Assessment of the Mate Retention Inventory-Short Form Using Item Response Theory

The mate retention inventory (MRI) has been a valuable tool in the field of evolutionary psychology for the past 30 years. The goal of the current research is to subject the MRI to rigorous psychometric analysis using item response theory to answer three broad questions. Do the individual items of the MRI fit the scale well? Does the overall function of the MRI match what is predicted? Finally, do men and women respond similarly to the MRI? Using a graded response model, it was found that all but two of the items fit acceptable model patterns. Test information function analysis found that the scale acceptably captures individual differences for participants with a high degree of mate retention but the scale is lacking in capturing information from participants with a low degree of mate retention. Finally, discriminate item function analysis reveals that the MRI is better at assessing male than female participants, indicating that the scale may not be the best indicator of female behavior in a relationship. Overall, we conclude that the MRI is a good scale, especially for assessing male behavior, but it could be improved for assessing female behavior and individuals lower on overall mate retention behavior. It is suggested that this paper be used as a framework for how the newest psychometrics techniques can be applied in order to create more robust and valid measures in the field of evolutionary psychology

Supervillin modulation of focal adhesions involving TRIP6/ZRP-1

Cell–substrate contacts, called focal adhesions (FAs), are dynamic in rapidly moving cells. We show that supervillin (SV)—a peripheral membrane protein that binds myosin II and F-actin in such cells—negatively regulates stress fibers, FAs, and cell–substrate adhesion. The major FA regulatory sequence within SV (SV342-571) binds to the LIM domains of two proteins in the zyxin family, thyroid receptor–interacting protein 6 (TRIP6) and lipoma-preferred partner (LPP), but not to zyxin itself. SV and TRIP6 colocalize within large FAs, where TRIP6 may help recruit SV. RNAi-mediated decreases in either protein increase cell adhesion to fibronectin. TRIP6 partially rescues SV effects on stress fibers and FAs, apparently by mislocating SV away from FAs. Thus, SV interactions with TRIP6 at FAs promote loss of FA structure and function. SV and TRIP6 binding partners suggest several specific mechanisms through which the SV–TRIP6 interaction may regulate FA maturation and/or disassembly

Export of malaria proteins requires co-translational processing of the PEXEL motif independent of phosphatidylinositol-3-phosphate binding

Acknowledgements We thank the Red Cross blood bank in Melbourne for human erythrocytes. We thank Svenja Gunther for expression of GBP130 66–196 proteins; Michelle Gazdik and Chris Burns for help in preparing lipids; Lachlan Whitehead (Centre for Dynamic Imaging, Walter and Eliza Hall Institute) for assistance with quantification of export; and David Bocher for help with generation of STEVOR constructs. This work was supported by the National Health and Medical Research Council of Australia (grants 637406, 1010326, 1049811 and 1057960), a Ramaciotti Foundation Establishment Grant (3197/2010), a Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIISS, and the Canadian Institutes for Health Research (MOP#130359). J.A.B is an Australian Research Council QEII Fellow, SF was supported by the Research Training Group GRK1459 of the German Research Foundation, and AFC is a Howard Hughes International Scholar.Peer reviewedPublisher PD

Formal Modeling and Analysis of the MAL-Associated Biological Regulatory Network: Insight into Cerebral Malaria

The discrete modeling formalism of René Thomas is a well known approach for the modeling and analysis of Biological Regulatory Networks (BRNs). This formalism uses a set of parameters which reflect the dynamics of the BRN under study. These parameters are initially unknown but may be deduced from the appropriately chosen observed dynamics of a BRN. The discrete model can be further enriched by using the model checking tool HyTech along with delay parameters. This paves the way to accurately analyse a BRN and to make predictions about critical trajectories which lead to a normal or diseased response. In this paper, we apply the formal discrete and hybrid (discrete and continuous) modeling approaches to characterize behavior of the BRN associated with MyD88-adapter-like (MAL) – a key protein involved with innate immune response to infections. In order to demonstrate the practical effectiveness of our current work, different trajectories and corresponding conditions that may lead to the development of cerebral malaria (CM) are identified. Our results suggest that the system converges towards hyperinflammation if Bruton's tyrosine kinase (BTK) remains constitutively active along with pre-existing high cytokine levels which may play an important role in CM pathogenesis

C5a Enhances Dysregulated Inflammatory and Angiogenic Responses to Malaria In Vitro: Potential Implications for Placental Malaria

Placental malaria (PM) is a leading cause of maternal and infant mortality. Although the accumulation of parasitized erythrocytes (PEs) and monocytes within the placenta is thought to contribute to the pathophysiology of PM, the molecular mechanisms underlying PM remain unclear. Based on the hypothesis that excessive complement activation may contribute to PM, in particular generation of the potent inflammatory peptide C5a, we investigated the role of C5a in the pathogenesis of PM in vitro and in vivo.Using primary human monocytes, the interaction between C5a and malaria in vitro was assessed. CSA- and CD36-binding PEs induced activation of C5 in the presence of human serum. Plasmodium falciparum GPI (pfGPI) enhanced C5a receptor expression (CD88) on monocytes, and the co-incubation of monocytes with C5a and pfGPI resulted in the synergistic induction of cytokines (IL-6, TNF, IL-1beta, and IL-10), chemokines (IL-8, MCP-1, MIP1alpha, MIP1beta) and the anti-angiogenic factor sFlt-1 in a time and dose-dependent manner. This dysregulated response was abrogated by C5a receptor blockade. To assess the potential role of C5a in PM, C5a plasma levels were measured in malaria-exposed primigravid women in western Kenya. Compared to pregnant women without malaria, C5a levels were significantly elevated in women with PM.These results suggest that C5a may contribute to the pathogenesis of PM by inducing dysregulated inflammatory and angiogenic responses that impair placental function

Natural Regulatory T Cells in Malaria: Host or Parasite Allies?

Plasmodium falciparum malaria causes 500 million clinical cases with approximately one million deaths each year. After many years of exposure, individuals living in endemic areas develop a form of clinical immunity to disease known as premunition, which is characterised by low parasite burdens rather than sterilising immunity. The reason why malaria parasites persist under a state of premunition is unknown but it has been suggested that suppression of protective immunity might be a mechanism leading to parasite persistence. Although acquired immunity limits the clinical impact of infection and provides protection against parasite replication, experimental evidence indicates that cell-mediated immune responses also result in detrimental inflammation and contribute to the aetiology of severe disease. Thus, an appropriate regulatory balance between protective immune responses and immune-mediated pathology is required for a favourable outcome of infection. As natural regulatory T (Treg) cells are identified as an immunosuppressive lineage able to modulate the magnitude of effector responses, several studies have investigated whether this cell population plays a role in balancing protective immunity and pathogenesis during malaria. The main findings to date are summarised in this review and the implication for the induction of pathogenesis and immunity to malaria is discussed

Spectrin-based skeleton as an actor in cell signaling

This review focuses on the recent advances in functions of spectrins in non-erythroid cells. We discuss new data concerning the commonly known role of the spectrin-based skeleton in control of membrane organization, stability and shape, and tethering protein mosaics to the cellular motors and to all major filament systems. Particular effort has been undertaken to highlight recent advances linking spectrin to cell signaling phenomena and its participation in signal transduction pathways in many cell types

Skeletal muscle properties and vascular function do not differ between healthy, young vegan and omnivorous men

A vegan diet is associated with reduced cardiovascular morbidity and mortality, but protein deficiencies may be detrimental to skeletal muscle structure and function. The aim of this study was to compare the vascular and skeletal muscle properties between young, healthy, recreationally active habitual vegan (VEG) and omnivorous (OMN) men. Sixteen OMN and nine VEG underwent ultrasound scans to determine brachial artery flow-mediated dilation (FMD) and carotid artery intima-media thickness (cIMT) and vastus lateralis (VL) muscle thickness and fascicle pennation angle. Knee extension maximal voluntary isometric contraction (MVIC) force was assessed on an isokinetic dynamometer, and V ˙ O 2 m a x on a cycle ergometer and online gas analysis system. A three-day food diary determined habitual dietary behaviour. Bayesian analyses of independent groups provided 'moderate' to 'very strong' evidence for lower consumption of absolute (63±21 g/d vs. 98±30 g/d; Bayes Factor (BF01)=0.140) and relative (0.86±0.29 g/kg/d vs. 1.36±0.52 g/kg/d; BF01=0.259) protein, absolute saturated fat (15.2±7.9 g vs. 30.3±11.8 g; BF01=0.089) and cholesterol (5.0±6.0 mg vs. 337.9±232.6 mg; BF01=0.019) in VEG compared to OMN, respectively. Further, there was 'anecdotal' evidence to support no differences in FMD (3.37±3.31% vs. 4.58±5.82%; BF01=2.591), cIMT (0.51±0.07mm vs. 0.49±0.04mm; BF01=2.510), VL thickness (26.1±3.7mm vs. 27.8±6.4mm; BF01=2.726), fascicle pennation angle (16.6±4.7° vs. 17.7±3.7°; BF01=2.844), MVIC (627±182 N vs. 551±102 N; BF01=1.656) or V ˙ O 2 m a x (40.8±9.8 ml/kg/min vs. 35.8±5.2 ml/kg/min; BF01=1.218) between VEG and OMN, respectively. Despite marked differences in habitual nutrient intake, healthy, young vegan and omnivorous men did not differ regarding vascular and skeletal muscle structure and function, or cardiovascular fitness

Post-transcriptional down-regulation of expression of transcription factor NF1 by Ha-ras oncogene.

NF1 is a family of polypeptides that binds to discrete DNA motifs and plays varying roles in the regulation of gene expression. These polypeptides are also thought to mediate the expression of differentiation-specific markers such as adipocyte and mammary cell type-specific genes. The expression of a number of cellular differentiation-specific markers is down-regulated during neoplastic transformation. We therefore investigated whether oncogenic transformation interferes with the action of NF1. Stable transfection of activated Ha-ras into a number of murine cells correlated with a down-regulation of the expression of the NF1 genes NF1/CTF and NF1/X. The down-regulation was not at the transcriptional level but at the level of stability of the NF1 mRNAs. The level of the DNA binding activity of the NF1 proteins was also reduced in Ha-v-ras-transformed cells, and the expression of a gene that depends on this family of transcription factors was specifically repressed. These results demonstrate that an activated Ha-ras-induced pathway destabilizes the half-life of mRNAs encoding specific members in the NF1 family of transcription factors, which leads to a decrease in NF1-dependent gene expression