Intramuscular Exposure to a Lethal Dose of Ricin Toxin Leads to Endothelial Glycocalyx Shedding and Microvascular Flow Abnormality in Mice and Swine

Ricin toxin isolated from the castor bean (Ricinus communis) is one of the most potent and lethal molecules known. While the pathophysiology and clinical consequences of ricin poisoning by the parenteral route, i.e., intramuscular penetration, have been described recently in various animal models, the preceding mechanism underlying the clinical manifestations of systemic ricin poisoning has not been completely defined. Here, we show that following intramuscular administration, ricin bound preferentially to the vasculature in both mice and swine, leading to coagulopathy and widespread hemorrhages. Increased levels of circulating VEGF and decreased expression of vascular VE-cadherin caused blood vessel impairment, thereby promoting hyperpermeability in various organs. Elevated levels of soluble heparan sulfate, hyaluronic acid and syndecan-1 were measured in blood samples following ricin intoxication, indicating that the vascular glycocalyx of both mice and swine underwent extensive damage. Finally, by using side-stream dark field intravital microscopy imaging, we determined that ricin poisoning leads to microvasculature malfunctioning, as manifested by aberrant blood flow and a significant decrease in the number of diffused microvessels. These findings, which suggest that glycocalyx shedding and microcirculation dysfunction play a major role in the pathology of systemic ricin poisoning, may serve for the formulation of specifically tailored therapies for treating parenteral ricin intoxication.     

Sleep patterns and sleep disruptions in school-age children.

This study assessed the sleep patterns, sleep disruptions, and sleepiness of school-age children. Sleep patterns of 140 children (72 boys and 68 girls; 2nd-, 4th-, and 6th-grade students) were evaluated with activity monitors (actigraphs). In addition, the children and their parents completed complementary sleep questionnaires and daily reports. The findings reflected significant age differences, indicating that older children have more delayed sleep onset times and increased reported daytime sleepiness. Girls were found to spend more time in sleep and to have an increased percentage of motionless sleep. Fragmented sleep was found in 18% of the children. No age differences were found in any of the sleep quality measures. Scores on objective sleep measures were associated with subjective reports of sleepiness. Family stress, parental age, and parental education were related to the child's sleep–wake measures. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Entropic Ligand Mixing for Engineering 2D Layered Perovskite from Colloidal Monolayer Building Blocks

Layered 2D perovskites are solution-processed quantum-wells. Their effective band-gap is determined via the inorganic perovskite layer thickness and exciton quantum confinement effects. Alternatively, by changing the organic moieties, one can tune the dielectric constant and distance between the monolayers modifying the excitonic interactions. In colloidal perovskites, a dynamic equilibrium exists between the free organic moieties in the solution and the surface of the nanocrystal. Colloidal synthesis is used to make single monolayer L₂PbBr₄ platelets and assemble these into layered 2D stacks. In the experiment, L is an alkylamine surface ligand whose length (4-18 carbons) determines the interlayer distances between the quantum-wells. The dynamic equilibrium of ligand mixtures in solution and perovskite surfaces leads to optimal mixing of the molecules. During the self-assembly of monolayers, the distance between the inorganic layers is thus engineered. The interlayer distance is proportional to the average ligand mixture length. This results in controlled interactions between the 2D-excitons, enabling red-shifted absorption and emission and extended lifetimes for longer alkyl chains. Using entropic mixing of ligands for the engineering of 2D excitonic interactions is therefore demonstrated. Formation of layered 2D perovskites from colloidal building blocks allows intermixing of dissimilar materials opening possibilities for new heterostructures and junctions.     

A Novel Rodent Model of Hypertensive Cerebral Small Vessel Disease with White Matter Hyperintensities and Peripheral Oxidative Stress

Cerebral small vessel disease (CSVD) is the second most common cause of stroke and a major contributor to dementia. Manifestations of CSVD include cerebral microbleeds, intracerebral hemorrhages (ICH), lacunar infarcts, white matter hyperintensities (WMH) and enlarged perivascular spaces. Chronic hypertensive models have been found to reproduce most key features of the disease. Nevertheless, no animal models have been identified to reflect all different aspects of the human disease. Here, we described a novel model for CSVD using salt-sensitive ‘Sabra’ hypertension-prone rats (SBH/y), which display chronic hypertension and enhanced peripheral oxidative stress. SBH/y rats were either administered deoxycorticosteroid acetate (DOCA) (referred to as SBH/y-DOCA rats) or sham-operated and provided with 1% NaCl in drinking water. Rats underwent neurological assessment and behavioral testing, followed by ex vivo MRI and biochemical and histological analyses. SBH/y-DOCA rats show a neurological decline and cognitive impairment and present multiple cerebrovascular pathologies associated with CSVD, such as ICH, lacunes, enlarged perivascular spaces, blood vessel stenosis, BBB permeability and inflammation. Remarkably, SBH/y-DOCA rats show severe white matter pathology as well as WMH, which are rarely reported in commonly used models. Our model may serve as a novel platform for further understanding the mechanisms underlying CSVD and for testing novel therapeutics.     

Selective Artificial Receptors Based on Micropatterned Surface‐Imprinted Polymers for Label‐Free Detection of Proteins by SPR Imaging

A novel concept to generate micropatterned surface‐imprinted polymers (SIPs) for protein recognition by using standard photolithographic technology is introduced. Avidin‐imprinted poly(3,4‐ethylenedioxythiophene)/poly(styrenesulfonate) (PEDOT/PSS) conducting polymer microbands are prepared directly on surface plasmon resonance (SPR) chips, which enable convenient label‐free monitoring of the binding events. The novel surface‐imprinted microstructures bind avidin, the template protein, with dissociation constants in the submicromolar range (125 nM ). The SIPs have an avidin binding capacity approximately one order of magnitude higher than the corresponding nonimprinted polymers and are able to discriminate among functional homologues of avidin, i.e., neutravidin, extravidin, and streptavidin.     

Role of the Diffusion Mechanism of Mass-Transfer Processes in Conic Capillaries Submerged in a Liquid

A study is made of one possible mechanism explaining the phenomenon of bilateral filling of dead-end conic capillaries submerged in a liquid: diffusion and recondensation of a liquid vapor from a meniscus with a small curvature to a meniscus with a larger curvature. A theory of this process has been constructed and the rate of growth of the near-vertex liquid column has been calculated based on this theory. A comparison with experiment shows that although the law of growth of the column predicted by the theory coincides with the experimental one, the numerical values of the rate are nearly two orders of magnitude lower. Conditions under which one can detect this mechanism experimentally are discussed.     

Children's gender-related inferences and judgments: A cross-cultural study.

This study compared the gender-related inferences and judgments of elementary school children (N?=?542) of 2 different age groups (3rd graders and 5th graders) from 2 different cultures: Taiwan, a traditional collectivistic culture, and Israel, an individualistic and less traditional culture. The children were presented with 4 stories, 2 about a male target and 2 about a female target with either traditionally masculine or traditionally feminine interests, and were asked to make cognitive and emotional-motivational inferences and judgments about them. Culture played an important role in children's gender-related inferences and judgments. Specifically, Taiwanese children distinguished more than did Israeli children between male targets behaving stereotypically and counterstereotypically. The findings are analyzed within the framework of the differences between the 2 cultures. (PsycINFO Database Record (c) 2010 APA, all rights reserved)