A human cell surface receptor activated by free fatty acids and thiazolidinedione drugs

Fatty acids, which are essential nutritional components, are also involved in cardiovascular and metabolic diseases. Here we report a human cell surface receptor that we name free fatty acid receptor (FFAR), because it is specifically activated by medium to long-chain free fatty acids. The receptor belongs to the class of seven-transmembrane, G-protein coupled receptors (GPCRs) and also mediates responses to antidiabetic drugs of the thiazolidinedione type. It is expressed in skeletal muscle, heart, liver, and pancreatic beta-cells. Stimulation of FFAR increases the intracellular calcium concentration in cells expressing the receptor in a native (pancreatic beta-cell line) or in a recombinant form. In view of the nature of the activating substances, their physiological role in the body, and the tissue distribution of FFAR we suggest the term "nutrient sensing receptor" for receptors acting at the interface between dietary components and signalling molecules.     

Directional Migration of Recirculating Lymphocytes through Lymph Nodes via Random Walks

Naive T lymphocytes exhibit extensive antigen-independent recirculation between blood and lymph nodes, where they may encounter dendritic cells carrying cognate antigen. We examine how long different T cells may spend in an individual lymph node by examining data from long term cannulation of blood and efferent lymphatics of a single lymph node in the sheep. We determine empirically the distribution of transit times of migrating T cells by applying the Least Absolute Shrinkage & Selection Operator () or regularised to fit experimental data describing the proportion of labelled infused cells in blood and efferent lymphatics over time. The optimal inferred solution reveals a distribution with high variance and strong skew. The mode transit time is typically between 10 and 20 hours, but a significant number of cells spend more than 70 hours before exiting. We complement the empirical machine learning based approach by modelling lymphocyte passage through the lymph node . On the basis of previous two photon analysis of lymphocyte movement, we optimised distributions which describe the transit times (first passage times) of discrete one dimensional and continuous (Brownian) three dimensional random walks with drift. The optimal fit is obtained when drift is small, i.e. the ratio of probabilities of migrating forward and backward within the node is close to one. These distributions are qualitatively similar to the inferred empirical distribution, with high variance and strong skew. In contrast, an optimised normal distribution of transit times (symmetrical around mean) fitted the data poorly. The results demonstrate that the rapid recirculation of lymphocytes observed at a macro level is compatible with predominantly randomised movement within lymph nodes, and significant probabilities of long transit times. We discuss how this pattern of migration may contribute to facilitating interactions between low frequency T cells and antigen presenting cells carrying cognate antigen.     

Potential impact of process parameters upon the bacterial diversity in the mesophilic anaerobic digestion of beet silage

The impact of the process parameters hydraulic retention time (HRT), organic loading rate (OLR) and substrate upon bacterial diversity was analyzed. Therefore, a controlled anaerobic fermentation (1755 days) of beet silage, only initially inoculated with manure, was monitored by the amplified “ribosomal DNA” restriction analysis. More than 85% of detected operational taxonomic units (OTUs) could not be assigned to described Bacteria. In contrast to studies analyzing the digestion of energy crops in the presence of manure, Chloroflexi were detected, whereas Clostridia and Chloroflexi were identified as persistent groups. Both groups are known as potential hydrogen producers or users. Species distribution patterns for Firmicutes, Bacteroidetes, Synergistetes and Thermotogae were not clearly linked to process parameters. The presence of Planctomycetes, Actinobacteria and Alcaligenaceae was related to long HRTs and short OLRs, while Acidobacteria were governed by short HRTs and high OLRs, respectively. The impact of substrate variations on diversity was minute.     

Genomics of natural bird populations: a gene-based set of reference markers evenly spread across the avian genome

Although there is growing interest to take genomics into the complex realms of natural populations, there is a general shortage of genomic resources and tools available for wild species. This applies not at least to birds, for which genomic approaches should be helpful to questions such as adaptation, speciation and population genetics. In this study, we describe a genome-wide reference set of conserved avian gene markers, broadly applicable across birds. By aligning protein-coding sequences from the recently assembled chicken genome with orthologous sequences in zebra finch, we identified particularly conserved exonic regions flanking introns of suitable size for subsequent amplification and sequencing. Primers were designed for 242 gene markers evenly distributed across the chicken genome, with a mean inter-marker interval of 4.2 Mb. Between 78% and 93% of the markers amplified a specific product in five species tested (chicken, peregrine falcon, collared flycatcher, great reed warbler and blue tit). Two hundred markers were sequenced in collared flycatcher, yielding a total of 122.41 kb of genomic DNA sequence (12096 bp coding sequence and 110 314 bp noncoding). Intron size of collared flycatcher and chicken was highly correlated, as was GC content. A polymorphism screening using these markers in a panel of 10 unrelated collared flycatchers identified 871 single nucleotide polymorphisms (pi = 0.0029) and 33 indels (mainly very short). Avian genome characteristics such as uniform genome size and low rate of syntenic rearrangements suggest that this marker set will find broad utility as a genome-wide reference resource for molecular ecological and population genomic analysis of birds. We envision that it will be particularly useful for obtaining large-scale orthologous targets in different species--important in, for instance, phylogenetics--and for large-scale identification of evenly distributed single nucleotide polymorphisms needed in linkage mapping or in studies of gene flow and hybridization.     

Reconstruction of gross avian genome structure,organization and evolution suggests that the chicken lineage most closely resembles the dinosaur avian ancestor

Background

The availability of multiple avian genome sequence assemblies greatly improves our ability to define overall genome organization and reconstruct evolutionary changes. In birds, this has previously been impeded by a near intractable karyotype and relied almost exclusively on comparative molecular cytogenetics of only the largest chromosomes. Here, novel whole genome sequence information from 21 avian genome sequences (most newly assembled) made available on an interactive browser (Evolution Highway) was analyzed.

Results

Focusing on the six best-assembled genomes allowed us to assemble a putative karyotype of the dinosaur ancestor for each chromosome. Reconstructing evolutionary events that led to each species’ genome organization, we determined that the fastest rate of change occurred in the zebra finch and budgerigar, consistent with rapid speciation events in the Passeriformes and Psittaciformes. Intra- and interchromosomal changes were explained most parsimoniously by a series of inversions and translocations respectively, with breakpoint reuse being commonplace. Analyzing chicken and zebra finch, we found little evidence to support the hypothesis of an association of evolutionary breakpoint regions with recombination hotspots but some evidence to support the hypothesis that microchromosomes largely represent conserved blocks of synteny in the majority of the 21 species analyzed. All but one species showed the expected number of microchromosomal rearrangements predicted by the haploid chromosome count. Ostrich, however, appeared to retain an overall karyotype structure of 2n = 80 despite undergoing a large number (26) of hitherto un-described interchromosomal changes.

Conclusions

Results suggest that mechanisms exist to preserve a static overall avian karyotype/genomic structure, including the microchromosomes, with widespread interchromosomal change occurring rarely (e.g., in ostrich and budgerigar lineages). Of the species analyzed, the chicken lineage appeared to have undergone the fewest changes compared to the dinosaur ancestor.

Electronic supplementary material

The online version of this article (doi:10.1186/1471-2164-15-1060) contains supplementary material, which is available to authorized users.     

Disentangling the roles of history and local selection in shaping clinal variation of allele frequencies and gene expression in Norway spruce (Picea abies)

Understanding the genetic basis of local adaptation is challenging due to the subtle balance among conflicting evolutionary forces that are involved in its establishment and maintenance. One system with which to tease apart these difficulties is clines in adaptive characters. Here we analyzed genetic and phenotypic variation in bud set, a highly heritable and adaptive trait, among 18 populations of Norway spruce (Picea abies), arrayed along a latitudinal gradient ranging from 47°N to 68°N. We confirmed that variation in bud set is strongly clinal, using a subset of five populations. Genotypes for 137 single-nucleotide polymorphisms (SNPs) chosen from 18 candidate genes putatively affecting bud set and 308 control SNPs chosen from 264 random genes were analyzed for patterns of genetic structure and correlation to environment. Population genetic structure was low (F(ST) = 0.05), but latitudinal patterns were apparent among Scandinavian populations. Hence, part of the observed clinal variation should be attributable to population demography. Conditional on patterns of genetic structure, there was enrichment of SNPs within candidate genes for correlations with latitude. Twenty-nine SNPs were also outliers with respect to F(ST). The enrichment for clinal variation at SNPs within candidate genes (i.e., SNPs in PaGI, PaPhyP, PaPhyN, PaPRR7, and PaFTL2) indicated that local selection in the 18 populations, and/or selection in the ancestral populations from which they were recently derived, shaped the observed cline. Validation of these genes using expression studies also revealed that PaFTL2 expression is significantly associated with latitude, thereby confirming the central role played by this gene in the control of phenology in plants.     

Timing of spring migration in birds: long-term trends, North Atlantic Oscillation and the significance of different migration routes

We studied long-term trends and the yearly variation in mean spring passage time in 36 passerine bird species trapped at Ottenby Bird Observatory in south-eastern Sweden. Between the years 1952–2002, data were available for 22–45 years depending on species. Most long-distance migrant species passed progressively earlier over the study period (range: 2.5 days earlier to 0.7 days later per 10 years, with an average of 0.9 days earlier per 10 years). The annual variation in timing of migration in most species, regardless of migration distance, correlated negatively with the winter index of the North Atlantic Oscillation (NAO), a large-scale climate phenomenon influencing the climate in the North Atlantic region. Birds passed earlier after mild and humid winters, corresponding to the high phase of the NAO. This corroborates the pattern found at a nearby migration site with a comparable dataset (Helgoland, 600 km WSW of Ottenby). However, short/medium-distance migrant species at Ottenby, in contrast to the situation at Helgoland, have shown no general trend of earlier passage in recent years. This was probably a consequence of the shorter study period at Ottenby, which included only the last 22–32 years (41 years at Helgoland), when the NAO showed no significant trend. At the species-specific level, the long-term trends in passage time were similar at the two sites, and there was some congruence to the extent that a given species was affected by NAO. Long-distance migrants wintering south and south-east of the breeding grounds showed some of the strongest changes in long-term trends (passing progressively earlier) at Ottenby, and for some of these species passage time varied negatively with NAO. Obviously, and contrary to previous suggestions, variations in NAO also influence birds migrating through eastern Europe, although the direct or indirect mechanisms through which this is achieved are unknown.