A Review of the Prevalence of Ophthalmologic Diseases in Native American Populations.

PURPOSE: Compared with the general population in North America, Native American/American Indian and Alaska Native (AI/AN) populations experience a disparate prevalence of eye diseases. Visual impairment is a barrier to communication, interferes with academic and social success, and decreases overall quality of life. The prevalence of ocular pathology could serve as an indicator of health and social disparities. Therefore, the objective of this research was to perform a thorough review comparing the prevalence of common ophthalmological pathologies between AI/AN and non-AI/AN individuals in North America. DESIGN: Retrospective, cross-sectional study. METHODS: A total of 57 articles were retrieved and reviewed, and 14 met the criteria outlined for inclusion. These articles were retrieved from PubMed, MEDLINE, and ISI Web of Knowledge. Only studies that were peer reviewed in the last 25 years and reported on the prevalence of eye diseases in AI/AN compared with a non-AI/AN population met criteria. RESULTS: Rates of retinopathy, cataracts, visual impairment, and blindness were clearly higher for AI/AN compared with non-AI/AN counterparts. Although rates of macular degeneration and glaucoma were similar between AI/AN and non-AI/AN populations, the treatment rates were lower and associated with poorer outcomes in AI/AN individuals. CONCLUSIONS: There are considerable inequities in the prevalence and treatment rates of ophthalmologic conditions in AI/AN individuals. A likely explanation is the barrier of lack of access to adequate health and eye care. Because of substantial underinsurance and geographic variability, attention needs to be brought to expanding eye care access to AI/AN communities. The results are subject to the availability of appropriate technology, health literacy, and language.

The Hsc70 disaggregation machinery removes monomer units directly from α-synuclein fibril ends.

Molecular chaperones contribute to the maintenance of cellular protein homoeostasis through assisting de novo protein folding and preventing amyloid formation. Chaperones of the Hsp70 family can further disaggregate otherwise irreversible aggregate species such as α-synuclein fibrils, which accumulate in Parkinson's disease. However, the mechanisms and kinetics of this key functionality are only partially understood. Here, we combine microfluidic measurements with chemical kinetics to study α-synuclein disaggregation. We show that Hsc70 together with its co-chaperones DnaJB1 and Apg2 can completely reverse α-synuclein aggregation back to its soluble monomeric state. This reaction proceeds through first-order kinetics where monomer units are removed directly from the fibril ends with little contribution from intermediate fibril fragmentation steps. These findings extend our mechanistic understanding of the role of chaperones in the suppression of amyloid proliferation and in aggregate clearance, and inform on possibilities and limitations of this strategy in the development of therapeutics against synucleinopathies.

Changing the firing threshold for normal optic nerve axons by the application of infra-red laser light.

Normal optic nerve axons exhibit a temperature dependence, previously explained by a membrane potential hyperpolarization on warming. We now report that near infra-red laser light, delivered via a fibre optic light guide, also affects axonal membrane potential and threshold, at least partly through a photo-thermal effect. Application of light to optic nerve, at the recording site, gave rise to a local membrane potential hyperpolarization over a period of about a minute, and increased the size of the depolarizing after potential. Application near the site of electrical stimulation reversibly raised current-threshold, and the change in threshold recorded over minutes of irradiation was significantly increased by the application of the Ih blocker, ZD7288 (50 µM), indicating Ih limits the hyperpolarizing effect of light. Light application also had fast effects on nerve behaviour, increasing threshold without appreciable delay (within seconds), probably by a mechanism independent of kinetically fast K+ channels and Na+ channel inactivation, and hypothesized to be caused by reversible changes in myelin function.

Unraveling the Physicochemical Determinants of Protein Liquid-liquid Phase Separation by Nanoscale Infrared Vibrational Spectroscopy.

The phenomenon of reversible liquid-liquid phase separation of proteins underlies the formation of membraneless organelles, which are crucial for cellular processes such as signalling and transport. In addition, it is also of great interest to uncover the mechanisms of further irreversible maturation of the functional dense liquid phase into aberrant insoluble assemblies due to its implication in human disease. Recent advances in methods based on atomic force microscopy (AFM) have made it possible to study protein condensates at the nanometer level, providing unprecedented information on the nature of the intermolecular interactions governing phase separation. Here, we provide an in-depth description of a protocol for the characterisation of the morphology, stiffness, and chemical properties of protein condensates using infrared nanospectroscopy (AFM-IR).