FASN regulates cellular response to genotoxic treatments by increasing PARP-1 expression and DNA repair activity via NF-κB and SP1

Fatty acid synthase (FASN), the sole cytosolic mammalian enzyme for de novo lipid synthesis, is crucial for cancer cell survival and associates with poor prognosis. FASN overexpression has been found to cause resistance to genotoxic insults. Here we tested the hypothesis that FASN regulates DNA repair to facilitate survival against genotoxic insults and found that FASN suppresses NF-κB but increases specificity protein 1 (SP1) expression. NF-κB and SP1 bind to a composite element in the poly(ADP-ribose) polymerase 1 (PARP-1) promoter in a mutually exclusive manner and regulate PARP-1 expression. Up-regulation of PARP-1 by FASN in turn increases Ku protein recruitment and DNA repair. Furthermore, lipid deprivation suppresses SP1 expression, which is able to be rescued by palmitate supplementation. However, lipid deprivation or palmitate supplementation has no effect on NF-κB expression. Thus, FASN may regulate NF-κB and SP1 expression using different mechanisms. Altogether, we conclude that FASN regulates cellular response against genotoxic insults by up-regulating PARP-1 and DNA repair via NF-κB and SP1

Culture as common sense: Perceived consensus versus personal beliefs as mechanisms of cultural influence

The authors propose that culture affects people through their perceptions of what is consensually believed. Whereas past research has examined whether cultural differences in social judgment are mediated by differences in individuals' personal values and beliefs, this article investigates whether they are mediated by differences in individuals' perceptions of the views of people around them. The authors propose that individuals who perceive that traditional views are culturally consensual (e.g., Chinese participants who believe that most of their fellows hold collectivistic values) will themselves behave and think in culturally typical ways. Four studies of previously well-established cultural differences found that cultural differences were mediated by participants' perceived consensus as much as by participants' personal views. This held true for cultural differences in the bases of compliance (Study 1), attributional foci (Study 2), and counterfactual thinking styles (Study 3). To tease apart the effect of consensus perception from other possibly associated individual differences, in Study 4, the authors experimentally manipulated which of 2 cultures was salient to bicultural participants and found that judgments were guided by participants' perception of the consensual view of the salient culture

A Conclusion, Yet an Opening to Enriching the Normative Approach of Culture

We compile in this article the target article authors' thoughtful responses to the commentaries. Their responses identify some common threads across the rich contents of the commentary pieces, interlink the observation and theoretical propositions in the commentaries with broader streams of research, present new perspectives inspired by the commentary contributors, and pose provocative questions to further ignite research efforts on the normative analysis of culture.SSCIEDITORIAL [email protected],SI1361-13714

Associations of long-term visit-to-visit blood pressure variability with subclinical kidney damage and albuminuria in adulthood: a 30-year prospective cohort study

Background: Recent evidence indicates that long-term visit-to-visit blood pressure variability (BPV) may be associated with risk of cardiovascular disease. We, therefore, aimed to determine the potential associations of long-term BPV from childhood to middle age with subclinical kidney damage (SKD) and albuminuria in adulthood. Methods: Using data from the ongoing cohort of Hanzhong Adolescent Hypertension study, which recruited children and adolescents aged 6 to 18 years at baseline, we assessed BPV by SD and average real variability (ARV) for 30 years (6 visits). Presence of SKD was defined as estimated glomerular filtration rate between 30 and 60 mL/min per 1.73 m2 or elevated urinary albumin-to creatinine ratio at least 30 mg/g. Albuminuria was defined as urinary albumin-to creatinine ratio ≥30 mg/g. Results: During 30 years of follow-up, of the 1771 participants, 204 SKD events occurred. After adjustment for demographic, clinical characteristics, and mean BP during 30 years, higher SDSBP, ARVSBP, SDDBP, ARVDBP, SDMAP, ARVMAP, and ARVPP were significantly associated with higher risk of SKD. When we used cumulative exposure to BP from childhood to adulthood instead of mean BP as adjustment factors, results were similar. In addition, greater long-term BPV was also associated with the risk of albuminuria. Long-term BPV from childhood to middle age was associated with higher risk of SKD and albuminuria in adulthood, independent of mean BP or cumulative exposure to BP during follow-up. Conclusions: Identifying long-term BPV from early age may assist in predicting kidney disease and cardiovascular disease in later life

The Euscaphis japonica genome and the evolution of malvids

Malvids is one of the largest clades of rosids, includes 58 families and exhibits remarkable morphological and ecological diversity. Here, we report a high-quality chromosome-level genome assembly for Euscaphis japonica, an early-diverging species within malvids. Genome-based phylogenetic analysis suggests that the unstable phylogenetic position of E. japonica may result from incomplete lineage sorting and hybridization event during the diversification of the ancestral population of malvids. Euscaphis japonica experienced two polyploidization events: the ancient whole genome triplication event shared with most eudicots (commonly known as the c event) and a more recent whole genome duplication event, unique to E. japonica. By resequencing 101 samples from 11 populations, we speculate that the temperature has led to the differentiation of the evergreen and deciduous of E. japonica and the completely different population histories of these two groups. In total, 1012 candidate positively selected genes in the evergreen were detected, some of which are involved in flower and fruit development. We found that reddening and dehiscence of the E. japonica pericarp and long fruit-hanging time promoted the reproduction of E. japonica populations, and revealed the expression patterns of genes related to fruit reddening, dehiscence and abscission. The key genes involved in pentacyclic triterpene synthesis in E. japonica were identified, and different expression patterns of these genes may contribute to pentacyclic triterpene diversification. Our work sheds light on the evolution of E. japonica and malvids, particularly on the diversification of E. japonica and the genetic basis for their fruit dehiscence and abscission.DATA AVAILABILITY STATEMENT : All sequences described in this manuscript have been submitted to the National Genomics Data Center (NGDC). The raw whole-genome data of E. japonica have been deposited in BioProject/GSA (https://bigd.big.ac.cn/gsa.) under the accession codes PRJCA005268/CRA004271, and the assembly and annotation data have been deposited at BioProject/GWH (https://bigd.big.ac.cn/gwh) under the accession codes PRJCA005268/GWHBCHS00000000. The raw transcriptomes data of E. japonica have been deposited in BioProject/GSA (https://bigd.big.ac.cn/gsa.) under the accession codes PRJCA005298/CRA004272.SUPPLEMENTARY MATERIAL 1: Supplementary Note 1. Chromosome number assessment. Supplementary Note 2. Whole-genome duplication identification and dating. Supplementary Note 3. Observation of E. japonica seed dispersal. Supplementary Note 4. Determination of pentacyclic triterpene substances. Figure S1. Cytogenetic analysis of E. japonica. Figure S2. Genome size and heterozygosity of E. japonica estimation using 17 k-mer distribution. Figure S3. Interchromosomal of Hi-C chromosome contact map of E. japonica genome. Figure S4. Gene structure prediction results of E. japonica and other species. Figure S5. Venn diagram shows gene families of malvids. Figure S6. Phylogenetic tree constructed by chloroplast genomes from 17 species. Figure S7. Concatenated- and ASTRAL-based phylogenetic trees. Figure S8. Ks distribution in E. japonica. Figure S9. Distributions of synonymous substitutions per synonymous site (Ks) of one-to-one orthologs identified between E. japonica and P. trichocarpa and V. vinifera. Figure S10. Population structure plot. Figure S11. Fixation index (FST) heat map among E. japonica populations. Figure S12. Phylogenetic analysis of MADS-box genes from O. sativa, A. thaliana, E. japonica, and T. cacao. Figure S13. Observation the fruit development. Figure S14. Animal seed dispersal. Figure S15. Anthocyanin biosynthesis in E. japonica fruits. Figure S16. Carotenoid accumulation and the chlorophyll degradation in E. japonica fruits. Figure S17. Expression profile of fruit dehiscence-related genes. Figure S18. Phylogenetic tree of DELLA genes obtained from six malvids species. Figure S19. Phylogenetic tree of CAD genes obtained from seven malvids species. Figure S20. Expression pattern of fruit abscission-related genes. Figure S21. Structure of pentacyclic triterpene compounds separated from Euscaphis. Figure S22. Phylogenetic tree of HMGR gene in plants. Figure S23. Phylogenetic tree of P450s gene family obtained from A. thaliana and E. japonica.SUPPLEMENTARY MATERIAL 2: Table S1. Assembled statistics of E. japonica genome. Table S2. Evaluation of E. japonica genome assembly. Table S3. Chromosome length of E. japonica. Table S4. Prediction of gene structures of the E. japonica genome. Table S5. Statistics on the function annotation of the E. japonica genome. Table S6. Non-coding RNA annotation results of E. japonica genome. Table S7. BUSCO assessment of the E. japonica annotated genome. Table S8. Statistic of repeat sequence in E. japonica genome. Table S9. Gene-clustering statistics for 17 species. Table S10. KEGG enrichment result of unique genes families of E. japonica. Table S11. Gene Ontology (GO) and KEGG enrichment result of significant shared by malvids species gene families. Table S12. Gene Ontology (GO) and KEGG enrichment result of significant expansion of E. japonica gene families. Table S13. Gene Ontology (GO) enrichment result of significant contraction of E. japonica gene families. Table S14. Statistical sampling population information. Table S15. Statistics population resequencing information. Table S16. Statistical nucleotide polymorphisms in the populations. Table S17. Candidate positive selection genes (PSGs) in the evergreen population. Table S18. Candidate positive selection genes (PSGs) in the deciduous population. Table S19. Gene Ontology (GO) enrichment result of significant PSGs in the evergreen population. Table S20. List of MADS-box genes identified in E. japonica. Table S21. Genes involved in anthocyanin biosynthesis, carotenoid biosynthesis, and chlorophyll degradation. Table S22. Identification fruit dehiscence-related genes in E. japonica. Table S23. Genes related to lignin synthesis that are highly expressed during pericarp dehiscence. Table S24. Gene expression levels (FPKMs) of fruit abscission-related genes in pericarp. Table S25. Triterpene compounds separated from Euscaphis. Table S26. Number of putative pentacyclic triterpene-related genes in the malvids species. Table S27. Identified pentacyclic triterpene synthesis-related genes in E. japonica genome. Table S28. Statistical simple sequence repeat.Fund for Excellent Doctoral Dissertation of Fujian Agriculture and Forestry University, China; Fujian Provincial Department of Science E. japonica Evolution and Selection of Ornamental Medicinal Resources, China; the Project of Forestry Peak Discipline at Fujian Agriculture and Forestry University, China; the Collection, Development and Utilization of Eascaphis konlshli Germplasm Resources; the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program and from Ghent University.https://onlinelibrary.wiley.com/journal/1365313xam2022BiochemistryGeneticsMicrobiology and Plant Patholog

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13