Whole-body integration of gene expression and single-cell morphology

Animal bodies are composed of cell types with unique expression programs that implement their distinct locations, shapes, structures, and functions. Based on these properties, cell types assemble into specific tissues and organs. To systematically explore the link between cell-type-specific gene expression and morphology, we registered an expression atlas to a whole-body electron microscopy volume of the nereid Platynereis dumerilii. Automated segmentation of cells and nuclei identifies major cell classes and establishes a link between gene activation, chromatin topography, and nuclear size. Clustering of segmented cells according to gene expression reveals spatially coherent tissues. In the brain, genetically defined groups of neurons match ganglionic nuclei with coherent projections. Besides interneurons, we uncover sensory-neurosecretory cells in the nereid mushroom bodies, which thus qualify as sensory organs. They furthermore resemble the vertebrate telencephalon by molecular anatomy. We provide an integrated browser as a Fiji plugin for remote exploration of all available multimodal datasets

Serum methylarginines and spirometry-measured lung function in older adults

Rationale: Methylarginines are endogenous nitric oxide synthase inhibitors that have been implicated in animal models of lung disease but have not previously been examined for their association with spirometric measures of lung function in humans. Objectives: This study measured serum concentrations of asymmetric and symmetric dimethylarginine in a representative sample of older community-dwelling adults and determined their association with spirometric lung function measures. Methods: Data on clinical, lifestyle, and demographic characteristics, methylated arginines, and L-arginine (measured using LC-MS/MS) were collected from a population-based sample of older Australian adults from the Hunter Community Study. The five key lung function measures included as outcomes were Forced Expiratory Volume in 1 second, Forced Vital Capacity, Forced Expiratory Volume in 1 second to Forced Vital Capacity ratio, Percent Predicted Forced Expiratory Volume in 1 second, and Percent Predicted Forced Vital Capacity. Measurements and Main Results: In adjusted analyses there were statistically significant independent associations between a) higher asymmetric dimethylarginine, lower Forced Expiratory Volume in 1 second and lower Forced Vital Capacity; and b) lower L-arginine/asymmetric dimethylarginine ratio, lower Forced Expiratory Volume in 1 second, lower Percent Predicted Forced Expiratory Volume in 1 second and lower Percent Predicted Forced Vital Capacity. By contrast, no significant associations were observed between symmetric dimethylarginine and lung function. Conclusions: After adjusting for clinical, demographic, biochemical, and pharmacological confounders, higher serum asymmetric dimethylarginine was independently associated with a reduction in key measures of lung function. Further research is needed to determine if methylarginines predict the decline in lung function

The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation

N-3 PUFA Supplementation Triggers PPAR-α Activation and PPAR-α/NF-κB Interaction: Anti-Inflammatory Implications in Liver Ischemia-Reperfusion Injury

Dietary supplementation with the n-3 polyunsaturated fatty acids (n-3 PUFA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) to rats preconditions the liver against ischemia-reperfusion (IR) injury, with reduction of the enhanced nuclear factor-κB (NF-κB) functionality occurring in the early phase of IR injury, and recovery of IR-induced pro-inflammatory cytokine response. The aim of the present study was to test the hypothesis that liver preconditioning by n-3 PUFA is exerted through peroxisone proliferator-activated receptor α (PPAR-α) activation and interference with NF-κB activation. For this purpose we evaluated the formation of PPAR-α/NF-κBp65 complexes in relation to changes in PPAR-α activation, IκB-α phosphorylation and serum levels and expression of interleukin (IL)-1β and tumor necrosis factor (TNF)-α in a model of hepatic IR-injury (1 h of ischemia and 20 h of reperfusion) or sham laparotomy (controls) in male Sprague Dawley rats. Animals were previously supplemented for 7 days with encapsulated fish oil (General Nutrition Corp., Pittsburg, PA) or isovolumetric amounts of saline (controls). Normalization of IR-altered parameters of liver injury (serum transaminases and liver morphology) was achieved by dietary n-3 PUFA supplementation. EPA and DHA suppression of the early IR-induced NF-κB activation was paralleled by generation of PPAR-α/NF-κBp65 complexes, in concomitance with normalization of the IR-induced IκB-α phosphorylation. PPAR-α activation by n-3 PUFA was evidenced by enhancement in the expression of the PPAR-α-regulated Acyl-CoA oxidase (Acox) and Carnitine-Palmitoyl-CoA transferase I (CPT-I) genes. Consistent with these findings, normalization of IR-induced expression and serum levels of NF-κB-controlled cytokines IL-lβ and TNF-α was observed at 20 h of reperfusion. Taken together, these findings point to an antagonistic effect of PPAR-α on NF-κB-controlled transcription of pro-inflammatory mediators. This effect is associated with the formation of PPAR-α/NF-κBp65 complexes and enhanced cytosolic IκB-α stability, as major preconditioning mechanisms induced by n-3 PUFA supplementation against IR liver injury

A Single Sex Pheromone Receptor Determines Chemical Response Specificity of Sexual Behavior in the Silkmoth Bombyx mori

In insects and other animals, intraspecific communication between individuals of the opposite sex is mediated in part by chemical signals called sex pheromones. In most moth species, male moths rely heavily on species-specific sex pheromones emitted by female moths to identify and orient towards an appropriate mating partner among a large number of sympatric insect species. The silkmoth, Bombyx mori, utilizes the simplest possible pheromone system, in which a single pheromone component, (E, Z)-10,12-hexadecadienol (bombykol), is sufficient to elicit full sexual behavior. We have previously shown that the sex pheromone receptor BmOR1 mediates specific detection of bombykol in the antennae of male silkmoths. However, it is unclear whether the sex pheromone receptor is the minimally sufficient determination factor that triggers initiation of orientation behavior towards a potential mate. Using transgenic silkmoths expressing the sex pheromone receptor PxOR1 of the diamondback moth Plutella xylostella in BmOR1-expressing neurons, we show that the selectivity of the sex pheromone receptor determines the chemical response specificity of sexual behavior in the silkmoth. Bombykol receptor neurons expressing PxOR1 responded to its specific ligand, (Z)-11-hexadecenal (Z11-16:Ald), in a dose-dependent manner. Male moths expressing PxOR1 exhibited typical pheromone orientation behavior and copulation attempts in response to Z11-16:Ald and to females of P. xylostella. Transformation of the bombykol receptor neurons had no effect on their projections in the antennal lobe. These results indicate that activation of bombykol receptor neurons alone is sufficient to trigger full sexual behavior. Thus, a single gene defines behavioral selectivity in sex pheromone communication in the silkmoth. Our findings show that a single molecular determinant can not only function as a modulator of behavior but also as an all-or-nothing initiator of a complex species-specific behavioral sequence

The variable link between PNA and NAO in observations and in multi-century CGCM simulations

The link between the Pacific/North American pattern (PNA) and the North Atlantic Oscillation (NAO) is investigated in reanalysis data (NCEP, ERA40) and multi-century CGCM runs for present day climate using three versions of the ECHAM model. PNA and NAO patterns and indices are determined via rotated principal component analysis on monthly mean 500 hPa geopotential height fields using the varimax criteria. On average, the multi-century CGCM simulations show a significant anti-correlation between PNA and NAO. Further, multi-decadal periods with significantly enhanced (high anti-correlation, active phase) or weakened (low correlations, inactive phase) coupling are found in all CGCMs. In the simulated active phases, the storm track activity near Newfoundland has a stronger link with the PNA variability than during the inactive phases. On average, the reanalysis datasets show no significant anti-correlation between PNA and NAO indices, but during the sub-period 1973–1994 a significant anti-correlation is detected, suggesting that the present climate could correspond to an inactive period as detected in the CGCMs. An analysis of possible physical mechanisms suggests that the link between the patterns is established by the baroclinic waves forming the North Atlantic storm track. The geopotential height anomalies associated with negative PNA phases induce an increased advection of warm and moist air from the Gulf of Mexico and cold air from Canada. Both types of advection contribute to increase baroclinicity over eastern North America and also to increase the low level latent heat content of the warm air masses. Thus, growth conditions for eddies at the entrance of the North Atlantic storm track are enhanced. Considering the average temporal development during winter for the CGCM, results show an enhanced Newfoundland storm track maximum in the early winter for negative PNA, followed by a downstream enhancement of the Atlantic storm track in the subsequent months. In active (passive) phases, this seasonal development is enhanced (suppressed). As the storm track over the central and eastern Atlantic is closely related to the NAO variability, this development can be explained by the shift of the NAO index to more positive values

Small rock-slope failures conditioned by Holocene permafrost degradation:a new approach and conceptual model based on Schmidt-hammer exposure-age dating, Jotunheimen, southern Norway

Rock-slope failures (RSFs) constitute significant natural hazards but the geophysical processes which control their timing are poorly understood. However, robust chronologies can provide valuable information on the environmental controls on RSF occurrence: information which can inform models of RSF activity in response to climatic forcing. This paper uses Schmidt-hammer exposure-age dating (SHD) of boulder deposits to construct a detailed regional Holocene chronology of the frequency and magnitude of small rock-slope failures (SRSFs) in Jotunheimen, Norway. By focusing on the depositional fans of SRSFs (≤ 103 m3), rather than on the corresponding features of massive RSFs (~108 m3), 92 single-event RSFs are targeted for chronology building. A weighted SHD age-frequency distribution and probability density function analysis indicate four centennial- to millennial-scale periods of enhanced SRSF frequency, with a dominant mode at ~4.5 ka. Using change detection and discreet Meyer wavelet analysis, in combination with existing permafrost depth models, we propose that enhanced SRSF activity was primarily controlled by permafrost degradation. Long-term relative change in permafrost depth provides a compelling explanation for the high-magnitude departures from the SRSF background rate and accounts for (i1) the timing of peak SRSF frequency, (2ii) the significant lag (~2.2 ka) between the Holocene Thermal Maximum and the SRSF frequency peak, and (3iii) the marked decline in frequency in the late-Holocene. This interpretation is supported by geomorphological evidence, as the spatial distribution of SRSFs is strongly correlated with the aspect-dependent lower altitudinal limit of mountain permafrost in cliff faces. Results are indicative of a causal relationship between episodes of relatively warm climate, permafrost degradation and the transition to a seasonal-freezing climatic regime. This study highlights permafrost degradation as a conditioning factor for cliff collapse, and hence the importance of paraperiglacial processes; a result with implications for slope instability in glacial and periglacial environments under global warming scenarios