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Background: MicroRNA-214 ( miR-214 ) has been shown to act as a tumour suppressor in human cervical and colorectal cancer cells. The aim of this study was to experimentally validate high mobility group AT-hook 1 as a novel target for miR-214- mediated suppression of growth and motility. Methods: HMGA1 and miR-214 expression levels were estimated in cervical and colorectal clinical specimens using qPCR. HMGA1 3′ untranslated region luciferase assays were performed to validate HMGA1 as a target of miR-214 . Effect of altering the expression of miR-214 or HMGA1 on proliferation, migration and invasion of human cervical and colorectal cancer cells was investigated. Results: miR-214 expression was poor while that of HMGA1 was high in cervical and colorectal cancer tissues. miR-214 -re-expression or HMGA1 downregulation inhibited proliferation, migration and invasion of cancer cells while miR-214 inhibition had opposite effects. miR-214 was demonstrated to bind to the wild-type 3′ untranslated region of HMGA1 but not with its mutant. Conclusions: Low expression of miR-214 concurrent with elevated levels of HMGA1 may contribute to cervical and colorectal cancer progression. miR-214 -mediated regulation of HMGA1 is a novel mechanism for its tumour-suppressive actions in human cervical and colorectal cancer cells and opens up avenues for novel therapeutic strategies for these two cancers.

Engineering educators have increasingly sought strategies for integrating the arts into their curricula. The primary objective of this integration varies, but one common objective is to improve students’ creative thinking skills. In this paper, we sought to quantify changes in student creativity that resulted from participation in a mechanical engineering course targeted at integrating engineering, technology, and the arts. The course was team taught by instructors from mechanical engineering and art. The art instructor introduced origami principles and techniques as a means for students to optimize engineering structures. Through a course project, engineering student teams interacted with art students to perform structural analysis on an origami-based art installation, which was the capstone project of the art instructor’s undergraduate origami course. Three engineering student teams extended this course project to collaborate with the art students in the final design and physical installation. To evaluate changes in student creativity, we used two instruments: a revised version of the Reisman Diagnostic Creativity Assessment (RDCA) and the Innovative Behavior Scales. Initially, the survey contained 12 constructs, but three were removed due to poor internal consistency reliability: Extrinsic Motivation; Intrinsic Motivation; and Tolerance of Ambiguity. The nine remaining constructs used for comparison herein included: • Originality: Confidence in developing original, innovative ideas • Ideation: Confidence in generating many ideas • Risk Taking: Adventurous; Brave • Openness of Process: Engaging various potentialities and resisting closure • Iterative Processing: Willingness to iterate on one’s solution • Questioning: Tendency to ask lots of questions • Experimenting/exploring: Tendency to physically or mentally take things apart • Idea networking: Tendency to engage with diverse others in communicative acts • Observing: Tendency to observe the surrounding world By conducting a series of paired t-tests to ascertain if pre and post-course responses were significantly different on the above constructs, we found five significant changes. In order of significance, these included Idea Networking; Questioning; Observing; Originality; and Ideation. To help explain these findings, and to identify how this course may be improved in subsequent offerings, the discussion includes the triangulation of these findings in light of teaching observations, responses from a mid-semester student focus group session, and informal faculty reflections. We close with questions that we and others ought to address as we strive to integrate engineering, technology, and the arts. We hope that these findings and discussion will guide other scholars and instructors as they explore the impact of art on engineering design learning, and as they seek to evaluate student creativity resulting from courses with similar aims.

Improving Conceptual Understanding of Signals and Systems in Undergraduate Engineering Students Using Collaborative In-Class Laboratory ExercisesCollaborative in-class MATLAB based laboratory exercises were introduced into the ‘Signalsand Systems’ course curriculum in the Electrical and Computer Engineering program atVanderbilt University in Fall 2013. In addition to traditional lecturing and problem solvingtechniques from our previous curriculum, these MATLAB based labs were designed to motivatedeeper learning by designing, implementing and analyzing practical applications of signals andsystems. This one year study, approved by the Vanderbilt Institutional Review Board, aims toquantify the impact of these labs on students’ conceptual understanding and retention of thecourse material.Signals and Systems is an introductory course in the analysis of continuous and discrete-timesignals and systems. Despite satisfying pre-requisites of electric circuits, calculus, and basicprogramming, students find it challenging to integrate these components to conceptualize signalsand system theories. Following general signals and systems lab curricula [1, 2, 3, 4, 5], threecollaborative in-class labs were developed based on the practical application of music synthesisand processing by modeling guitar notes to generate music as signals, and adding various soundeffects designed as systems.A pre-lab module introduces key concepts and resources for the lab, while the in-class modulecomprises of MATLAB exercises to implement and test these concepts. Students record theirinterpretations and problems encountered in a technical lab report that contributes to their finalgrade. Since the labs do not test conceptual understanding directly, we are using the Signals andSystems Concept Inventory (SSCI) [6], to directly measure students’ conceptual understandingof continuous and discrete time signals and systems [7, 8, 9]. Individual lab surveys and smallgroup interviews providing student feedback will complement the SSCI scores.The new curriculum was implemented in Fall 2013 in EECE 214 ‘Signals and Systems’ course atVanderbilt University. Two groups of students will participate in this study in the Fall 2013 andSpring 2014 semesters – students in the new curriculum (NC) and students who took EECE 214prior to Fall 2013 in the old curriculum (OC). Pre and post-course SSCI scores will be obtainedfrom the NC group. Post-course scores will also be obtained from Fall NC group in the Springsemester to test retention. Post-course scores will be obtained from the OC group at thebeginning of the semesters. A battery of within group and between group statistical comparisonsof these SSCI scores will be performed to determine (a) gain in conceptual understanding in theNC group, (b) retention of concepts in the NC and OC groups and, (c) benefits of NC over OC.Currently, pre-course scores in the NC group and post-course scores in OC group have beenobtained. We propose to have the data collection and analysis for the Fall semester completedwith results before the final submission of our paper.The findings from our study not only have the potential to impact the engineering curriculum ofVanderbilt University, but also reinforce the significance of practical laboratory exercisesemphasized by previous studies [10, 11], thereby contributing to the development of goodeducational practices. References[1] http://www.ece.cmu.edu/~ece290/f13/labs/lab3.pdf[2] http://www.lcsee.wvu.edu/classes/ee328/Project.pdf[3] http://ptolemy.eecs.berkeley.edu/~eal/publications/lab-manual.pdfhttp://www.engr.uky.edu/~donohue/ee422/mfiles/MatlabEE422.htm[4] http://eeweb.poly.edu/iselesni/EE3054/EE3054_Labs.pdf[5] http://www.engr.colostate.edu/ECE423/signals_labs/lab04/Lab_Notes_4.pdf[6] Wage, Kathleen E., et al. \"The signals and systems concept inventory.\"Education, IEEETransactions on 48.3 (2005): 448-461.[7] Streveler, Ruth A., et al. \"Learning conceptual knowledge in the engineering sciences:Overview and future research directions.\" Journal of Engineering Education 97.3 (2008): 279-294.Yoder, Mark A., and Bruce A. Black. \"Work in progress: A study of graphical vs. textualprogramming for DSP.\" Frontiers in Education Conference, 36th Annual. IEEE, 2006.[8] Nelson, Jill K. \"Work in progress: Project-based assignments for a graduate-level digitalsignal processing course.\" Frontiers in Education Conference, 36th Annual. IEEE, 2006.[9] Gassert, John D., et al. \"Cross-Disciplinary Biomedical Engineering Laboratories andAssessment of their Impact on Student Learning.\" American Society for Engineering Education.American Society for Engineering Education, 2011.[10] http://dwb.unl.edu/diss/ssrinivasan/srilekhas.pdf [11] Lee, Edward A. \"Designing a relevant lab for introductory signals and systems.\"Proc. ofthe First Signal Processing Education Workshop. 2000.

Transfer RNA-derived fragments (tRFs) have become a significant category of small non-coding RNAs that likely play vital roles in various cellular functions. Initially, research on small RNAs overlooked tRFs as simple byproducts of tRNA degradation, but recent findings show they are precisely produced molecules that regulate gene expression. Studies have demonstrated that tRFs regulate genes and proteins through various mechanisms, from miRNA-like targeting that relies on Argonaute (AGO) protein to lesser-known modes of action. Recent reports also suggest that tRFs are involved in multiple diseases, including cancer, where they may be utilized as biomarkers. Notably, tRFs can be transported between different cells and tissues of an organism or even across different organisms, further emphasizing their biological significance. Although evidence increasingly indicates that tRFs may function as new regulatory agents in health and disease, their biogenesis and underlying mechanisms are not yet fully understood. Conducting a thorough exploratory analysis of the tRF modes of action could be a valuable resource for advancing this growing field. Our goal in this review is to gather and examine the latest research on tRF biology, focusing on its diverse and dynamic molecular mechanisms discovered in different disease contexts, with a view toward potential applications in medicine. We aim to gain a deeper understanding of tRFs and explore their potential for new therapeutic breakthroughs by combining insights from molecular studies, disease models, and clinical research.

Rabies is a fatal encephalitis caused by the Rabies lyssavirus (RABV). The presence of minimal neuropathological changes observed in rabies indicates that neuronal dysfunction, rather than neuronal death contributes to the fatal outcome. The role of mitochondrial changes has been suggested as a possible mechanism for neuronal dysfunction in rabies. However, these findings are mostly based on studies that have employed experimental models and laboratory-adapted virus. Studies on brain tissues from naturally infected human and animal hosts are lacking. The current study investigated the role of mitochondrial changes in rabies by morphological, biochemical and proteomic analysis of RABV-infected human and canine brains. Morphological analysis showed minimal inflammation with preserved neuronal and disrupted mitochondrial structure in both human and canine brains. Proteomic analysis revealed involvement of mitochondrial processes (oxidative phosphorylation, cristae formation, homeostasis and transport), synaptic proteins and autophagic pathways, with over-expression of subunits of mitochondrial respiratory complexes. Consistent with these findings, human and canine brains displayed elevated activities of complexes I (p < 0.05), IV (p < 0.05) and V (p < 0.05). However, this did not result in elevated ATP production (p < 0.0001), probably due to lowered mitochondrial membrane potential as noted in RABV-infected cells in culture. These could lead to mitochondrial dysfunction and mitophagy as indicated by expression of FKBP8 (p < 0.05) and PINK1 (p < 0.001)/PARKIN (p > 0.05) and ensuing autophagy, as shown by the status of LCIII (p < 0.05), LAMP1 (p < 0.001) and pertinent ultrastructural markers. We propose that altered mitochondrial bioenergetics and cristae architecture probably induce mitophagy, leading to autophagy and consequent neuronal dysfunction in rabies.

Transfer-RNA-derived fragments (tRFs) are a relatively recently discovered class of non-coding RNAs derived from both precursor and mature transfer RNAs (tRNAs). Research on these molecules has been expanding rapidly, revealing their diverse roles in cellular processes, both in normal physiology and in disease states, often via post-transcriptional regulation of target genes. Altered tRFs abundances have been implicated in various conditions, where they may act as either drivers of disease progression or as protective agents. For instance, specific tRFs are associated with increased risk for cancer metastasis, while others may suppress tumor cell proliferation. Despite the growing recognition of tRFs as functional RNAs rather than sequencing noise, this field of study faces numerous challenges. Inconsistent naming conventions and variability in experimental approaches hinder the comparison of findings across studies, limiting our understanding of the common roles and mechanisms of tRFs. This review provides a comprehensive analysis of current literature on the various roles of tRFs in different diseases, particularly focusing on four broad areas: cancer, neurological, cardiovascular, and musculoskeletal disorders. We analyze studies that link specific tRFs to various aspects of human diseases and provide a convenient classification of these studies regarding the depth of the provided evidence. Further, we note gaps in current investigations and consider strategies to address methodological inconsistencies, including validation experiments and unified nomenclature. By consolidating research in this manner, we aim to facilitate comparisons across diverse studies, enhancing our ability to identify functional commonalities and furthering our understanding of the mechanisms by which tRFs act.