Reduced Visual Cortex Gray Matter Volume and Thickness in Young Adults Who Witnessed Domestic Violence during Childhood

Exposure to interparental violence is associated with negative outcomes, such as depression, post-traumatic stress disorder and reduced cognitive abilities. However, little is known about the potential effects of witnessing domestic violence during childhood on gray matter volume (GMV) or cortical thickness. High-resolution 3.0 T volumetric scans (Siemens Trio Scanner) were obtained on 52 subjects (18–25 years) including 22 (6 males/16 females) with a history of visually witnessing episodes of domestic violence, and 30 (8 males/22 females) unexposed control subjects, with neither a current nor past DSM-IV Axis I or II disorder. Potential confounding effects of age, gender, level of parental verbal aggression, parental education, financial stress, full scale IQ, and total GMV, or average thickness were modeled using voxel based morphometry and FreeSurfer. Witnessing domestic violence subjects had a 6.1% GMV reduction in the right lingual gyrus (BA18) (P = 0.029, False Discovery Rate corrected peak level). Thickness in this region was also reduced, as was thickness in V2 bilaterally and left occipital pole. Theses regions were maximally sensitive to exposure to witnessing domestic violence between 11–13 years of age. Regional reductions in GMV and thickness were observed in both susceptible and resilient witnessing domestic violence subjects. Results in subjects witnessing domestic violence were similar to previously reported results in subjects with childhood sexual abuse, as the primary region affected was visual cortex. Brain regions that process and convey the adverse sensory input of the abuse may be specifically modified by this experience, particularly in subjects exposed to a single type of maltreatment. Exposure to multiple types of maltreatment is more commonly associated with morphological alterations in corticolimbic regions. These findings fit with preclinical studies showing that visual cortex is a highly plastic structure.     

A Study in Neo‐conservative Populism: Richard Trudgen's Why Warriors Lie Down and Die

First appearing in 2000, and with 20,000 copies sold as it entered its sixth printing in 2004, Richard Trudgen's Why Warriors Lie down and Die is a minor publishing phenomenon. Although scholarly forums have generally ignored the book, Christian media outlets, the popular press and neo‐conservative political activists have enthusiastically received and promoted it. An examination of the merits of Why Warriors Lie down and Die suggests that its popularity is only partly explained by original observations or insights on the part of the author. The most important explanation, and implication, of the book's remarkable take‐up lies in the opportune way in which it corresponds with now ascendant neo‐conservative political perspectives on indigenous policy.     

Isolation and characterization of hog thyroid actin

When the thyroglobulin content is subtracted, actin represents approximately 4.6% of the total protein content in the hog thyroid gland. Actin has been isolated from acetone-dehydrated slices and purified to homogeneity by gel filtration, DEAE-cellulose chromatography and two polymerization-depolymerization cycles. Purified actin (Mr = 42000) contains the beta and gamma species with a 2 to 1 stoichiometry. In the presence of 0.1 M KCl and 2 mM MgCl2 thyroid actin polymerized into 6 nm diameter filaments; under these conditions the critical concentration was 30 micrograms/ml and the intrinsic viscosity 4.7 dl/g.     

The conformation of calmodulin: a substantial environmentally sensitive helical transition in Ca4-calmodulin with potential mechanistic function

The conformation of Ca4-calmodulin in solution, as assessed by far-UV peptide circular dichroism, contains significantly less alpha-helix than the proposed X-ray crystal structure. We now show that Ca4-calmodulin adopts significant additional helical structure in solution in the presence of a helicogenic solvent (50%, v/v, aqueous 2,2,2-trifluoroethanol or 50%, v/v, methylpentane-5,5-diol). We suggest that the long continuous helix (residues 66-92 of the crystal structure) is not necessarily a normal feature of the calmodulin structure in solution, and may be due in part to the conditions of crystallisation. This result is supported by time-resolved tyrosine fluorescence anisotropy studies indicating that Ca4-calmodulin in solution is an essentially compact globular structure which undergoes isotropic rotational motion. We conclude that, under appropriate ionic and apolar environmental conditions, Ca4-calmodulin undergoes a substantial helical transition, which may involve residues in the central region of the molecule. Such a transition could have an important function in determining specificity and affinity in interactions of calmodulin with different target sequences of Ca2+-dependent regulatory enzymes.     

POSTPARTUM PHLEBECTOMY

Saphenous vein ligation and stripping was performed on 27 patients in the immediate postpartum period without complications. Doing the operation at this time saves time and money. Technically it is easier to do postpartum than during pregnancy, and the patients have less postoperative discomfort than is usual with phlebectomy at other times.     

Drug2ways: Reasoning over causal paths in biological networks for drug discovery

Elucidating the causal mechanisms responsible for disease can reveal potential therapeutic targets for pharmacological intervention and, accordingly, guide drug repositioning and discovery. In essence, the topology of a network can reveal the impact a drug candidate may have on a given biological state, leading the way for enhanced disease characterization and the design of advanced therapies. Network-based approaches, in particular, are highly suited for these purposes as they hold the capacity to identify the molecular mechanisms underlying disease. Here, we present drug2ways, a novel methodology that leverages multimodal causal networks for predicting drug candidates. Drug2ways implements an efficient algorithm which reasons over causal paths in large-scale biological networks to propose drug candidates for a given disease. We validate our approach using clinical trial information and demonstrate how drug2ways can be used for multiple applications to identify: i) single-target drug candidates, ii) candidates with polypharmacological properties that can optimize multiple targets, and iii) candidates for combination therapy. Finally, we make drug2ways available to the scientific community as a Python package that enables conducting these applications on multiple standard network formats.