Mechanisms governing a neuron’s regenerative ability are important but not well understood. We identified Rtca, RNA 3′-terminal phosphate cyclase, as an inhibitor for axon regeneration. Removal of dRtca cell-autonomously enhanced axon regrowth in the Drosophila central nervous system, whereas its overexpression reduced axon regeneration in the periphery. Rtca along with the RNA ligase Rtcb and its catalyst Archease operate in the RNA repair/splicing pathway important for stress induced mRNA splicing, including that of Xbp1, a cellular stress sensor. dRtca and dArchease had opposing effects on Xbp1 splicing, and deficiency of dArchease or Xbp1 impeded axon regeneration in Drosophila. Moreover, overexpressing mammalian Rtca in cultured rodent neurons reduced axonal complexity in vitro, whereas reducing its function promoted retinal ganglion cell axon regeneration after optic nerve crush in mice. Our study thus links axon regeneration to cellular stress and RNA metabolism, revealing new potential therapeutic targets for treating nervous system trauma.

Smoke-free policies are effective population-based strategies to reduce tobacco use yet are uncommon in permanent supportive housing (PSH) for formerly homeless individuals who have high rates of smoking. In this study, we partnered with six supportive housing agencies in the San Francisco Bay Area to examine the implementation of smoke-free policies and cessation services. We administered a questionnaire and conducted in-depth, semistructured interviews with agency directors (n = 6), property management staff (n = 23), and services staff (n = 24) from 23 PSH sites on the barriers to implementing tobacco control interventions. All properties restricted smoking in indoor shared areas, but only two had policies restricting smoking in living areas. While there was staff consensus that smoke-free policies were important to reduce tobacco-related harm, participants disagreed on whether smoke-free policies were aligned with PSH’s harm reduction framework. Residents’ comorbid mental illness and substance use and the lack of appropriate enforcement tools were barriers to implementation. Using these formative findings, we present a framework for a toolkit of strategies to increase implementation of smoke-free policies and cessation interventions in PSH. Successful implementation of indoor smoke-free policies in PSH will require concurrent cessation services to support smoking cessation efforts and address the mental health and substance use needs of residents.

Purpose: Interventions for tobacco dependence are most effective when combined with smoke-free policies, yet such policies are rare in permanent supportive housing (PSH) for formerly homeless adults. We aimed to provide in-depth analysis of attitudes and barriers to and facilitators of implementing smoke-free policies in PSH. Approach: Current smokers living in PSH completed a questionnaire and participated in in-depth, semistructured interviews on smoking history, attitudes toward smoke-free policies, and perceived barriers to cessation. Setting: We collaborated with 6 San Francisco Bay Area PSH agencies. Participants: Thirty-six residents in PSH. Methods: Interviews, conducted by trained interviewers, were digitally recorded, transcribed, and analyzed using content analysis methods. Participants were recruited until we reached thematic saturation, or no new themes emerged from the interviews. Results: Over half of participants (52.8%, n = 19) reported depression, and 97.2% (n = 35) reported current substance use. Support for indoor smoking bans in living areas was modest (33.1%), although most residents anticipated cutting down (61%) and reported they would not move because of a smoking ban (77.8%). There was interest in quitting smoking, although co-use of tobacco with other substances was a major barrier. Conclusion: This study is the first to explore attitudes toward smoke-free policies in PSH. We found that residents in PSH support smoke-free policies and consider them feasible if implementation processes are sound. Our findings underscore the need to address barriers to adopting smoke-free policies and accessing smoking cessation services. In particular, interventions must address the co-use of tobacco with other substances and the impact of smoking on financial and housing stability.

No abstract

Calreticulin (CR) is a multifunctional, calcium-binding protein that has recently been shown to bind to and promote the replication of the rubella virus genome in mammalian cells. While CR is now widely recognized as a new human autoantigen, the relationship between CR and the Ro/SS-A ribonucleo-protein (RNP) autoantigen has been somewhat controversial. In this work, we demonstrate that unphosphorylated human rCR binds specifically and distinctly to in vitro transcribed forms of hYRNA, the RNA backbone of the Ro/SS-A RNP particle. This interaction appears to be mediated by binding through the N- and C-terminal domains of CR, but not by the central proline-rich domain. Furthermore, our studies indicate that CR can facilitate the binding of the 60-kDa polypeptide component of the Ro/SS-A RNP (Ro60) to hYRNA. In addition, CR and the 52-kDa Ro/SS-A polypeptide (Ro52) appear to be capable of interacting through direct protein-protein binding. These studies confirm that CR is an hYRNA-binding protein, and provide for the first time a molecular mechanism by which Ro52 can be linked physically to hYRNA. Through these molecular interactions and its known functional role as a chaperone, it is suggested that CR plays a supportive role in the formation of the Ro/SS-A RNP complex. The capacity of CR to interact with RNA viruses such as rubella provides an additional argument for an infectious trigger for autoantibody production against self RNP particles such as Ro/SS-A.