Regulation of lin-4 miRNA expression, organismal growth and development by a conserved RNA binding protein in C. elegans

AbstractTranscription and multiple processing steps are required to produce specific 22 nucleotide microRNAs (miRNAs) that can regulate the expression of target genes. In C. elegans, mature lin-4 miRNA accumulates at the end of the first larval stage to repress its direct targets lin-14 and lin-28, allowing the progression of several somatic cell types to later larval fates. In this study, we characterized the expression of endogenous lin-4 and found that temporally regulated independent transcripts, but not constitutive lin-4 containing RNAs derived from an overlapping gene, are processed to mature lin-4 miRNA. Through an RNAi screen, we identified a conserved RNA binding protein gene rbm-28 (R05H10.2), homologous to the human RBM28 and yeast Nop4p proteins, that is important for lin-4 expression in C. elegans. We also demonstrate that rbm-28 genetically interacts with the lin-4 developmental timing pathway and uncover a previously unrecognized role for lin-14 and lin-28 in coordinating organismal growth

The Period protein homolog LIN-42 negatively regulates microRNA biogenesis in C. elegans

AbstractMicroRNAs (miRNAs) are small RNAs that post-transcriptionally regulate gene expression in many multicellular organisms. They are encoded in the genome and transcribed into primary (pri-) miRNAs before two processing steps that ultimately produce the mature miRNA. In order to generate the appropriate amount of a particular miRNA in the correct location at the correct time, proper regulation of miRNA biogenesis is essential. Here we identify the Period protein homolog LIN-42 as a new regulator of miRNA biogenesis in Caenorhabditis elegans. We mapped a spontaneous suppressor of the normally lethal let-7(n2853) allele to the lin-42 gene. Mutations in this allele (ap201) or a second lin-42 allele (n1089) caused increased mature let-7 miRNA levels at most time points when mature let-7 miRNA is normally expressed. Levels of pri-let-7 and a let-7 transcriptional reporter were also increased in lin-42(n1089) worms. These results indicate that LIN-42 normally represses pri-let-7 transcription and thus the accumulation of let-7 miRNA. This inhibition is not specific to let-7, as pri- and mature levels of lin-4 and miR-35 were also increased in lin-42 mutants. Furthermore, small RNA-seq analysis showed widespread increases in the levels of mature miRNAs in lin-42 mutants. Thus, we propose that the period protein homolog LIN-42 is a global regulator of miRNA biogenesis

When Should We Use Care Robots? The Nature-of-Activities Approach

When should we use care robots? In this paper we endorse the shift from a simple normative approach to care robots ethics to a complex one: we think that one main task of a care robot ethics is that of analysing the different ways in which different care robots may affect the different values at stake in different care practices. We start filling a gap in the literature by showing how the philosophical analysis of the nature of healthcare activities can contribute to (care) robot ethics. We rely on the nature-of-activities approach recently proposed in the debate on human enhancement, and we apply it to the ethics of care robots. The nature-of-activities approach will help us to understand why certain practice-oriented activities in healthcare should arguably be left to humans, but certain (predominantly) goal-directed activities in healthcare can be fulfilled (sometimes even more ethically) with the assistance of a robot. In relation to the latter, we aim to show that even though all healthcare activities can be considered as practice-oriented, when we understand the activity in terms of different legitimate ‘fine-grained’ descriptions, the same activities or at least certain components of them can be seen as clearly goal-directed. Insofar as it allows us to ethically assess specific functionalities of specific robots to be deployed in well-defined circumstances, we hold the nature-of-activities approach to be particularly helpful also from a design perspective, i.e. to realize the Value Sensitive Design approach

Prediction of Women\u27s Utilization of Resistance Strategies in a Sexual Assault Situation A Prospective Study

The present study prospectively explored the predictors of resistance strategies to a sexual assault situation. Participants were assessed at the beginning of an academic quarter on a number of variables, including past history of sexual victimization, perceived risk of sexual victimization, and intentions to use specific types of resistance strategies. Only women who reported being victimized over the interim ( N = 68) were included in the analyses, which suggested that women\u27s Time 1 intentions to utilize assertive resistance strategies (e.g., physically fight, run away) and offender aggression predicted women\u27s use of assertive resistance strategies in response to the assault that occurred over the follow-up. Women\u27s utilization of nonforceful verbal resistance (e.g., reason, plead, quarrel) was predicted by perpetrator aggression and previous sexual victimization. Women\u27s immobility (e.g., turn cold, freeze) during the assault that took place over the interim was predicted by experiences of childhood sexual victimization and previous sexual victimization

College Women\u27s Aggression in Relationships: The Role of Childhood and Adolescent Victimization

Despite growing evidence suggesting that women engage in verbal and physical dating aggression, there is a dearth of research examining the predictors of women\u27s engagement in these behaviors. Utilizing a college sample, the purpose of the current study was to explore women\u27s perpetration of dating aggression within the context of victimization experiences. Women (N = 374) completed surveys at the beginning and end of a 10-week academic quarter for course credit. Results from two retrospective regression analyses (all Time 1 variables) suggested that (1) paternal physical abuse and adolescent/adulthood verbal victimization predicted women\u27s reports of verbal perpetration and (2) childhood sexual abuse, adolescent/adulthood verbal victimization, adolescent/adulthood physical victimization, and adolescent/adulthood verbal perpetration predicted women\u27s reports of physical perpetration. Results from the two prospective, longitudinal regression analyses suggested that (1) verbal perpetration (as measured at Time 1) and verbal victimization over the interim predicted women\u27s reports of verbal perpetration over the interim and (2) physical perpetration (as measured at Time 1), verbal perpetration over the interim, and physical victimization over the interim predicted women\u27s reports of physical perpetration over the interim. These data suggest the importance of considering previous victimization experiences, mutual partner aggression, and a history of aggressive behaviors when examining women\u27s use of aggression in dating relationships