Molecular and electrophysiological features of spinocerebellar ataxia type seven in induced pluripotent stem cells.

Spinocerebellar ataxia type 7 (SCA7) is an inherited neurodegenerative disease caused by a polyglutamine repeat expansion in the ATXN7 gene. Patients with this disease suffer from a degeneration of their cerebellar Purkinje neurons and retinal photoreceptors that result in a progressive ataxia and loss of vision. As with many neurodegenerative diseases, studies of pathogenesis have been hindered by a lack of disease-relevant models.

Wholemount imaging reveals abnormalities of the aqueous outflow pathway and corneal vascularity in Foxc1 and Bmp4 heterozygous mice.

Mutations in the FOXC1/Foxc1 gene in humans and mice and Bmp4 in mice are associated with congenital anterior segment dysgenesis (ASD) and the development of the aqueous outflow structures throughout the limbus. The aim of this study was to advance our understanding of anterior segment abnormalities in mouse models of ASD using a 3-D imaging approach. Holistic imaging information combined with quantitative measurements were carried out on PECAM-1 stained individual components of the aqueous outflow vessels and corneal vasculature of Foxc1(+/-) on the C57BL/6Jx129 and ICR backgrounds, Bmp4(+/-) ICR mice, and wildtype mice from each background.

Melanocyte migration is influenced by E-cadherin-dependent adhesion of keratinocytes in both two- and three-dimensional in vitro wound models.

During wound healing, melanocytes are required to migrate into the wounded area that is still in the process of re-construction. The role and behaviour of melanocytes during this process is poorly understood, that is, whether melanocyte migration into the wound is keratinocyte-dependent or not. This paper attempts, through the use of both two- and three-dimensional in vitro models, to understand the role and behaviour of melanocytes during the process of wound healing.

The three-dimensional organisation of the post-trabecular aqueous outflow pathway and limbal vasculature in the mouse.

The mouse eye has been used as a model for studies on the microanatomy of the outflow pathways but most of what is known comes from histological sections. These studies have focused mainly on the morphological features of the trabecular meshwork, Schlemm's canal and aqueous channels that link to the superficial episcleral vasculature. However, the anatomical architecture of the aqueous outflow vessels and their relationship to each other and to the general vascular circulation is not well understood.

Eye development in the Cape dune mole rat.

Studies on mammalian species with naturally reduced eyes can provide valuable insights into the evolutionary developmental mechanisms underlying the reduction of the eye structures. Because few naturally microphthalmic animals have been studied and eye reduction must have evolved independently in many of the modern groups, novel evolutionary developmental models for eye research have to be sought. Here, we present a first report on embryonic eye development in the Cape dune mole rat, Bathyergus suillus.

Signals from the lens and Foxc1 regulate the expression of key genes during the onset of corneal endothelial development.

Correct formation of the corneal endothelium is essential for continued development of the anterior segment of the eye. Corneal endothelial development is initiated at E12 when precursor peri-ocular mesenchyme cells migrate into the space between the lens and the presumptive corneal epithelium and begin to respond to signals from the lens, undergoing a mesenchymal to epithelial transition (MET) that is complete by E15.5.

Corticotropin-releasing factor: a possible key to gut dysfunction in the critically ill.

Critically ill patients frequently display unexplained or incompletely explained features of gastrointestinal (GI) dysfunction, including gastric stasis, ileus, and diarrhea. This makes nutrition delivery challenging, and may contribute to poor outcomes. The typical bowel dysfunction seen in severely ill patients includes retarded gastric emptying, unsynchronized intestinal motility, and intestinal hyperpermeability.

Simultaneous immunofluorescent labeling using anti-BrdU monoclonal antibody and a melanocyte-specific marker in formalin-fixed paraffin-embedded human skin samples.

Immunolabeling of tissue sections requires careful optimization of protocols in order to achieve accurate and consistent data. Multiple immunolabeling is desirable when determining the exact location and phenotype of cell populations in the same cellular compartment. 5-bromodeoxyuridine (BrdU)-immunolabeling is commonly used to assess cellular proliferation in vitro.

Melanomas display increased cytoprotection to hypericin-mediated cytotoxicity through the induction of autophagy.

Photodynamic therapy (PDT) as a regime for melanoma is of limited success due to factors such as the efficacy of the photosensitizer used, penetration depth and the presence of pigment. We characterised a pigmented and an unpigmented melanoma cell line with respect to their phenotypes. Cell viability was assessed after exposure to hypericin, a UVA-activated photosensitizer.

Hypericin phototoxicity induces different modes of cell death in melanoma and human skin cells.

Hypericin, the major component of St. John's Wort, absorbs light in the UV and visible ranges whereupon it becomes phototoxic through the production of reactive oxygen species. Although photodynamic mechanisms (i.

Structure of the integument of southern right whales, Eubalaena australis.

Skin (integument) anatomy reflects adaptations to particular environments. It is hypothesized that cetacean (whale) integument will show unique anatomical adaptations to an aquatic environment, particularly regarding differences in temperature, density, and pressure. In this study, the gross and histological structure of the southern right whale integument is described and compared with terrestrial mammals and previous descriptions of mysticete (baleen whale) and odontocete (toothed whale) species.

Immunofluorescent identification of melanocytes in murine hair follicles.

Immunocytochemical identification of skin cells are difficult due to numerous endogenous autofluorescent components within the cell and the environment. This is particularly evident in hair follicles. This paper reports on a serendipitous modification to an existing method which results in a drastically reduced background fluorescence.

Identification of Tgf beta1i4 as a downstream target of Foxc1.

Craniofacial development is severely affected by null mutations in Foxc1, indicating a multifunctional role for Foxc1 in ocular, maxilla and mandible, skull and facial gland development. To delineate signaling pathways in which Foxc1 is involved we compared the transcriptomes of whole heads of Foxc1+/+ and Foxc1-/- embryos using a candidate cDNA array comprising genes expressed in the head mesenchyme and ocular region, and a 7K oligo array. Absence of Foxc1 led to downregulation of Stat1 and Galnt4, and upregulation of Tgf beta1i4 at embryonic day 13.

The role of the forkhead transcription factor, Foxc1, in the development of the mouse lacrimal gland.

The lacrimal gland produces secretions that lubricate and protect the cornea of the eye. Foxc1 encodes a forkhead/winged helix transcription factor required for the development of many embryonic organs. Autosomal dominant mutations in human FOXC1 cause eye disorders such as Axenfeld-Rieger Syndrome and glaucoma iris hypoplasia, resulting from malformation of the anterior segment of the eye.

Postnatal development of the eye in the naked mole rat (Heterocephalus glaber).

The naked mole rat (Heterocephalus glaber) is a subterranean rodent whose eyes are thought to be visually nonfunctional and as such is an ideal animal with which to pursue questions in evolutionary developmental biology. This report is the first in-depth study on the development and morphology of the naked mole rat eye. Using standard histological analysis and scanning and transmission electron microscopy, we describe the structural features of the eye.

Melanoma patient staging: histopathological versus molecular evaluation of the sentinel node.

Lymphatic mapping and sentinel lymphadenectomy provide a minimally invasive means of directly determining the status of the regional lymph nodes in all patients who have a primary melanoma >1 mm thick but no clinical evidence of nodal involvement. Since the histological status of the sentinel node (SN) has been shown to be the most important prognostic factor in primary melanoma patients, the World Health Organization has recently recommended that sentinel lymphadenectomy should become the new standard of care for primary melanoma patients. This paper reviews the literature with regards to developments in and the current status of SN evaluation.

The active fraction of plasmatic plasminogen activator inhibitor type 1 as a possible indicator of increased risk for metastatic melanoma.

Plasminogen activator inhibitor type 1 (PAI1) is considered to be the main regulator of fibrinolytic activity in blood and has been identified as a key-enzyme in the metastasis and vascularization of solid tumors. The aim of this study was to determine whether high or low plasma levels and/or activity of PAI1 correlate with the presence of metastatic disease for patients with melanoma. We hypothesized that the presence of metastases could result in a disturbance of the fibrinolytic balance of the blood.