Pre-M Phase-promoting Factor Associates with Annulate Lamellae in Xenopus Oocytes and Egg Extracts

We have used complementary biochemical and in vivo approaches to study the compartmentalization of M phase-promoting factor (MPF) in prophase Xenopus eggs and oocytes. We first examined the distribution of MPF (Cdc2/CyclinB2) and membranous organelles in high-speed extracts of Xenopus eggs made during mitotic prophase. These extracts were found to lack mitochondria, Golgi membranes, and most endoplasmic reticulum (ER) but to contain the bulk of the pre-MPF pool. This pre-MPF could be pelleted by further centrifugation along with components necessary to activate it. On activation, Cdc2/CyclinB2 moved into the soluble fraction. Electron microscopy and Western blot analysis showed that the pre-MPF pellet contained a specific ER subdomain comprising "annulate lamellae" (AL): stacked ER membranes highly enriched in nuclear pores. Colocalization of pre-MPF with AL was demonstrated by anti-CyclinB2 immunofluorescence in prophase oocytes, in which AL are positioned close to the vegetal surface. Green fluorescent protein-CyclinB2 expressed in oocytes also localized at AL. These data suggest that inactive MPF associates with nuclear envelope components just before activation. This association may explain why nuclei and centrosomes stimulate MPF activation and provide a mechanism for targeting of MPF to some of its key substrates

Coordination by Cdc42 of actin, contractility, and adhesion for melanoblast movement in mouse skin

YesThe individual molecular pathways downstream of Cdc42, Rac, and Rho GTPases are well documented, but we know surprisingly little about how these pathways are coordinated when cells move in a complex environment in vivo. In the developing embryo, melanoblasts originating from the neural crest must traverse the dermis to reach the epidermis of the skin and hair follicles. We previously established that Rac1 signals via Scar/WAVE and Arp2/3 to effect pseudopod extension and migration of melanoblasts in skin. Here we show that RhoA is redundant in the melanocyte lineage but that Cdc42 coordinates multiple motility systems independent of Rac1. Similar to Rac1 knockouts, Cdc42 null mice displayed a severe loss of pigmentation, and melanoblasts showed cell-cycle progression, migration, and cytokinesis defects. However, unlike Rac1 knockouts, Cdc42 null melanoblasts were elongated and displayed large, bulky pseudopods with dynamic actin bursts. Despite assuming an elongated shape usually associated with fast mesenchymal motility, Cdc42 knockout melanoblasts migrated slowly and inefficiently in the epidermis, with nearly static pseudopods. Although much of the basic actin machinery was intact, Cdc42 null cells lacked the ability to polarize their Golgi and coordinate motility systems for efficient movement. Loss of Cdc42 de-coupled three main systems: actin assembly via the formin FMNL2 and Arp2/3, active myosin-II localization, and integrin-based adhesion dynamics.Cancer Research UK (to L.M.M. [A17196], R.H.I. [A19257], and S.W.G.T.) and NIH grants P01-GM103723 and P41-EB002025 (to K.M.H.). N.R.P. is supported by a Pancreatic Cancer Research Fund grant (to L.M.M.). Funding to Prof. Rottner by the Deutsche Forschungsgemeinschaft (grant RO2414/3-2)

Social mindfulness predicts concern for nature and immigrants across 36 nations

People cooperate every day in ways that range from largescale contributions that mitigate climate change to simple actions such as leaving another individual with choice – known as social mindfulness. It is not yet clear whether and how these complex and more simple forms of cooperation relate. Prior work has found that countries with individuals who made more socially mindful choices were linked to a higher country environmental performance – a proxy for complex cooperation. Here we replicated this initial finding in 41 samples around the world, demonstrating the robustness of the association between social mindfulness and environmental performance, and substantially built on it to show this relationship extended to a wide range of complex cooperative indices, tied closely to many current societal issues. We found that greater social mindfulness expressed by an individual was related to living in countries with more social capital, more community participation and reduced prejudice towards immigrants. Our findings speak to the symbiotic relationship between simple and more complex forms of cooperation in societies

Moral expansiveness around the world:The role of societal factors across 36 countries

International audienceWhat are the things that we think matter morally, and how do societal factors influence this? To date, research has explored several individual-level and historical factors that influence the size of our ‘moral circles.' There has, however, been less attention focused on which societal factors play a role. We present the first multi-national exploration of moral expansiveness—that is, the size of people’s moral circles across countries. We found low generalized trust, greater perceptions of a breakdown in the social fabric of society, and greater perceived economic inequality were associated with smaller moral circles. Generalized trust also helped explain the effects of perceived inequality on lower levels of moral inclusiveness. Other inequality indicators (i.e., Gini coefficients) were, however, unrelated to moral expansiveness. These findings suggest that societal factors, especially those associated with generalized trust, may influence the size of our moral circles

A 32-society investigation of the influence of perceived economic inequality on social class stereotyping

International audienceThere is a growing body of work suggesting that social class stereotypes are amplified when people perceive higher levels of economic inequality-that is, the wealthy are perceived as more competent and assertive and the poor as more incompetent and unassertive. The present study tested this prediction in 32 societies and also examines the role of wealth-based categorization in explaining this relationship. We found that people who perceived higher economic inequality were indeed more likely to consider wealth as a meaningful basis for categorization. Unexpectedly, however, higher levels of perceived inequality were associated with perceiving the wealthy as less competent and assertive and the poor as more competent and assertive. Unpacking this further, exploratory analyses showed that the observed tendency to stereotype the wealthy negatively only emerged in societies with lower social mobility and democracy and higher corruption. This points to the importance of understanding how socio-structural features that co-occur with economic inequality may shape perceptions of the wealthy and the poor

Common Gene Variants in the Tumor Necrosis Factor (TNF) and TNF Receptor Superfamilies and NF-kB Transcription Factors and Non-Hodgkin Lymphoma Risk

BACKGROUND:A promoter polymorphism in the pro-inflammatory cytokine tumor necrosis factor (TNF) (TNF G-308A) is associated with increased non-Hodgkin lymphoma (NHL) risk. The protein product, TNF-alpha, activates the nuclear factor kappa beta (NF-kappaB) transcription factor, and is critical for inflammatory and apoptotic responses in cancer progression. We hypothesized that the TNF and NF-kappaB pathways are important for NHL and that gene variations across the pathways may alter NHL risk. METHODOLOGY/PRINCIPAL FINDINGS:We genotyped 500 tag single nucleotide polymorphisms (SNPs) from 48 candidate gene regions (defined as 20 kb 5', 10 kb 3') in the TNF and TNF receptor superfamilies and the NF-kappaB and related transcription factors, in 1946 NHL cases and 1808 controls pooled from three independent population-based case-control studies. We obtained a gene region-level summary of association by computing the minimum p-value ("minP test"). We used logistic regression to compute odds ratios and 95% confidence intervals for NHL and four major NHL subtypes in relation to SNP genotypes and haplotypes. For NHL, the tail strength statistic supported an overall relationship between the TNF/NF-kappaB pathway and NHL (p = 0.02). We confirmed the association between TNF/LTA on chromosome 6p21.3 with NHL and found the LTA rs2844484 SNP most significantly and specifically associated with the major subtype, diffuse large B-cell lymphoma (DLBCL) (p-trend = 0.001). We also implicated for the first time, variants in NFKBIL1 on chromosome 6p21.3, associated with NHL. Other gene regions identified as statistically significantly associated with NHL included FAS, IRF4, TNFSF13B, TANK, TNFSF7 and TNFRSF13C. Accordingly, the single most significant SNPs associated with NHL were FAS rs4934436 (p-trend = 0.0024), IRF4 rs12211228 (p-trend = 0.0026), TNFSF13B rs2582869 (p-trend = 0.0055), TANK rs1921310 (p-trend = 0.0025), TNFSF7 rs16994592 (p-trend = 0.0024), and TNFRSF13C rs6002551 (p-trend = 0.0074). All associations were consistent in each study with no apparent specificity for NHL subtype. CONCLUSIONS/SIGNIFICANCE:Our results provide consistent evidence that variation in the TNF superfamily of genes and specifically within chromosome 6p21.3 impacts lymphomagenesis. Further characterization of these susceptibility loci and identification of functional variants are warranted

Anopheles larval abundance and diversity in three rice agro-village complexes Mwea irrigation scheme, central Kenya

<p>Abstract</p> <p>Background</p> <p>The diversity and abundance of <it>Anopheles </it>larvae has significant influence on the resulting adult mosquito population and hence the dynamics of malaria transmission. Studies were conducted to examine larval habitat dynamics and ecological factors affecting survivorship of aquatic stages of malaria vectors in three agro-ecological settings in Mwea, Kenya.</p> <p>Methods</p> <p>Three villages were selected based on rice husbandry and water management practices. Aquatic habitats in the 3 villages representing planned rice cultivation (Mbui Njeru), unplanned rice cultivation (Kiamachiri) and non-irrigated (Murinduko) agro-ecosystems were sampled every 2 weeks to generate stage-specific estimates of mosquito larval densities, relative abundance and diversity. Records of distance to the nearest homestead, vegetation coverage, surface debris, turbidity, habitat stability, habitat type, rice growth stage, number of rice tillers and percent <it>Azolla </it>cover were taken for each habitat.</p> <p>Results</p> <p>Captures of early, late instars and pupae accounted for 78.2%, 10.9% and 10.8% of the total <it>Anopheles </it>immatures sampled (n = 29,252), respectively. There were significant differences in larval abundance between 3 agro-ecosystems. The village with 'planned' rice cultivation had relatively lower <it>Anopheles </it>larval densities compared to the villages where 'unplanned' or non-irrigated. Similarly, species composition and richness was higher in the two villages with either 'unplanned' or limited rice cultivation, an indication of the importance of land use patterns on diversity of larval habitat types. Rice fields and associated canals were the most productive habitat types while water pools and puddles were important for short periods during the rainy season. Multiple logistic regression analysis showed that presence of other invertebrates, percentage <it>Azolla </it>cover, distance to nearest homestead, depth and water turbidity were the best predictors for <it>Anopheles </it>mosquito larval abundance.</p> <p>Conclusion</p> <p>These results suggest that agricultural practices have significant influence on mosquito species diversity and abundance and that certain habitat characteristics favor production of malaria vectors. These factors should be considered when implementing larval control strategies which should be targeted based on habitat productivity and water management.</p

A synthesis of evidence for policy from behavioural science during COVID-19

Scientific evidence regularly guides policy decisions1, with behavioural science increasingly part of this process2. In April 2020, an influential paper3 proposed 19 policy recommendations (‘claims’) detailing how evidence from behavioural science could contribute to efforts to reduce impacts and end the COVID-19 pandemic. Here we assess 747 pandemic-related research articles that empirically investigated those claims. We report the scale of evidence and whether evidence supports them to indicate applicability for policymaking. Two independent teams, involving 72 reviewers, found evidence for 18 of 19 claims, with both teams finding evidence supporting 16 (89%) of those 18 claims. The strongest evidence supported claims that anticipated culture, polarization and misinformation would be associated with policy effectiveness. Claims suggesting trusted leaders and positive social norms increased adherence to behavioural interventions also had strong empirical support, as did appealing to social consensus or bipartisan agreement. Targeted language in messaging yielded mixed effects and there were no effects for highlighting individual benefits or protecting others. No available evidence existed to assess any distinct differences in effects between using the terms ‘physical distancing’ and ‘social distancing’. Analysis of 463 papers containing data showed generally large samples; 418 involved human participants with a mean of 16,848 (median of 1,699). That statistical power underscored improved suitability of behavioural science research for informing policy decisions. Furthermore, by implementing a standardized approach to evidence selection and synthesis, we amplify broader implications for advancing scientific evidence in policy formulation and prioritization