Differential regulation of bladder pain and voiding function by sensory afferent populations revealed by selective optogenetic activation

Bladder-innervating primary sensory neurons mediate reflex-driven bladder function under normal conditions, and contribute to debilitating bladder pain and/or overactivity in pathological states. The goal of this study was to examine the respective roles of defined subtypes of afferent neurons in bladder sensation and function in vivo via direct optogenetic activation. To accomplish this goal, we generated transgenic lines that express a Channelrhodopsin-2-eYFP fusion protein (ChR2-eYFP) in two distinct populations of sensory neurons: TRPV1-lineage neurons (Trpv1Cre;Ai32, the majority of nociceptors) and Nav1.8+ neurons (Scn10aCre;Ai32, nociceptors and some mechanosensitive fibers). In spinal cord, eYFP+ fibers in Trpv1Cre;Ai32 mice were observed predominantly in dorsal horn (DH) laminae I-II, while in Scn10aCre;Ai32 mice they extended throughout the DH, including a dense projection to lamina X. Fiber density correlated with number of retrogradely-labeled eYFP+ dorsal root ganglion neurons (82.2% Scn10aCre;Ai32 vs. 62% Trpv1Cre;Ai32) and degree of DH excitatory synaptic transmission. Photostimulation of peripheral afferent terminals significantly increased visceromotor responses to noxious bladder distension (30–50 mmHg) in both transgenic lines, and to non-noxious distension (20 mmHg) in Scn10aCre;Ai32 mice. Depolarization of ChR2+ afferents in Scn10aCre;Ai32 mice produced low- and high-amplitude bladder contractions respectively in 53% and 27% of stimulation trials, and frequency of high-amplitude contractions increased to 60% after engagement of low threshold (LT) mechanoreceptors by bladder filling. In Trpv1Cre;Ai32 mice, low-amplitude contractions occurred in 27% of trials before bladder filling, which was pre-requisite for light-evoked high-amplitude contractions (observed in 53.3% of trials). Potential explanations for these observations include physiological differences in the thresholds of stimulated fibers and their connectivity to spinal circuits

Pollen grains in lake sediments: Pollen percentages in surface sediments from southern Michigan

Pollen in surface sediments from five lakes in southern Michigan shows evidence of differential deposition. In most lakes, pollen from ragweed occurs in a higher ratio to tree pollen in shallow-water sediment than in deep water. Pine and certain herbs with small pollen grains follow the same pattern. One very deep lake is an exception, with the ratio of ragweed to tree pollen highest in deep-water sediment. Pollen from local aquatics and from willow, which grows along the lake shore, is also unevenly distributed, occurring in highest frequencies near the parent plants. Pollen from deciduous trees, however, occurs in similar ratios at all sampling stations within each lake. Deciduous pollen occurs in uniform ratios, also in older sediment, deposited in the early 19th century, when the landscape was still forested.Percentages of deciduous tree pollen (as percent tree pollen) were compared among lakes. Single samples were taken for this purpose from the deepest part of each lake basin. Oak pollen percentages are higher in three lakes in western Washtenaw County than in three lakes in eastern Washtenaw County. This difference reflects a similar difference in present-day vegetation: second-growth oak forests grow near the lakes in the western half of the county, while all but 5% of the area in the eastern part of the county is farmland. (The difference in the ratio of farmland to forestland in the two parts of the county is not reflected clearly in the ratio of herb pollen to tree pollen, because there is so much variation within each lake.) In 140-year-old sediment, on the other hand, tree pollen percentages in the six samples are homogeneous as shown by a chi-square test. The homogeneity in sediment deposited before the forest was cleared is surprising, because witness-tree data from presettlement time show that the frequencies of tree species in the two areas were quite different. Pollen dispersal at that time must have been effective enough, to counteract differences over distances of a few tens of kilometers in the amounts and kinds of pollen produced by the vegetation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/33513/1/0000011.pd

The 1997 Los Angeles Basin Passive Seismic Experiment – a dense, urban seismic array to investigate basin lithospheric structures

In 1997, 18 seismic stations were installed in the Los Angeles basin to record teleseismic, regional, and local earthquakes. The goals of the experiment were to quantify amplification of ground motion due to variations in sedimentary environments and subsurface structures, and to examine the tectonic extensional and compressional history of the Los Angeles basin and San Gabriel Mountains by tomograhic imaging. The linear array spanned the entire basin between Seal Beach to the south and Azusa to the north. The stations consisted of three-component, short-period seismometers and timing was controlled by GPS receivers. Most locations were homeowner backyards with continuous A/C power sources and battery backup. The stations operated between March and November, 1997. The long experiment time was needed to record as many large teleseisms as possible at the seismically and culturally noisy Los Angeles basin sites. Data were recorded continuously at 25 sps and triggered at 50 sps. The total array length was 50 km with an average station spacing of 3-4 km. This was a much denser seismic array than any other in the region, and the close spacing of seismometers is providing high-resolution information about the geometry of structures several kilometers below the surface. The high density of stations is making it possible to observe amplitude variations on length scales of a few kilometers and to obtain travel times in seismically and culturally noisy regions by cross-correlation with quiet stations using the highly coherent waveforms. This array location was chosen because it spans the entire Los Angeles basin, and it covers an area known for its high seismic hazard, unique geology and active plate motion. It was also the site of one leg of the 1994 Los Angeles Region Seismic Experiment in which onshore and offshore explosions were recorded along essentially the same line for very detailed structure in the upper 20 km of the Earth's crust

Evaluation of T2Candida Panel for detection of Candida in peritoneal dialysates

Fungal peritonitis in the peritoneal dialysis population is difficult to diagnose promptly due to the inherently slow cultivation-based methods currently required for identification of peritonitis pathogens. Because of the moderate risk for severe complications, the need for rapid diagnostics is considerable. One possible solution to this unmet need is the T2Candida Panel, a new technology designed to detect the most common pathogenic Candida spp. directly from whole blood specimens in as little as a few hours. We hypothesized that this technology could be applied to the detection of Candida in peritoneal dialysate, a matrix not currently approved by the Food and Drug Administration for testing by this system. Remnant dialysate samples from three healthy (noninfected) pediatric peritoneal dialysis patients were spiked with Candida glabrata, serially diluted, and tested in triplicate with unaltered dialysate specimens. The assay detected C. glabrata in 100% of spiked dialysate samples across the full spectrum of dilutions tested, and no assay inhibition or cross-reactivity was noted. These findings suggest one of possibly more applications of this technology. The positive clinical implications of this test will continue to be realized as its use is validated in peritoneal dialysate and other patient specimen types

Exploring Galaxy Formation Models and Cosmologies with Galaxy Clustering

Using N-body simulations and galaxy formation models, we study the galaxy stellar mass correlation and the two-point auto-correlation. The simulations are run with cosmological parameters from the WMAP first, third and seven year results, which mainly differ in the perturbation amplitude of \sigma_{8}. The stellar mass of galaxies are determined using either a semi-analytical galaxy formation model or a simple empirical abundance matching method. Compared to the SDSS DR7 data at z=0 and the DEEP2 results at z=1, we find that the predicted galaxy clusterings from the semi-analytical model are higher than the data at small scales, regardless of the adopted cosmology. Conversely, the abundance matching method predicts good agreement with the data at both z=0 and z=1 for high \sigma_8 cosmologies (WMAP1 & WMAP7), but the predictions from a low \sigma_8 cosmology (WMAP3) are significantly lower than the data at z=0. We find that the excess clustering at small-scales in the semi-analytical model mainly arises from satellites in massive haloes, indicating that either the star formation is too efficient in low-mass haloes or tidal stripping is too inefficient at high redshift. Our results show that galaxy clustering is strongly affected by the models for galaxy formation, thus can be used to constrain the baryonic physics. The weak dependence of galaxy clustering on cosmological parameters makes it difficult to constrain the WMAP1 and WMAP7 cosmologies.Comment: 8 pages, 7 figures. Accepted to MNRA