Vascular changes in diabetic retinopathy-a longitudinal study in the Nile rat.

Diabetic retinopathy is the most common microvascular complication of diabetes and is a major cause of blindness, but an understanding of the pathogenesis of the disease has been hampered by a lack of accurate animal models. Here, we explore the dynamics of retinal cellular changes in the Nile rat (Arvicanthis niloticus), a carbohydrate-sensitive model for type 2 diabetes. The early retinal changes in diabetic Nile rats included increased acellular capillaries and loss of pericytes that correlated linearly with the duration of diabetes. These vascular changes occurred in the presence of microglial infiltration but in the absence of retinal ganglion cell loss. After a prolonged duration of diabetes, the Nile rat also exhibits a spectrum of retinal lesions commonly seen in the human condition including vascular leakage, capillary non-perfusion, and neovascularization. Our longitudinal study documents a range and progression of retinal lesions in the diabetic Nile rat remarkably similar to those observed in human diabetic retinopathy, and suggests that this model will be valuable in identifying new therapeutic strategies

iPS Cells for Modelling and Treatment of Retinal Diseases

For many decades, we have relied on immortalised retinal cell lines, histology of enucleated human eyes, animal models, clinical observation, genetic studies and human clinical trials to learn more about the pathogenesis of retinal diseases and explore treatment options. The recent availability of patient-specific induced pluripotent stem cells (iPSC) for deriving retinal lineages has added a powerful alternative tool for discovering new disease-causing mutations, studying genotype-phenotype relationships, performing therapeutics-toxicity screening and developing personalised cell therapy. This review article provides a clinical perspective on the current and potential benefits of iPSC for managing the most common blinding diseases of the eye: inherited retinal diseases and age-related macular degeneration

Collapse of the hyperfine magnetic field at the Ru site in ferromagnetic rare earth intermetallics

The M\"{o}ssbauer Effect(ME) is frequently used to investigate magnetically ordered systems. One usually assumes that the magnetic order induces a hyperfine magnetic field, $B_{hyperfine}$, at the ME active site. This is the case in the ruthenates, where the temperature dependence of $B_{hyperfine}$ at $^{99}$Ru sites tracks the temperature dependence of the ferromagnetic or antiferromagnetic order. However this does not happen in the rare-earth intermetallics, GdRu$_2$ and HoRu$_2$. Specific heat, magnetization, magnetic susceptibility, M\"{o}ssbauer effect, and neutron diffraction have been used to study the nature of the magnetic order in these materials. Both materials are found to order ferromagnetically at 82.3 and 15.3 K, respectively. Despite the ferromagnetic order of the rare earth moments in both systems, there is no evidence of a correspondingly large $B_{hyperfine}$ in the M\"{o}ssbauer spectrum at the Ru site. Instead the measured spectra consist of a narrow peak at all temperatures which points to the absence of magnetic order. To understand the surprising absence of a transferred hyperfine magnetic field, we carried out {\it ab initio} calculations which show that spin polarization is present only on the rare-earth site. The electron spin at the Ru sites is effectively unpolarized and, as a result, $B_{hyperfine}$ is very small at those sites. This occurs because the 4$d$ Ru electrons form broad conduction bands rather than localized moments. These 4$d$ conduction bands are polarized in the region of the Fermi energy and mediate the interaction between the localized rare earth moments.Comment: 34 pages -Revtex + 17 ps figure

Rescue of the MERTK phagocytic defect in a human iPSC disease model using translational read-through inducing drugs.

Inherited retinal dystrophies are an important cause of blindness, for which currently there are no effective treatments. In order to study this heterogeneous group of diseases, adequate disease models are required in order to better understand pathology and to test potential therapies. Induced pluripotent stem cells offer a new way to recapitulate patient specific diseases in vitro, providing an almost limitless amount of material to study. We used fibroblast-derived induced pluripotent stem cells to generate retinal pigment epithelium (RPE) from an individual suffering from retinitis pigmentosa associated with biallelic variants in MERTK. MERTK has an essential role in phagocytosis, one of the major functions of the RPE. The MERTK deficiency in this individual results from a nonsense variant and so the MERTK-RPE cells were subsequently treated with two translational readthrough inducing drugs (G418 & PTC124) to investigate potential restoration of expression of the affected gene and production of a full-length protein. The data show that PTC124 was able to reinstate phagocytosis of labeled photoreceptor outer segments at a reduced, but significant level. These findings represent a confirmation of the usefulness of iPSC derived disease specific models in investigating the pathogenesis and screening potential treatments for these rare blinding disorders

Effect of individual environmental heat stress variables on training and recovery in professional team sport

Context: Exercise in hot environments increases body temperature and thermoregulatory strain. However, little is known regarding the magnitude of effect that ambient temperature (Ta), relative humidity (RH), and solar radiation individually have on team-sport athletes. Purpose: To determine the effect of these individual heat-stress variables on team-sport training performance and recovery. Methods: Professional Australian Rules Football players (N = 45) undertook 8-wk preseason training producing a total of 579 outdoor field-based observations with Ta, RH, and solar radiation recorded at every training session. External load (distance covered, in m/min; percentage high-speed running [%HSR] >14.4 km/h) was collected via a global positioning system. Internal load (ratings of perceived exertion and heart rate) and recovery (subjective ratings of well-being and heart-rate variability [root mean square of the successive differences]) were monitored throughout the training period. Mixed-effects linear models analyzed relationships between variables using standardized regression coefficients. Results: Increased solar-radiation exposure was associated with reduced distance covered (−19.7 m/min, P 85% HRmax (3.9%, P a was associated with increased distance covered (19.7 m/min, P < .001) and %HSR (3.5%, P = .005). Conclusions: The authors show the importance of considering the individual factors contributing to thermal load in isolation for team-sport athletes and that solar radiation and RH reduce work capacity during team-sport training and have the potential to slow recovery between sessions.</p

Ferrofluids as thermal ratchets

Colloidal suspensions of ferromagnetic nano-particles, so-called ferrofluids, are shown to be suitable systems to demonstrate and investigate thermal ratchet behavior: By rectifying thermal fluctuations, angular momentum is transferred to a resting ferrofluid from an oscillating magnetic field without net rotating component. Via viscous coupling the noise driven rotation of the microscopic ferromagnetic grains is transmitted to the carrier liquid to yield a macroscopic torque. For a simple setup we analyze the rotation of the ferrofluid theoretically and show that the results are compatible with the outcome of a simple demonstration experiment.Comment: 4 pages, 3 figures, corrected version, improved figures, to be published in Phys. Rev. Let

Cross-talk between epidermal growth factor receptor and protein kinase C during calcium-induced differentiation of keratinocytes

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74029/1/j.1600-0625.2000.009003192.x.pd