The structures of non-CG-repeat Z-DNAs co-crystallized with the Z-DNA-binding domain, hZαADAR1

The Z-DNA conformation preferentially occurs at alternating purine-pyrimidine repeats, and is specifically recognized by Zα domains identified in several Z-DNA-binding proteins. The binding of Zα to foreign or chromosomal DNA in various sequence contexts is known to influence various biological functions, including the DNA-mediated innate immune response and transcriptional modulation of gene expression. For these reasons, understanding its binding mode and the conformational diversity of Zα bound Z-DNAs is of considerable importance. However, structural studies of Zα bound Z-DNA have been mostly limited to standard CG-repeat DNAs. Here, we have solved the crystal structures of three representative non-CG repeat DNAs, d(CACGTG)2, d(CGTACG)2 and d(CGGCCG)2 complexed to hZαADAR1 and compared those structures with that of hZαADAR1/d(CGCGCG)2 and the Zα-free Z-DNAs. hZαADAR1 bound to each of the three Z-DNAs showed a well conserved binding mode with very limited structural deviation irrespective of the DNA sequence, although varying numbers of residues were in contact with Z-DNA. Z-DNAs display less structural alterations in the Zα-bound state than in their free form, thereby suggesting that conformational diversities of Z-DNAs are restrained by the binding pocket of Zα. These data suggest that Z-DNAs are recognized by Zα through common conformational features regardless of the sequence and structural alterations

ZBP1 subcellular localization and association with stress granules is controlled by its Z-DNA binding domains

Z-DNA binding protein 1 (ZBP1) belongs to a family of proteins that contain the Zα domain, which binds specifically to left-handed Z-DNA and Z-RNA. Like all vertebrate proteins in the Zα family, it contains two Zα-like domains and is highly inducible by immunostimulation. Using circular dichroism spectroscopy and electrophoretic mobility shift assays we show that both Zα domains can bind Z-DNA independently and that substrate binding is greatly enhanced when both domains are linked. Full length ZBP1 and a prominent splice variant lacking the first Zα domain (ΔZα) showed strikingly different subcellular localizations. While the full length protein showed a finely punctate cytoplasmatic distribution, ZBP1ΔZα accumulated in large cytoplasmic granules. Mutation of residues important for Z-DNA binding in the first Zα domain resulted in a distribution comparable to that of ZBP1ΔZα. The ZBP1ΔZα granules are distinct from stress granules (SGs) and processing bodies but dynamically interacted with these. Polysome stabilization led to the disassembly of ZBP1ΔZα granules, indicating that mRNA are integral components. Heat shock and arsenite exposure had opposing effects on ZBP1 isoforms: while ZBP1ΔZα granules disassembled, full length ZBP1 accumulated in SGs. Our data link ZBP1 to mRNA sorting and metabolism and indicate distinct roles for ZBP1 isoforms

Do children's expectations about future physical activity predict their physical activity in adulthood?

BACKGROUND: Much of the population fails to meet recommended physical activity (PA) levels, but there remains considerable individual variation. By understanding drivers of different trajectories, interventions can be better targeted and more effective. One such driver may be a person's physical activity identity (PAI)-the extent to which a person perceives PA as central to who they are. METHODS: Using survey information and a unique body of essays written at age 11 from the National Child Development Study (N = 10 500), essays mentioning PA were automatically identified using the machine learning technique support vector classification and PA trajectories were estimated using latent class analysis. Analyses tested the extent to which childhood PAI correlated with activity levels from age 23 through 55 and with trajectories across adulthood. RESULTS: 42.2% of males and 33.5% of females mentioned PA in their essays, describing active and/or passive engagement. Active PAI in childhood was correlated with higher levels of activity for men but not women, and was correlated with consistently active PA trajectories for both genders. Passive PAI was not related to PA for either gender. CONCLUSIONS: This study offers a novel approach for analysing large qualitative datasets to assess identity and behaviours. Findings suggest that at as young as 11 years old, the way a young person conceptualizes activity as part of their identity has a lasting association with behaviour. Still, an active identity may require a supportive sociocultural context to manifest in subsequent behaviour

Personal values and political activism: A cross-national study

Using data from 28 countries in four continents, the present research addresses the question of how basic values may account for political activism. Study 1 (N = 35,116) analyses data from representative samples in 20 countries that responded to the 21-item version of the Portrait Values Questionnaire (PVQ-21) in the European Social Survey. Study 2 (N = 7,773) analyses data from adult samples in six of the same countries (Finland, Germany, Greece, Israel, Poland, and United Kingdom) and eight other countries (Australia, Brazil, Chile, Italy, Slovakia, Turkey, Ukraine, and United States) that completed the full 40-item PVQ. Across both studies, political activism relates positively to self-transcendence and openness to change values, especially to universalism and autonomy of thought, a subtype of self-direction. Political activism relates negatively to conservation values, especially to conformity and personal security. National differences in the strength of the associations between individual values and political activism are linked to level of democratization

Women are warmer but no less assertive than men: gender and language on Facebook

Using a large social media dataset and open-vocabulary methods from computational linguistics, we explored differences in language use across gender, affiliation, and assertiveness. In Study 1, we analyzed topics (groups of semantically similar words) across 10 million messages from over 52,000 Facebook users. Most language differed little across gender. However, topics most associated with self-identified female participants included friends, family, and social life, whereas topics most associated with self-identified male participants included swearing, anger, discussion of objects instead of people, and the use of argumentative language. In Study 2, we plotted male- and female-linked language topics along two interpersonal dimensions prevalent in gender research: affiliation and assertiveness. In a sample of over 15,000 Facebook users, we found substantial gender differences in the use of affiliative language and slight differences in assertive language. Language used more by self-identified females was interpersonally warmer, more compassionate, polite, and—contrary to previous findings—slightly more assertive in their language use, whereas language used more by self-identified males was colder, more hostile, and impersonal. Computational linguistic analysis combined with methods to automatically label topics offer means for testing psychological theories unobtrusively at large scale.This work was supported by the Templeton Religion Trust

Predicting individual-level income from Facebook profiles

Information about a person's income can be useful in several business-related contexts, such as personalized advertising or salary negotiations. However, many people consider this information private and are reluctant to share it. In this paper, we show that income is predictable from the digital footprints people leave on Facebook. Applying an established machine learning method to an income-representative sample of 2,623 U.S. Americans, we found that (i) Facebook Likes and Status Updates alone predicted a person's income with an accuracy of up to r = 0.43, and (ii) Facebook Likes and Status Updates added incremental predictive power above and beyond a range of socio-demographic variables (ΔR2 = 6-16%, with a correlation of up to r = 0.49). Our findings highlight both opportunities for businesses and legitimate privacy concerns that such prediction models pose to individuals and society when applied without individual consent

Living in the past, present, and future: measuring temporal orientation with language

OBJECTIVE: Temporal orientation refers to individual differences in the relative emphasis one places on the past, present, or future, and is related to academic, financial, and health outcomes. We propose and evaluate a method for automatically measuring temporal orientation through language expressed on social media. METHOD: Judges rated the temporal orientation of 4,302 social media messages. We trained a classifier based on these ratings, which could accurately predict the temporal orientation of new messages in a separate validation set (accuracy/mean sensitivity = .72; mean specificity = .77). We used the classifier to automatically classify 1.3 million messages written by 5,372 participants (50% female, aged 13-48). Finally, we tested whether individual differences in past, present, and future orientation differentially related to gender, age, Big Five personality, satisfaction with life, and depressive symptoms. RESULTS: Temporal orientations exhibit several expected correlations with age, gender, and Big Five personality. More future-oriented people were older, more likely to be female, more conscientious, less impulsive, less depressed, and more satisfied with life; present orientation showed the opposite pattern. CONCLUSION: Language-based assessments can complement and extend existing measures of temporal orientation, providing an alternative approach and additional insights into language and personality relationships. This article is protected by copyright. All rights reserved.Support for this article was provided by grant #63597 from the Robert Wood Johnson Foundation (M. E. P. Seligman, PI) and by a grant from the Templeton Religion Trust (M.E.P. Seligman, H. A. Schwartz, L. H. Ungar, co-PIs)

Personality, gender, and age in the language of social media: the open-vocabulary approach

We analyzed 700 million words, phrases, and topic instances collected from the Facebook messages of 75,000 volunteers, who also took standard personality tests, and found striking variations in language with personality, gender, and age. In our open-vocabulary technique, the data itself drives a comprehensive exploration of language that distinguishes people, finding connections that are not captured with traditional closed-vocabulary word-category analyses. Our analyses shed new light on psychosocial processes yielding results that are face valid (e.g., subjects living in high elevations talk about the mountains), tie in with other research (e.g., neurotic people disproportionately use the phrase ‘sick of’ and the word ‘depressed’), suggest new hypotheses (e.g., an active life implies emotional stability), and give detailed insights (males use the possessive ‘my’ when mentioning their ‘wife’ or ‘girlfriend’ more often than females use ‘my’ with ‘husband’ or 'boyfriend’). To date, this represents the largest study, by an order of magnitude, of language and personalit

Modulation of antigen-specific T-cells as immune therapy for chronic infectious diseases and cancer

Copyright: © 2014 Li, Symonds, Miao, Sanderson and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.This article has been made available through the Brunel Open Access Publishing Fund.T-cell responses are induced by antigen presenting cells (APC) and signals from the microenvironment. Antigen persistence and inflammatory microenvironments in chronic infections and cancer can induce a tolerant state in T-cells resulting in hyporesponsiveness, loss of effector function, and weak biochemical signaling patterns in response to antigen stimulation. Although the mechanisms of T-cell tolerance induced in chronic infection and cancer may differ from those involved in tolerance to self-antigen, the impaired proliferation and production of IL-2 in response to antigen stimulation are hallmarks of all tolerant T cells. In this review, we will summarize the evidence that the immune responses change from non-self to “self”-like in chronic infection and cancer, and will provide an overview of strategies for re-balancing the immune response of antigen-specific T cells in chronic infection and cancer without affecting the homeostasis of the immune system.Arthritis Research UK and Medical Research Council UK