Reciprocally, caspase-1, as well as caspase-8, regulated LUBAC activity by proteolytically processing HOIP at Asp-348 and Asp-387 during the execution of cell death. HOIP processing impeded substrate ubiquitination in the NF-κB pathway and resulted in enhanced apoptosis. These results highlight a regulatory mechanism underlying efficient apoptosis in keratinocytes and provide further evidence of a cross-talk between inflammatory and cell death pathways. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.Heterotrimeric G proteins are the core upstream elements that transduce and amplify the cellular signals from G protein-coupled receptors (GPCRs) to intracellular effectors. GPCRs are the largest family of membrane proteins encoded in the human genome and are the targets of about one third of prescription medicines. However, to date, no single therapeutic agent exerts its effects via perturbing heterotrimeric G protein function, despite a plethora of evidence linking G protein malfunction to human disease. Several recent studies have brought to light that the Gq family-specific inhibitor FR900359 (FR) is unexpectedly efficacious in silencing the signaling of Gq oncoproteins, mutant Gq variants that mostly exist in the active state. These data not only raise the hope that researchers working in drug discovery may be able to potentially strike Gq oncoproteins from the list of undruggable targets, but also raise questions as to how FR achieves its therapeutic effect. Here we place emphasis on these recent studies and explain why they expand our pharmacological armamentarium for targeting Gq protein oncogenes as well as broaden our mechanistic understanding of Gq protein oncogene function. We also highlight how this novel insight impacts the significance and utility of using G(q) proteins as targets in drug discovery efforts. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.To induce cell type-specific forms of gene regulation, pioneer factors open tightly packed, inaccessible chromatin sites, enabling the molecular machinery to act on functionally significant information encoded in DNA. While previous studies of pioneer factors have revealed their functions in transcriptional regulation, pioneer factors that open chromatin for other physiological events remain undetermined. In this issue of Genes & Development, Spruce and colleagues (pp. 398-412) report the functional significance of a "pioneer complex" in mouse meiotic recombination. This complex, comprised of the zinc finger DNA-binding protein PRDM9 and the SNF2 family chromatin remodeler HELLS, exposes nucleosomal DNA to designate the sites of DNA double-strand breaks that initiate meiotic recombination. Both HELLS and PRDM9 are required for the determination of these recombination hot spots. Through the identification of a pioneer complex for meiotic recombination, this study broadens the conceptual scope of pioneer factors, indicating their functional significance in biological processes beyond transcriptional regulation. © 2020 Alavattam et al.; Published by Cold Spring Harbor Laboratory Press.BACKGROUND AND OBJECTIVE In clinical practice, the evidence of acupuncture used as a treatment for migraine without aura is employed interchangeably to guide treatment for menstrual migraine. However, its effect and safety are not substantiated. This study aimed to assess the efficacy of acupuncture on the frequency and pain intensity of menstrual migraine. METHODS We searched PubMed, Cochrane Library, China National Knowledge Infrastructure (CNKI) and other two Chinese databases from their inception to 1 May 2019. This study included randomised controlled trials of women with menstrual migraine receiving acupuncture or a valid control. Two reviewers independently completed study selection, data extraction and risk of bias assessment. We combined data with a fixed-effect model in RevMan. Clinical outcomes included migraine frequency and duration, headache intensity, and adverse events. RESULTS Thirteen studies with 826 subjects were included, 9 of which had data suitable for meta-analyses. Current evidence showed that acupuncture was not superior to sham acupuncture in reducing monthly migraine frequency and duration, average headache intensity, and analgesic use at completion of treatment or follow-up. Pooled data demonstrated a significant improvement in mean headache intensity in the acupuncture group compared with drugs. However, all studies were underpowered and associated with moderate to high risk of bias. No serious adverse event was related to acupuncture treatment. CONCLUSIONS There is no convincing evidence to support the use of acupuncture in treating menstrual migraine. Acupuncture cannot yet be recommended to patients with menstrual migraine until more solid evidence is produced. TRIAL REGISTRATION NUMBER CRD42019119337. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.BACKGROUND The idea that individuals are responsible for their health has been the focus of debate in the theoretical literature and in its concrete application to healthcare policy in many countries. Controversies persist regarding the form, substance and fairness of allocating health responsibility to the individual, particularly in universal, need-based healthcare systems. OBJECTIVE To examine how personal health responsibility has been framed and rationalised in Norwegian key policy documents on priority setting. METHODS Documents issued or published by the Ministry of Health and Care Services between 1987 and 2018 were thematically analysed (n=14). We developed a predefined conceptual framework that guided the analysis. The framework included (1) the subject and object of responsibility, (2) the level of conceptual abstraction, (3) temporality, (4) normative justificatory arguments and (5) objections to the application of personal health responsibility. RESULTS As an additional criterion, personal health responsibility has been interpreted as relevant if (A) the patient's harmful behaviour is repeated after receiving treatment (retrospectively), and if (B) the success of the treatment is conditional on the patient's behavioural change (prospectively). When discussed as a retrospective criterion, considerations of reciprocal fairness have been dominant. When discussed as a prospective criterion, the expected benefit of treatment justified its relevance. CONCLUSION Personal health responsibility appears to challenge core values of equality, inclusion and solidarity in the Norwegian context and has been repeatedly rejected as a necessary criterion for priority setting.  https://www.selleckchem.com/products/sb297006.html  However, the responsibility criterion seems to have some relevance in particular priority setting decisions. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.