Neurophysiological modeling of voiding in rats: urethral nerve response to urethral pressure and flow

In male urethan-anesthetized rats, activity was measured in nerves that run over the proximal urethra. The urethral nerve response to stepwise urethral perfusion could be described by a four-parameter model (fit error < 6%). At the onset of perfusion, the urethra was closed and the pressure increased with the infused volume. The nerve activity (NA) increased linearly with this inserted volume to a maximum (NAmax), which was proportional to the instantaneous pressure. The duration of this first episode (delta t) was inversely proportional to the perfusion rate. After infusion of a fixed volume, the urethra opened and the NA decreased with a time constant phi -1 (approximately 1.8 s) to an elevated level (NAlevel). NAlevel was linearly related to the steady-state pressure. Accordingly, sensors in the urethra are sensitive to pressure rather than to the perfusion rate. The parameters NAmax, NAlevel, and delta t showed very good reproducibility (SD approximately 19% of mean). The measured activity was most likely afferent and conducted to the major pelvic ganglion

Threshold for efferent bladder nerve firing in the rat

In this study, the mechanism involved in the initiation of voiding was investigated. Bladder pressure and bladder and urethral nerve activity were recorded in the anesthetized rat. Bladder nerve activity was resolved into afferent and efferent activity by means of a theoretical model. The beginning of an active bladder contraction was defined as the onset of bladder efferent firing at a certain time (t0). From t0 onward, bladder efferent activity increased linearly during deltat seconds (rise time) to a maximum. The pressure at t0 was 1.0 +/- 0.4 kPa, the afferent nerve activity at t0 was 2.0 +/- 0.6 microV (53 +/- 15% of maximum total nerve activity), and deltat was 11 +/- 13 s. Between contractions the afferent activity at t0 was never exceeded. Urethral afferent nerve activity started at bladder pressures of 2.1 +/- 1.1 kPa. Therefore, we concluded that urethral afferent nerve activity does not play a role in the initiation of bladder contractions; voiding contractions presumably are initiated by bladder afferent nerve activity exceeding a certain threshold

How can field margin management contribute to invertebrate biodiversity?

Farmland invertebrates are vital for healthy ecosystem functioning. Many groups have declined due to agricultural intensification. Arable field margins potentially can increase food resources and provide winter refuges for invertebrates. They might also buffer them from agrochemical applications and farm operations. This chapter describes a series of field and farm-scale experiments which show that ways in which arable field margins are established and managed can have profound effects on their invertebrate assemblages. Field margin swards established by sowing with a grass and wildflower seed mixture attracted more butterflies than naturally regenerated swards. In the short term, larger and more species-rich invertebrate assemblages were fostered on unmanaged margins than on those managed by cutting. The timing of cutting was critical, with mid-summer cutting having the most persistent, negative effects on invertebrates, while cutting in spring and autumn was generally less damaging and may help maintain sward species richness. Fallowed land (set-aside) configured as blocks rather than margins constituted qualitatively different habitats for invertebrates. Margin width had complex effects on invertebrate abundance and species richness. Boundary hedgerows increased numbers of most invertebrate groups in the adjacent margin. The chapter suggests that blanket management approaches for invertebrates at the farm scale are not optimal. A diverse farmed landscape, with margins of different sizes and different sward structures, will provide for the different ecological requirements of invertebrate populations, and promote their diversity in the characteristically unstable environment of arable systems

Does organic farming affect biodiversity?

Farmland biodiversity in Europe has been declining for some time, particularly steeply in the second half of the twentieth century. The consensus is that agricultural intensification is largely responsible. Organic farming is a low intensity system, offering benefits to biodiversity. Using two paired-farm studies, we explored the responses of different taxonomic groups to organic farming. In the first, smaller-scale, study, positive impacts of organic farming on butterflies and spiders were found. In the second, large-scale, study of eighty-nine farm pairs across England, organic farming was mainly associated with positive effects on biodiversity, although there was substantial variation in the size of effects among taxonomic groups surveyed. The largest and most consistent (positive) effects were for plants and the smallest effects were for carabid beetles. Spiders were influenced by farming system, surrounding landscape, and their dispersal ability. Hunting spiders, which tend to have lower dispersal ability, were more abundant and species-rich on organic compared to conventional farms (this effect was more pronounced in landscapes with less arable). There were no farming system or landscape effects found on web-building spiders, which have generally higher dispersal abilities. There was little evidence that non-cropped habitat effects explained the observed differences for either group. The chapter suggests that the farming system differences for spiders in the crop were largely attributable to differences in crop management (such as reduced inputs of pesticides and fertilizers). The results highlight the importance of developing strategies for managing farmland at the landscape scale for most effective conservation of biodiversity

The benefits of organic farming for biodiversity

Previous studies suggest widespread positive responses of biodiversity to organic farming. Many of these studies, however, have been small-scale. This project tested the generality of habitat and biodiversity differences between matched pairs of organic and non-organic farms containing cereal crops in lowland England on a large-scale across a range of taxa including plants, insects, birds and bats. The extent of both cropped and un-cropped habitats together with their composition and management on a range of scales were also compared. Organic farms was likely to favour higher levels of biodiversity and indeed organic farms tended to support higher numbers of species and overall abundance across most taxa. However, the magnitude of the response differed strikingly; plants showed stronger and more consistent responses than other taxa. Some, but not all, differences in biodiversity between systems appear to be a consequence of differences in habitat quantity

Organic Farming: Biodiversity Impacts Can Depend on Dispersal Characteristics and Landscape Context

Organic farming, a low intensity system, may offer benefits for a range of taxa, but what affects the extent of those benefits is imperfectly understood. We explored the effects of organic farming and landscape on the activity density and species density of spiders and carabid beetles, using a large sample of paired organic and conventional farms in the UK. Spider activity density and species density were influenced by both farming system and surrounding landscape. Hunting spiders, which tend to have lower dispersal capabilities, had higher activity density, and more species were captured, on organic compared to conventional farms. There was also evidence for an interaction, as the farming system effect was particularly marked in the cropped area before harvest and was more pronounced in complex landscapes (those with little arable land). There was no evidence for any effect of farming system or landscape on web-building spiders (which include the linyphiids, many of which have high dispersal capabilities). For carabid beetles, the farming system effects were inconsistent. Before harvest, higher activity densities were observed in the crops on organic farms compared with conventional farms. After harvest, no difference was detected in the cropped area, but more carabids were captured on conventional compared to organic boundaries. Carabids were more species-dense in complex landscapes, and farming system did not affect this. There was little evidence that non-cropped habitat differences explained the farming system effects for either spiders or carabid beetles. For spiders, the farming system effects in the cropped area were probably largely attributable to differences in crop management; reduced inputs of pesticides (herbicides and insecticides) and fertilisers are possible influences, and there was some evidence for an effect of non-crop plant species richness on hunting spider activity density. The benefits of organic farming may be greatest for taxa with lower dispersal abilities generally. The evidence for interactions among landscape and farming system in their effects on spiders highlights the importance of developing strategies for managing farmland at the landscape-scale for most effective conservation of biodiversity

Organic farming: biodiversity impacts can depend on dispersal characteristics and landscape context

Organic farming, a low intensity system, may offer benefits for a range of taxa, but what affects the extent of those benefits is imperfectly understood. We explored the effects of organic farming and landscape on the activity density and species density of spiders and carabid beetles, using a large sample of paired organic and conventional farms in the UK. Spider activity density and species density were influenced by both farming system and surrounding landscape. Hunting spiders, which tend to have lower dispersal capabilities, had higher activity density, and more species were captured, on organic compared to conventional farms. There was also evidence for an interaction, as the farming system effect was particularly marked in the cropped area before harvest and was more pronounced in complex landscapes (those with little arable land). There was no evidence for any effect of farming system or landscape on web-building spiders (which include the linyphiids, many of which have high dispersal capabilities). For carabid beetles, the farming system effects were inconsistent. Before harvest, higher activity densities were observed in the crops on organic farms compared with conventional farms. After harvest, no difference was detected in the cropped area, but more carabids were captured on conventional compared to organic boundaries. Carabids were more species-dense in complex landscapes, and farming system did not affect this. There was little evidence that non-cropped habitat differences explained the farming system effects for either spiders or carabid beetles. For spiders, the farming system effects in the cropped area were probably largely attributable to differences in crop management; reduced inputs of pesticides (herbicides and insecticides) and fertilisers are possible influences, and there was some evidence for an effect of non-crop plant species richness on hunting spider activity density. The benefits of organic farming may be greatest for taxa with lower dispersal abilities generally. The evidence for interactions among landscape and farming system in their effects on spiders highlights the importance of developing strategies for managing farmland at the landscape-scale for most effective conservation of biodiversity

A novel cell-type deconvolution algorithm reveals substantial contamination by immune cells in saliva, buccal and cervix

AIM: An outstanding challenge in epigenome studies is the estimation of cell-type proportions in complex epithelial tissues. MATERIALS & METHODS: Here, we construct and validate a DNA methylation reference and algorithm for complex tissues that contain epithelial, immune and nonimmune stromal cells. RESULTS: Using this reference, we show that easily accessible tissues such as saliva, buccal and cervix exhibit substantial variation in immune cell (IC) contamination. We further validate our reference in the context of oral cancer, where it correctly predicts an increased IC infiltration in cancer but suppressed in patients with highest smoking exposure. Finally, our method can improve the specificity of differentially methylated CpG calls in epithelial cancer. CONCLUSION: The degree and variation of IC contamination in complex epithelial tissues is substantial. We provide a valuable resource and tool for assessing the epithelial purity and IC contamination of samples and for identifying differential methylation in such complex tissues

Geochemical considerations for Hot, Dry Rock Systems

Circulating systems intended to model the P-T conditions found in the natural HDR (Hot Dry Rock) geothermal system at Los Alamos have been built. Experiments with these systems have determined the following parameters for the ''down hole'' reservoir: sample weight loss, circulating solution composition, textural changes in the rock, mineral loss from the rock and effects of chemical additives on rock erosion. The analyses of solutions generated from rock-water interactions in the experimental systems show the extremely dilute nature of the working fluid. These solutions are not brines. Silica scaling in the surface heat exchanger was found to account for the difference between loss of sample rate and analyzed silica in the solution. The weight loss data indicate that there was continuous transport of silica from the ''down hole'' rock to the heat exchanger. Experiments contrasting felsic and mafic rocks in the HDR concept indicate that a reservoir consisting of glass bearing basaltic rock would tend to produce greater scaling problems than systems emplaced in granite. Experimental results suggest that Na{sub 2}CO{sub 3} solutions may provide a means of increasing permeability and thereby increasing the effective heat transfer area of the reservoir. A brief description is given of a small test loop for simulating the flow of a geothermal solution through a heat exchanger. This loop, which is being built, will be used to study the coagulation and precipitation of silica under conditions similar to those expected in the field

A functional methylome map of ulcerative colitis

The etiology of inflammatory bowel diseases is only partially explained by the current genetic risk map. It is hypothesized that environmental factors modulate the epigenetic landscape and thus contribute to disease susceptibility, manifestation, and progression. To test this, we analyzed DNA methylation (DNAm), a fundamental mechanism of epigenetic long-term modulation of gene expression. We report a three-layer epigenome-wide association study (EWAS) using intestinal biopsies from 10 monozygotic twin pairs (n = 20 individuals) discordant for manifestation of ulcerative colitis (UC). Genome-wide expression scans were generated using Affymetrix UG 133 Plus 2.0 arrays (layer 1). Genome-wide DNAm scans were carried out using Illumina 27k Infinium Bead Arrays to identify methylation variable positions (MVPs, layer 2), and MeDIP-chip on Nimblegen custom 385k Tiling Arrays to identify differentially methylated regions (DMRs, layer 3). Identified MVPs and DMRs were validated in two independent patient populations by quantitative real-time PCR and bisulfite-pyrosequencing (n = 185). The EWAS identified 61 disease-associated loci harboring differential DNAm in cis of a differentially expressed transcript. All constitute novel candidate risk loci for UC not previously identified by GWAS. Among them are several that have been functionally implicated in inflammatory processes, e.g., complement factor CFI, the serine protease inhibitor SPINK4, and the adhesion molecule THY1 (also known as CD90). Our study design excludes nondisease inflammation as a cause of the identified changes in DNAm. This study represents the first replicated EWAS of UC integrated with transcriptional signatures in the affected tissue and demonstrates the power of EWAS to uncover unexplained disease risk and molecular events of disease manifestation