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Canonical roles for macrophages in mediating the fibrotic response after a heart attack include extracellular matrix turnover and activation of cardiac fibroblasts to initiate collagen deposition. Here we reveal that macrophages directly contribute collagen to the forming post-injury scar. Unbiased transcriptomics shows an upregulation of collagens in both zebrafish and mouse macrophages following heart injury. Adoptive transfer of macrophages, from either collagen-tagged zebrafish or adult mouse GFP tpz -collagen donors, enhances scar formation via cell autonomous production of collagen. In zebrafish, the majority of tagged collagen localises proximal to the injury, within the overlying epicardial region, suggesting a possible distinction between macrophage-deposited collagen and that predominantly laid-down by myofibroblasts. Macrophage-specific targeting of col4a3bpa and cognate col4a1 in zebrafish significantly reduces scarring in cryoinjured hosts. Our findings contrast with the current model of scarring, whereby collagen deposition is exclusively attributed to myofibroblasts, and implicate macrophages as direct contributors to fibrosis during heart repair. Macrophages mediate the fibrotic response after a heart attack by extracellular matrix turnover and cardiac fibroblasts activation. Here the authors identify an evolutionarily-conserved function of macrophages that contributes directly to the forming post-injury scar through cell-autonomous deposition of collagen.

The use of social marketing (SM) interventions for salt/sodium reduction has drawn increased attention worldwide. This systematic review investigates the application of social marketing principles to the design, implementation, and evaluation of salt/sodium reduction interventions globally and provides recommendations for future public health practice. Using PRISMA, searches were conducted on PubMed, Web of Science, CINAHL, and PsychInfo, with 51 final studies identified, abstracted, and synthesized using the matrix method. Studies conducted more recently contained a greater number of social marketing benchmark criteria (behavioral focus, formative research, segmentation, exchange, competition, marketing mix, community involvement, and integration). Studies reporting greater success used more benchmark criteria. Community-based initiatives using personalized/localized tactics combined with upstream policy-supported structural measures and management-supported place-based initiatives implemented in hospitals, workplaces, and schools were the most self-reported effective interventions. Future salt/sodium reduction initiatives should apply the full social marketing framework to multilevel interventions designed with culturally responsive community-based processes.

Cellular transcripts encode important information regarding cell identity and disease status. The activation of CRISPR in response to RNA biomarkers holds the potential for controlling CRISPR activity with spatiotemporal precision. This would enable the restriction of CRISPR activity to specific cell types expressing RNA biomarkers of interest while preventing unwanted activity in other cells. Here, we present a simple and specific platform for modulating CRISPR activity in response to RNA detection through engineering Streptococcus pyogenes Cas9 single-guide RNAs (sgRNAs). sgRNAs are engineered to fold into complex secondary structures that, in the ground state, inhibit their activity. Engineered sgRNAs become activated upon recognising complementary RNAs, thus enabling Cas9 to perform its function. Our approach enables CRISPR activation in response to RNA detection in both HEK293T cells and zebrafish embryos. Iterative design optimisations allowed the development of computational tools for generating sgRNAs capable of detecting RNA sequences of choice. Mechanistic investigations reveal that engineered sgRNAs are cleaved during RNA detection, and we identify key positions that benefit from chemical modifications to improve the stability of engineered sgRNAs in vivo. Our sensors open up novel opportunities for developing new research and therapeutic applications using CRISPR activation in response to endogenous RNA biomarkers.

Due to its genetic amenability coupled with advances in genome editing, zebrafish is an excellent model to examine the function of (epi)genomic elements. Here, we repurposed the Ac/Ds maize transposition system to efficiently characterise zebrafish cis-regulated elements, also known as enhancers, in F0-microinjected embryos. We further used the system to stably express guide RNAs enabling CRISPR/dCas9-interference (CRISPRi) perturbation of enhancers without disrupting the underlying genetic sequence. In addition, we probed the phenomenon of antisense transcription at two neural crest gene loci. Our study highlights the utility of Ac/Ds transposition as a new tool for transient epigenome modulation in zebrafish.

The ongoing shortage of psychiatrists and rising rates of mental illness have led to increased advocacy for granting prescriptive authority (RxP) to appropriately trained psychologists. Proponents argue that RxP can reduce wait times, expand access in underserved areas, and offer integrated care by combining psychotherapy with medication management. However, minimal research has examined how prescriptive authority functions in real-world clinical settings. This mixed-methods study explored whether the lived experiences of prescribing psychologists align with the expectations and promises historically used to support RxP. Using a dominant-less dominant mixed-methods design, this study included qualitative interviews with 17 prescribing psychologists across four RxP states (Louisiana, New Mexico, Illinois, and Idaho) and quantitative data from five RxP states. Thematic analysis of interview data revealed four core themes: (1) commitment to underserved populations, (2) integration of therapy and prescribing, (3) evolving professional identity, and (4) systems-level challenges and reflections on RxP's future. Quantitative data, drawn from licensing boards and public directories, provided context regarding practice locations, disciplinary actions, and insurance acceptance. Findings suggest that while RxP often fulfills its intended goals, ongoing systemic barriers, such as limited rural coverage, inconsistent insurance acceptance, and lack of mentorship hinder its full potential. These results support many of the early claims made by RxP advocates while highlighting the need for continued policy reform, infrastructure development, and professional support to ensure that RxP remains an ethical, effective, and accessible tool in psychological practice.

Consider an ideal 𝛪 ⊆ 𝐾[𝑥, 𝑦, 𝑧] corresponding to a point configuration in ℙ² where all but one of the points lies on a single line. In this paper, we study the symbolic generic initial system {gin (𝛪(𝑚))}𝑚 obtained by taking the reverse lexicographic generic initial ideals of the uniform fat point ideals 𝛪(𝑚). We describe the limiting shape of {gin (𝛪(𝑚))}𝑚 and, in proving this result, demonstrate that infinitely many of the ideals 𝛪(𝑚) are componentwise linear.

Cellular transcripts encode important information regarding cell identity and disease status. The activation of CRISPR in response to RNA biomarkers holds the potential for controlling CRISPR activity with spatiotemporal precision. This would enable the restriction of CRISPR activity to specific cell types expressing RNA biomarkers of interest while preventing unwanted activity in other cells. Here, we present a simple and specific platform for modulating CRISPR activity in response to RNA detection through engineering Streptococcus pyogenes Cas9 single-guide RNAs (sgRNAs). sgRNAs are engineered to fold into complex secondary structures that, in the ground state, inhibit their activity. Engineered sgRNAs become activated upon recognising complementary RNAs, thus enabling Cas9 to perform its function. Our approach enables CRISPR activation in response to RNA detection in both HEK293T cells and zebrafish embryos. Iterative design optimisations allowed the development of computational tools for generating sgRNAs capable of detecting RNA sequences of choice. Mechanistic investigations reveal that engineered sgRNAs are cleaved during RNA detection, and we identify key positions that benefit from chemical modifications to improve the stability of engineered sgRNAs in vivo. Our sensors open up novel opportunities for developing new research and therapeutic applications using CRISPR activation in response to endogenous RNA biomarkers.

Educators are in a time of change, as the emergence, availability, and growth of AI technology challenge long-standing assumptions about the purpose and pedagogies in higher education. In this commentary, I argue that service course designers and instructors have been facing similar dilemmas for over 30 years. I propose that educators can learn from the practices of service course coordinators, and that a service mindset — where we willingly place ourselves in the role of a servant to our students, colleagues, and other stakeholders — is one that we need if we are going to do big things in the face of the challenges ahead. I provide an illustration of the considerations that I made to serve multiple stakeholders as I designed one aspect of a very large, multisection calculus course, and how a service mindset helped to simplify my work.

We compute the reverse lexicographic generic initial ideals of the powers of a 2-complete intersection ideal 𝐼. In particular, we present six algorithms to compute these generic initial ideals; the power and the relative degrees of the minimal generators of 𝐼 determine the algorithm to be used.