Investigating the Role of the IP₃ Signalling Pathway in RNA Interference in C. elegans

Both inositol 1,4,5-trisphosphate (IP₃) mediated signalling and RNA interference are widespread processes with fundamental roles in animal cell function. In the nematode C. elegans these two pathways have been shown to intersect such that IP₃ signalling mutants display an altered exogenous RNAi response. IP₃ is a key second messenger in the transduction of intracellular signals. Produced by the hydrolysis of membrane phospholipid PIP₂ by phospholipase C (PLC), IP₃ triggers Ca²⁺ release from internal stores by binding to the IP₃ receptor, a ligand gated calcium channel in the ER, thus triggering downstream calcium signalling pathways. It has been previously shown that loss of function in the IP₃ receptor (ITR-1) or in PLCβ (EGL-8) results in an enhanced response to exogenous dsRNA, with a more robust silencing response than that seen in WT worms. Conversely the potentiation of IP₃ signalling by the loss of function IPP-5, a phosphatase which catalyses the hydrolysis of IP₃, results in resistance to RNAi. In order to better understand the context of the IP₃ signalling events which are regulating the RNAi response I sought to identify the upstream activator of EGL-8 in this mechanism. EGL-8 is canonically activated by Gαq homologue ELG-30. However, by screening the RNAi responses of Gα signalling mutants using a range of assays, EGL-30 was ruled out as an activator of EGL-8 in the pathway regulating RNAi, since EGL-30 loss of function does not result in an enhanced RNAi response. The Gαo/i homologue, GOA-1, was identified as the most likely activator of EGL-8 due to the strongly enhanced RNAi response in goa-1 loss of function mutants in a number of assays. Other Gα subunits and known regulators of GOA-1 and EGL-30 signalling were also analysed. The RNAi response is a multistep process in which the exogenous RNAi pathway must compete with the closely related and interlinked endogenous small RNA pathways for resources. With the aim of better understanding how changes in IP₃ signalling might be influencing the RNAi response, small RNA sequencing was performed to look for evidence of change in the endogenous small RNA pathways of itr-1 mutants, and followed up with qPCR. However, no substantial changes to the endogenous small RNA pathways were found. Downstream of the production of primary siRNAs from exogenous dsRNA, separate argonautes mediate cytoplasmic and nuclear RNAi responses. I utilised an established assay to test for effects of IP₃ signalling on nuclear RNAi. The results suggest no specific alterations to the nuclear RNAi pathway in these mutants.BBSR

Belgian family policy from a comparative perspective: does it support fertility and gender equity?

The aim of this article is to compare the Belgian family policy to policies in other countries within the so-called conservative welfare state regime group, namely, France, Germany and the Netherlands, and to the policy applied in one country that has adopted a social-democratic model, i.e., Sweden. Based on previous studies, we aim to identify strengths and weaknesses according to two criteria: efficacy in promoting fertility and promoting gender equity, the latter being understood as mothers’ involvement in the labour market and fathers’ involvement in care. We maintain that the Belgian family policy presents several features that have the potential to positively affect fertility. Such positive features mainly pertain to family allowances and birth premiums, together with enrolment rates for children under three years of age (albeit with worrisome, low public spending on childcare). However, other aspects of the Belgian policy are more critical for gender equity. Such aspects include the remuneration of parental leave and time credit, a lack of radical reforms to support fathers’ involvement, and regional disparities in several family policy measures. Counterintuitively, short durations for maternity leave and parental leave might also negatively affect gender equity.

Priming scalar and ad hoc enrichment in children

Sentences can be enriched by considering what the speaker does not say but could have done. Children, however, struggle to derive one type of such enrichments, scalar implicatures. A popular explanation for this, the lexical alternatives account, is that they do not have lexical knowledge of the appropriate alternatives to generate the implicature. Namely, children are unaware of the scalar relationship between some and all. We conducted a priming study with N = 72 children, aged 5;1 years, and an adult sample, N = 51, to test this hypothesis. Participants were exposed to prime trials of strong, alternative, or weak sentences involving scalar or ad hoc expressions, and then saw a target trial that could be interpreted in either way. Consistent with previous studies, children were reluctant to derive scalar implicatures. However, there were two novel findings. (1) Children responded with twice the rate of ad hoc implicature responses than adults, suggesting that the implicature was the developmentally prior interpretation for ad hoc expressions. (2) Children showed robust priming effects, suggesting that children are aware of the scalar relationship between some and all, even if they choose not to derive the implicature. This suggests that the root cause of the scalar implicature deficit is not due to the absence of lexical knowledge of the relationship between some and all