Gun violence and the voices of youth on community safety in the time of COVID-19 in East Harlem, NY: a youth participatory action research cross-sectional study.

BACKGROUND: The USA has failed to codify the protection of children from gun violence (GV) as a human right. This study employs a youth participatory action research methodology, within the framework of the United Nations Convention on the Rights of the Child (UNCRC), to investigate the relationships between GV exposure, self-identified gender and perceptions of children's rights and safety. METHODS: An anonymous survey based on UNICEF USA's Child Friendly Cities Initiative interactive survey tool targeting adolescents was modified by East Harlem, New York high school student co-researchers in collaboration with near-peer graduate students. The 61-question survey was administered at an East Harlem high school. Analysis consisted of univariate, bivariate and logistic regression using SPSS®. RESULTS: A total of 153 students completed the survey: 48.4% self-identified as male and 45.8% as female. Thirty-five percent reported witnessing GV. Most (79.1%) were aware of child rights regardless of gender or GV exposure but there were differences in perceptions of safety. Fifteen percent of females reported never feeling safe at school compared to 3% of males (p = 0.01). Females were 2.2 times as likely as males to report transportation waiting areas as never safe (p = 0.008). Almost a third of females reported never feeling safe from sexual harassment in public, compared to 10% of males (p = 0.004). In multivariable logistic regression adjusted for gender, race/ethnicity and grade level, students who witnessed GV were 4.6 times more likely to report never feeling safe from violence (95% CI 1.7-12.4). Thirty percent of students who witnessed GV reported not attending school because of safety concerns. Students who witnessed GV had 2.2 times the odds of carrying a weapon to school (95% CI 1.1-4.5). These patterns continued for other perceptions of safety. CONCLUSIONS: The students in this study affirmed their rights to participate and express their views on matters that may affect them, as articulated in the UNCRC. The study revealed differences in perceptions of safety by self-identified gender and identified gun violence as a major contributor of youth's perception of lack of safety. The study evinces the efficacy of employing YPAR methodology to identify and answer youth concerns of community safety and prioritize honoring child rights.

A conserved, N-terminal tyrosine signal directs Ras for inhibition by Rabex-5.

Dysregulation of the Ras oncogene in development causes developmental disorders, "Rasopathies," whereas mutational activation or amplification of Ras in differentiated tissues causes cancer. Rabex-5 (also called RabGEF1) inhibits Ras by promoting Ras mono- and di-ubiquitination. We report here that Rabex-5-mediated Ras ubiquitination requires Ras Tyrosine 4 (Y4), a site of known phosphorylation. Ras substitution mutants insensitive to Y4 phosphorylation did not undergo Rabex-5-mediated ubiquitination in cells and exhibited Ras gain-of-function phenotypes in vivo. Ras Y4 phosphomimic substitution increased Rabex-5-mediated ubiquitination in cells. Y4 phosphomimic substitution in oncogenic Ras blocked the morphological phenotypes associated with oncogenic Ras in vivo dependent on the presence of Rabex-5. We developed polyclonal antibodies raised against an N-terminal Ras peptide phosphorylated at Y4. These anti-phospho-Y4 antibodies showed dramatic recognition of recombinant wild-type Ras and RasG12V proteins when incubated with JAK2 or SRC kinases but not of RasY4F or RasY4F,G12V recombinant proteins suggesting that JAK2 and SRC could promote phosphorylation of Ras proteins at Y4 in vitro. Anti-phospho-Y4 antibodies also showed recognition of RasG12V protein, but not wild-type Ras, when incubated with EGFR. A role for JAK2, SRC, and EGFR (kinases with well-known roles to activate signaling through Ras), to promote Ras Y4 phosphorylation could represent a feedback mechanism to limit Ras activation and thus establish Ras homeostasis. Notably, rare variants of Ras at Y4 have been found in cerebellar glioblastomas. Therefore, our work identifies a physiologically relevant Ras ubiquitination signal and highlights a requirement for Y4 for Ras inhibition by Rabex-5 to maintain Ras pathway homeostasis and to prevent tissue transformation.