Coronavirus Replicase-Reporter Fusions Provide Quantitative Analysis of Replication and Replication Complex Formation

The replication of coronaviruses occurs in association with multiple virus-induced membrane structures that evolve during the course of infection; however, the dynamics of this process remain poorly understood. Previous studies of coronavirus replication complex organization and protein interactions have utilized protein overexpression studies and immunofluorescence of fixed cells. Additionally, live-imaging studies of coronavirus replicase proteins have used fluorescent reporter molecules fused to replicase proteins, but expressed from nonnative locations, mostly late-transcribed subgenomic mRNAs, in the presence or absence of the native protein. Thus, the timing and targeting of native replicase proteins expressed in real time from native locations in the genome remain unknown. In this study, we tested whether reporter molecules could be expressed from the replicase polyprotein of murine hepatitis virus as fusions with nonstructural protein 2 or 3 and whether such reporters could define the targeting and activity of replicase proteins during infection. We demonstrate that the fusion of green fluorescent protein and firefly luciferase with either nonstructural protein 2 or 3 is tolerated and that these reporter-replicase fusions can be used to quantitate replication complex formation and virus replication. The results show that the replicase gene has flexibility to accommodate a foreign gene addition and can be used directly to study replicase complex formation and evolution during infection as well as to provide highly sensitive and specific markers for protein translation and genome replication

Social Media Use and Access to Digital Technology in US Young Adults in 2016.

BACKGROUND: In 2015, 90% of US young adults with Internet access used social media. Digital and social media are highly prevalent modalities through which young adults explore identity formation, and by extension, learn and transmit norms about health and risk behaviors during this developmental life stage. OBJECTIVE: The purpose of this study was to provide updated estimates of social media use from 2014 to 2016 and correlates of social media use and access to digital technology in data collected from a national sample of US young adults in 2016. METHODS: Young adult participants aged 18-24 years in Wave 7 (October 2014, N=1259) and Wave 9 (February 2016, N=989) of the Truth Initiative Young Adult Cohort Study were asked about use frequency for 11 social media sites and access to digital devices, in addition to sociodemographic characteristics. Regular use was defined as using a given social media site at least weekly. Weighted analyses estimated the prevalence of use of each social media site, overlap between regular use of specific sites, and correlates of using a greater number of social media sites regularly. Bivariate analyses identified sociodemographic correlates of access to specific digital devices. RESULTS: In 2014, 89.42% (weighted n, 1126/1298) of young adults reported regular use of at least one social media site. This increased to 97.5% (weighted n, 965/989) of young adults in 2016. Among regular users of social media sites in 2016, the top five sites were Tumblr (85.5%), Vine (84.7%), Snapchat (81.7%), Instagram (80.7%), and LinkedIn (78.9%). Respondents reported regularly using an average of 7.6 social media sites, with 85% using 6 or more sites regularly. Overall, 87% of young adults reported access or use of a smartphone with Internet access, 74% a desktop or laptop computer with Internet access, 41% a tablet with Internet access, 29% a smart TV or video game console with Internet access, 11% a cell phone without Internet access, and 3% none of these. Access to all digital devices with Internet was lower in those reporting a lower subjective financial situation; there were also significant differences in access to specific digital devices with Internet by race, ethnicity, and education. CONCLUSIONS: The high mean number of social media sites used regularly and the substantial overlap in use of multiple social media sites reflect the rapidly changing social media environment. Mobile devices are a primary channel for social media, and our study highlights disparities in access to digital technologies with Internet access among US young adults by race/ethnicity, education, and subjective financial status. Findings from this study may guide the development and implementation of future health interventions for young adults delivered via the Internet or social media sites

SafeCare®: Historical Perspective and Dynamic Development of an Evidence-Based Scaled-Up Model for the Prevention of Child Maltreatment

AbstractSafeCare is an evidence-based parent-training program that reduces child maltreatment, particularly neglect. The risk of child maltreatment, a public health issue affecting millions of U.S. children each year, can be markedly reduced by interventions such as SafeCare that deliver in-home services. Drawing from applied behavioral analysis roots, SafeCare focuses on providing parents with concrete skills in three areas: health, home safety, and parent-child/-infant interaction. This paper will include an overview of the SafeCare model, an historical perspective of its history and dynamic development, description of the theoretical underpinnings of the model, a description of the program targets and content by describing its modules and delivery, an overview of program outcomes, and data discussion of dissemination and implementation

The State of Digital Media Data Research, 2024

The purpose of this report is to reflect on the state of digital media data research in 2024. This is the second in a series of reports on the state of digital media research, which we originally published in 2023. We reflect on changes to digital media research since our report in 2023. Specifically, we highlight the following trends: 1. From 2023 to 2024, access to digital media data changed drastically. Researchers were largely priced out of the Twitter API, and Pushshift–a commonly used archive for Reddit data–went private to comply with Reddit’s API policies. Meta also announced the imminent sunsetting of CrowdTangle, a transparency tool popular amongst researchers and journalists alike. At the same time, however, many platforms announced academic programs for data access, including the YouTube researcher program, TikTok’s Research API, and the Meta Content Library. 2. Federated social media platforms became more popular. Following Elon Musk’s purchase of Twitter, Twitter users flocked to Mastodon, Threads, BlueSky, and other federated (or soon to be federated) platforms. This presents unique challenges for researchers studying digital media data. As new platforms are created, researchers must build new tools to analyze them or wait for third parties or the platforms themselves to make data available. 3. Generative AI’s explosion may change how we study digital media. First, researchers using computational methods to measure social media content have turned to OpenAI’s ChatGPT and other Large Language Models (LLMs) to classify content. Second, researchers and civil society groups are increasingly concerned about the possibility for Generative AI to flood the information environment with fake content. 4. In February 2024, the EU Digital Services Act (DSA) went into effect, mandating that large platforms give researchers near real-time access to public data. We don’t yet know how these policies will impact data access in the United States, and it remains unclear what this data access will look like in practice. In the United States, legislative efforts to mandate researcher access stalled. While the last year brought many welcome and unwelcome changes to digital media data research, the findings in this report renew our encouragement that digital media data research should be guided by collaboration, transparency, preparation, and consistency.Journalism and Medi

Propionibacterium acnes bacteriophages display limited genetic diversity and broad killing activity against bacterial skin isolates.

UnlabelledInvestigation of the human microbiome has revealed diverse and complex microbial communities at distinct anatomic sites. The microbiome of the human sebaceous follicle provides a tractable model in which to study its dominant bacterial inhabitant, Propionibacterium acnes, which is thought to contribute to the pathogenesis of the human disease acne. To explore the diversity of the bacteriophages that infect P. acnes, 11 P. acnes phages were isolated from the sebaceous follicles of donors with healthy skin or acne and their genomes were sequenced. Comparative genomic analysis of the P. acnes phage population, which spans a 30-year temporal period and a broad geographic range, reveals striking similarity in terms of genome length, percent GC content, nucleotide identity (>85%), and gene content. This was unexpected, given the far-ranging diversity observed in virtually all other phage populations. Although the P. acnes phages display a broad host range against clinical isolates of P. acnes, two bacterial isolates were resistant to many of these phages. Moreover, the patterns of phage resistance correlate closely with the presence of clustered regularly interspaced short palindromic repeat elements in the bacteria that target a specific subset of phages, conferring a system of prokaryotic innate immunity. The limited diversity of the P. acnes bacteriophages, which may relate to the unique evolutionary constraints imposed by the lipid-rich anaerobic environment in which their bacterial hosts reside, points to the potential utility of phage-based antimicrobial therapy for acne.ImportancePropionibacterium acnes is a dominant member of the skin microflora and has also been implicated in the pathogenesis of acne; however, little is known about the bacteriophages that coexist with and infect this bacterium. Here we present the novel genome sequences of 11 P. acnes phages, thereby substantially increasing the amount of available genomic information about this phage population. Surprisingly, we find that, unlike other well-studied bacteriophages, P. acnes phages are highly homogeneous and show a striking lack of genetic diversity, which is perhaps related to their unique and restricted habitat. They also share a broad ability to kill clinical isolates of P. acnes; phage resistance is not prevalent, but when detected, it appears to be conferred by chromosomally encoded immunity elements within the host genome. We believe that these phages display numerous features that would make them ideal candidates for the development of a phage-based therapy for acne

The atypical chemokine receptor Ackr2 constrains NK cell migratory activity and promotes metastasis

Chemokines have been shown to be essential players in a range of cancer contexts. In this study, we demonstrate that mice deficient in the atypical chemokine receptor Ackr2 display impaired development of metastasis in vivo in both cell line and spontaneous models. Further analysis reveals that this relates to increased expression of the chemokine receptor CCR2, specifically by KLRG1+ NK cells from the Ackr2−/− mice. This leads to increased recruitment of KLRG1+ NK cells to CCL2-expressing tumors and enhanced tumor killing. Together, these data indicate that Ackr2 limits the expression of CCR2 on NK cells and restricts their tumoricidal activity. Our data have important implications for our understanding of the roles for chemokines in the metastatic process and highlight Ackr2 and CCR2 as potentially manipulable therapeutic targets in metastasis

Optimising text messaging to improve adherence to web-based smoking cessation treatment: a randomised control trial protocol

Introduction Millions of smokers use the Internet for smoking cessation assistance each year; however, most smokers engage minimally with even the best designed websites. The ubiquity of mobile devices and their effectiveness in promoting adherence in other areas of health behaviour change make them a promising tool to address adherence in Internet smoking cessation interventions. Text messaging is used by most adults, and messages can proactively encourage use of a web-based intervention. Text messaging can also be integrated with an Internet intervention to facilitate the use of core Internet intervention components. Methods and analysis We identified four aspects of a text message intervention that may enhance its effectiveness in promoting adherence to a web-based smoking cessation programme: personalisation, integration, dynamic tailoring and message intensity. Phase I will use a two-level full factorial design to test the impact of these four experimental features on adherence to a web-based intervention. The primary outcome is a composite metric of adherence that incorporates general utilisation metrics (eg, logins, page views) and specific feature utilisation shown to predict abstinence. Participants will be N=860 adult smokers who register on an established Internet cessation programme and enrol in its text message programme. Phase II will be a two-arm randomised trial to compare the efficacy of the web-based cessation programme alone and in conjunction with the optimised text messaging intervention on 30-day point prevalence abstinence at 9 months. Phase II participants will be N=600 adult smokers who register to use an established Internet cessation programme and enrol in text messaging. Secondary analyses will explore whether adherence mediates the effect of treatment condition on outcome. Ethics and dissemination This protocol was approved by Chesapeake IRB. We will disseminate study results through peer-reviewed manuscripts and conference presentations related to the methods and design, outcomes and exploratory analyses. Trial registration number NCT02585206

Towards discovery of gravitationally lensed explosive transients: the brightest galaxies in massive galaxy clusters from Planck-SZ2

We combine the Planck-SZ2 galaxy cluster catalogue with near-infrared photometry of galaxies from the VISTA Hemisphere Survey to identify candidate brightest cluster galaxies (BCGs) in 306 massive clusters in the Southern skies at redshifts of $z>0.1$. We find that 91% of these clusters have at least one candidate BCG within the 95% confidence interval on the cluster centers quoted by the Planck collaboration, providing reassurance that our analyses are statistically compatible, and find 92% to be reasonable candidates following a manual inspection. We make our catalog publicly available to assist colleagues interested in multi-wavelength studies of cluster cores, and the search for gravitationally lensed explosive transients in upcoming surveys including the Legacy Survey of Space and Time by the Vera C. Rubin Observatory.Comment: Published in RNAAS in March 2023. 3 pages, 1 figur

ApoA-I binding protein (AIBP) decreases mechanical hypersensitivity after plantar incision in a rat model of post-operative pain

https://openworks.mdanderson.org/sumexp22/1090/thumbnail.jp