Team composition and conflict : the role of individual differences

The effects of team composition and conflict on team outcomes have been largely contradictory. In this dissertation, I strive to unravel these relationships through better incorporating two key factors when understanding relationships between team composition, conflict, and team outcomes - the role of individual differences in perceptions and behaviors and the role of power as a critical determinant of team compositions. Using a mixture of field and laboratory data, I show that understanding individual differences and team-level power structures may shed more light on the relationships between team composition, conflict, and team outcomes.LEI Universiteit LeidenSocial decision makin

Oxytocin Motivates Non-Cooperation in Intergroup Conflict to Protect Vulnerable In-Group Members

Intergroup conflict is often driven by an individual's motivation to protect oneself and fellow group members against the threat of out-group aggression, including the tendency to pre-empt out-group threat through a competitive approach. Here we link such defense-motivated competition to oxytocin, a hypothalamic neuropeptide involved in reproduction and social bonding. An intergroup conflict game was developed to disentangle whether oxytocin motivates competitive approach to protect (i) immediate self-interest, (ii) vulnerable in-group members, or (iii) both. Males self-administered oxytocin or placebo (double-blind placebo-controlled) and made decisions with financial consequences to themselves, their fellow in-group members, and a competing out-group. Game payoffs were manipulated between-subjects so that non-cooperation by the out-group had high vs. low impact on personal payoff (personal vulnerability), and high vs. low impact on payoff to fellow in-group members (in-group vulnerability). When personal vulnerability was high, non-cooperation was unaffected by treatment and in-group vulnerability. When personal vulnerability was low, however, in-group vulnerability motivated non-cooperation but only when males received oxytocin. Oxytocin fuels a defense-motivated competitive approach to protect vulnerable group members, even when personal fate is not at stake

Systematic approach to developing splice modulating antisense oligonucleotides

The process of pre-mRNA splicing is a common and fundamental step in the expression of most human genes. Alternative splicing, whereby different splice motifs and sites are recognised in a developmental and/or tissue-specific manner, contributes to genetic plasticity and diversity of gene expression. Redirecting pre-mRNA processing of various genes has now been validated as a viable clinical therapeutic strategy, providing treatments for Duchenne muscular dystrophy (inducing specific exon skipping) and spinal muscular atrophy (promoting exon retention). We have designed and evaluated over 5000 different antisense oligonucleotides to alter splicing of a variety of pre-mRNAs, from the longest known human pre-mRNA to shorter, exon-dense primary gene transcripts. Here, we present our guidelines for designing, evaluating and optimising splice switching antisense oligomers in vitro. These systematic approaches assess several critical factors such as the selection of target splicing motifs, choice of cells, various delivery reagents and crucial aspects of validating assays for the screening of antisense oligonucleotides composed of 2′-O-methyl modified bases on a phosphorothioate backbone

Toy nanoindentation model and incipient plasticity

A toy model of two dimensional nanoindentation in finite crystals is proposed. The crystal is described by periodized discrete elasticity whereas the indenter is a rigid strain field of triangular shape representing a hard knife-like indenter. Analysis of the model shows that there are a number of discontinuities in the load vs penetration depth plot which correspond to the creation of dislocation loops. The stress vs depth bifurcation diagram of the model reveals multistable stationary solutions that appear as the dislocation-free branch of solutions develops turning points for increasing stress. Dynamical simulations show that an increment of the applied load leads to nucleation of dislocation loops below the nanoindenter tip. Such dislocations travel inside the bulk of the crystal and accommodate at a certain depth in the sample. In agreement with experiments, hysteresis is observed if the stress is decreased after the first dislocation loop is created. Critical stress values for loop creation and their final location at equilibrium are calculated.Comment: 22 pages, 5 figures, to appear in Chaos, Solitons and Fractal

Single stranded fully Modified-Phosphorothioate oligonucleotides can induce structured nuclear inclusions, alter nuclear protein localization and disturb the transcriptome In Vitro

Oligonucleotides and nucleic acid analogues that alter gene expression are now showing therapeutic promise in human disease. Whilst the modification of synthetic nucleic acids to protect against nuclease degradation and to influence drug function is common practice, such modifications may also confer unexpected physicochemical and biological properties. Gapmer mixed-modified and DNA oligonucleotides on a phosphorothioate backbone can bind non-specifically to intracellular proteins to form a variety of toxic inclusions, driven by the phosphorothioate linkages, but also influenced by the oligonucleotide sequence. Recently, the non-antisense or other off-target effects of 2′ O- fully modified phosphorothioate linkage oligonucleotides are becoming better understood. Here, we report chemistry-specific effects of oligonucleotides composed of modified or unmodified bases, with phosphorothioate linkages, on subnuclear organelles and show altered distribution of nuclear proteins, the appearance of highly stable and strikingly structured nuclear inclusions, and disturbed RNA processing in primary human fibroblasts and other cultured cells. Phosphodiester, phosphorodiamidate morpholino oligomers, and annealed complimentary phosphorothioate oligomer duplexes elicited no such consequences. Disruption of subnuclear structures and proteins elicit severe phenotypic disturbances, revealed by transcriptomic analysis of transfected fibroblasts exhibiting such disruption. Our data add to the growing body of evidence of off-target effects of some phosphorothioate nucleic acid drugs in primary cells and suggest alternative approaches to mitigate these effects

The Williams Scale of Attitude toward Paganism: development and application among British Pagans

This article builds on the tradition of attitudinal measures of religiosity established by Leslie Francis and colleagues with the Francis Scale of Attitude toward Christianity (and reflected in the Sahin-Francis Scale of Attitude toward Islam, the Katz-Francis Scale of Attitude toward Judaism, and the Santosh-Francis Scale of Attitude toward Hinduism) by introducing a new measure to assess the attitudinal disposition of Pagans. A battery of items was completed by 75 members of a Pagan Summer Camp. These items were reduced to produce a 21-item scale that measured aspects of Paganism concerned with: the God/Goddess, worshipping, prayer, and coven. The scale recorded an alpha coefficient of 0.93. Construct validity of the Williams Scale of Attitude toward Paganism was demonstrated by the clear association with measures of participation in private rituals

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Team composition and conflict : the role of individual differences

The effects of team composition and conflict on team outcomes have been largely contradictory. In this dissertation, I strive to unravel these relationships through better incorporating two key factors when understanding relationships between team composition, conflict, and team outcomes - the role of individual differences in perceptions and behaviors and the role of power as a critical determinant of team compositions. Using a mixture of field and laboratory data, I show that understanding individual differences and team-level power structures may shed more light on the relationships between team composition, conflict, and team outcomes.</table