Preclinical and Preliminary Clinical Evaluation of Genetically Transduced Dermal Tissue Implants for the Sustained Secretion of Erythropoietin and Interferon α.

Protein drugs are currently delivered by bolus injection and although treatment frequently is successful, these methods also have major drawbacks, which call for the development of alternative technologies allowing prolonged delivery of these drugs. We developed a new ex vivo gene therapy platform called Transduced Autologous Restorative Gene Therapy (TARGT) for sustained long term production and secretion of autologous therapeutic proteins. A biopsy of dermal tissue taken from the patient is transduced ex vivo with a viral vector encoding the required gene under a constitutive promoter.

Ex vivo transduction of human dermal tissue structures for autologous implantation production and delivery of therapeutic proteins.

Systemic delivery of therapeutic proteins through gene transfer approaches has been carried out mostly by ex vivo transduction of single cells or by direct in vivo injection of an expression vector. In this work an intact miniature biopsy of human dermis (microdermis) is harvested and transduced ex vivo by a viral vector encoding a gene for the therapeutic protein. The microdermis preserves its three-dimensional structure and viability during the ex vivo manipulations.

Reproductive development according to elevation in a seasonally breeding male songbird.

Seasonal temperate zone breeders respond to increasing day length to anticipate the approach of spring breeding conditions. Other (supplementary) environmental cues, such as temperature and precipitation, were historically thought to play unimportant roles in reproductive timing. We demonstrate variation in reproductive timing across small geographic distances by examining the vernal testicular recrudescence of adult song sparrows (Melospiza melodia morphna) breeding in coastal (0-10 m elevation) and montane (280-1220 m elevation) habitats.

Anatomical and histological changes in the alimentary tract of migrating blackcaps (Sylvia atricapilla): a comparison among fed, fasted, food-restricted, and refed birds.

During northward migration, blackcaps that arrive to refuel at stopover sites in Israel's Negev Desert have reduced masses of organs that are important in food digestion and assimilation. We tested several predictions from the general hypothesis that smaller organs of digestion (small intestine and pancreas) and nutrient assimilation (liver) bring about a lower capacity to consume food and that the organs must be restored before blackcaps can feed and digest at a high rate. We used a fasting protocol to create a group of blackcaps with reduced intestine and liver mass (reduced by 45% and 36%, respectively) compared with controls fed ad lib.

The effects of season and dietary salt content on body temperature daily rhythms of common spiny mice from different micro-habitats.

We compared body temperature (T(b)) daily rhythms in two populations of common spiny mice, Acomys cahirinus, during summer and winter months in relation to increasing dietary salt content. Mice were collected from the North and South facing slopes (NFS and SFS) of the same valley, that are exhibiting mesic and xeric habitats, respectively. During the summer, whilst mice were offered a water source containing 0.

Comparative non-shivering thermogenesis in adjacent populations of the common spiny mouse (Acomys cahirinus) from opposite slopes: the effects of increasing salinity.

We compared non-shivering thermogenesis between two adjacent populations of the common spiny mouse Acomys cahirinus from different habitats, in relation to increasing salinity. Individuals were captured from the north- and south-facing slopes of the same valley, that represent "Mediterranean" and "desert" habitats, respectively. We hypothesized that the two populations of mice would differ in their thermoregulatory capacities, reflecting their need to cope with the environmental stress in each habitat.