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BackgroundRestraining or slowing ageing hallmarks at the cellular level have been proposed as a route to increased organismal lifespan and healthspan. Consequently, there is great interest in anti-ageing drug discovery. However, this currently requires laborious and lengthy longevity analysis. Here, we present a novel screening readout for the expedited discovery of compounds that restrain ageing of cell populations in vitro and enable extension of in vivo lifespan.MethodsUsing Illumina methylation arrays, we monitored DNA methylation changes accompanying long-term passaging of adult primary human cells in culture. This enabled us to develop, test, and validate the CellPopAge Clock, an epigenetic clock with underlying algorithm, unique among existing epigenetic clocks for its design to detect anti-ageing compounds in vitro. Additionally, we measured markers of senescence and performed longevity experiments in vivo in Drosophila, to further validate our approach to discover novel anti-ageing compounds. Finally, we bench mark our epigenetic clock with other available epigenetic clocks to consolidate its usefulness and specialisation for primary cells in culture.ResultsWe developed a novel epigenetic clock, the CellPopAge Clock, to accurately monitor the age of a population of adult human primary cells. We find that the CellPopAge Clock can detect decelerated passage-based ageing of human primary cells treated with rapamycin or trametinib, well-established longevity drugs. We then utilise the CellPopAge Clock as a screening tool for the identification of compounds which decelerate ageing of cell populations, uncovering novel anti-ageing drugs, torin2 and dactolisib (BEZ-235). We demonstrate that delayed epigenetic ageing in human primary cells treated with anti-ageing compounds is accompanied by a reduction in senescence and ageing biomarkers. Finally, we extend our screening platform in vivo by taking advantage of a specially formulated holidic medium for increased drug bioavailability in Drosophila. We show that the novel anti-ageing drugs, torin2 and dactolisib (BEZ-235), increase longevity in vivo.ConclusionsOur method expands the scope of CpG methylation profiling to accurately and rapidly detecting anti-ageing potential of drugs using human cells in vitro, and in vivo, providing a novel accelerated discovery platform to test sought after anti-ageing compounds and geroprotectors.

Many universities have, or are facing, the task of providing high quality essential customer services with fewer financial and human resources. The growing diversity of students, their needs and proficiencies, along with the increasing variety of university program offerings, make providing customized, ondemand, automated solutions crucial to delivering high quality customer service. In this paper, the authors describe the development of an artificial intelligence-backed chatbot to aid in answering student advisement questions. The main objective of the chatbot is to provide 24/7 supplemental program specific advising assistance to graduate computer science majors to lessen the advising load of university faculty. In this paper, the authors describe the development of a chatbot prototype using IBM Watson Assistant running on a specially designed website and Slack platform to address frequently asked questions of computer science graduate students. Results of a pilot study conducted on 99 graduate students indicate that the prototype is a positive step forward in making student advising accessible, usable, and scalable to a broader audience.

Following publication of the original article [1], the authors reported two errors in Fig. 1B and Fig. 2B. 1. The two EP + siGLO and DS + siGLO brightfield/β-gal images from Fig. 2A were accidentally duplicated in Fig. 1B. The images in Fig. 2A are correct. The images in Fig. 1B are replaced with representative images of untransfected EP and DS cells. The incorrect and the correct figure are given below. The incorrect Fig. 1: (Figure presented.) The correct Fig. 1: (Figure presented.) The replacement of these images does not change any of the other data in this figure, nor the conclusion of this figure. 2. The authors also noticed that the panels in Fig. 2B labelled with “DS” were incorrectly labelled. The bar charts and figure legend correctly state that these images are “DS + siGLO” images. These panels are now relabelled as “DS + siGLO”. This proposed relabelling does not change any of the other data in this figure, nor the conclusion of Fig. 2B. The incorrect and the correct figure are given below. The incorrect Fig. 2: (Figure presented.) The correct Fig. 2: (Figure presented.) In both instances, these errors do not change any data associated with these figures, nor do they change the conclusions of the corresponding figures and the paper.

Objective: Little is known about availability of resources for managing intimate partner violence (IPV) at rural hospitals. We assessed differences in availability of resources for IPV screening and management between rural and urban emergency departments (EDs) in Oregon. Methods: We conducted a standardized telephone interview of Oregon ED directors and nurse managers on six IPV-related resources: official screening policies, standardized screening tools, public displays regarding IPV, on-site advocacy, intervention checklists and regular clinician education. We used chi-square analysis to test differences in reported resource availability between urban and rural EDs. Results: Of 57 Oregon EDs, 55 (96%) completed the survey. A smaller proportion of rural EDs, compared to urban EDs, reported official screening policies (74% vs. 100%, p=0.01), standardized screening instruments (21% vs. 55%, p=0.01), clinician education (38% vs. 70%, p=0.02) or on-site violence advocacy (44% vs. 95%, p

Objective: Little is known about the factors important to applicants when selecting an emergency medicine residency. We sought to identify which residency-specific criteria applicants value in selecting a training program.Methods: We conducted an anonymous survey of emergency medicine interviewees at our residency. Applicants were asked to rate each of 18 factors on a four-point scale from 1 (“not at all important”) to 4 (“very important”) in their selection of a residency.Results: Of 82 interviewees, 73 (89%) completed the survey. The factors with the top six mean scores were: how happy the residents seemed (3.9), program personality (3.8), faculty enthusiasm (3.7), geographic location (3.6), experience during interview day (3.5), and pediatrics training (3.5).Conclusion: The top three factors deemed most important to emergency medicine applicants are primarily intangibles, while programs have no control over the fourth most important factor, location.[WestJEM. 2009;10:159-162.]

Now in its 52nd year of continuous operations, the Protein Data Bank (PDB) is the premiere open-access global archive housing three-dimensional (3D) biomolecular structure data. It is jointly managed by the Worldwide Protein Data Bank (wwPDB) partnership. The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB) is funded by the National Science Foundation, National Institutes of Health, and US Department of Energy and serves as the US data center for the wwPDB. RCSB PDB is also responsible for the security of PDB data in its role as wwPDB-designated Archive Keeper. Every year, RCSB PDB serves tens of thousands of depositors of 3D macromolecular structure data (coming from macromolecular crystallography, nuclear magnetic resonance spectroscopy, electron microscopy, and micro-electron diffraction). The RCSB PDB research-focused web portal (RCSB.org) makes PDB data available at no charge and without usage restrictions to many millions of PDB data consumers around the world. The RCSB PDB training, outreach, and education web portal (PDB101.RCSB.org) serves nearly 700 K educators, students, and members of the public worldwide. This invited Tools Issue contribution describes how RCSB PDB (i) is organized; (ii) works with wwPDB partners to process new depositions; (iii) serves as the wwPDB-designated Archive Keeper; (iv) enables exploration and 3D visualization of PDB data via RCSB.org; and (v) supports training, outreach, and education via PDB101.RCSB.org. New tools and features at RCSB.org are presented using examples drawn from high-resolution structural studies of proteins relevant to treatment of human cancers by targeting immune checkpoints.

BackgroundLong-term follow-up for clinician-scientist training programs is sparse. We describe the outcomes of clinician-scientist scholars in the National Heart Lung and Blood Institute (NHLBI) K12 program in emergency care research up to 8.7 years after matriculation in the program.MethodsThis was a cohort study of faculty clinician-scientist scholars enrolled in a NHLBI K12 research training program at 6 sites across the US, with median follow-up 7.7 years (range 5.7-8.7 years) from the date of matriculation. Scholars completed electronic surveys in 2017 and 2019, with the 2019 survey collecting information for their current work setting, percent time for research, and grant funding from all sources. We used NIH RePorter and online resources to verify federal grants through March 2021. The primary outcome was a funded career development award (CDA) or research project grant (RPG) where the scholar was principal investigator. We included funding from all federal sources and national foundations.ResultsThere were 43 scholars, including 16 (37%) women. Over the follow-up period, 32 (74%) received an individual CDA or RPG, with a median of 36 months (range 9-83 months) after entering the program. Of the 43 scholars, 23 (54%) received a CDA and 22 (51%) received an RPG, 7 (16%) of which were R01s. Of the 23 scholars who received a CDA, 13 (56%) subsequently had an RPG funded. Time to CDA or RPG did not differ by sex (women vs. men log-rank test p = 0.27) or specialty training (emergency medicine versus other specialties, p = 0.59).ConclusionsAfter 7 years of follow-up for this NHLBI K12 emergency care research training program, three quarters of clinician-scientist scholars had obtained CDA or RPG funding, with no notable differences by sex or clinical training.

There has been much research on the connections between second language (L2) writing and learner motivation. However, few studies have focused on contexts in which L2 learning is mandatory, rather than elective. This technical action research-based study evaluated a project in which teenage learners in Argentina were engaged in creative writing tasks, with the goal of including their final written pieces in a formal publication. Through focus group interviews and group discussions, it was found that the project had increased the motivation not only of the learners, but also of the teachers. Further, the study highlights the importance of making such writing tasks student-centered, and calls attention to the role played by the teachers in motivating and engaging students. The study suggests that effort should be made to develop more initiatives in formal education settings in order to motivate and engage learners involved in mandatory language study. [Note: The page range (401-422) shown on the PDF is incorrect. The correct page range for this article is p401-421.]

As English has developed into a global language, comprehensive suggestions have been made for the integration of World Englishes (WE) and English as a Lingua Franca (ELF) into language education. However, such suggestions have often encountered considerable resistance, in part due to the complexities in the formation of language teacher identity. In this paper, the authors employ a duoethnographic research method to explore how their encounters with WE and ELF have impacted their identities as a "native speaker" and a "non-native speaker" teacher of English. Through comparisons between their life histories, they demonstrate how their experience with WE and ELF have led to feelings of newfound legitimacy, and lingering incompleteness. The paper argues in order for the promotion of WE/ELF to be successful, more focus needs to be paid to the identity work required of teachers so that they can successfully and sensitively form a new conception of language teaching.

Communication and collaboration are key science competencies that support sharing of scientific knowledge with experts and non-experts alike. On the one hand, they facilitate interdisciplinary conversations between students, educators, and researchers, while on the other they improve public awareness, enable informed choices, and impact policy decisions. Herein, we describe an interdisciplinary undergraduate course focused on using data from various bioinformatics data resources to explore the molecular underpinnings of diabetes mellitus (Types 1 and 2) and introducing students to science communication. Building on course materials and original student-generated artifacts, a series of collaborative activities engaged students, educators, researchers, healthcare professionals and community members in exploring, learning about, and discussing the molecular bases of diabetes. These collaborations generated novel educational materials and approaches to learning and presenting complex ideas about major global health challenges in formats accessible to diverse audiences.

This article presents a critical assessment of 40 years of research that may be brought under the umbrella of energy efficiency, spanning different aggregations and domains-from individual producing and consuming agents to economy-wide effects to the role of innovation to the influence of policy. After 40 years of research, energy efficiency initiatives are generally perceived as highly effective. Innovation has contributed to lowering energy technology costs and increasing energy productivity. Energy efficiency programs in many cases have reduced energy use per unit of economic output and have been associated with net improvements in welfare, emission reductions, or both. Rebound effects at the macro level still warrant careful policy attention, as they may be nontrivial. Complexity of energy efficiency dynamics calls for further methodological and empirical advances, multidisciplinary approaches, and granular data at the service level for research in this field to be of greatest societal benefit.

Senescence, a state of stable growth arrest, plays an important role in ageing and age-related diseases in vivo. Although the INK4/ARF locus is known to be essential for senescence programmes, the key regulators driving p16 and ARF transcription remain largely underexplored. Using siRNA screening for modulators of the p16/pRB and ARF/p53/p21 pathways in deeply senescent human mammary epithelial cells (DS HMECs) and fibroblasts (DS HMFs), we identified EGR2 as a novel regulator of senescence. EGR2 expression is up-regulated during senescence, and its ablation by siRNA in DS HMECs and HMFs transiently reverses the senescent phenotype. We demonstrate that EGR2 activates the ARF and p16 promoters and directly binds to both the ARF and p16 promoters. Loss of EGR2 down-regulates p16 levels and increases the pool of p16- p21- 'reversed' cells in the population. Moreover, EGR2 overexpression is sufficient to induce senescence. Our data suggest that EGR2 is a direct transcriptional activator of the p16/pRB and ARF/p53/p21 pathways in senescence and a novel marker of senescence.