n−3 polyunsaturated N-acylethanolamines are CB2 cannabinoid receptor-preferring endocannabinoids

Anandamide, the first identified endogenous cannabinoid and TRPV1 agonist, is one of a series of endogenous N-acylethanolamines, NAEs. We have generated novel assays to quantify the levels of multiple NAEs in biological tissues and their rates of hydrolysis through fatty acid amide hydrolase. This range of NAEs was also tested in rapid response assays of CB₁, CB₂ cannabinoid and TRPV1 receptors. The data indicate that PEA, SEA and OEA are not endocannabinoids or endovanilloids, and that the higher endogenous levels of these metabolites compared to polyunsaturated analogues are a correlate of their slow rates of hydrolysis. The n?6 NAEs (AEA, docosatetraenoyl and docosapentaenoyl derivatives) activated both CB₁ and CB₂ receptors, as well as TRPV1 channels, suggesting them to be ‘genuine’ endocannabinoids and ‘endovanilloids’. The n?3 NAEs (eicosapentaenoyl, docosapentaenoyl and docosahexaenoyl derivatives) activated CB₂ receptors and some n?3 NAEs (docosapentaenoyl and docosahexaenoyl derivatives) also activated TRPV1 channels, but failed to activate the CB₁ receptor. We hypothesise that the preferential activation of CB₂ receptors by n?3 PUFA NAEs contributes, at least in some part, to their broad anti-inflammatory profile.     

Characteristic miRNA expression signature and random forest survival analysis identify potential cancer-driving miRNAs in a broad range of head and neck squamous cell carcinoma subtypes

Aim

To characterize the miRNA expression profile in head and neck squamous cell carcinoma (HNSSC) accounting for a broad range of cancer subtypes and consequently identify an optimal miRNA signature with prognostic value.

Social Networks and Knowledge Transmission Strategies among Baka Children,Southeastern Cameroon

The dynamics of knowledge transmission and acquisition, or how different aspects of culture are passed from one individual to another and how they are acquired and embodied by individuals, are central to understanding cultural evolution. In small-scale societies, cultural knowledge is largely acquired early in life through observation, imitation, and other forms of social learning embedded in daily experiences. However, little is known about the pathways through which such knowledge is transmitted, especially during middle childhood and adolescence. This study presents new empirical data on cultural knowledge transmission during childhood. Data were collected among the Baka, a forager-farmer society in southeastern Cameroon. We conducted structured interviews with children between 5 and 16 years of age (n?=?58 children; 177 interviews, with children being interviewed 1–6 times) about group composition during subsistence activities. Children’s groups were generally diverse, although children tended to perform subsistence activities primarily without adults and with same-sex companions. Group composition varied from one subsistence activity to another, which suggests that the flow of knowledge might also vary according to the activity performed. Analysis of the social composition of children’s subsistence groups shows that vertical and oblique transmission of subsistence-related knowledge might not be predominant during middle childhood and adolescence. Rather, horizontal transmission appears to be the most common knowledge transmission strategy used by Baka children during middle childhood and adolescence, highlighting the importance of other children in the transmission of knowledge.     

Analysis of Human Nuclear Protein Complexes by Quantitative Mass Spectrometry Profiling

Analysis of protein complexes provides insights into how the ensemble of expressed proteome is organized into functional units. While there have been advances in techniques for proteome‐wide profiling of cytoplasmic protein complexes, information about human nuclear protein complexes are very limited. To close this gap, we combined native size exclusion chromatography (SEC) with label‐free quantitative MS profiling to characterize hundreds of nuclear protein complexes isolated from human glioblastoma multiforme T98G cells. We identified 1794 proteins that overlapped between two biological replicates of which 1244 proteins were characterized as existing within stably associated putative complexes. co‐IP experiments confirmed the interaction of PARP1 with Ku70/Ku80 proteins and HDAC1 (histone deacetylase complex 1) and CHD4. HDAC1/2 also co‐migrated with various SIN3A and nucleosome remodeling and deacetylase components in SEC fractionation including SIN3A, SAP30, RBBP4, RBBP7, and NCOR1. Co‐elution of HDAC1/2/3 with both the KDM1A and RCOR1 further confirmed that these proteins are integral components of human deacetylase complexes. Our approach also demonstrated the ability to identify potential moonlighting complexes and novel complexes containing uncharacterized proteins. Overall, the results demonstrated the utility of SEC fractionation and LC–MS analysis for system‐wide profiling of proteins to predict the existence of distinct forms of nuclear protein complexes.     

Absorption of foliar applied Zn is decreased in Zn deficient sunflower (Helianthus annuus) due to changes in leaf properties

Plant and Soil - Arabidopsis thaliana is the model plant that is mainly used in studying cellulose and hemicellulose (CH) biosynthesis. Unfortunately, A. thaliana does not associate with mycorrhiza...     

An evaluation of educators’ views on the e-Bug resources in England

Introduction: e-Bug is an international educational resource for young people covering microbes, hygiene and antibiotics. e-Bug supports NICE guidance on changing public behaviour around antibiotic use. This study aimed to determine educators’ views of the e-Bug teacher resources to inform further development and dissemination of e-Bug. Methods: Age appropriate e-Bug resource packs were posted to every primary school (N = 19,142) and secondary school (N = 5637) in England with a cover letter signed by the Chief Medical Officer, Chief Executive of PHE and e-Bug Project Lead inviting educators to complete an online survey to evaluate the e-Bug resources. The online survey consisted of nine questions and took approximately 15 min to complete. Results: 695 participants completed the online survey. 94% of participants rated the e-Bug resource as excellent or good; one fifth of respondents used the e-Bug resources at least termly. Educators who used e-Bug rated the different lesson plans as excellent or good including ‘Introduction to Microbes’ (98%) and ‘Hand Hygiene’ (95%). Educators provided suggestions for the development of additional lessons plans. Conclusions: Educators view e-Bug as a valuable resource for teaching children about hygiene and antibiotics. Further e-Bug promotion and resource development is required to increase awareness and usage in schools.     

Structural Basis for the Interaction of Mutasome Assembly Factor REV1 with Ubiquitin

REV1 is an evolutionarily conserved translesion synthesis (TLS) DNA polymerase and an assembly factor key for the recruitment of other TLS polymerases to DNA damage sites. REV1-mediated recognition of ubiquitin in the proliferative cell nuclear antigen is thought to be the trigger for TLS activation. Here we report the solution NMR structure of a 108-residue fragment of human REV1 encompassing the two putative ubiquitin-binding motifs UBM1 and UBM2 in complex with ubiquitin. While in mammals UBM1 and UBM2 are both required for optimal association of REV1 with replication factories after DNA damage, we show that only REV1 UBM2 binds ubiquitin. Structure-guided mutagenesis in Saccharomyces cerevisiae further highlights the importance of UBM2 for REV1-mediated mutagenesis and DNA damage tolerance.