Ghrelin selectively reduces mechanosensitivity of upper gastrointestinal vagal afferents

Ghrelin is a peptide released from gastric endocrine cells that has an orexigenic effect via a vagal pathway. Here we determine the effect of ghrelin on mechanosensitivity of upper-intestinal vagal afferent fibers in ferret and mouse. The responses of gastroesophageal vagal afferents to graded mechanical stimulation were determined in vitro before and during application of ghrelin to their peripheral endings. Three types of vagal afferent were tested: tension receptors responding to circumferential tension, mucosal receptors responding only to mucosal stroking, and tension/mucosal (TM) receptors in ferret esophagus that responded to both stimuli. In the mouse, ghrelin did not significantly affect the response of mucosal receptors to mucosal stroking with calibrated von Frey hairs. However, it significantly reduced responses of tension receptors to circumferential tension (P < 0.005; two-way ANOVA) by up to 40%. This inhibition was reversed by the ghrelin receptor antagonist [d-Lys-3]-growth hormone-releasing peptide (GHRP)-6. In the ferret, ghrelin significantly reduced the response of mucosal and TM receptors to mucosal stroking with calibrated von Frey hairs. Surprisingly, ghrelin did not significantly alter the response to circumferential tension in either tension or TM receptors. RT-PCR analysis indicated that both ghrelin and its receptor are expressed in vagal afferent cell bodies in mouse nodose ganglia. In conclusion, ghrelin selectively inhibits subpopulations of mechanically sensitive gastroesophageal vagal afferents; there is also potential for ghrelin release from vagal afferents. However, the subpopulation of afferents inhibited differs between species. These data have broad implications for ghrelin's role in food intake regulation and reflex control of gastrointestinal function.     

Geographic Distribution and Mortality Risk Factors during the Cholera Outbreak in a Rural Region of Haiti, 2010-2011

BackgroundIn 2010 and 2011, Haiti was heavily affected by a large cholera outbreak that spread throughout the country. Although national health structure-based cholera surveillance was rapidly initiated, a substantial number of community cases might have been missed, particularly in remote areas. We conducted a community-based survey in a large rural, mountainous area across four districts of the Nord department including areas with good versus poor accessibility by road, and rapid versus delayed response to the outbreak to document the true cholera burden and assess geographic distribution and risk factors for cholera mortality.Conclusions/SignificanceThese results highlight important geographical disparities and demonstrate that the epidemic caused the highest burden both in terms of cases and deaths in the most remote areas, where up to 5% of the population may have died during the first months of the epidemic. Adapted strategies are needed to rapidly provide treatment as well as prevention measures in remote communities.     

Uplift,Erosion, and Phosphorus Limitation in Terrestrial Ecosystems

ABSTRACT Primary productivity on old, weathered soils often is assumed to be limited by phosphorus (P), especially in the lowland tropics where climatic conditions promote the rapid depletion of rock-derived nutrients. This assumption is based on a static view of soils weathering in place with no renewal of the bedrock source. In reality, advection of material through the soil column introduces a spatially variable supply of rock-derived nutrients. This flux is dependent on the residence time of soil, which can range from a few hundred years in rapidly uplifting collisional mountain belts to tens of millions of years in tectonically quiescent tropical cratons. We modeled the effects of tectonic uplift, erosion, and soil depth on the advection of P through the soil column and P availability, calibrating rate of change in biologically available P over time with data from two basaltic chronosequences in Hawai’i and a series of greywacke terraces in New Zealand. Combining our model with the global distribution of tectonic uplift rates and soil depths, we identified tectonic settings that are likely to support P-depleted ecosystems—assuming that tectonic uplift and erosion are balanced (that is, landscape development has reached steady state). The model captures the occurrence of transient P limitation in rapidly uplifting young ecosystems where mineral weathering is outpaced by physical erosion—a likely occurrence where biological N fixation is important. However, we calculate that P depletion is unlikely in areas of moderate uplift, such as most of Central America and Southeast Asia, due to the continuous advection of P into the rooting zone. Finally, where soil advection is slow, such as the Amazon Basin, we expect widespread P depletion in the absence of exogenous nutrient inputs.     

phyB-1 sorghum maintains responsiveness to simulated shade, irradiance and red light: far-red light

The sorghum [Sorghum bicolor (L.) Moench] phyB-1 mutant exhibits a constitutive shade-avoidance phenotype including excessive shoot elongation. It was previously shown that this mutant also overproduces ethylene. Although phytochrome B (phyB) is assumed to be the pigment most important in sensing and transducing shade signals, the sorghum phyB-1 mutant still responds to light signals characteristic of shade. Specifically, it was determined that the leaf blade : leaf sheath elongation of phyB-1 is responsive to red : far red (R : FR), but this response is opposite that of wild type (WT). Reducing the photosynthetic photon flux density (PPFD) strongly reduced the leaf blade : leaf sheath of WT but did not affect phyB-1, demonstrating a role for phyB in sensing PPFD. Using light-emitting diode (LED) lighting, it was found that WT ethylene production was increased with low R : FR while PPFD had no effect. Conversely, phyB-1 ethylene production increased only with high PPFD, high R : FR which was the treatment resulting in the least ethylene production by WT. Elevated ethylene production inhibits shoot elongation, but may contribute to shade avoidance by reducing leaf blade : leaf sheath elongation. Ethylene responses to light treatments designed to promote or reduce phytochrome A (phyA) activity, and the analysis of PHYA levels in the two cultivars suggests that phyA could be involved in transducing shade signals in light-grown sorghum. Responses potentially tranduced by phyA are elevated in phyB-1 which also over-expresses PHYA.     

Proteomic analysis of mouse mammary terminal end buds identifies axonal growth cone proteins

Ductal morphogenesis in the mouse mammary gland occurs mainly postnatally and is driven by specialized structures at the ends of the developing ducts, the terminal end buds (TEBs), which later regress once ductal growth is complete. To identify proteins that are specifically associated with migration of TEBs we developed a novel method of isolating TEBs, which eliminated the mammary stroma. The protein expression profile of the TEBs was then compared with that of isolates taken from the 4th inguinal mammary gland of adult virgin mice using two-dimensional (2-D) gel electrophoresis and mass spectrometry (MS) analysis (matrix-assisted laser desorption/ionization and quadrupole time of flight). Following construction of an integrated protein expression database, 44 protein features which showed differential expression levels between the two sets were chosen for MS analysis. Of these, 24 gave protein annotations whereas the other 20 produced unidentified peptides. Fourteen unequivocal proteins were identified from these 24, whereas the remaining 10 matched more than one protein within a single 2-D gel feature. Several of the identified proteins were associated with the cytoskeleton and have previously been reported in axonal growth cones, suggesting that they may influence cell shape and motility within the advancing TEBs, in a similar fashion to migrating axons.     

Change in Mesoherbivore Browsing Is Mediated by Elephant and Hillslope Position

Elephant are considered major drivers of ecosystems, but their effects within small-scale landscape features and on other herbivores still remain unclear. Elephant impact on vegetation has been widely studied in areas where elephant have been present for many years. We therefore examined the combined effect of short-term elephant presence (< 4 years) and hillslope position on tree species assemblages, resource availability, browsing intensity and soil properties. Short-term elephant presence did not affect woody species assemblages, but did affect height distribution, with greater sapling densities in elephant access areas. Overall tree and stem densities were also not affected by elephant. By contrast, slope position affected woody species assemblages, but not height distributions and densities. Variation in species assemblages was statistically best explained by levels of total cations, Zinc, sand and clay. Although elephant and mesoherbivore browsing intensities were unaffected by slope position, we found lower mesoherbivore browsing intensity on crests with high elephant browsing intensity. Thus, elephant appear to indirectly facilitate the survival of saplings, via the displacement of mesoherbivores, providing a window of opportunity for saplings to grow into taller trees. In the short-term, effects of elephant can be minor and in the opposite direction of expectation. In addition, such behavioural displacement promotes recruitment of saplings into larger height classes. The interaction between slope position and elephant effect found here is in contrast with other studies, and illustrates the importance of examining ecosystem complexity as a function of variation in species presence and topography. The absence of a direct effect of elephant on vegetation, but the presence of an effect on mesoherbivore browsing, is relevant for conservation areas especially where both herbivore groups are actively managed.     

COGA phenotypes and linkages on chromosome 2

An initial linkage analysis of the alcoholism phenotype as defined by DSM-III-R criteria and alcoholism defined by DSM-IV criteria showed many, sometimes striking, inconsistencies. These inconsistencies are greatly reduced by making the definition of alcoholism more specific. We defined new phenotypes combining the alcoholism definitions and the latent variables, defining an individual as affected if that individual is alcoholic under one of the definitions (either DSM-III-R or DSM-IV), and indicated having a symptom defined by one of the latent variables. This was done for each of the two alcoholism definitions and five latent variables, selected from a canonical discriminant analyses indicating they formed significant groupings using the electrophysiological variables. We found that linkage analyses utilizing these latent variables were much more robust and consistent than the linkage results based on DSM-III-R or DSM-IV criteria for definition of alcoholism. We also performed linkage analyses on two first principal components derived phenotypes, one derived from the electrophysiological variables, and the other derived from the latent variables. A region on chromosome 2 at 250 cM was found to be linked to both of these derived phenotypes. Further examination of the SNPs in this region identified several haplotypes strongly associated with these derived phenotypes.     

Engineering Temperature‐Dependent Carrier Concentration in Bulk Composite Materials via Temperature‐Dependent Fermi Level Offset

Precise control of carrier concentration in both bulk and thin‐film materials is crucial for many solid‐state devices, including photovoltaic cells, superconductors, and high mobility transistors. For applications that span a wide temperature range (thermoelectric power generation being a prime example) the optimal carrier concentration varies as a function of temperature. This work presents a modified modulation doping method to engineer the temperature dependence of the carrier concentration by incorporating a nanosize secondary phase that controls the temperature‐dependent doping in the bulk matrix. This study demonstrates this technique by de‐doping the heavily defect‐doped degenerate semiconductor GeTe, thereby enhancing its average power factor by 100% at low temperatures, with no deterioration at high temperatures. This can be a general method to improve the average thermoelectric performance of many other materials.