeding behaviors, such as leptin and melanin concentrating hormone (MCH). Interestingly, we found that cilia mediated hedgehog signaling, generally associated with developmental processes, can influence ciliary GPCR signaling (Mchr1) in terminally differentiated neurons. Specifically, pharmacological activation of the hedgehog-signaling pathway using the smoothened agonist, SAG, attenuated the ability of neurons to respond to ligands (MCH) of ciliary GPCRs. Understanding how the hedgehog pathway influences cilia GPCR signaling in terminally differentiated neurons could reveal the molecular mechanisms associated with clinical features of ciliopathies, such as hyperphagia-associated obesity

Differential expression analysis with global network adjustment

<p>Background: Large-scale chromosomal deletions or other non-specific perturbations of the transcriptome can alter the expression of hundreds or thousands of genes, and it is of biological interest to understand which genes are most profoundly affected. We present a method for predicting a gene’s expression as a function of other genes thereby accounting for the effect of transcriptional regulation that confounds the identification of genes differentially expressed relative to a regulatory network. The challenge in constructing such models is that the number of possible regulator transcripts within a global network is on the order of thousands, and the number of biological samples is typically on the order of 10. Nevertheless, there are large gene expression databases that can be used to construct networks that could be helpful in modeling transcriptional regulation in smaller experiments.</p> <p>Results: We demonstrate a type of penalized regression model that can be estimated from large gene expression databases, and then applied to smaller experiments. The ridge parameter is selected by minimizing the cross-validation error of the predictions in the independent out-sample. This tends to increase the model stability and leads to a much greater degree of parameter shrinkage, but the resulting biased estimation is mitigated by a second round of regression. Nevertheless, the proposed computationally efficient “over-shrinkage” method outperforms previously used LASSO-based techniques. In two independent datasets, we find that the median proportion of explained variability in expression is approximately 25%, and this results in a substantial increase in the signal-to-noise ratio allowing more powerful inferences on differential gene expression leading to biologically intuitive findings. We also show that a large proportion of gene dependencies are conditional on the biological state, which would be impossible with standard differential expression methods.</p> <p>Conclusions: By adjusting for the effects of the global network on individual genes, both the sensitivity and reliability of differential expression measures are greatly improved.</p&gt

Revisiting Action Research

Purpose: The focus of this paper is to examine what is action research, how it is different from scientific research and how each can contribute to the body of knowledge, while emphasizing that one does not replace the other. Design/Methodology/Approach: The trajectories of action research are reviewed in this paper. Research Findings: Findings suggest action research brings about significant contributions to social change. Further, action research investigators are in a prime position to determine the best method for action research depending on the research issue(s). Research Limitations/Implications: This paper is limited to a general review of action research in the broad fields of education, science, and social science. Nonetheless, this paper argues that the continued growth of action research should strengthen the position and contribution of action research towards knowledge creation and extension. Originality/Value: This paper sheds light on the trajectories, current position, and future of action research. Further, some comparisons with general scientific research are offered

A CreER Mouse to Study Melanin Concentrating Hormone Signaling in the Developing Brain

The neuropeptide, melanin concentrating hormone (MCH), and its G protein‐coupled receptor, melanin concentrating hormone receptor 1 (Mchr1), are expressed centrally in adult rodents. MCH signaling has been implicated in diverse behaviors such as feeding, sleep, anxiety, as well as addiction and reward. While a model utilizing the Mchr1 promoter to drive constitutive expression of Cre recombinase (Mchr1‐Cre) exists, there is a need for an inducible Mchr1‐Cre to determine the roles for this signaling pathway in neural development and adult neuronal function. Here, we generated a BAC transgenic mouse where the Mchr1 promotor drives expression of tamoxifen inducible CreER recombinase. Many aspects of the Mchr1‐Cre expression pattern are recapitulated by the Mchr1‐CreER model, though there are also notable differences. Most strikingly, compared to the constitutive model, the new Mchr1‐CreER model shows strong expression in adult animals in hypothalamic brain regions involved in feeding behavior but diminished expression in regions involved in reward, such as the nucleus accumbens. The inducible Mchr1‐CreER allele will help reveal the potential for Mchr1 signaling to impact neural development and subsequent behavioral phenotypes, as well as contribute to the understanding of the MCH signaling pathway in terminally differentiated adult neurons and the diverse behaviors that it influences

RIP1-HAT1-SirT complex identification and targeting in treatment and prevention of cancer

Purpose: Alteration in cell death is a hallmark of cancer. A functional role regulating survival, apoptosis, and necroptosis has been attributed to RIP1/3 complexes.Experimental Design: We have investigated the role of RIP1 and the effects of MC2494 in cell death induction, using different methods as flow cytometry, transcriptome analysis, immunoprecipitation, enzymatic assays, transfections, mutagenesis, and in vivo studies with different mice models.Results: Here, we show that RIP1 is highly expressed in cancer, and we define a novel RIP1/3-SIRT1/2-HAT1/4 complex. Mass spectrometry identified five acetylations in the kinase and death domain of RIP1. The novel characterized pan-SIRT inhibitor, MC2494, increases RIP1 acetylation at two additional sites in the death domain. Mutagenesis of the acetylated lysine decreases RIP1-dependent cell death, suggesting a role for acetylation of the RIP1 complex in cell death modulation. Accordingly, MC2494 displays tumor-selective potential in vitro, in leukemic blasts ex vivo, and in vivo in both xenograft and allograft cancer models. Mechanistically, MC2494 induces bona fide tumor-restricted acetylated RIP1/caspase-8-mediated apoptosis. Excitingly, MC2494 displays tumor-preventive activity by blocking 7,12-dimethylbenz(α)anthracene-induced mammary gland hyperproliferation in vivoConclusions: These preventive features might prove useful in patients who may benefit from a recurrence-preventive approach with low toxicity during follow-up phases and in cases of established cancer predisposition. Thus, targeting the newly identified RIP1 complex may represent an attractive novel paradigm in cancer treatment and prevention

Practical Steps for the Utilization of Action Research in Your Organization: A Qualitative Approach for Non-Academic Research

Action research is different from traditional research. Action research is more practice based as it is implementing an intervention to improve a problem. Action research involves collaboration and communication between the researcher and the participants within the study. The purpose of this article is to explain the multi-step process for a non-academic researcher or novice researcher when employing qualitative action research in an organization that is looking to solve a complex issue. The article will explore the action research steps for conducting phone employment interviews within the organization and an example of the process to follow. The outlined steps can be adjusted to any organization looking to create sustainable improvements for any problem the organization is looking to change

Phoning it in? Examining Pre-Employment Phone Interview Procedure in Higher Education

In the United States, the employment screening process for hiring full-time faculty in higher education involves the vetting of curricula vitae, phone interview(s), and/or campus visits (Cardeiro, 2010; Shively, Woodward, & Stanly, 1999). The purpose of this research was to examine the phone interview procedure at one institute of higher education, and from there, formulate a systematic phone interviewing procedure that could be put to use at this particular university. After conducting a review of relevant literature, the researchers engaged in action research that utilized qualitative data of 10 participants who took part in the pre-interview, professional development intervention, and the post-interviews for this research project. The action research protocol involved identifying the problem to bring about a positive organizational change, selecting the needed change, implementing the proposed change, and evaluating the results of the change. Upon completion of which, three emerging themes from the collected data were determined: a) phone interview procedure and structure, b) assessment and screening procedures, c) organizational fit. This research proves to be significant because it expands the current knowledge on the topic of conducting employment phone interviews in higher education for tenure track faculty. How higher educational institution conduct faculty screening is often considered a trade secrete, resulting in other institutions unwillingness to provide information on how they conducting faculty screening (Trower, 2012). By sharing this protocol with the field, places of higher learning can begin to assess and measure their own hiring procedures, and correct practices that may be flawed, inequitable, or possibly illegal

Employment Interview Screening: Is The Ink Worth It?

This article focuses on how employment interview screeners view applicants with tattoos. Tattoos have been in existence for centuries, for they have been traced back to 400 B.C. In some cultures, tattoos have been used to identify criminals; whereas in other cultures, tattoos represent a rites of passage. There once was a time when tattoos were associated with sub cultures, such as gang members or those classified as a menace to society. Today, tattoos are not only worn by the average citizens but also by public servants and individuals in the armed forces. This qualitative study analyzed data from 578 participants while breaking down the data into gender responses concerning the hiring of individuals with tattoos. One major theme emerged from all responses, revealing that 67% of male responses and 33% female are accepting of tattoos during the interview screening process. With today’s acceptance of tattoos, employment interview screeners must consider what impact does a candidates’ tattoo has on the screening process

Early targets of miR-34a in neuroblastoma

Several genes encoding for proteins involved in proliferation, invasion, and apoptosis are known to be direct miR-34a targets. Here, we used proteomics to screen for targets of miR-34a in neuroblastoma (NBL), a childhood cancer that originates from precursor cells of the sympathetic nervous system. We examined the effect of miR-34a overexpression using a tetracycline inducible system in two NBL cell lines (SHEP and SH-SY5Y) at early time points of expression (6, 12, and 24 h). Proteome analysis using post-metabolic labeling led to the identification of 2,082 proteins, and among these 186 were regulated (112 proteins down-regulated and 74 up-regulated). Prediction of miR-34a targets via bioinformatics showed that 32 transcripts held miR-34a seed sequences in their 3′-UTR. By combining the proteomics data with Kaplan Meier geneexpression studies, we identified seven new gene products (ALG13, TIMM13, TGM2, ABCF2, CTCF, Ki67, and LYAR) that were correlated with worse clinical outcomes. These were further validated in vitro by 3′-UTR seed sequence regulation. In addition, Michigan Molecular Interactions searches indicated that together these proteins affect signaling pathways that regulate cell cycle and proliferation, focal adhesions, and other cellular properties that overall enhance tumor progression (including signaling pathways such as TGF-β, WNT, MAPK, and FAK). In conclusion, proteome analysis has here identified early targets of miR-34a with relevance to NBL tumorigenesis. Along with the results of previous studies, our data strongly suggest miR-34a as a useful tool for improving the chance of therapeutic success with NBL