VEGF189 binds NRP1 and is sufficient for VEGF/NRP1-dependent neuronal patterning in the developing brain

© 2015. Published by The Company of Biologists Ltd. This research was funded by a Wellcome Trust PhD fellowship to M.T. [092839/Z/10/Z] and a BBSRC project grant to C.R. and L.E. [BB/J00930X/1]. Deposited in PMC for immediate release.Peer reviewedPublisher PD

Tamoxifen exacerbates morbidity and mortality in male mice receiving medetomidine anaesthesia

Tamoxifen-induced CreER-LoxP recombination is often used to induce spatiotemporally controlled gene deletion in genetically modified mice. Prior work has shown that tamoxifen and tamoxifen-induced CreER activation can have off-target effects that should be controlled. However, it has not yet been reported whether tamoxifen administration, independently of CreER expression, interacts adversely with commonly used anaesthetic drugs such as medetomidine or its enantiomer dexmedetomidine in laboratory mice (Mus musculus). Here, we report a high incidence of urinary plug formation and morbidity in male mice on a mixed C57Bl6/J6 and 129/SvEv background when tamoxifen treatment was followed by ketamine-medetomidine anaesthesia. Medetomidine is therefore contra-indicated for male mice after tamoxifen treatment. As dexmedetomidine causes morbidity and mortality in male mice at higher rates than medetomidine even without tamoxifen treatment, our findings suggest that dexmedetomidine is not a suitable alternative for anaesthesia of male mice after tamoxifen treatment. We conclude that the choice of anaesthetic drug needs to be carefully evaluated in studies using male mice that have undergone tamoxifen treatment for inducing CreER-LoxP recombination

VEGF-A and neuropilin 1 (NRP1) shape axon projections in the developing CNS via dual roles in neurons and blood vessels

We thank Vann Bennett and Daizing Zhou (Department of Biochemistry, Duke University Medical Center) for the design and generation of the Brn3bCre knock-in mice. We are grateful to Bennett Alakakone and Susan Reijntjes for help with preliminary experiments and to Anastasia Lampropoulou for preparing tissue culture media. We thank the staff of the Biological Resource Unit at the UCL Institute of Ophthalmology and the University of Aberdeen Institute of Medical Sciences Microscopy and Histology Facility and Medical Research Facility for technical assistance. Funding This research was funded by project grants from the Wellcome Trust [085476/A/08/Z to L.E., C.R.] and Biotechnology and Biological Sciences Research Council (BBSRC) [BB/J00815X/1 to L.E.; BB/J00930X/1 to C.R.] and a Wellcome Trust PhD Fellowship [092839/Z/10/Z to M.T.]. Deposited in PMC for immediate release.Peer reviewedPublisher PD

Erythro-myeloid progenitors contribute endothelial cells to blood vessels

The earliest blood vessels in mammalian embryos are formed when endothelial cells differentiate from angioblasts and coalesce into tubular networks. Thereafter, the endothelium is thought to expand solely by proliferation of pre-existing endothelial cells. Here we show that a complementary source of endothelial cells is recruited into pre-existing vasculature after differentiation from the earliest precursors of erythrocytes, megakaryocytes and macrophages, the erythro-myeloid progenitors (EMPs) that are born in the yolk sac. A first wave of EMPs contributes endothelial cells to the yolk sac endothelium, and a second wave of EMPs colonizes the embryo and contributes endothelial cells to intraembryonic endothelium in multiple organs, where they persist into adulthood. By demonstrating that EMPs constitute a hitherto unrecognized source of endothelial cells, we reveal that embryonic blood vascular endothelium expands in a dual mechanism that involves both the proliferation of pre-existing endothelial cells and the incorporation of endothelial cells derived from haematopoietic precursors

KIT Is Required for Fetal Liver Hematopoiesis

In the mouse embryo, endothelial cell (EC) progenitors almost concomitantly give rise to the first blood vessels in the yolk sac and the large vessels of the embryo proper. Although the first blood cells form in the yolk sac before blood vessels have assembled, consecutive waves of hematopoietic progenitors subsequently bud from hemogenic endothelium located within the wall of yolk sac and large intraembryonic vessels in a process termed endothelial-to-hematopoietic transition (endoHT). The receptor tyrosine kinase KIT is required for late embryonic erythropoiesis, but KIT is also expressed in hematopoietic progenitors that arise via endoHT from yolk sac hemogenic endothelium to generate early, transient hematopoietic waves. However, it remains unclear whether KIT has essential roles in early hematopoiesis. Here, we have combined single-cell expression studies with the analysis of knockout mice to show that KIT is dispensable for yolk sac endoHT but required for transient definitive hematopoiesis in the fetal liver

CXCL12 promotes the crossing of retinal ganglion cell axons at the optic chiasm

Open Access via the JISC/CUP agreement Funding This work was supported by a University of Aberdeen Elphinstone Scholarship to V.-H.L., a Deutsche Forschungsgemeinschaft grant [TU295/10-1] to R.S. and a Wellcome Trust New Investigator Award [095623/Z/11/Z] to C.R. Open Access funding provided by University of Aberdeen. Deposited in PMC for immediate release.Peer reviewe

Antimicrobial activity of a standardized medical honey on bacterial isolates from infected skin lesions of non-traditional companion animals

: In recent years, due to the growing phenomenon of antimicrobial resistance, the search for alternative strategies to antibiotic treatments is increasing and a considerable interest for the use of medical honey in clinical practice has emerged. Honey has been used for the treatment of skin lesions, in both humans and animals. However, knowledge concerning the use of medical honey in non‑traditional companion animals is scarce. The aim of this study was to assess the antibacterial activity of a standardized medical honey (Revamil, BFactory) against bacterial strains isolated from skin lesions of non‑traditional companion animals. The minimum bactericidal concentration (MBC) of Revamil honey against seventeen clinical isolates and three reference strains was established.The medical honey showed antimicrobial activity against both Gram‑positive and Gram‑negative bacteria. Growth was inhibited for all the strains at concentrations of medical honey ranging from 10 to 40%. Pseudomonas oryzihabitans and Alcaligenes faecalis showed the lowest MBC (10%). The reference strain Staphylococcus aureus ATCC25923 showed a higher sensitivity to 20% honey compare to the corresponding clinical isolate (P = 0.001). The observed results suggest that Revamil could represent an effective therapeutic aid, useful for the reduction of antibiotic use, in case of pathological skin infections in non‑traditional companion animals

KIT is dispensable for physiological organ vascularisation in the embryo

Blood vessels form vast networks in all vertebrate organs to sustain tissue growth, repair and homeostatic metabolism, but they also contribute to a range of diseases with neovascularisation. It is, therefore, important to define the molecular mechanisms that underpin blood vessel growth. The receptor tyrosine kinase KIT is required for the normal expansion of hematopoietic progenitors that arise during embryogenesis from hemogenic endothelium in the yolk sac and dorsal aorta. Additionally, KIT has been reported to be expressed in endothelial cells during embryonic brain vascularisation and has been implicated in pathological angiogenesis. However, it is neither known whether KIT expression is widespread in normal organ endothelium nor whether it promotes blood vessel growth in developing organs. Here, we have used single-cell analyses to show that KIT is expressed in endothelial cell subsets of several organs, both in the adult and in the developing embryo. Knockout mouse analyses revealed that KIT is dispensable for vascularisation of growing organs in the midgestation embryo, including the lung, liver and brain. By contrast, vascular changes emerged during late-stage embryogenesis in these organs from KIT-deficient embryos, concurrent with severe erythrocyte deficiency and growth retardation. These findings suggest that KIT is not required for developmental tissue vascularisation in physiological conditions, but that KIT deficiency causes foetal anaemia at late gestation and thereby pathological vascular remodelling

La didáctica en la enseñanza del código de lecto-escritura braille, en estudiantes sin deficiencia visual, cursantes de la carrera de formación docente en educación especial. 16H275

Lista de actividades realizadas durante el período: - Se definió de modo exhaustivo el problema del proyecto, a través de la elaboración de un árbol de problemas. - Exploración de fuentes bibliográficas. - Los objetivos se reanalizaron y se consideró que los planteados inauguralmente fueron adecuados. Se elaboró una primera aproximación al estado del arte y al marco teórico