Co-rumination buffers the link between social anxiety and depressive symptoms in early adolescence

Objectives: We examined whether co-rumination with online friends buffered the link between social anxiety and depressive symptoms over time in a community sample. Methods: In a sample of 526 participants (358 girls; Mage = 14.05) followed at three time points, we conducted a latent cross-lagged model with social anxiety, depressive symptoms, and co-rumination, controlling for friendship stability and friendship quality, and adding a latent interaction between social anxiety and co-rumination predicting depressive symptoms. Results: Social anxiety predicted depressive symptoms, but no direct links between social anxiety and co-rumination emerged. Instead, co-rumination buffered the link between social anxiety and depressive symptoms for adolescents with higher but not lower levels of social anxiety. Conclusions: These findings indicate that co-rumination exerted a positive influence on interpersonal relationships by diminishing the influence from social anxiety on depressive symptoms over time

Chelators in Iron and Copper Toxicity

Purpose of Review Chelation therapy is used for diseases causing an imbalance of iron levels (for example haemochromatosis and thalassaemia) or copper levels (for example Menkes’ and Wilson’s diseases). Currently, most pharmaceutical chelators are relatively simple but often have side effects. Some have been taken off the market. This review attempts to find theory and knowledge required to design or find better chelators. Recent Findings Recent research attempting to understand the biological mechanisms of protection against iron and copper toxicity is reviewed. Understanding of molecular mechanisms behind normal iron/copper regulation may lead to the design of more sophisticated chelators. The theory of metal ion toxicity explains why some chelators, such as EDTA, which chelate metal ions in a way which exposes the ion to the surrounding environment are shown to be unsuitable except as a means of killing cancer cells. The Lewis theory of acids and bases suggests which amino acids favour the attachment of the hard/intermediate ions Fe2+, Fe3+, Cu2+ and soft ion Cu+. Non-polar amino acids will chelate the ion in a position not in contact with the surrounding cellular environment. The conclusion is that only the soft ion binding cysteine and methionine appear as suitable chelators. Clearly, nature has developed proteins which are less restricted. Recent research on naturally produced chelators such as siderophores and phytochemicals show some promise as pharmaceuticals. Summary Although an understanding of natural mechanisms of Fe/Cu regulation continues to increase, the pharmaceutical chelators for metal overload diseases remain simple non-protein molecules. Natural and synthetic alternatives have been studied but require further research before being accepted

Utilising a simulation platform to understand the effect of domain model assumptions

Computational and mathematical modelling approaches are increasingly being adopted in attempts to further our understanding of complex biological systems. This approach can be subjected to strong criticism as substantial aspects of the biological system being captured are not currently known, meaning assumptions need to be made that could have a critical impact on simulation response. We have utilised the CoSMoS process in the development of an agent-based simulation of the formation of Peyer’s patches (PP), gut-associated lymphoid organs that have a key role in the initiation of adaptive immune responses to infection. Although the use of genetic tools, imaging technologies and ex vivo culture systems has provided significant insight into the cellular components and associated pathways involved in PP development, interesting questions remain that cannot be addressed using these approaches, and as such well justified assumptions have been introduced into our model to counter this. Here we focus not on the development of the model itself, but instead demonstrate how the resultant simulation can be used to assess how these assumptions impact the simulation response. For example, we consider the impact of our assumption that the migration rate of lymphoid tissue cells into the gut remains constant throughout PP development. We demonstrate that an analysis of the assumptions made in the construction of the domain model may either increase confidence in the model as a representation of the biological system it captures, or may suggest areas where further biological experimentation is required

The use of bone morphogenetic protein-6 gene therapy for percutaneous spinal fusion in rabbits

Object. Fusion procedures in the lumbar spine have been performed in the US since 1911. Since that time, the indications and techniques for spinal fusion have evolved. Despite technical advancements, spinal fusion remains a major operation, and fusion nonunion rates of up to 35% are still reported. In this study, the authors were able to induce intertransverse process fusions in immune-competent New Zealand White rabbits by percutaneous administration of an adenoviral vector containing the bone morphogenetic protein (BMP-6) gene (Ad-BMP-6). The results represent an important step forward in finding new methods to increase the success and decrease the morbidity associated with spinal fusion. Methods. Five New Zealand White rabbits were used. Injection of the adenoviral construct was performed at multiple levels (bilaterally) in each animal while using fluoroscopic guidance. Injection consisted of either Ad-BMP-6 or Ad—ß-galactosidase (ß-gal) (control). Because multiple levels were injected, each animal served as an internal control. The animals underwent postinjection computerized tomography (CT) scanning at 7 and 14 weeks. After undergoing final CT scanning, the animals were killed and the spines were harvested. The fusion sites were analyzed by gross inspection, histopathological methods, and micro—CT studies. Conclusions. The results of this study show that an anatomically precise fusion can be accomplished by percutaneous administration of gene therapy. The next step in these studies will be extension of the technique to nonhuman primates and eventually to human clinical studies