The effectiveness of the anti-CD11d treatment is reduced in rat models of spinal cord injury that produce significant levels of intraspinal hemorrhage

We have previously reported that administration of a CD11d monoclonal antibody (mAb) improves recovery in a clip-compression model of SCI. In this model the CD11d mAb reduces the infiltration of activated leukocytes into the injured spinal cord (as indicated by reduced intraspinal MPO). However not all anti-inflammatory strategies have reported beneficial results, suggesting that success of the CD11d mAb treatment may depend on the type or severity of the injury. We therefore tested the CD11d mAb treatment in a rat hemi-contusion model of cervical SCI. In contrast to its effects in the clip-compression model, the CD11d mAb treatment did not improve forelimb function nor did it significantly reduce MPO levels in the hemi-contused cord. To determine if the disparate results using the CD11d mAb were due to the biomechanical nature of the cord injury (compression SCI versus contusion SCI) or to the spinal level of the injury (12th thoracic level versus cervical) we further evaluated the CD11d mAb treatment after a T12 contusion SCI. In contrast to the T12 clip compression SCI, the CD11d mAb treatment did not improve locomotor recovery or significantly reduce MPO levels after T12 contusion SCI. Lesion analyses revealed increased levels of hemorrhage after contusion SCI compared to clip-compression SCI. SCI that is accompanied by increased intraspinal hemorrhage would be predicted to be refractory to the CD11d mAb therapy as this approach targets leukocyte diapedesis through the intact vasculature. These results suggest that the disparate results of the anti-CD11d treatment in contusion and clip-compression models of SCI are due to the different pathophysiological mechanisms that dominate these two types of spinal cord injuries

Atomic characterization of Si nanoclusters embedded in SiO2 by atom probe tomography

Silicon nanoclusters are of prime interest for new generation of optoelectronic and microelectronics components. Physical properties (light emission, carrier storage...) of systems using such nanoclusters are strongly dependent on nanostructural characteristics. These characteristics (size, composition, distribution, and interface nature) are until now obtained using conventional high-resolution analytic methods, such as high-resolution transmission electron microscopy, EFTEM, or EELS. In this article, a complementary technique, the atom probe tomography, was used for studying a multilayer (ML) system containing silicon clusters. Such a technique and its analysis give information on the structure at the atomic level and allow obtaining complementary information with respect to other techniques. A description of the different steps for such analysis: sample preparation, atom probe analysis, and data treatment are detailed. An atomic scale description of the Si nanoclusters/SiO2 ML will be fully described. This system is composed of 3.8-nm-thick SiO layers and 4-nm-thick SiO2 layers annealed 1 h at 900°C

NGF Causes TrkA to Specifically Attract Microtubules to Lipid Rafts

Membrane protein sorting is mediated by interactions between proteins and lipids. One mechanism that contributes to sorting involves patches of lipids, termed lipid rafts, which are different from their surroundings in lipid and protein composition. Although the nerve growth factor (NGF) receptors, TrkA and p75NTR collaborate with each other at the plasma membrane to bind NGF, these two receptors are endocytosed separately and activate different cellular responses. We hypothesized that receptor localization in membrane rafts may play a role in endocytic sorting. TrkA and p75NTR both reside in detergent-resistant membranes (DRMs), yet they responded differently to a variety of conditions. The ganglioside, GM1, caused increased association of NGF, TrkA, and microtubules with DRMs, but a decrease in p75NTR. When microtubules were induced to polymerize and attach to DRMs by in vitro reactions, TrkA, but not p75NTR, was bound to microtubules in DRMs and in a detergent-resistant endosomal fraction. NGF enhanced the interaction between TrkA and microtubules in DRMs, yet tyrosine phosphorylated TrkA was entirely absent in DRMs under conditions where activated TrkA was detected in detergent-sensitive membranes and endosomes. These data indicate that TrkA and p75NTR partition into membrane rafts by different mechanisms, and that the fraction of TrkA that associates with DRMs is internalized but does not directly form signaling endosomes. Rather, by attracting microtubules to lipid rafts, TrkA may mediate other processes such as axon guidance

Leptin in pregnancy and development: A contributor to adulthood disease?

Emerging research has highlighted the importance of leptin in fetal growth and development independent of its essential role in the maintenance of hunger and satiety through the modulation of neuropeptide Y and proopiomelanocortin neurons. Alterations in maternal-placental-fetal leptin exchange may modify the development of the fetus and contribute to the increased risk of developing disease in adulthood. In addition, leptin also plays an important role in reproductive functions, with plasma leptin concentrations rising in pregnant women, peaking during the third trimester. Elevated plasma leptin concentrations occur at the completion of organogenesis, and research in animal models has demonstrated that leptin is involved in the development and maturation of a number of organs, including the heart, brain, kidneys, and pancreas. Elevated maternal plasma leptin is associated with maternal obesity, and reduced fetal plasma leptin is correlated with intrauterine growth restriction. Alterations in plasma leptin during development may be associated with an increased risk of developing a number of adulthood diseases, including cardiovascular, metabolic, and renal diseases via altered fetal development and organogenesis. Importantly, research has shown that leptin antagonism after birth significantly reduces maturation of numerous organs. Conversely, restoration of the leptin deficiency after birth in growth-restricted animals restores the offspring's body weight and improves organogenesis. Therefore, leptin appears to play a major role in organogenesis, which may adversely affect the risk of developing a number of diseases in adulthood. Therefore, greater understanding of the role of leptin during development may assist in the prevention and treatment of a number of disease states that occur in adulthood.No Full Tex

Growth restriction in the rat alters expression of cardiac JAK/STAT genes in a sex-specific manner.

Uteroplacental insufficiency resulting in intrauterine growth restriction has been associated with the development of cardiovascular disease, coronary heart disease and increased blood pressure, particularly in males. The molecular mechanisms that result in the programming of these phenotypes are not clear. This study investigated the expression of cardiac JAK/STAT signalling genes in growth restricted offspring born small due to uteroplacental insufficiency. Bilateral uterine vessel ligation was performed on day 18 of pregnancy to induce growth restriction (Restricted) or sham surgery (Control). Cardiac tissue at embryonic day (E) 20, postnatal day (PN) 1, PN7 and PN35 in male and female Wistar (WKY) rats (n=7-10 per group per age) was isolated and mRNA extracted. In the heart, there was an effect of age for males for all genes examined there was a decrease in expression after PN1. With females, JAK2 expression was significantly reduced after E20, while PI3K in females was increased at E30 and PN35. Further, mRNA expression was significantly altered in JAK/STAT signalling targets in Restricteds in a sex-specific manner. Compared with Controls, in males, JAK2 and STAT3 were significantly reduced in the Restricted, while in females SOCS3 was significantly increased and PI3K significantly decreased in the Restricted offspring. Finally, there were specific differences in the levels of gene expression within the JAK/STAT pathway when comparing males to females. Thus, growth restriction alters specific targets in the JAK/STAT signalling pathway, with altered JAK2 and STAT3 potentially contributing to the increased risk of cardiovascular disease in the growth restricted males

Sand aging field study

Aging effects in sand, such as increases in penetration resistance with time after deposition, densification, and/or liquefaction, are known to occur in situ, but the causes of these effects are not fully understood. Nonetheless, these effects have important ramifications in earthquake engineering. First, the lack of understanding of the phenomenon is an impediment to quality assurance/quality control (QA/QC) for ground densification projects aimed at mitigating the damaging effects of liquefaction. This can be understood by considering that most liquefaction evaluation procedures correlate liquefaction susceptibility to in situ indices, such as penetration resistance (SPT and CPT) and small strain shear wave velocity (V S), all of which are influenced by aging. Consequently, it is unclear as to how long after ground densification QA/QC in situ tests should be performed to ensure that the densification was sufficient to mitigate liquefaction susceptibility. Presented herein is an overview of an ongoing sand aging field study where liquefaction is being induced by explosives, vibrocompaction (using a vibroflot), and a NEES vibroseis in a heavily instrumented sand deposit. The state and properties of the sand are being monitored as a function of time after the disruption of the soil structure. © 2008 ASCE