Restoring the balance: regeneration of hair cells in the vestibular system of the inner ear

Loss of the sensory “hair cells” (HCs) from the vestibular (balance) system of the inner ear results in dizziness and balance dysfunction contributing to falls. In the inner ears of non-mammalian vertebrates, there is spontaneous and complete replacement of lost HCs. The regenerates derive from the non-sensory supporting cells (SCs) that surround each HC either from the daughter cells following SC division or by direct, non-mitotic conversion of SCs. In mammals, there is a very limited capacity to regenerate vestibular HCs but only a small percentage is replaced. They arise exclusively by SC conversion. Recent work in mice, and some in humans, has shown possibilities for inducing SCs to convert to cells expressing some HC characteristics, but that differentiation to fully functional HCs is incomplete. Identification of necessary transcription factors, and/or epigenetic modifiers as well as targets to promote SC proliferation is ongoing

Structural changes in the human stria vascularis induced by aminoglycosides and loop diuretics

The human stria vascularis has been examined both by scanning and transmission electron microscopy in normal controls and from individuals who had received loop diuretics, aminoglycoside antibiotics or some combination of the two prior to their deaths. The tissues were preserved by perilymphatic perfusion of fixative within an hour of death and preservation was adequate. The normal ultrastructure is described and does not differ significantly from that found in experimental animals. The loop diuretics are associated with structural changes that cannot be distinguished from those found in animals treated with large doses of the same drugs. The aminoglycosides caused some changes, but the patients had been in renal failure and this probably contributed to the structural alterations. The combination of a loop diuretic and aminoglycoside was associated with a range of alterations from mild to severe. Overall, the three treatment groups had a series of ultrastructural changes resembling those found in animal models thereby justifying the use of experimental animals to predict human ototoxicity

Markets, marketing and production issues for aquaculture in East Africa: the case of Uganda

Aquaculture is currently responsible for an insignificant proportion of total fish production in Uganda. However, given the increasing demand for fresh fish in urban and peri-urban araes, and threats to the supply of fish from natural catch fisheries, the potential exists for a strong market in aquaculture. Small-scale fish farmers located relatively close to markets or all-season roads, and who can supply consistent and high quality produce, will have the widest range of marketing opportunities, and will likely be within the area of operation of potential traders and intermediaries that deliver fish to markets. Fish farmers that are not close to roads, or produce unreliable quantities and variable quality products may face high transaction costs of marketing their product, and decreasing net returns to production. The authors found that significant on-farm labor, and access to input markets are important factors leading to positive net returns to fish production. Areas with high population density and relatively low wages will be well suited to labor intensive aquaculture. The authors concluded that aquaculture development has good potential in certain areas of Uganda and should therefore be pursued as a potential development pathway. However, policy makers should consider the importance of the price of fresh fish relative to the cost of labor, as well as other factors including the importance of smallholder credit and access to extension services, when directing investments in aquaculture technology

Characterizing human vestibular sensory epithelia for experimental studies: new hair bundles on old tissue and implications for therapeutic interventions in ageing.

Balance disequilibrium is a significant contributor to falls in the elderly. The most common cause of balance dysfunction is loss of sensory cells from the vestibular sensory epithelia of the inner ear. However, inaccessibility of inner ear tissue in humans severely restricts possibilities for experimental manipulation to develop therapies to ameliorate this loss. We provide a structural and functional analysis of human vestibular sensory epithelia harvested at trans-labyrinthine surgery. We demonstrate the viability of the tissue and labeling with specific markers of hair cell function and of ion homeostasis in the epithelium. Samples obtained from the oldest patients revealed a significant loss of hair cells across the tissue surface, but we found immature hair bundles present in epithelia harvested from patients >60 years of age. These results suggest that the environment of the human vestibular sensory epithelium could be responsive to stimulation of developmental pathways to enhance hair cell regeneration, as has been demonstrated successfully in the vestibular organs of adult mice

Gamma-ray bursts and terrestrial planetary atmospheres

We describe results of modeling the effects on Earth-like planets of long-duration gamma-ray bursts (GRBs) within a few kiloparsecs. A primary effect is generation of nitrogen oxide compounds which deplete ozone. Ozone depletion leads to an increase in solar UVB radiation at the surface, enhancing DNA damage, particularly in marine microorganisms such as phytoplankton. In addition, we expect increased atmospheric opacity due to buildup of nitrogen dioxide produced by the burst and enhanced precipitation of nitric acid. We review here previous work on this subject and discuss recent developments, including further discussion of our estimates of the rates of impacting GRBs and the possible role of short-duration bursts.Comment: 12 pages including 5 figures (4 in color). Added discussion of GRB rates and biological effects. Accepted for publication in New Journal of Physics, for special issue "Focus on Gamma-Ray Bursts

Age-related changes in P2Y receptor signalling in mouse cochlear supporting cells

Our sense of hearing depends on the function of a specialised class of sensory cells, the hair cells, which are found in the organ of Corti of the mammalian cochlea. The unique physiological environment in which these cells operate is maintained by a syncitium of non-sensory supporting cells, which are crucial for regulating cochlear physiology and metabolic homeostasis. Despite their importance for cochlear function, the role of these supporting cells in age-related hearing loss, the most common sensory deficit in the elderly, is poorly understood. Here, we investigated the age-related changes in the expression and function of metabotropic purinergic receptors (P2Y1 , P2Y2 and P2Y4 ) in the supporting cells of the cochlear apical coil. Purinergic signalling in supporting cells is crucial during the development of the organ of Corti and purinergic receptors are known to undergo changes in expression during ageing in several tissues. Immunolabelling and Ca2+ imaging experiments revealed a downregulation of P2Y receptor expression and a decrease of purinergic-mediated calcium responses after early postnatal stages in the supporting cells. An upregulation of P2Y receptor expression was observed in the aged cochlea when compared to 1 month-old adults. The aged mice also had significantly larger calcium responses and displayed calcium oscillations during prolonged agonist applications. We conclude that supporting cells in the aged cochlea upregulate P2Y2 and P2Y4 receptors and display purinergic-induced Ca2+ responses that mimic those observed during pre-hearing stages of development, possibly aimed at limiting or preventing further damage to the sensory epithelium. KEY POINTS: Age-related hearing loss is associated with lower hearing sensitivity and decreased ability to understand speech. We investigated age-related changes in the expression and function of metabotropic purinergic (P2Y) receptors in cochlear non-sensory supporting cells of mice displaying early-onset (C57BL/6N) and late-onset (C3H/HeJ) hearing loss. The expression of P2Y1 , P2Y2 and P2Y4 receptors in the supporting cells decreased during cochlear maturation, but that of P2Y2 and P2Y4 was upregulated in the aged cochlea. P2Y2 and P2Y4 receptors were primarily responsible for the ATP-induced Ca2+ responses in the supporting cells. The degree of purinergic expression upregulation in aged supporting cells mirrored hearing loss progression in the different mouse strains. We propose that the upregulation of purinergic-mediated signalling in the aged cochlea is subsequent to age-related changes in the hair cells and may act as a protective mechanism to limit or to avoid further damage to the sensory epithelium

Toward Increased Utilization of Historical Hurricane Chronologies

The record of past tropical cyclones provides an important means to evaluate the hurricane hazard. Historical chronologies are a source of information about tropical cyclones prior to the modern era. Chenoweth (2006) describes an archive of 383 tropical cyclones occurring during the eighteenth and nineteenth centuries, largely before the official hurricane record. The present study demonstrates a novel way this archive can be used to articulate historical tropical cyclone activity across space. First, an event in the archive is assigned a series of latitude/longitude coordinates approximating the descriptive locations of the cyclone’s affect. Second, tropical cyclones from the modern record that approach these locations (modern analogs) are mapped. Third, a probable pathway and a realistic track of the archived event is created by averaging the modern analog tracks. As an example, the procedure is used to generate a map showing the tracks of the Atlantic tropical cyclones of 1766. Sensitivity of the methodology to changes in event location and event timing are considered. The study shows that historical hurricane chronologies when combined with a history of cyclone tracks can provide useful information about the older events that is not directly related to where the original information was gathered. When this information is available for all cyclones it should help climatologists better understand long-term variations in tropical cyclone activity