Adolescent Relationship Violence: Help-Seeking and Help-Giving Behaviors among Peers

Young people tend to disclose relationship violence experiences to their peers, if they disclose at all, yet little is known about the nature and frequency of adolescent help-seeking and help-giving behaviors. Conducted within a sample of 1,312 young people from four New York City high schools, this is the first paper to ask adolescent help-givers about the various forms of help they provide and among the first to examine how ethnicity and nativity impact help-seeking behaviors. Relationship violence victims who had ever disclosed (61 %) were more likely to choose their friends for informal support. Ethnicity was predictive of adolescent disclosure outlets, whereas gender and nativity were not. Latinos were significantly less likely than non-Latinos to ever disclose to only friends, as compared to disclosing to at least one adult. The likelihood of a young person giving help to their friend in a violent relationship is associated with gender, ethnicity, and nativity, with males being significantly less likely than females to give all forms of help to their friends (talking to their friends about the violence, suggesting options, and taking action). Foreign-born adolescents are less likely to talk or suggest options to friends in violent relationships. This study also found that Latinos were significantly more likely than non-Latinos to report taking action with or on behalf of a friend in a violent relationship. This research shows that adolescents often rely on each other to address relationship violence, underlining the importance of adolescents’ receipt of training and education on how to support their friends, including when to seek help from more formal services. To further understand the valuable role played by adolescent peers of victims, future research should explore both which forms of help are perceived by the victim to be most helpful and which are associated with more positive outcomes

Spliceosome malfunction causes neurodevelopmental disorders with overlapping features

Pre-mRNA splicing is a highly coordinated process. While its dysregulation has been linked to neurological deficits, our understanding of the underlying molecular and cellular mechanisms remains limited. We implicated pathogenic variants in U2AF2 and PRPF19, encoding spliceosome subunits in neurodevelopmental disorders (NDDs), by identifying 46 unrelated individuals with 23 de novo U2AF2 missense variants (including 7 recurrent variants in 30 individuals) and 6 individuals with de novo PRPF19 variants. Eight U2AF2 variants dysregulated splicing of a model substrate. Neuritogenesis was reduced in human neurons differentiated from human pluripotent stem cells carrying two U2AF2 hyper-recurrent variants. Neural loss of function (LoF) of the Drosophila orthologs U2af50 and Prp19 led to lethality, abnormal mushroom body (MB) patterning, and social deficits, which were differentially rescued by wild-type and mutant U2AF2 or PRPF19. Transcriptome profiling revealed splicing substrates or effectors (including Rbfox1, a third splicing factor), which rescued MB defects in U2af50deficient flies. Upon reanalysis of negative clinical exomes followed by data sharing, we further identified 6 patients with NDD who carried RBFOX1 missense variants which, by in vitro testing, showed LoF. Our study implicates 3 splicing factors as NDD-causative genes and establishes a genetic network with hierarchy underlying human brain development and function

Molecularly barcoded Zika virus libraries to probe <i>in vivo</i> evolutionary dynamics

<div><p>Defining the complex dynamics of Zika virus (ZIKV) infection in pregnancy and during transmission between vertebrate hosts and mosquito vectors is critical for a thorough understanding of viral transmission, pathogenesis, immune evasion, and potential reservoir establishment. Within-host viral diversity in ZIKV infection is low, which makes it difficult to evaluate infection dynamics. To overcome this biological hurdle, we constructed a molecularly barcoded ZIKV. This virus stock consists of a “synthetic swarm” whose members are genetically identical except for a run of eight consecutive degenerate codons, which creates approximately 64,000 theoretical nucleotide combinations that all encode the same amino acids. Deep sequencing this region of the ZIKV genome enables counting of individual barcodes to quantify the number and relative proportions of viral lineages present within a host. Here we used these molecularly barcoded ZIKV variants to study the dynamics of ZIKV infection in pregnant and non-pregnant macaques as well as during mosquito infection/transmission. The barcoded virus had no discernible fitness defects <i>in vivo</i>, and the proportions of individual barcoded virus templates remained stable throughout the duration of acute plasma viremia. ZIKV RNA also was detected in maternal plasma from a pregnant animal infected with barcoded virus for 67 days. The complexity of the virus population declined precipitously 8 days following infection of the dam, consistent with the timing of typical resolution of ZIKV in non-pregnant macaques and remained low for the subsequent duration of viremia. Our approach showed that synthetic swarm viruses can be used to probe the composition of ZIKV populations over time <i>in vivo</i> to understand vertical transmission, persistent reservoirs, bottlenecks, and evolutionary dynamics.</p></div

Ocular and uteroplacental pathology in a macaque pregnancy with congenital Zika virus infection

<div><p>Congenital Zika virus (ZIKV) infection impacts fetal development and pregnancy outcomes. We infected a pregnant rhesus macaque with a Puerto Rican ZIKV isolate in the first trimester. The pregnancy was complicated by preterm premature rupture of membranes (PPROM), intraamniotic bacterial infection and fetal demise 49 days post infection (gestational day 95). Significant pathology at the maternal-fetal interface included acute chorioamnionitis, placental infarcts, and leukocytoclastic vasculitis of the myometrial radial arteries. ZIKV RNA was disseminated throughout fetal tissues and maternal immune system tissues at necropsy, as assessed by quantitative RT-PCR for viral RNA. Replicating ZIKV was identified in fetal tissues, maternal uterus, and maternal spleen by fluorescent in situ hybridization for viral replication intermediates. Fetal ocular pathology included a choroidal coloboma, suspected anterior segment dysgenesis, and a dysplastic retina. This is the first report of ocular pathology and prolonged viral replication in both maternal and fetal tissues following congenital ZIKV infection in a rhesus macaque. PPROM followed by fetal demise and severe pathology of the visual system have not been described in macaque congenital ZIKV infection previously. While this case of ZIKV infection during pregnancy was complicated by bacterial infection with PPROM, the role of ZIKV on this outcome cannot be precisely defined, and further nonhuman primate studies will determine if increased risk for PPROM or other adverse pregnancy outcomes are associated with congenital ZIKV infection.</p></div

Vector competence of <i>Aedes aegypti</i> following peroral exposure to ZIKV-BC-1.0-infected pregnant macaque 4 days post inoculation.

<p>Vector competence of <i>Aedes aegypti</i> following peroral exposure to ZIKV-BC-1.0-infected pregnant macaque 4 days post inoculation.</p

Number of viral templates used to characterize the full genome sequences of the two ZIKV stocks.

<p>Number of viral templates used to characterize the full genome sequences of the two ZIKV stocks.</p

Number of viral templates sequenced from nonpregnant animals infected with ZIKV-IC or ZIKV-BC-1.0.

<p>Number of viral templates sequenced from nonpregnant animals infected with ZIKV-IC or ZIKV-BC-1.0.</p