Genomics of lithium action and response

Lithium is the most successful mood stabiliser treatment for bipolar disorder. However, unlike conventional drugs that are designed to interact with a specific molecular target, the actions of lithium are distributed across many biological processes and pathways. Treatment response is subject to genetic variation between individuals and similar genetic variation may dictate susceptibility to side-effects. Transcriptomic, genomic and cell model research strategies have all been deployed in the search for the genetic factors and biological systems that mediate the interaction between genetics and the therapeutic actions of lithium. In this review, recent findings from genome-wide studies and patient cell lines will be summarised and discussed from a standpoint that genuine progress is being made to define clinically useful mechanisms of this treatment, to place it in the context of bipolar disorder pathology, and to move towards a time when the prescription of lithium is targeted to those individuals who will derive the greatest benefit

Schizophrenia biomarkers : translating the descriptive into the diagnostic

While schizophrenia and mental health are qualitatively distinct at the level of clinical presentation, the specific molecular signatures that underlie, or associate with, illness are not. Biomarker identification in schizophrenia is intended to offer a number of important benefits to patient well-being including prediction of future illness, diagnostic clarity and a level of disease description that would guide treatment choice. However, the choice of sample and form of analysis used to produce useful biomarkers is still uncertain. In this review, advances from recent studies spanning the technical spectrum are presented together with comment on their comparative strengths and weaknesses. To date, these studies have aided our understanding of the pathological processes associated with illness much more than they have provided robust biomarkers. A number of reasons for this observation are suggested, as are new strategies for the extraction of biomarkers from large '-omics' datasets

A First Principles Theory of Nuclear Magnetic Resonance J-Coupling in solid-state systems

A method to calculate NMR J-coupling constants from first principles in extended systems is presented. It is based on density functional theory and is formulated within a planewave-pseudopotential framework. The all-electron properties are recovered using the projector augmented wave approach. The method is validated by comparison with existing quantum chemical calculations of solution-state systems and with experimental data. The approach has been applied to verify measured J-coupling in a silicophosphate structure, Si5O(PO4)6Comment: 9 page

Crystal Structure of the ZrO Phase at Zirconium/Zirconium Oxide Interfaces

Zirconium-based alloys are used in water-cooled nuclear reactors for both nuclear fuel cladding and structural components. Under this harsh environment, the main factor limiting the service life of zirconium cladding, and hence fuel burn-up efficiency, is water corrosion. This oxidation process has recently been linked to the presence of a sub-oxide phase with well-defined composition but unknown structure at the metal–oxide interface. In this paper, the combination of first-principles materials modeling and high-resolution electron microscopy is used to identify the structure of this sub-oxide phase, bringing us a step closer to developing strategies to mitigate aqueous oxidation in Zr alloys and prolong the operational lifetime of commercial fuel cladding alloys

An efficient k.p method for calculation of total energy and electronic density of states

An efficient method for calculating the electronic structure in large systems with a fully converged BZ sampling is presented. The method is based on a k.p-like approximation developed in the framework of the density functional perturbation theory. The reliability and efficiency of the method are demostrated in test calculations on Ar and Si supercells

Effects of Meditation on Heart Rate and Blood Pressure: A Mindfulness-based Study

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Enhanced gene expression in the brain following intravenous administration of lactoferrin-bearing polypropylenimine dendriplex

The possibility of using gene therapy for the treatment of brain diseases such as brain cancer, Alzheimer's and Parkinson's diseases, is currently hampered by the lack of gene delivery systems able to cross the blood–brain barrier and deliver DNA to the brain following intravenous administration. On the basis that lactoferrin can effectively reach the brain by using specific receptors for crossing the blood–brain barrier, we propose to investigate if a lactoferrin-bearing generation 3-diaminobutyric polypropylenimine (DAB) dendrimer would allow the transport of plasmid DNA to the brain after intravenous administration. In this work, we demonstrated that the conjugation of lactoferrin to the dendrimer led to an enhanced DNA uptake by 2.1-fold in bEnd.3 murine brain capillary endothelial cells compared to the unmodified dendriplex in vitro. In vivo, the intravenous administration of lactoferrin-bearing DAB dendriplex resulted in a significantly increased gene expression in the brain, by more than 6.4-fold compared to that of DAB dendriplex, while decreasing gene expression in the lung and the kidneys. Gene expression in the brain was significantly higher than in any other major organs of the body. Lactoferrin-bearing generation 3 polypropylenimine dendrimer is therefore a highly promising delivery system for systemic gene delivery to the brain

Mindfulness and emotional regulation as sequential mediators in the relationship between attachment security and depression

Depression is a significant global health issue that has previously been associated with negative early care experiences and insecure attachment styles. This has led to much interest in identifying variables that may interrupt this relationship and prevent detrimental personal, social and economic outcomes. Recent research has indicated associations between the two seemingly distinct constructs of secure attachment and mindfulness, with similar positive outcomes. One hundred and forty eight participants completed an online survey exploring a possible sequential cognitive processing model, which predicted that higher levels of mindfulness and then emotional regulation would mediate the relationship between attachment and depression. Full mediation was found in regards to secure, preoccupied and dismissive attachment, whereas partial mediation was identified in the case of fearful attachment. The results support the possibility of an alternative cognitive processing pathway that may interrupt the association between negative early care experiences and concomitant negative mental health outcomes. Further exploration of this relationship is indicated