New and Exciting in PLoS ONE

There are 24 new articles in PLoS ONE today. As always, you should rate the articles, post notes and comments and send trackbacks when you blog about the papers. You can now also easily place articles on various social services (CiteULike, Connotea, Stumbleupon, Facebook and Digg) with just one click. Here are my own picks for the week - you go and look for your own favourites:

Regulation of Clock-Controlled Genes in Mammals:

The complexity of tissue- and day time-specific regulation of thousands of clock-controlled genes (CCGs) suggests that many regulatory mechanisms contribute to the transcriptional output of the circadian clock. We aim to predict these mechanisms using a large scale promoter analysis of CCGs. Our study is based on a meta-analysis of DNA-array data from rodent tissues. We searched in the promoter regions of 2065 CCGs for highly overrepresented transcription factor binding sites. In order to compensate the relatively high GC-content of CCG promoters, a novel background model to avoid a bias towards GC-rich motifs was employed. We found that many of the transcription factors with overrepresented binding sites in CCG promoters exhibit themselves circadian rhythms. Among the predicted factors are known regulators such as CLOCK:BMAL1, DBP, HLF, E4BP4, CREB, RORα and the recently described regulators HSF1, STAT3, SP1 and HNF-4α. As additional promising candidates of circadian transcriptional regulators PAX-4, C/EBP, EVI-1, IRF, E2F, AP-1, HIF-1 and NF-Y were identified. Moreover, GC-rich motifs (SP1, EGR, ZF5, AP-2, WT1, NRF-1) and AT-rich motifs (MEF-2, HMGIY, HNF-1, OCT-1) are significantly overrepresented in promoter regions of CCGs. Putative tissue-specific binding sites such as HNF-3 for liver, NKX2.5 for heart or Myogenin for skeletal muscle were found. The regulation of the erythropoietin (Epo) gene was analysed, which exhibits many binding sites for circadian regulators. We provide experimental evidence for its circadian regulated expression in the adult murine kidney. Basing on a comprehensive literature search we integrate our predictions into a regulatory network of core clock and clock-controlled genes. Our large scale analysis of the CCG promoters reveals the complexity and extensiveness of the circadian regulation in mammals. Results of this study point to connections of the circadian clock to other functional systems including metabolism, endocrine regulation and pharmacokinetics.

Learning of Arbitrary Association between Visual and Auditory Novel Stimuli in Adults: The "Bond Effect" of Haptic Exploration:

It is well-known that human beings are able to associate stimuli (novel or not) perceived in their environment. For example, this ability is used by children in reading acquisition when arbitrary associations between visual and auditory stimuli must be learned. The studies tend to consider it as an "implicit" process triggered by the learning of letter/sound correspondences. The study described in this paper examined whether the addition of the visuo-haptic exploration would help adults to learn more effectively the arbitrary association between visual and auditory novel stimuli. Adults were asked to learn 15 new arbitrary associations between visual stimuli and their corresponding sounds using two learning methods which differed according to the perceptual modalities involved in the exploration of the visual stimuli. Adults used their visual modality in the "classic" learning method and both their visual and haptic modalities in the "multisensory" learning one. After both learning methods, participants showed a similar above-chance ability to recognize the visual and auditory stimuli and the audio-visual associations. However, the ability to recognize the visual-auditory associations was better after the multisensory method than after the classic one. This study revealed that adults learned more efficiently the arbitrary association between visual and auditory novel stimuli when the visual stimuli were explored with both vision and touch. The results are discussed from the perspective of how they relate to the functional differences of the manual haptic modality and the hypothesis of a "haptic bond" between visual and auditory stimuli.

Association and Haplotype Analyses of Positional Candidate Genes in Five Genomic Regions Linked to Scrotal Hernia in Commercial Pig Lines:

Scrotal hernia in pigs is a complex trait likely affected by genetic and environmental factors. A large-scale association analysis of positional and functional candidate genes was conducted in four previously identified genomic regions linked to hernia susceptibility on Sus scrofa chromosomes 2 and 12, as well as the fifth region around 67 cM on chromosome 2, respectively. In total, 151 out of 416 SNPs discovered were genotyped successfully. Using a family-based analysis we found that four regions surrounding ELF5, KIF18A, COL23A1 on chromosome 2, and NPTX1 on chromosome 12, respectively, may contain the genetic variants important for the development of the scrotal hernia in pigs. These findings were replicated in another case-control dataset. The SNPs around the ELF5 region were in high linkage disequilibrium with each other, and a haplotype containing SNPs from ELF5 and CAT was highly significantly associated with hernia development. Extensive re-sequencing work focused on the KIF18A gene did not detect any further SNPs with extensive association signals. These genes may be involved in the estrogen receptor signaling pathway (KIF18A and NPTX1), the epithelial-mesenchymal transition (ELF5) and the collagen metabolism pathway (COL23A1), which are associated with the important molecular characteristics of hernia pathophysiology. Further investigation on the molecular mechanisms of these genes may provide more molecular clues on hernia development in pigs.