DNA double-strand breaks (DSBs) pose a threat to genome stability and are repaired through multiple mechanisms. Rarely, telomerase, the enzyme that maintains telomeres, acts upon a DSB in a mutagenic process termed telomere healing. The probability of telomere addition is increased at specific genomic sequences termed sites of repair-associated telomere addition (SiRTAs). By monitoring repair of an induced DSB, we show that SiRTAs on chromosomes V and IX share a bipartite structure in which a core sequence (Core) is directly targeted by telomerase, while a proximal sequence (Stim) enhances the probability of de novo telomere formation. The Stim and Core sequences are sufficient to confer a high frequency of telomere addition to an ectopic site. Cdc13, a single-stranded DNA binding protein that recruits telomerase to endogenous telomeres, is known to stimulate de novo telomere addition when artificially recruited to an induced DSB. Here we show that the ability of the Stim sequence to enhance de novo telomere addition correlates with its ability to bind Cdc13, indicating that natural sites at which telomere addition occurs at high frequency require binding by Cdc13 to a sequence 20 to 100 bp internal from the site at which telomerase acts to initiate de novo telomere addition. Chromosomes in the budding yeast Saccharomyces cerevisiae, as in all eukaryotes, terminate with specialized nucleoprotein structures called telomeres. S. cerevisiae telomeric DNA consists of ϳ250 to 350 bp of TG 1-3 /AC 1-3 repeats and a short (ϳ10-bp) terminal G-rich 3= overhang (1). Because the conventional DNA replication machinery cannot fully replicate chromosome ends, telomeres shorten with each cell division cycle. In most eukaryotes, telomere shortening is counteracted by the enzyme telomerase, a ribonucleoprotein complex that uses an intrinsic RNA subunit as the template for telomeric DNA synthesis. Associated with telomeric DNA are proteins that protect chromosome ends from nucleolytic resection and prevent chromosome end-to-end fusions by distinguishing natural chromosome ends from ends generated by DNA double-strand breaks (DSBs) (2). These protective functions make telomeres essential for the maintenance of genome integrity and cell viability.In S. cerevisiae, optimal telomere length requires a balance between positive and negative regulatory mechanisms mediated by telomere-binding proteins, including Cdc13 and Rap1 (3). Cdc13, a telomere sequence-specific single-stranded DNA (ssDNA) binding protein, recruits telomerase to telomeres during the S/G 2 phase of the cell cycle through interaction with Est1, a subunit of the telomerase holoenzyme (reviewed in reference 3). Rap1 binds to the double-stranded telomeric repeat, forming a telomere length-regulatory complex through interactions of its C-terminal domain with Rif1 and Rif2 (4,5). Regulation occurs through a counting mechanism in which telomere length is inversely proportional to the number of Rif1 and Rif2 molecules present at a telomere (6, 7).Cells experience insults to t...

Moderate improvements in cardiac performance have been reported in some clinical settings after delivery of bone marrow mononuclear cells to patients with cardiovascular disease (CVD). However, mechanistic insights into how these cells impact outcomes are lacking. To address this, the NHLBI Cardiovascular Cell Therapy Research Network (CCTRN) established a Biorepository Core for extensive phenotyping and cell function studies, and storing bone marrow and peripheral blood for 10 years. Analyzing cell populations and cell function in the context of clinical parameters and clinical outcomes, after cell or placebo treatment, empower the development of novel diagnostic and prognostics. Developing such biomarkers that define the safety and efficacy of cell therapy is a major Biorepository aim.

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Introduction: Despite growing public health efforts to discourage teens from using hazardous tobacco products, their use of ENDS (electronic nicotine delivery system) remain piqued due to direct youth targeting by tobacco and vaping companies. ENDs especially e-cigs most often have a fruit or candy flavor that are particularly attractive to young people and may have high nicotine - which is highly addicting. Methods: 1) analyzed national/local nicotine product use in youth by gender, age, and racial/ethnic groups, 2) explored socio-ecological context of tobacco/vape shops via geo-spatial mapping within Los Angeles Service Planning Area 3 (SPA 3), 3) conducted environmental scan of social media platforms combined with Google and Yellow Pages searches. Results: Population level results were drawn from US Census, 2013-2017 American Community Survey (ACS) and California Tobacco Facts and Figures, 2019. 13.5% middle schoolers and 37.7% high schoolers reported ever using e-cigarettes. Use of basic or disposable devices was associated with younger age especially among Latinos (5% reported use in the past month compared to < 3% among other ethnicities). To explore socioecological contexts of tobacco and vape shops in SPA 3. Regardless of income, a higher number of tobacco and vape shops appear to correspond with higher percentage ethnic minorities. Lower income cities tended to have more tobacco and vape shops compared to very high-income cities. Tobacco products cost less in neighborhoods with a lower median household income and in neighborhoods with a higher proportion of Hispanic residents, even after adjusting for store type.Additionally, prior to the presentation, we will conduct geospatial mapping analysis: We will utilize open GIS software (QGIS) and open web map tools (Leaflet) to geocode locations of smoke/vape shops and overlay them with city demography to illustrate their spatial relationships and proximity to various neighborhoods. Discussion: Sustained implementation of population-based tobacco, including vaping, prevention and control strategies, in coordination with the Food and Drug Administration, are critical to reducing tobacco use including vaping and initiation among all U.S. population especially ethnic minorities and youths. There are associations of Tobacco Products marketing (price, placement, promotion, or product availability) with a neighborhood demographic (socioeconomic challenged, minority race/ethnicity and high traffic volume). Vape shops are more likely to be concentrated in low resourced communities with less political clout - these areas tend to be minority dense with fewer restrictions. Findings could inform initiatives aimed at a stronger licensing requirement for vape shops and federal and state-level regulations of this industry to prevent tobacco/vape shop from targeting minority and other socially challenged groups. Citation Format: Kimlin T. Ashing, Brian Tiep, Jonjon Macalintal, Sophia Yeung, Timothy O'Connor, Bin Xie, Udochukwu Obodo, Ming-Hsiang Tsou, Gaole Song, Faith Abuan, Christyl Dawson. A geospatial approach to explore the socioecological context of tobacco and vape shop locations [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT087.

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