Larger than Life: Humans' Nonverbal Status Cues Alter Perceived Size

Social dominance and physical size are closely linked. Nonverbal dominance displays in many non-human species are known to increase the displayer's apparent size. Humans also employ a variety of nonverbal cues that increase apparent status, but it is not yet known whether these cues function via a similar mechanism: by increasing the displayer's apparent size.We generated stimuli in which actors displayed high status, neutral, or low status cues that were drawn from the findings of a recent meta-analysis. We then conducted four studies that indicated that nonverbal cues that increase apparent status do so by increasing the perceived size of the displayer. Experiment 1 demonstrated that nonverbal status cues affect perceivers' judgments of physical size. The results of Experiment 2 showed that altering simple perceptual cues can affect judgments of both size and perceived status. Experiment 3 used objective measurements to demonstrate that status cues change targets' apparent size in the two-dimensional plane visible to a perceiver, and Experiment 4 showed that changes in perceived size mediate changes in perceived status, and that the cue most associated with this phenomenon is postural openness.We conclude that nonverbal cues associated with social dominance also affect the perceived size of the displayer. This suggests that certain nonverbal dominance cues in humans may function as they do in other species: by creating the appearance of changes in physical size

Feasible mitigation actions in developing countries

Energy use is not only crucial for economic development, but is also the main driver of greenhouse-gas emissions. Developing countries can reduce emissions and thrive only if economic growth is disentangled from energy-related emissions. Although possible in theory, the required energy-system transformation would impose considerable costs on developing nations. Developed countries could bear those costs fully, but policy design should avoid a possible 'climate rent curse', that is, a negative impact of financial inflows on recipients' economies. Mitigation measures could meet further resistance because of adverse distributional impacts as well as political economy reasons. Hence, drastically re-orienting development paths towards low-carbon growth in developing countries is not very realistic. Efforts should rather focus on 'feasible mitigation actions' such as fossil-fuel subsidy reform, decentralized modern energy and fuel switching in the power sector

A 'synthetic-sickness' screen for senescence re-engagement targets in mutant cancer backgrounds.

Senescence is a universal barrier to immortalisation and tumorigenesis. As such, interest in the use of senescence-induction in a therapeutic context has been gaining momentum in the past few years; however, senescence and immortalisation remain underserved areas for drug discovery owing to a lack of robust senescence inducing agents and an incomplete understanding of the signalling events underlying this complex process. In order to address this issue we undertook a large-scale morphological siRNA screen for inducers of senescence phenotypes in the human melanoma cell line A375P. Following rescreen and validation in a second cancer cell line, HCT116 colorectal carcinoma, a panel of 16 of the most robust hits were selected for further validation based on significance and the potential to be targeted by drug-like molecules. Using secondary assays for detection of senescence biomarkers p21, 53BP1 and senescence associated beta-galactosidase (SAβGal) in a panel of HCT116 cell lines carrying cancer-relevant mutations, we show that partial senescence phenotypes can be induced to varying degrees in a context dependent manner, even in the absence of p21 or p53 expression. However, proliferation arrest varied among genetic backgrounds with predominantly toxic effects in p21 null cells, while cells lacking PI3K mutation failed to arrest. Furthermore, we show that the oncogene ECT2 induces partial senescence phenotypes in all mutant backgrounds tested, demonstrating a dependence on activating KRASG13D for growth suppression and a complete senescence response. These results suggest a potential mechanism to target mutant KRAS signalling through ECT2 in cancers that are reliant on activating KRAS mutations and remain refractory to current treatments

CDK1 is a synthetic lethal target for KRAS mutant tumours.

Activating KRAS mutations are found in approximately 20% of human cancers but no RAS-directed therapies are currently available. Here we describe a novel, robust, KRAS synthetic lethal interaction with the cyclin dependent kinase, CDK1. This was discovered using parallel siRNA screens in KRAS mutant and wild type colorectal isogenic tumour cells and subsequently validated in a genetically diverse panel of 26 colorectal and pancreatic tumour cell models. This established that the KRAS/CDK1 synthetic lethality applies in tumour cells with either amino acid position 12 (p.G12V, pG12D, p.G12S) or amino acid position 13 (p.G13D) KRAS mutations and can also be replicated in vivo in a xenograft model using a small molecule CDK1 inhibitor. Mechanistically, CDK1 inhibition caused a reduction in the S-phase fraction of KRAS mutant cells, an effect also characterised by modulation of Rb, a master control of the G1/S checkpoint. Taken together, these observations suggest that the KRAS/CDK1 interaction is a robust synthetic lethal effect worthy of further investigation

The Perceived Benefits of Height: Strength, Dominance, Social Concern, and Knowledge among Bolivian Native Amazonians

Research in industrial countries suggests that, with no other knowledge about a person, positive traits are attributed to taller people and correspondingly, that taller people have slightly better socioeconomic status (SES). However, research in some non-industrialized contexts has shown no correlation or even negative correlations between height and socioeconomic outcomes. It remains unclear whether positive traits remain attributed to taller people in such contexts. To address this question, here we report the results of a study in a foraging-farming society of native Amazonians in Bolivia (Tsimane’)–a group in which we have previously shown little association between height and socioeconomic outcomes. We showed 24 photographs of pairs of Tsimane’ women, men, boys, and girls to 40 women and 40 men >16 years of age. We presented four behavioral scenarios to each participant and asked them to point to the person in the photograph with greater strength, dominance, social concern, or knowledge. The pairs in the photographs were of the same sex and age, but one person was shorter. Tsimane’ women and men attributed greater strength, dominance, and knowledge to taller girls and boys, but they did not attribute most positive traits to taller adults, except for strength, and more social concern only when women assessed other women in the photographs. These results raise a puzzle: why would Tsimane’ attribute positive traits to tall children, but not tall adults? We propose three potential explanations: adults’ expectations about the more market integrated society in which their children will grow up, height as a signal of good child health, and children’s greater variation in the traits assessed corresponding to maturational stages

Density Contrast Sedimentation Velocity for the Determination of Protein Partial-Specific Volumes

The partial-specific volume of proteins is an important thermodynamic parameter required for the interpretation of data in several biophysical disciplines. Building on recent advances in the use of density variation sedimentation velocity analytical ultracentrifugation for the determination of macromolecular partial-specific volumes, we have explored a direct global modeling approach describing the sedimentation boundaries in different solvents with a joint differential sedimentation coefficient distribution. This takes full advantage of the influence of different macromolecular buoyancy on both the spread and the velocity of the sedimentation boundary. It should lend itself well to the study of interacting macromolecules and/or heterogeneous samples in microgram quantities. Model applications to three protein samples studied in either H2O, or isotopically enriched H218O mixtures, indicate that partial-specific volumes can be determined with a statistical precision of better than 0.5%, provided signal/noise ratios of 50–100 can be achieved in the measurement of the macromolecular sedimentation velocity profiles. The approach is implemented in the global modeling software SEDPHAT

A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes

dentification of sequence variants robustly associated with predisposition to diabetic kidney disease (DKD) has the potential to provide insights into the pathophysiological mechanisms responsible. We conducted a genome-wide association study (GWAS) of DKD in type 2 diabetes (T2D) using eight complementary dichotomous and quantitative DKD phenotypes: the principal dichotomous analysis involved 5,717 T2D subjects, 3,345 with DKD. Promising association signals were evaluated in up to 26,827 subjects with T2D (12,710 with DKD). A combined T1D+T2D GWAS was performed using complementary data available for subjects with T1D, which, with replication samples, involved up to 40,340 subjects with diabetes (18,582 with DKD). Analysis of specific DKD phenotypes identified a novel signal near GABRR1 (rs9942471, P = 4.5 x 10(-8)) associated with microalbuminuria in European T2D case subjects. However, no replication of this signal was observed in Asian subjects with T2D or in the equivalent T1D analysis. There was only limited support, in this substantially enlarged analysis, for association at previously reported DKD signals, except for those at UMOD and PRKAG2, both associated with estimated glomerular filtration rate. We conclude that, despite challenges in addressing phenotypic heterogeneity, access to increased sample sizes will continue to provide more robust inference regarding risk variant discovery for DKD.Peer reviewe

International Migration in the Atlantic Economy, 1850-1940

This chapter focuses on the economic analysis of what has been called the age of mass migration, 1850 to 1913, and its aftermath up to 1940. This has captured the interest of generations of economic historians and is still a highly active area of research. Here we concentrate on migration from Europe to the New World as this is where the bulk of the literature lies. We provide an overview of this literature focusing on key topics: the determinants of migration, the development of immigration policy, immigrant selection and assimilation, and the economic effects of mass migration as well as its legacy through to the present day. We explain how what were once orthodoxies have been revisited and revised, and how changes in our understanding have been influenced by advances in methodology, which in turn have been made possible by the availability of new and more comprehensive data. Despite these advances some issues remain contested or unresolved and, true to cliometric tradition, we conclude by calling for more research

Synthetic lethal therapies for cancer: what's next after PARP inhibitors?

The genetic concept of synthetic lethality has now been validated clinically through the demonstrated efficacy of poly(ADP-ribose) polymerase (PARP) inhibitors for the treatment of cancers in individuals with germline loss-of-function mutations in either BRCA1 or BRCA2. Three different PARP inhibitors have now been approved for the treatment of patients with BRCA-mutant ovarian cancer and one for those with BRCA-mutant breast cancer; these agents have also shown promising results in patients with BRCA-mutant prostate cancer. Here, we describe a number of other synthetic lethal interactions that have been discovered in cancer. We discuss some of the underlying principles that might increase the likelihood of clinical efficacy and how new computational and experimental approaches are now facilitating the discovery and validation of synthetic lethal interactions. Finally, we make suggestions on possible future directions and challenges facing researchers in this field