The lens as a model for fibrotic disease

Fibrosis affects multiple organs and is associated with hyperproliferation, cell transdifferentiation, matrix modification and contraction. It is therefore essential to discover the key drivers of fibrotic events, which in turn will facilitate the development of appropriate therapeutic strategies. The lens is an elegant experimental model to study the processes that give rise to fibrosis. The molecular and cellular organization of the lens is well defined and consequently modifications associated with fibrosis can be clearly assessed. Moreover, the avascular and non-innervated properties of the lens allow effective in vitro studies to be employed that complement in vivo systems and relate to clinical data. Using the lens as a model for fibrosis has direct relevance to millions affected by lens disorders, but also serves as a valuable experimental tool to understand fibrosis per se

Charging for Nature: Marine Park Fees and Management from a User Perspective

User fees can contribute to the financial sustainability of marine protected areas (MPAs), yet they must be acceptable to users. We explore changes in the fee system and management of Bonaire National Marine Park (BNMP) from the perspective of users. Responses from 393 tourists indicated that 90% were satisfied with park conditions and considered current user fees reasonable. However, only 47% of divers and 40% of non-divers were prepared to pay more. Diver willingness-to-pay (WTP) appears to have decreased since 1991, but this difference could be due in part to methodological differences between studies. Although current fees are close to diver maximum stated WTP, revenues could potentially be increased by improving the current fee system in ways that users deem acceptable. This potential surplus highlights the value of understanding user perceptions toward MPA fees and management

Water Quality in Selected Shallow Wells in Dar es Salaam

Majority of Dar es Salaam residents depend mostly on ground water fortheir domestic use because, they are not connected to the city water supply system,or the supply system is not reliable. Due to widespread use of groundwater (shallowand deep wells), the scientific determination of quality of this mass consumedproduct is essential. In this study the water quality parameters: physical, chemicaland biological contaminants on the shallow wells were investigated around Dar esSalaam City.Except for Total Dissolved Solids (TDS) and Total Hardness, other physicalparameters tested were within the WHO acceptable range. Levels of phosphate insamples from Temeke district ranges from 0.42 – 1.20 ppm, while samples fromIlala ranges from 0.16 – 0.36. Meanwhile chloride levels in samples from Temekeranges between 158.40 – 624.14 ppm and Ilala ranges between 142.34 – 359.52ppm. This could be due to human activities such as small industries and unplanned waste dumping sites close to water source.All water samples were contaminated with both Total Coliform (TC) and Fecal Coliform (FC). The highest TC and FC levels were detected in the sample from Vikunai Village in Temeke municipality (2160/100ml and 67/100ml respectively).This was due to proximity of pit latrines and runoff during rainfall because shallowwells are neither covered nor built up above ground level to create barriers againststorm water inflow.Generally, water from shallow wells in Dar es Salaam City is bacteriologically and chemically contaminated. The source of contamination is on-site waste disposal andpoor hygiene education. It is recommended that water from wells must be treatedprior to consumption in order to prevent potential infections. Residents ought to beprovided with water quality management education so that they could know how totreat, store and maintain the quality of drinking water.Key words: shallow well, phosphate, water quality, nitrate, faecal coliform,chloride

Transcriptome-wide analysis reveals different categories of response to a standardised immune challenge in a wild rodent

Individuals vary in their immune response and, as a result, some are more susceptible to infectious disease than others. Little is known about the nature of this individual variation in natural populations, or which components of immune pathways are most responsible, but defining this underlying landscape of variation is an essential first step to understanding the drivers of this variation and, ultimately, predicting the outcome of infection. We describe transcriptome-wide variation in response to a standardised immune challenge in wild field voles. We find that markers can be categorised into a limited number of types. For the majority of markers, the response of an individual is dependent on its baseline expression level, with significant enrichment in this category for conventional immune pathways. Another, moderately sized, category contains markers for which the responses of different individuals are also variable but independent of their baseline expression levels. This category lacks any enrichment for conventional immune pathways. We further identify markers which display particularly high individual variability in response, and could be used as markers of immune response in larger studies. Our work shows how a standardised challenge performed on a natural population can reveal the patterns of natural variation in immune response

The flip-graph of the 4-dimensional cube is connected

Flip-graph connectedness is established here for the vertex set of the 4-dimensional cube. It is found as a consequence that this vertex set has 92 487 256 triangulations, partitioned into 247 451 symmetry classes.Comment: 20 pages, 3 figures, revised proofs and notation

Transcriptional adaptation of Mycobacterium tuberculosis within macrophages: Insights into the phagosomal environment

Little is known about the biochemical environment in phagosomes harboring an infectious agent. To assess the state of this organelle we captured the transcriptional responses of Mycobacterium tuberculosis (MTB) in macrophages from wild-type and nitric oxide (NO) synthase 2–deficient mice before and after immunologic activation. The intraphagosomal transcriptome was compared with the transcriptome of MTB in standard broth culture and during growth in diverse conditions designed to simulate features of the phagosomal environment. Genes expressed differentially as a consequence of intraphagosomal residence included an interferon � – and NO-induced response that intensifies an iron-scavenging program, converts the microbe from aerobic to anaerobic respiration, and induces a dormancy regulon. Induction of genes involved in the activation and �-oxidation of fatty acids indicated that fatty acids furnish carbon and energy. Induction of �E-dependent, sodium dodecyl sulfate–regulated genes and genes involved in mycolic acid modification pointed to damage and repair of the cell envelope. Sentinel genes within the intraphagosomal transcriptome were induced similarly by MTB in the lungs of mice. The microbial transcriptome thus served as a bioprobe of the MTB phagosomal environment

Growth factor restriction impedes progression of wound healing following cataract surgery: identification of VEGF as a putative therapeutic target

Secondary visual loss occurs in millions of patients due to a wound-healing response, known as posterior capsule opacification (PCO), following cataract surgery. An intraocular lens (IOL) is implanted into residual lens tissue, known as the capsular bag, following cataract removal. Standard IOLs allow the anterior and posterior capsules to become physically connected. This places pressure on the IOL and improves contact with the underlying posterior capsule. New open bag IOL designs separate the anterior capsule and posterior capsules and further reduce PCO incidence. It is hypothesised that this results from reduced cytokine availability due to greater irrigation of the bag. We therefore explored the role of growth factor restriction on PCO using human lens cell and tissue culture models. We demonstrate that cytokine dilution, by increasing medium volume, significantly reduced cell coverage in both closed and open capsular bag models. This coincided with reduced cell density and myofibroblast formation. A screen of 27 cytokines identified nine candidates whose expression profile correlated with growth. In particular, VEGF was found to regulate cell survival, growth and myofibroblast formation. VEGF provides a therapeutic target to further manage PCO development and will yield best results when used in conjunction with open bag IOL designs