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The TINCR (Terminal differentiation-Induced Non-Coding RNA) gene is selectively expressed in epithelium tissues and is involved in the control of human epidermal differentiation and wound healing. Despite its initial report as a long non-coding RNA, the TINCR locus codes for a highly conserved ubiquitin-like microprotein associated with keratinocyte differentiation. Here we report the identification of TINCR as a tumor suppressor in squamous cell carcinoma (SCC). TINCR is upregulated by UV-induced DNA damage in a TP53-dependent manner in human keratinocytes. Decreased TINCR protein expression is prevalently found in skin and head and neck squamous cell tumors and TINCR expression suppresses the growth of SCC cells in vitro and in vivo. Consistently, Tincr knockout mice show accelerated tumor development following UVB skin carcinogenesis and increased penetrance of invasive SCCs. Finally, genetic analyses identify loss-of-function mutations and deletions encompassing the TINCR gene in SCC clinical samples supporting a tumor suppressor role in human cancer. Altogether, these results demonstrate a role for TINCR as protein coding tumor suppressor gene recurrently lost in squamous cell carcinomas.

Kids are drawn to dolls and dump trucks, and crashing the two together might just be a child's favorite pastime. Who knew such a simple pleasure could serve as an accessible, compelling phenomenon for instigating investigations of force and motion. With a few inexpensive materials straight out of the toy box (literally, a doll, a dump truck, a ramp, and some weights), teachers can set up and facilitate a whole suite of Crash Test Physics investigations that are easily adaptable, and that have been effectively piloted in classrooms, festivals, and outreach events alike with student populations that range from preschool to pre-service elementary teachers.

As the coronavirus pandemic unfolded, the use of the term "Chinavirus" to refer to the virus that causes COVID-19 had societal consequences, resulting in discrimination against individuals of Asian descent. In this study of the language used when talking about COVID-19, we used an emergent thematic analysis to explore the potential for induced perspective taking to inform participants' development of arguments regarding the appropriateness of the term "Chinavirus." The following questions guided our inquiry: (1) What evidence do undergraduates draw on and reason about when prompted to argue for and against the appropriateness of the term "Chinavirus" when referring to the virus that causes COVID-19? and (2) How do undergraduates prompted to argue both sides of the "Chinavirus" controversy use these differing perspectives in formulating their own position statements on the controversy? The large majority of 43 participants (pre-service elementary teachers in a mid-sized university in the Southeastern USA) were able, having undertaken an asynchronous, on-line coronavirus-themed unit, to articulate arguments both for and against referring to the virus responsible for COVID-19 as the "Chinavirus" and to use various perspectives in articulating their own position on the issue. Arguments in favor of the appropriateness of the term "Chinavirus" tended to maintain that as China was the origin of the virus, "Chinavirus" is an appropriate term; a number of undergraduates went further and argued that China was, in one way or another, responsible for the origin of the virus, and that this makes the term "Chinavirus" appropriate. Arguments in favor of the inappropriateness of the term "Chinavirus" mostly maintained that this was discriminatory, even racist, and could be harmful to those of Asian descent. The majority of students ultimately addressed both perspectives in their position statements before arguing for their own standpoints, the overwhelming majority of which concluded that it is inappropriate to call the coronavirus "Chinavirus." We conclude that induced perspective taking has the potential for exposing evidence and reasoning employed by opposing sides of socioscientific issues. Furthermore, given that taking alternative perspectives requires effort that individuals aren't often willing to expend on their own, tasking students with taking alternative perspectives through induced perspective taking could aid their development of functional scientific literacy while increasing the likelihood that progressive dialogue ensues.

Socio-scientific issues (SSI) are informed by science concepts but require consideration of societal aspects in order to be effectively understood and resolved. As a result, functional scientific literacy necessitates fluency with science as well as other domains of knowledge when engaged in reasoning about science and societal dimensions of SSI (i.e., socio-scientific reasoning (SSR)). However, a holistic examination of those domains of knowledge that inform a particular SSI has not been undertaken. In this investigation, thematic analysis is employed to explore domains of knowledge undergraduates (N = 91) used when reasoning about a regionally relevant SSI after completing a semester-long course about contemporary water-related issues. We found that participants used a number of knowledge domains, including science and ethics, as well as domains from the social sciences, though the number and type of knowledge domains differed within and across SSR dimensions. These findings inform SSI research and instruction in the context of SSI, as they begin to make concrete the diversity of knowledge domains with which individuals need familiarity and which must be synthesized to effectively understand and respond to SSI and thus exhibit functional scientific literacy.

Background and aimsBone and mineral metabolism has been implicated in the pathophysiology of cardiac valve calcification. Whether bone demineralization, a common aging-related disorder, promotes calcific valve disease remains uncertain. We tested the hypothesis that low bone mineral density (BMD) is associated with greater incidence/progression of cardiac valve calcification in the Multi-Ethnic Study of Atherosclerosis.MethodsUsing linear mixed-effects models, we related baseline measurement of BMD of the thoracic vertebrae by computed tomography (CT) in 6768 participants to serial CT assessments of aortic valve calcification (AVC) and mitral annular calcification (MAC) obtained over a >10-year period.ResultsAfter multivariable adjustment, lower BMD (per SD decrement) was associated with accelerated increase in AVC over time in women (0.76 [95% CI 0.42,1.09] Agatston -units [AU]/year) and men (1.41 [95% CI 0.48,2.33] AU/year), as well as for MAC in women (3.22 [95% CI 1.16,5.28] AU/year) and men (3.59 [95% CI 2.09,5.09] AU/year). Significant effect modification was observed, with more pronounced BMD-related acceleration of AVC and MAC progression in older or white participants of one or both sexes, as well as by estimated glomerular filtration rate, though the latter differed by sex for AVC and MAC.ConclusionsIn this multi-ethnic cohort, low thoracic BMD was significantly, but modestly, associated with increased AVC and MAC progression. This suggests that altered bone mineral metabolism does not have a major impact on calcific valve disease in the general population, but the possibility of a more meaningful influence in higher-risk individuals with osteoporosis will require further investigation.

ObjectivesCurrent estimates of aortic stenosis (AS) frequency have mostly relied on cross-sectional echocardiographic or longitudinal administrative data, making understanding of AS burden incomplete. We performed case adjudications to evaluate the frequency of AS and assess differences by age, sex and race in an older cohort with long-term follow-up.MethodsWe developed case-capture methods using study echocardiograms, procedure and diagnosis codes, heart failure events and deaths for targeted review of medical records in the Cardiovascular Health Study to identify moderate or severe AS and related procedures or hospitalisations. The primary outcome was clinically significant AS (severe AS or procedure). Assessment of incident AS burden was based on subdistribution survival methods, while associations with age, sex and race relied on cause-specific survival methods.ResultsThe cohort comprised 5795 participants (age 73±6, 42.2% male, 14.3% Black). Cumulative frequency of clinically significant AS at maximal 25-year follow-up was 3.69% (probable/definite) to 4.67% (possible/probable/definite), while the corresponding 20-year cumulative incidence was 2.88% to 3.71%. Of incident cases, about 85% had a hospitalisation for severe AS, but roughly half did not undergo valve intervention. The adjusted incidence of clinically significant AS was higher in men (HR 1.62 [95% CI 1.21 to 2.17]) and increased with age (HR 1.08 [95% CI 1.04 to 1.11]), but was lower in Blacks (HR 0.43 [95% CI 0.23 to 0.81]).ConclusionsIn this community-based study, we identified a higher burden of clinically significant AS than reported previously, with differences by age, sex and race. These findings have important implications for public health resource planning, although the lower burden in Blacks merits further study.

In this design case, we describe our work to develop a gameful learning design for use in an introductory, undergraduate biology laboratory course for science majors. Our design team included three university-based mathematics and science educators and a biologist responsible for the management of curriculum and instruction in the course under study. The gameful learning design was employed during the four weeks of plant evolutionary life history instruction. Key challenges to the design and implementation of gameful learning included the adaptation of instruction from teacher-centered to student-centered and establishing novel learning conditions in the eight laboratory sections so as to determine the value of two different elements of game design, repeat-testing and leaderboard with badges.

We investigated pre-service elementary teachers' engagement in science and English language arts (ELA) instruction integrated in the context of a children's book. Teachers developed models and conducted a compare-and-contrast analysis after exposure to different accounts of the butterfly life cycle: a popular children's book, "The Very Hungry Caterpillar," and a scientific account from "National Geographic" called "Butterfly: A Life." The mixed-methods research was guided by the following question: What are the affordances and limitations of children's literature toward engendering an understanding of the butterfly life cycle for pre-service elementary teachers? Content analysis indicated that pre-service elementary teachers' abilities to compare and contrast the two accounts were not exceptional, as they failed to discriminate between ideas offered in the accounts and missed details of the key aspect of the butterfly life-cycle phenomenon: metamorphosis. However, the quality of participants' butterfly life-cycle models significantly increased after exposure to the scientific account. We suggest the potential for an additional ELA standard, asking and answering such questions as who, what, where, when, why, and how to demonstrate understanding of key details in a text, as a means for enhancing compare-and-contrast skills following these activities.

The identification of high-leverage teaching practices that can be improved through targeted practice should contribute to the enhancement of teachers' facilitation of instruction and improve student learning outcomes. Researchers have begun to identify subject-specific teaching practices that are expected to enhance science teaching specifically. However, it is not clear what teaching practices look like in classrooms engaging students in learning science through socio-scientific issues. In this instrumental case study, we set out to identify those practices that an experienced secondary biology teacher employed during her successful enactment of socio-scientific issues (SSI) instruction about antibiotic resistance. Using both deductive codes from the literature and inductive coding, we analyzed nine 90-min video-taped lessons that comprised the unit. We identified science teaching practices that were particularly important for her enactment, as well as SSI-specific teaching practices not previously identified in the teaching practices literature, which included contextualizing teaching and learning in the issue, challenging students to analyze the issue from multiple perspectives, and urging students to employ skepticism when analyzing potentially biased information regarding the issue. These findings suggest that the manner in which teachers are currently being prepared is likely lacking in terms of helping teachers develop a full suite of teaching practices that contribute to the successful enactment of SSI instruction. Further research directed at how ideal SSI instruction is achieved and identifying those practices that are requisite to doing so is recommended.

Cells are transplanted to regenerate an organs' parenchyma, but how transplanted parenchymal cells induce stromal regeneration is elusive. Despite the common use of a decellularized matrix, little is known as to the pivotal signals that must be restored for tissue or organ regeneration. We report that Alx3, a developmentally important gene, orchestrated adult parenchymal and stromal regeneration by directly transactivating Wnt3a and vascular endothelial growth factor. In contrast to the modest parenchyma formed by native adult progenitors, Alx3-restored cells in decellularized scaffolds not only produced vascularized stroma that involved vascular endothelial growth factor signalling, but also parenchymal dentin via the Wnt/β-catenin pathway. In an orthotopic large-animal model following parenchyma and stroma ablation, Wnt3a-recruited endogenous cells regenerated neurovascular stroma and differentiated into parenchymal odontoblast-like cells that extended the processes into newly formed dentin with a structure-mechanical equivalency to native dentin. Thus, the Alx3-Wnt3a axis enables postnatal progenitors with a modest innate regenerative capacity to regenerate adult tissues. Depleted signals in the decellularized matrix may be reinstated by a developmentally pivotal gene or corresponding protein.

Objectives: There is concern that junior doctors are not prepared for their post-graduate attachments in ENT. The aims of this study were to capture the learning priorities of those in the ENT first on-call role and facilitate further educational opportunities to address these needs. Method: Semi-structured interviews were undertaken to explore the learning needs of junior doctors with seven junior and two senior ENT clinicians. Results: The thematic analysis generated three themes: the role of the ENT Junior; the perceived, expressed and prescribed learning needs; and attitudes towards future learning. These themes explored the misalignment between undergraduate training and post-graduate expectations, the lack of competence in ENT practical skills and the need for focused ENT training prior to commencing on-call shifts. Conclusion: All interviewees identified the need for greater experience in practical interventional skills prior to their ENT attachments and expressed interest towards a standardised, bootcamp-style induction with simulated emergency experience. [ABSTRACT FROM AUTHOR]

Socio‐scientific issues (SSI) instruction positions the understanding and practice of science in the context of issues that are informed by science but require reasoning about their societal dimensions to respond to those issues effectively. For this reason, instruction in the context of SSI has been considered the gateway to contemporary visions of scientific literacy. SSI instruction is often framed in line with the Socio‐Scientific Issues Teaching and Learning (SSI‐TL) framework, which is prominent in the literature and well‐used by researchers to frame professional development but potentially less familiar to classroom teachers. Given that teachers are likely familiar with the 5E learning cycle, they might experience an easier transition to developing and facilitating SSI instruction using the SSI‐TL model if framed through a lens of 5E. In this article, we unpack the SSI‐TL model of instruction through a 5E lens, then provide an exemplary prototype of the new SSI‐TL infused 5E instruction in the context of a globally relevant SSI to highlight the overlap between engagement in essential science practices and socio‐scientific reasoning. We hope that teachers become more comfortable developing science literacy by addressing both science and societal dimensions of contemporary SSI by considering the SSI‐TL Framework through a 5E lens. [ABSTRACT FROM AUTHOR]

Several studies have found active learning to enhance students' motivation and attitudes. Yet, faculty indicate that students resist active learning and censure them on evaluations after incorporating active learning into their instruction, resulting in an apparent paradox. We argue that the disparity in findings across previous studies is the result of variation in the active learning instruction that was implemented. The purpose of this study was to illuminate sources of motivation from and resistance to active learning that resulted from a novel, exemplary active-learning approach rooted in essential science practices and supported by science education literature. This approach was enacted over the course of 4 weeks in eight sections of an introductory undergraduate biology laboratory course. A plant concept inventory, administered to students as a pre-, post-, and delayed-posttest indicated significant proximal and distal learning gains. Qualitative analysis of open-response questionnaires and interviews elucidated sources of motivation and resistance that resulted from this active-learning approach. Several participants indicated this approach enhanced interest, creativity, and motivation to prepare, and resulted in a challenging learning environment that facilitated the sharing of diverse perspectives and the development of a community of learners. Sources of resistance to active learning included participants' unfamiliarity with essential science practices, having to struggle with uncertainty in the absence of authoritative information, and the extra effort required to actively construct knowledge as compared to learning via traditional, teacher-centered instruction. Implications for implementation, including tips for reducing student resistance to active learning, are discussed.

In this article, we introduce and analyze learning experiences made possible by a teaching framework that we have developed and call "digital spatial story lines" (DSSLs). DSSLs offer a novel approach to learning on the move by engaging learners with related conceptual practices of archival curation, digital mapping, and the production of public history. Learners collaborate to make and follow map-based story lines that bridge archival media they curate in public libraries and museums onto city neighborhoods these media describe. Story lines can be followed as tours to explore under- or untold stories about a city's public history at walking scale. To illustrate and study learning within the DSSL framework, we describe and analyze one design iteration from a larger, multi-year research project with local museum, library, and high school partners. Our analysis shows how making and following story lines provided opportunities for pre-service social studies teachers to engage with and learn about the public history of racial segregation, Civil Rights Movement activism, and American Roots Music in Nashville, Tennessee (aka the "Music City"). Our analysis focuses on using archival material to create and share public history as a mobile experience of being both "here-and-then"--a form of palimpsest in which learning on the move layers together historic places and the voices of different historical actors. We end with a discussion of who speaks for the public history of city neighborhoods and the prospects and limitations for teaching and learning with the DSSL framework.

BackgroundMitral annular calcium (MAC), commonly identified by cardiac imaging, is associated with cardiovascular events and predisposes to the development of clinically important mitral valve regurgitation and mitral valve stenosis. However, its biological determinants remain largely unknown.ObjectivesThe authors sought to evaluate whether a genetic predisposition to elevations in plasma lipids is associated with the presence of MAC.MethodsThe authors used 3 separate Mendelian randomization techniques to evaluate the associations of lipid genetic risk scores (GRS) with MAC in 3 large patient cohorts: the Framingham Health Study, MESA (Multiethnic European Study of Atherosclerosis), and the AGE-RS (Age, Gene/Environment Susceptibility-Reykjavik Study). The authors provided cross-ethnicity replication in the MESA Hispanic-American participants.ResultsMAC was present in 1,149 participants (20.4%). In pooled analyses across all 3 cohorts, a triglyceride GRS was significantly associated with the presence of MAC (odds ratio [OR] per triglyceride GRS unit: 1.73; 95% confidence interval [CI]: 1.24 to 2.41; p = 0.0013). Neither low- nor high-density lipoprotein cholesterol GRS was significantly associated with MAC. Results were consistent in cross-ethnicity analyses among the MESA Hispanic-Americans cohort (OR per triglyceride GRS unit: 2.04; 95% CI: 1.03 to 4.03; p = 0.04). In joint meta-analysis across all included cohorts, the triglyceride GRS was associated with MAC (OR per triglyceride GRS unit: 1.79; 95% CI: 1.32 to 2.41; p = 0.0001). The results were robust to several sensitivity analyses that limit both known and unknown forms of genetic pleiotropy.ConclusionsGenetic predisposition to elevated triglyceride levels was associated with the presence of MAC, a risk factor for clinically significant mitral valve disease, suggesting a causal association. Whether reducing triglyceride levels can lower the incidence of clinically significant mitral valve disease requires further study.

In addition to considering sociocultural, political, economic, and ethical factors (to name a few), effectively engaging socioscientific issues (SSI) requires that students understand and apply scientific explanations and the nature of science (NOS). Promoting such understandings can be achieved through immersing students in authentic real-world contexts where the SSI impacts occur and teaching those students about how scientists comprehend, research, and debate those SSI. This triangulated mixed-methods investigation explored how 60 secondary students' trophic cascade explanations changed through their experiencing place-based SSI instruction focused on the Yellowstone wolf reintroduction, including scientists' work and debates regarding that issue. Furthermore, this investigation determined the association between the students' post place-based SSI instruction trophic cascade explanations and NOS views. Findings from this investigation demonstrate that through the place-based SSI instruction students' trophic cascade explanations became significantly more accurate and complex and included more ecological causal mechanisms. Also, significant and moderate to moderately large correlations were found between the accuracy and contextualization of students' post place-based SSI instruction NOS views and the complexity of their trophic cascade explanations. Empirical substantiation of the association between the complexity of students' scientific explanations and their NOS views responds to an understudied area in the science education research. It also encourages the consideration of several implications, drawn from this investigation's findings and others' prior work, which include the need for NOS to be forefront alongside and in connection with science content in curricular standards and through instruction focused on relevant and authentic place-based SSI.