Intermittent Explosive Disorder amongst Women in Conflict Affected Timor-Leste: Associations with Human Rights Trauma,Ongoing Violence,Poverty, and Injustice

Introduction

Women in conflict-affected countries are at risk of mental disorders such as posttraumatic stress disorder and depression. No studies have investigated the association between experiences of abuse and injustice and explosive anger amongst women in these settings, and the impact of anger on women''s health, family relationships and ability to participate in development.

Methods

A mixed methods study including an epidemiological survey (n = 1513, 92.6% response) and qualitative interviews (n = 77) was conducted in Timor-Leste. The indices measured included Intermittent Explosive Disorder, posttraumatic stress disorder; severe distress; days out of role (the number of days that the person was unable to undertake normal activities); gender-specific trauma; conflict/violence; poverty; and preoccupations with injustice.

Results

Women with Intermittent Explosive Disorder (n = 184, 12.2%) were more disabled than those without the disorder (for >5 days out of role, 40.8% versus 31.5%, X² ₍₂₎  = 12.93 p = 0.0016). Multivariable associations with Intermittent Explosive Disorder, controlling for the presence of PTSD, psychological distress and other predictors in the model, included the sense of being sick (OR 1.73; 95% CI 1.08–2.77); victimization as a result of helping the resistance movement (OR 2.33, 95% CI 1.48–3.68); war-related trauma specific to being a woman (OR 1.95, 95%, CI 1.09–3.50); ongoing family violence and community conflict (OR 1.88, 95% CI 1.27–2.77); extreme poverty (OR 1.23, 95%, CI 1.08–1.39); and distressing preoccupations with injustice (relating to 2/3 historical periods, OR 2.10, 95% CI 1.35–3.28). In the qualitative study, women elaborated on the determinants of anger and its impact on their health, family and community functioning, child-rearing, and capacity to engage in development. Women reflected on the strategies that might help them overcome their anger.

Conclusions

Intermittent Explosive Disorder is prevalent and disabling amongst women in conflict-affected Timor-Leste, impacting on their health, child-rearing and ability to participate fully in socio-economic development.     

Breast Cancer Anti-estrogen Resistance 3 (BCAR3) Protein Augments Binding of the c-Src SH3 Domain to Crk-associated Substrate (p130cas)

The focal adhesion adapter protein p130(cas) regulates adhesion and growth factor-related signaling, in part through Src-mediated tyrosine phosphorylation of p130(cas). AND-34/BCAR3, one of three NSP family members, binds the p130(cas) carboxyl terminus, adjacent to a bipartite p130(cas) Src-binding domain (SBD) and induces anti-estrogen resistance in breast cancer cell lines as well as phosphorylation of p130(cas). Only a subset of the signaling properties of BCAR3, specifically augmented motility, are dependent upon formation of the BCAR3-p130(cas) complex. Using GST pull-down and immunoprecipitation studies, we show that among NSP family members, only BCAR3 augments the ability of p130(cas) to bind the Src SH3 domain through an RPLPSPP motif in the p130(cas) SBD. Although our prior work identified phosphorylation of the serine within the p130(cas) RPLPSPP motif, mutation of this residue to alanine or glutamic acid did not alter BCAR3-induced Src SH3 domain binding to p130(cas). The ability of BCAR3 to augment Src SH3 binding requires formation of a BCAR3-p130(cas) complex because mutations that reduce association between these two proteins block augmentation of Src SH3 domain binding. Similarly, in MCF-7 cells, BCAR3-induced tyrosine phosphorylation of the p130(cas) substrate domain, previously shown to be Src-dependent, was reduced by an R743A mutation that blocks BCAR3 association with p130(cas). Immunofluorescence studies demonstrate that BCAR3 expression alters the intracellular location of both p130(cas) and Src and that all three proteins co-localize. Our work suggests that BCAR3 expression may regulate Src signaling in a BCAR3-p130(cas) complex-dependent fashion by altering the ability of the Src SH3 domain to bind the p130(cas) SBD.     

Increased Carotid Intima-Media Thickness and Reduced Distensibility in Human Class III Obesity: Independent and Differential Influences of Adiposity and Blood Pressure on the Vasculature

Carotid intima-media-thickness (cIMT) and carotid distensibility (distensibility), structural and functional properties of carotid arteries respectively, are early markers, as well as strong predictors of cardiovascular disease (CVD). The characteristic of these two parameters in individuals with BMI>40.0 kg/m² (Class III obesity), however, are largely unknown. The present study was designed to document cIMT and distensibility in this population and to relate these to other factors with established association with CVD in obesity. The study included 96 subjects (65 with BMI>40.0 kg/m² and 31, age- and gender-matched, with BMI of 18.5 to 30.0 kg/m²). cIMT and distensibility were measured by non-invasive high resolution ultrasonography, circulatory CD133⁺/KDR⁺ angiogenic cells and endothelial microparticles (EMP) by flow cytometry, and plasma levels of adipokines, growth factors and cytokines by Luminex immunoassay kits. The study results demonstrated increased cIMT (0.62±0.11 mm vs. 0.54±0.08 mm, P = 0.0002) and reduced distensibility (22.52±10.79 10⁻³kpa⁻¹ vs. 29.91±12.37 10⁻³kpa⁻¹, P<0.05) in individuals with BMI>40.0 kg/m². Both cIMT and distensibility were significantly associated with traditional CVD risk factors, adiposity/adipokines and inflammatory markers but had no association with circulating angiogenic cells. We also demonstrated, for the first time, elevated plasma EMP levels in individuals with BMI>40.0 kg/m². In conclusion, cIMT is increased and distensibility reduced in Class III obesity with the changes predominantly related to conventional CVD risk factors present in this condition, demonstrating that both cIMT and distensibility remain as CVD markers in Class III obesity.     

Developmental enhancement of adenylate kinase-AMPK metabolic signaling axis supports stem cell cardiac differentiation

Background

Energetic and metabolic circuits that orchestrate cell differentiation are largely unknown. Adenylate kinase (AK) and associated AMP-activated protein kinase (AMPK) constitute a major metabolic signaling axis, yet the role of this system in guiding differentiation and lineage specification remains undefined.

Methods and Results

Cardiac stem cell differentiation is the earliest event in organogenesis, and a suitable model of developmental bioenergetics. Molecular profiling of embryonic stem cells during cardiogenesis revealed here a distinct expression pattern of adenylate kinase and AMPK genes that encode the AK-AMP-AMPK metabolic surveillance axis. Cardiac differentiation upregulated cytosolic AK1 isoform, doubled AMP-generating adenylate kinase activity, and increased AMP/ATP ratio. At cell cycle initiation, AK1 translocated into the nucleus and associated with centromeres during energy-consuming metaphase. Concomitantly, the cardiac AMP-signal receptor AMPKα2 was upregulated and redistributed to the nuclear compartment as signaling-competent phosphorylated p-AMPKα(Thr172). The cardiogenic growth factor TGF-β promoted AK1 expression, while knockdown of AK1, AK2 and AK5 activities with siRNA or suppression by hyperglycemia disrupted cardiogenesis compromising mitochondrial and myofibrillar network formation and contractile performance. Induction of creatine kinase, the alternate phosphotransfer pathway, compensated for adenylate kinase-dependent energetic deficits.

Conclusions

Developmental deployment and upregulation of the adenylate kinase/AMPK tandem provides a nucleocytosolic energetic and metabolic signaling vector integral to execution of stem cell cardiac differentiation. Targeted redistribution of the adenylate kinase-AMPK circuit associated with cell cycle and asymmetric cell division uncovers a regulator for cardiogenesis and heart tissue regeneration.     

Testing fundamental evolutionary hypotheses

Sober and Steel (J. Theor. Biol. 218, 395-408) give important limits on the use of current models with sequence data for studying ancient aspects of evolution; but they go too far in suggesting that several fundamental aspects of evolutionary theory cannot be tested in a normal scientific manner. To the contrary, we show examples of how some alternatives to the theory of descent can be formulated in such a way that they lead to predictions that can be evaluated (and rejected). The critical factor is a logical formulation of the alternatives, even though not all possible alternatives can be tested simultaneously. Similarly, some of the limits using DNA sequence data can be overcome by other types of sequence derived characters. The uniqueness (or not) of the origin of life, though still difficult, is similarly amenable to the testing of alternative hypotheses.     

Interploid St. Augustinegrass [<Emphasis Type="Italic">Stenotaphrum secundatum</Emphasis> (Walt.) Kuntze] hybrids recovered by embryo rescue

St. Augustinegrass is one of the most important warm season turfgrasses in the southern United States because of its shade tolerance. Most cultivars are diploids (2n = 2x = 18) and are susceptible to various diseases and insects. Polyploid cultivars in the species have some resistance to pests, but most lack cold tolerance. In this study, eight polyploid genotypes were crossed with six diploid cultivars to transfer pest resistance to the diploids. Because interploid crosses often result in aborted seed, it was necessary to use in vitro techniques. Using embryo rescue, 268 plants were recovered from 2,463 emasculated and pollinated florets (10.88% crossability). Because of the heterogeneous nature of the species, these purported hybrids could not be verified by phenotype. DNA markers were used for hybrid identification. A subset of 25 plants from crosses between the aneuploid cultivar Floratam (2n = 4x = 32) and five diploid cultivars were analyzed using 144 expressed sequence tags–simple sequence repeats (EST-SSRs) developed from buffelgrass cDNA sequence data. Chi-square tests for paternal-specific markers revealed that all analyzed progeny were true F₁ hybrids and none originated from self-fertilization or unintended outcrossing. In addition to identifying DNA polymorphism, the EST-SSRs revealed that genetic variation exists among all analyzed cultivars and is not partitioned between ploidy levels. The findings demonstrate that these embryo rescue techniques will enable the entire spectrum of St. Augustinegrass genetic variation to be better used through the recovery of interploid hybrids.     

Surface functionalization of carbon nanomaterials by self‐assembling hydrophobin proteins

Class I fungal hydrophobins are small surface‐active proteins that self‐assemble to form amphipathic monolayers composed of amyloid‐like rodlets. The monolayers are extremely robust and can adsorb onto both hydrophobic and hydrophilic surfaces to reverse their wettability. This adherence is particularly strong for hydrophobic materials. In this report, we show that the class I hydrophobins EAS and HYD3 can self‐assemble to form a single‐molecule thick coating on a range of nanomaterials, including single‐walled carbon nanotubes (SWCNTs), graphene sheets, highly oriented pyrolytic graphite, and mica. Moreover, coating by class I hydrophobin results in a stable, dispersed preparation of SWCNTs in aqueous solutions. No cytotoxicity is detected when hydrophobin or hydrophobin‐coated SWCNTs are incubated with Caco‐2 cells in vitro. In addition, we are able to specifically introduce covalently linked chemical moieties to the hydrophilic side of the rodlet monolayer. Hence, class I hydrophobins provide a simple and effective strategy for controlling the surfaces of a range of materials at a molecular level and exhibit strong potential for biomedical applications. © 2012 Wiley Periodicals, Inc.     

Indexes to the reassociation and stability of solution DNA hybrids

Summary The computation, assumptions, and properties of DNA-hybrid stability and reassociation indexes were reviewed. Different methods of computing the same index typically yielded similar values. However, because dissociation curves change from asymmetric to symmetric as increasingly divergent DNAs are compared, adequate determination of mode required fitting a complex function. Delta Tm, delta mode, and delta T50H correlated well up to ca. 12, and all were found to be useful indexes of genomic similarity in that range. They also exhibited similar levels of error, even though T50H comprises a percent reassociation component with relatively large variance. At greater distances, the delta Tm scale became markedly compressed because of the boundary imposed by the temperature of hybrid formation (incubation temperature). Though not compressed or technically limited by it, delta mode and delta T50H could not be extrapolated with certainty below the incubation temperature. Among theoretical problems discussed: Tm and mode index an increasingly small percentage of the genome as the extent of reassociation decreases, and they may compare different genomic segments as DNAs become highly diverged. T50H relies upon the assumptions that all sequences evolve at a constant rate and that reassociation behavior is the same among all sequences regardless of their extent of divergence. Tm and T50H may be biased by selfhybridization of repetitive elements or cross-hybridization of paralogous sequences. Delta mode is free of such biases as long as the genomes under comparison are not too diverged. No index was found to be best in all circumstances.     

Structure and function come unglued in the visual cortex

In this issue of Neuron, Chowdhury and DeAngelis report that training monkeys to perform a fine depth discrimination abolishes the contribution of signals from area MT to the execution of a different, coarse depth discrimination. This result calls into question the principle of associating particular visual areas with particular visual functions, by showing that such associations are modifiable by experience.     

Pyrolysis-gas chromatography of the fungus Metarhizium anisopliae: An aid to strain identification

Six strains of the entomopathogenic fungus Matarhizium anisopliae var. anisopliae from North and South America and one strain of M. anisopliae var. major from Samoa were compared by pyrolysis-gas chromatography of conidia. Two strains established to be very similar by other methods proved 98% similar by pyrolysis-gas chromatography. Similarities of the other strains ranged from 62 to 88%. The method is proposed as a simple technique for routine identification of M. anisopliae strains.