Polymorphisms in the glucocorticoid receptor gene that modulate glucocorticoid sensitivity are associated with rheumatoid arthritis

Introduction  

The glucocorticoid receptor (GR) plays an important regulatory role in the immune system. Four polymorphisms in the GR gene are associated with differences in glucocorticoid (GC) sensitivity; the minor alleles of the polymorphisms N363 S and BclI are associated with relative hypersensitivity to GCs, while those of the polymorphisms ER22/23EK and 9β are associated with relative GC resistance. Because differences in GC sensitivity may influence immune effector functions, we examined whether these polymorphisms are associated with the susceptibility to develop Rheumatoid Arthritis (RA) and RA disease severity.     

The prognostic value of baseline erosions in undifferentiated arthritis

Introduction  

Undifferentiated arthritis (UA) has a variable disease course; 40 to 50% of UA patients remit spontaneously, while 30% develop rheumatoid arthritis (RA). Identifying the UA patients who will develop RA is essential to initiate early disease-modifying anti-rheumatic drug (DMARD) therapy. Although the presence of bone erosions at baseline is predictive for a severe destructive disease course in RA, the prognostic importance of erosive joints for disease outcome in UA is unknown. This study evaluates the predictive value of erosive joints for the disease outcome in UA as measured by RA development and disease persistency.     

The composition and origins of genomic variation among individuals of the soybean reference cultivar Williams 82

Soybean (Glycine max) is a self-pollinating species that has relatively low nucleotide polymorphism rates compared with other crop species. Despite the low rate of nucleotide polymorphisms, a wide range of heritable phenotypic variation exists. There is even evidence for heritable phenotypic variation among individuals within some cultivars. Williams 82, the soybean cultivar used to produce the reference genome sequence, was derived from backcrossing a Phytophthora root rot resistance locus from the donor parent Kingwa into the recurrent parent Williams. To explore the genetic basis of intracultivar variation, we investigated the nucleotide, structural, and gene content variation of different Williams 82 individuals. Williams 82 individuals exhibited variation in the number and size of introgressed Kingwa loci. In these regions of genomic heterogeneity, the reference Williams 82 genome sequence consists of a mosaic of Williams and Kingwa haplotypes. Genomic structural variation between Williams and Kingwa was maintained between the Williams 82 individuals within the regions of heterogeneity. Additionally, the regions of heterogeneity exhibited gene content differences between Williams 82 individuals. These findings show that genetic heterogeneity in Williams 82 primarily originated from the differential segregation of polymorphic chromosomal regions following the backcross and single-seed descent generations of the breeding process. We conclude that soybean haplotypes can possess a high rate of structural and gene content variation, and the impact of intracultivar genetic heterogeneity may be significant. This detailed characterization will be useful for interpreting soybean genomic data sets and highlights important considerations for research communities that are developing or utilizing a reference genome sequence.     

Generating social network data using partially described networks: an example informing avian influenza control in the British poultry industry

Background

The United Kingdom (UK) government has been recording the births, deaths, and movements of cattle for the last decade. Despite reservations about the accuracy of these data, they represent a large and valuable body of information about the demographics of the UK cattle herd and its contact structure. In this article, a range of demographic data about UK cattle, and particularly their movements, are presented, as well as yearly trends in the patterns of movements.

Results

A clear seasonal pattern is evident in the number of movements of cattle, as are the reductions in movement volume due to foot and mouth disease outbreaks in 2001 and 2007. The distribution of ages of cattle at their time of death is multimodal, and the impact of the over thirty months rule is marked. Most movements occur between agricultural holdings, markets, and slaughterhouses, and there is a non-random pattern to the types of holdings movements occur between. Most animals move only a short distance and a few times in their life. Most movements between any given pair of holdings only occurred once in the last 10 years, but about a third occurred between 2 and 10 times in that period. There is no clear trend to movement patterns in the UK since 2002.

Conclusions

Despite a substantial number of regulatory interventions during the last decade, movement patterns show no clear trend since 2002. The observed patterns in the repeatability of movements, the types of holdings involved in movements, the distances and frequencies of cattle movements, and the batch sizes involved give an insight into the structure of the UK cattle industry, and could act as the basis for a predictive model of livestock movements in the UK.     

Impact of Elevated Plasma Serotonin on Global Gene Expression of Murine Megakaryocytes

Background

Serotonin (5-HT) is a biogenic amine that also acts as a mitogen and a developmental signal early in rodent embryogenesis. Genetic and pharmacological disruption of 5-HT signaling causes various diseases and disorders via mediating central nervous system, cardiovascular system, and serious abnormalities on a growing embryo. Today, neither the effective modulators on 5-HT signaling pathways nor the genes affected by 5-HT signal are well known yet.

Methodology/Principal Findings

In an attempt to identify the genes altered by 5-HT signaling pathways, we analyzed the global gene expression via the Illumina array platform using the mouse WG-6 v2.0 Expression BeadChip containing 45,281 probe sets representing 30,854 genes in megakaryocytes isolated from mice infused with 5-HT or saline. We identified 723 differentially expressed genes of which 706 were induced and 17 were repressed by elevated plasma 5-HT.

Conclusions/Significance

Hierarchical gene clustering analysis was utilized to represent relations between groups and clusters. Using gene ontology mining tools and canonical pathway analyses, we identified multiple biological pathways that are regulated by 5-HT: (i) cytoskeletal remodeling, (ii) G-protein signaling, (iii) vesicular transport, and (iv) apoptosis and survival. Our data encompass the first extensive genome-wide based profiling in the progenitors of platelets in response to 5-HT elevation in vivo.     

The development of tag-based cooperation via a socially acquired trait

Recent theoretical models have demonstrated that phenotypic traits can support the non-random assortment of cooperators in a population, thereby permitting the evolution of cooperation. In these “tag-based models”, cooperators modulate cooperation according to an observable and hard-to-fake trait displayed by potential interaction partners. Socially acquired vocalizations in general, and speech accent among humans in particular, are frequently proposed as hard to fake and hard to hide traits that display sufficient cross-populational variability to reliably guide such social assortment in fission–fusion societies. Adults’ sensitivity to accent variation in social evaluation and decisions about cooperation is well-established in sociolinguistic research. The evolutionary and developmental origins of these biases are largely unknown, however. Here, we investigate the influence of speech accent on 5–10-year-old children's developing social and cooperative preferences across four Brazilian Amazonian towns. Two sites have a single dominant accent, and two sites have multiple co-existing accent varieties. We found that children's friendship and resource allocation preferences were guided by accent only in sites characterized by accent heterogeneity. Results further suggest that this may be due to a more sensitively tuned ear for accent variation. The demonstrated local-accent preference did not hold in the face of personal cost. Results suggest that mechanisms guiding tag-based assortment are likely tuned according to locally relevant tag-variation.     

Apoptosis induced by the fungal pathogen gliotoxin requires a triple phosphorylation of Bim by JNK

We previously reported that gliotoxin (GT), the major virulence factor of the mold Aspergillus fumigatus causing invasive aspergillosis (IA) in immunocompromised patients, induces apoptosis in a Bak-dependent manner. The signaling pathway leading to Bak activation and subsequent mitochondrial outer membrane permeabilization (MOMP) is elusive. Here, we show that GT and the supernatant of A. fumigatus (but not its GT-defective mutant) activate the JNK pathway and require a co-operative JNK-mediated Bim_EL phosphorylation at three sites (S100, T112 and S114) to induce apoptosis in mouse fibroblasts, human bronchial and mouse alveolar epithelial cells. Cells (i) treated with the JNK inhibitor SP600125, (ii) deleted or knocked down for JNK1/2 or Bim or (iii) carrying the Bim_EL triple phosphomutant S100A/T112A/S114A instead of wild-type Bim_EL are similarly resistant to GT-induced apoptosis. Triple-phosphorylated Bim_EL is more stable, redistributes from a cytoskeletal to a membrane fraction, better interacts with Bcl-2 and Bcl-x_L and more effectively activates Bak than the unphosphorylated mutant. These data indicate that JNK-mediated Bim_EL phosphorylation at S100, T112 and S114 constitutes a novel regulatory mechanism to activate Bim in response to apoptotic stimuli.     

Phylogenetic relationships within the aplocheiloid fish genus Rivulus (Cyprinodontiformes, Rivulidae): implications for Caribbean and Central American biogeography

We examined the phylogenetic relationships of 16 northern species of the aplocheiloid genus Rivulus inhabiting the Caribbean, Central America, and South America. A total of 714 base pairs per taxon were sequenced from two segments of the mitochondrial genome, 12S rRNA and cytochrome b. Both parsimony and neighbor-joining analyses suggest an ancient vicariant origin of the Greater Antillean taxa, in addition to a quite recent dispersal of species into the Lesser Antilles from the South American mainland. Combined analyses support the monophyly of the northern South American assemblage as the sister group of a Central American/Columbian biota. However, the monophyly of the Central American biota remains uncertain. Divergence estimates for the Central American taxa are calibrated from the Last Cretaceous separation of the proto-Antilles from the Americas. These data suggest that the extant Central American taxa represent the descendants of at least two separate invasions during the Cenozoic, prior to the closing of the Panamanian isthmus. Times are consistent with the extensive evidence for reptilian and mammalian exchange throughout the Cenozoic.      

Modeling residue usage in aligned protein sequences via maximum likelihood

A computational method is presented for characterizing residue usage, i.e., site-specific residue frequencies, in aligned protein sequences. The method obtains frequency estimates that maximize the likelihood of the sequences in a simple model for sequence evolution, given a tree or a set of candidate trees computed by other methods. These maximum- likelihood frequencies constitute a profile of the sequences, and thus the method offers a rigorous alternative to sequence weighting for constructing such a profile. The ability of this method to discard misleading phylogenetic effects allows the biochemical propensities of different positions in a sequence to be more clearly observed and interpreted.      

Why developmental psychology is incomplete without comparative and cross-cultural perspectives

As a discipline, developmental psychology has a long history of relying on animal models and data collected among distinct cultural groups to enrich and inform theories of the ways social and cognitive processes unfold through the lifespan. However, approaches that draw together developmental, cross-cultural and comparative perspectives remain rare. The need for such an approach is reflected in the papers by Heyes (2015 Phil. Trans. R. Soc. B 371, 20150069. (doi:10.1098/rstb.2015.0069)), Schmelz & Call (2015 Phil. Trans. R. Soc. B 371, 20150067. (doi:10.1098/rstb.2015.0067)) and Keller (2015 Phil. Trans. R. Soc. B 371, 20150070. (doi:10.1098/rstb.2015.0070)) in this theme issue. Here, we incorporate these papers into a review of recent research endeavours covering a range of core aspects of social cognition, including social learning, cooperation and collaboration, prosociality, and theory of mind. In so doing, we aim to highlight how input from comparative and cross-cultural empiricism has altered our perspectives of human development and, in particular, led to a deeper understanding of the evolution of the human cultural mind.