Experiential contributions to social dominance in a rat model of Fragile-X syndrome

Social withdrawal is one phenotypic feature of the monogenic neurodevelopmental disorder Fragile-X. Using a ‘knock-out’ rat model of Fragile-X, we examined whether deletion of the Fmr1 gene that causes this condition would affect the ability to form and express a social hierarchy as measured in a tube-test. Male Fragile-X ‘knock-out’ rats living together could successfully form a social dominance hierarchy, but were significantly subordinate to wild-type animals in mixed group cages. Over 10 days of repeated testing, the Fragile-X mutant rats gradually showed greater variance and instability of rank during their tube-test encounters. This affected the outcome of future encounters with stranger animals from other cages, with the initial phenotype of wild-type dominance lost to a more complex picture that reflected, regardless of genotype, the prior experience of winning or losing. Our findings offer a novel insight into the complex dynamics of social interactions between laboratory living groups of Fragile X and wild-type rats. Even though this is a monogenic condition, experience has an impact upon future interactions with other animals. Gene/environment interactions should therefore be considered in the development of therapeutics

The delivery of personalised, precision medicines via synthetic proteins

Introduction: The design of advanced drug delivery systems based on synthetic and su-pramolecular chemistry has been very successful. Liposomal doxorubicin (Caelyx®), and liposomal daunorubicin (DaunoXome®), estradiol topical emulsion (EstrasorbTM) as well as soluble or erodible polymer systems such as pegaspargase (Oncaspar®) or goserelin acetate (Zoladex®) represent considerable achievements. The Problem: As deliverables have evolved from low molecular weight drugs to biologics (currently representing approximately 30% of the market), so too have the demands made of advanced drug delivery technology. In parallel, the field of membrane trafficking (and endocytosis) has also matured. The trafficking of specific receptors i.e. material to be recycled or destroyed, as well as the trafficking of protein toxins has been well characterized. This, in conjunction with an ability to engineer synthetic, recombinant proteins provides several possibilities. The Solution: The first is using recombinant proteins as drugs i.e. denileukin diftitox (Ontak®) or agalsidase beta (Fabrazyme®). The second is the opportunity to use protein toxin architecture to reach targets that are not normally accessible. This may be achieved by grafting regulatory domains from multiple species to form synthetic proteins, engineered to do multiple jobs. Examples include access to the nucleocytosolic compartment. Herein the use of synthetic proteins for drug delivery has been reviewed

Aeration During Bread Dough Mixing: II. A Population Balance Model of Aeration

A novel model for the aeration of dough during mixing is presented. A population balance model was used to model bubble entrainment, break-up and disentrainment over the whole duration of a mix. Following a series of simplifying assumptions, including that all bubbles are entrained with the same volume, the model parameters were fitted to original and previously published experimental dough voidage profiles over the duration of a mix involving a pressure step-change. The assumption that no bubble breakup occurred during mixing enabled a simple model to be derived which quantitatively represented the experimental data, for both a pressure step-up and down midway through mixing, with two mixing parameters: the volumetric entrainment rate and the disentrainment coefficient. Assuming that instantaneous bubble break-up occurred enabled a model to be derived which, with the same two parameters, could qualitatively represent experimental bubble number densities calculated through measurements of dough bubble size distributions