Chronic systemic therapy with low-dose morpholino oligomers ameliorates the pathology and normalizes locomotor behavior in mdx Mice

The administration of antisense oligonucleotides (AOs) to skip one or more exons in mutated forms of the DMD gene and so restore the reading frame of the transcript is one of the most promising approaches to treat Duchenne muscular dystrophy (DMD). At present, preclinical studies demonstrating the efficacy and safety of long-term AO administration have not been conducted. Furthermore, it is essential to determine the minimal effective dose and frequency of administration. In this study, two different low doses (LDs) of phosphorodiamidate morpholino oligomer (PMO) designed to skip the mutated exon 23 in the mdx dystrophic mouse were administered for up to 12 months. Mice treated for 50 weeks showed a substantial dose-related amelioration of the pathology, particularly in the diaphragm. Moreover, the generalized physical activity was profoundly enhanced compared to untreated mdx mice showing that widespread, albeit partial, dystrophin expression restores the normal activity in mdx mice. Our results show for the first time that a chronic long-term administration of LDs of unmodified PMO, equivalent to doses in use in DMD boys, is safe, significantly ameliorates the muscular dystrophic phenotype and improves the activity of dystrophin-deficient mice, thus encouraging the further clinical translation of this approach in humans.

Influencing energy efficient occupant behavior through improved building and control design

There is growing pressure on the construction industry to deliver energy efficient, sustainable buildings but there is evidence to suggest that, in practice, designs regularly fail to achieve the anticipated levels of in-use energy consumption. One of the key factors behind this discrepancy is the behavior of the building occupants. This paper explores how insights from experimental psychology could potentially be used to reduce the gap between the predicted and actual energy performance of buildings. It demonstrates why traditional methods to engage with the occupants are not always successful and proposes a model for a more holistic approach to this issue. The paper concludes that achieving energy efficiency in buildings is not solely a technological issue and that the construction industry needs to adopt a more user-centred approach.

Optimal sting use in the feeding behavior of the scorpion Hadrurus spadix

Since venom is costly to produce and stinging is not obligatory in prey capture for scorpions, the need to optimize use of resources suggests that venom should be reserved for prey that cannot otherwise be overpowered, (i.e., larger and/or more active prey). In accordance with these predictions, sting use by Hadrurus spadix Stahnke 1940 increased with prey size, reaching 100% once prey items were longer than the scorpion’s pedipalp patella length, and with prey activity, which we manipulated by varying prey temperature. Surprisingly, the scorpions were slower to capture less active (cooler) prey than those that exhibited higher rates of activity. We suggest this is because prey are located by vibrations in the substrate, with less active prey producing fewer vibrations. Keywords: Optimal foraging, venom, pectines

Rhythmic behavior of social insects from single to multibody

Revealing the evolution of well-organized social behavior requires understanding a mechanism by which collective behavior is produced. A well-organized group may be produced by two possible mechanisms, namely, a central control and a distributed control. In the second case, local interactions between interchangeable components function at the bottom of the collective behavior. We focused on a simple behavior of an individual ant and analyzed the interactions between a pair of ants. In an experimental set-up, we placed the workers in a hemisphere without a nest, food, and a queen, and recorded their trajectories. The temporal pattern of velocity of each ant was obtained. From this bottom-up approach, we found the characteristic behavior of a single worker and a pair of workers as follows: (1) Activity of each individual has a rhythmic component. (2) Interactions between a pair of individuals result in two types of coupling, namely the anti-phase and the in-phase coupling. The direct physical contacts between the pair of workers might cause a phase shift of the rhythmic components in individual ants. We also build up a simple model based on the coupled oscillators toward the understanding of the whole colony behavior.

Modeling the patrol behavior of the Diacamma's gamergate

The gamergate (generally called the “queen”) of the Diacamma sp. walks around in the nest and comes into contact with the workers. The gamergate informs the workers of its presence by physical contact. This behavior is called a “patrol.” In previous work, it was reported that the gamergate controls its patrolling time depending on the colony size. How does the gamergate know the colony size, and how does it control the patrolling time? In this article, we propose a simple dynamics to explain this behavior. We assume that the gamergate and the workers have internal states which interact by physical contacts. By numerical simulations, we confirm that the patrol time of the proposed model depends on the size of the colony.

Analysis and modeling of ants’ behavior from single to multi-body

In order to shed light on the collective behavior of social insects, we analyzed the behavior of ants from single to multi-body. In an experimental set-up, ants are placed in hemisphere without a nest and food. Trajectory of ants is recorded. From this bottom-up approach, we found that collective behavior of ants as follows: 1. Activity of single ant increases and decreases periodically. 2. Spontaneous meeting process is observed between two ants and meeting spot of two ants is localized in hemisphere. 3. Result on division of labor is obtained between two ants.

The treatment of mental contamination: a case series

The recommended treatment for obsessive-compulsive disorder (OCD) is cognitive behavior therapy (CBT) incorporating exposure and response prevention (ERP), which is effective for approximately 50% of patients. However, there has been little advance in treatment outcomes since the introduction of ERP in 1979. It has been suggested that some progress can be made in treating contamination obsessions and washing compulsions by addressing feelings of dirtiness and contamination that arise without physical contact with a tangible contaminant. To date, the treatment of these “mental contamination” fears in OCD has not been systematically explored. This paper reports on a case series of 12 participants with OCD who received 10 to 20 sessions of a CBT-based treatment for mental contamination. At the end of treatment, 7 participants no longer met the diagnostic criteria for OCD and mental contamination and these gains were maintained at 6-month follow-up. The clinical implications of these findings are discussed.

Predicting outcomes following cognitive behavior therapy in child anxiety disorders: the influence of genetic, demographic and clinical information

Background. Within a therapeutic gene by environment (GxE) framework, we recently demonstrated that variation in the Serotonin Transporter Promoter Polymorphism; 5HTTLPR and marker rs6330 in Nerve Growth Factor gene; NGF is associated with poorer outcomes following cognitive behaviour therapy (CBT) for child anxiety disorders. The aim of this study was to explore one potential means of extending the translational reach of G×E data in a way that may be clinically informative. We describe a ‘risk-index’ approach combining genetic, demographic and clinical data and test its ability to predict diagnostic outcome following CBT in anxious children. Method. DNA and clinical data were collected from 384 children with a primary anxiety disorder undergoing CBT. We tested our risk model in five cross-validation training sets. Results. In predicting treatment outcome, six variables had a minimum mean beta value of 0.5: 5HTTLPR, NGF rs6330, gender, primary anxiety severity, comorbid mood disorder and comorbid externalising disorder. A risk index (range 0-8) constructed from these variables had moderate predictive ability (AUC = .62-.69) in this study. Children scoring high on this index (5-8) were approximately three times as likely to retain their primary anxiety disorder at follow-up as compared to those children scoring 2 or less. Conclusion. Significant genetic, demographic and clinical predictors of outcome following CBT for anxiety-disordered children were identified. Combining these predictors within a risk-index could be used to identify which children are less likely to be diagnosis free following CBT alone or thus require longer or enhanced treatment. The ‘risk-index’ approach represents one means of harnessing the translational potential of G×E data.