Multiple apical plasma membrane constituents are associated with susceptibility to meconium ileus in individuals with cystic fibrosis

Variants associated with meconium ileus in cystic fibrosis were identified in 3,763 affected individuals by genome-wide association study (GWAS). Five SNPs at two loci near SLC6A14 at Xq23-24 (minimum P = 1.28 × 10(-12) at rs3788766) and SLC26A9 at 1q32.1 (minimum P = 9.88 × 10(-9) at rs4077468) accounted for ~5% of phenotypic variability and were replicated in an independent sample of affected individuals (n = 2,372; P = 0.001 and 0.0001, respectively). By incorporating the knowledge that disease-causing mutations in CFTR alter electrolyte and fluid flux across surface epithelium into a hypothesis-driven GWAS (GWAS-HD), we identified associations with the same SNPs in SLC6A14 and SLC26A9 and established evidence for the involvement of SNPs in a third solute carrier gene, SLC9A3. In addition, GWAS-HD provided evidence of association between meconium ileus and multiple genes encoding constituents of the apical plasma membrane where CFTR resides (P = 0.0002; testing of 155 apical membrane genes jointly and in replication, P = 0.022). These findings suggest that modulating activities of apical membrane constituents could complement current therapeutic paradigms for cystic fibrosis.     

Description,molecular phylogeny,and natural history of a new kleptoparasitic species of gelechiid moth (Lepidoptera) associated with Melastomataceae galls in Brazil

The male, female, pupa and larva of a new species of Gelechiidae (Lepidoptera), Locharcha opportuna Moreira and Becker, are described and illustrated with the aid of optical and scanning electron microscopy. A preliminary analysis of mitochondrial DNA sequences including members of related lineages is also provided. The immature stages are associated with galls induced by a species of Palaeomystella Fletcher (Lepidoptera: Momphidae) on Tibouchina sellowiana (Cham.) Cogn. (Melastomataceae), endemic to the Atlantic Rainforest. Larvae are kleptoparasitic, usurping the gall internal space and thereafter feeding on the internal tissues. By determining the variation in population density of both species and following gall development individually throughout ontogeny under field conditions, we demonstrated that the kleptoparasite completes its life cycle inside galls induced by Palaeomystella, where pupation occurs. The variation in seasonal abundance of the kleptoparasite is tied to that of the cecidogenous species, with their corresponding peaks in density occurring sequentially.

http://zoobank.org/urn:lsid:zoobank.org:pub:525F6D52-8CE1-47D1-A0D9-78B564DF5565     

Bayesian Forecasting for Time Series of Categorical Data

Time series of categorical data is not a widely studied research topic. Particularly, there is no available work on the Bayesian analysis of categorical time series processes. With the objective of filling that gap, in the present paper we consider the problem of Bayesian analysis including Bayesian forecasting for time series of categorical data, which is modelled by Pegram's mixing operator, applicable for both ordinal and nominal data structures. In particular, we consider Pegram's operator‐based autoregressive process for the analysis. Real datasets on infant sleep status are analysed for illustrations. We also illustrate that the Bayesian forecasting is more accurate than the corresponding frequentist's approach when we intend to forecast a large time gap ahead. Copyright © 2016 John Wiley & Sons, Ltd.     

A new class of anthelmintics effective against drug-resistant nematodes

Anthelmintic resistance in human and animal pathogenic helminths has been spreading in prevalence and severity to a point where multidrug resistance against the three major classes of anthelmintics--the benzimidazoles, imidazothiazoles and macrocyclic lactones--has become a global phenomenon in gastrointestinal nematodes of farm animals. Hence, there is an urgent need for an anthelmintic with a new mode of action. Here we report the discovery of the amino-acetonitrile derivatives (AADs) as a new chemical class of synthetic anthelmintics and describe the development of drug candidates that are efficacious against various species of livestock-pathogenic nematodes. These drug candidates seem to have a novel mode of action involving a unique, nematode-specific clade of acetylcholine receptor subunits. The AADs are well tolerated and of low toxicity to mammals, and overcome existing resistances to the currently available anthelmintics.     

Translational control of intron splicing in eukaryotes

Most eukaryotic genes are interrupted by non-coding introns that must be accurately removed from pre-messenger RNAs to produce translatable mRNAs. Splicing is guided locally by short conserved sequences, but genes typically contain many potential splice sites, and the mechanisms specifying the correct sites remain poorly understood. In most organisms, short introns recognized by the intron definition mechanism cannot be efficiently predicted solely on the basis of sequence motifs. In multicellular eukaryotes, long introns are recognized through exon definition and most genes produce multiple mRNA variants through alternative splicing. The nonsense-mediated mRNA decay (NMD) pathway may further shape the observed sets of variants by selectively degrading those containing premature termination codons, which are frequently produced in mammals. Here we show that the tiny introns of the ciliate Paramecium tetraurelia are under strong selective pressure to cause premature termination of mRNA translation in the event of intron retention, and that the same bias is observed among the short introns of plants, fungi and animals. By knocking down the two P. tetraurelia genes encoding UPF1, a protein that is crucial in NMD, we show that the intrinsic efficiency of splicing varies widely among introns and that NMD activity can significantly reduce the fraction of unspliced mRNAs. The results suggest that, independently of alternative splicing, species with large intron numbers universally rely on NMD to compensate for suboptimal splicing efficiency and accuracy.