New and Exciting in PLoS ONE

There are 30 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, Mendeley, 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:

Performance of Humans vs. Exploration Algorithms on the Tower of London Test:

The Tower of London Test (TOL) used to assess executive functions was inspired in Artificial Intelligence tasks used to test problem-solving algorithms. In this study, we compare the performance of humans and of exploration algorithms. Instead of absolute execution times, we focus on how the execution time varies with the tasks and/or the number of moves. This approach used in Algorithmic Complexity provides a fair comparison between humans and computers, although humans are several orders of magnitude slower. On easy tasks (1 to 5 moves), healthy elderly persons performed like exploration algorithms using bounded memory resources, i.e., the execution time grew exponentially with the number of moves. This result was replicated with a group of healthy young participants. However, for difficult tasks (5 to 8 moves) the execution time of young participants did not increase significantly, whereas for exploration algorithms, the execution time keeps on increasing exponentially. A pre-and post-test control task showed a 25% improvement of visuo-motor skills but this was insufficient to explain this result. The findings suggest that naive participants used systematic exploration to solve the problem but under the effect of practice, they developed markedly more efficient strategies using the information acquired during the test.

Negative Feedback Governs Gonadotrope Frequency-Decoding of Gonadotropin Releasing Hormone Pulse-Frequency:

The synthesis of the gonadotropin subunits is directed by pulsatile gonadotropin-releasing hormone (GnRH) from the hypothalamus, with the frequency of GnRH pulses governing the differential expression of the common α-subunit, luteinizing hormone β-subunit (LHβ) and follicle-stimulating hormone β-subunit (FSHβ). Three mitogen-activated protein kinases, (MAPKs), ERK1/2, JNK and p38, contribute uniquely and combinatorially to the expression of each of these subunit genes. In this study, using both experimental and computational methods, we found that dual specificity phosphatase regulation of the activity of the three MAPKs through negative feedback is required, and forms the basis for decoding the frequency of pulsatile GnRH. A fourth MAPK, ERK5, was shown also to be activated by GnRH. ERK5 was found to stimulate FSHβ promoter activity and to increase FSHβ mRNA levels, as well as enhancing its preference for low GnRH pulse frequencies. The latter is achieved through boosting the ultrasensitive behavior of FSHβ gene expression by increasing the number of MAPK dependencies, and through modulating the feedforward effects of JNK activation on the GnRH receptor (GnRH-R). Our findings contribute to understanding the role of changing GnRH pulse-frequency in controlling transcription of the pituitary gonadotropins, which comprises a crucial aspect in regulating reproduction. Pulsatile stimuli and oscillating signals are integral to many biological processes, and elucidation of the mechanisms through which the pulsatility is decoded explains how the same stimulant can lead to various outcomes in a single cell.

The Genome of the Stick Insect Medauroidea extradentata Is Strongly Methylated within Genes and Repetitive DNA:

Cytosine DNA methylation has been detected in many eukaryotic organisms and has been shown to play an important role in development and disease of vertebrates including humans. Molecularly, DNA methylation appears to be involved in the suppression of initiation or of elongation of transcription. Resulting organismal functions are suggested to be the regulation of gene silencing, the suppression of transposon activity and the suppression of initiation of transcription within genes. However, some data concerning the distribution of methylcytosine in insect species appear to contradict such roles. By comparison of MspI and HpaII restriction patterns in genomic DNA of several insects we show that stick insects (Phasmatodea) have highly methylated genomes. We isolated methylated DNA fragments from the Vietnamese Walking Stick Medauroidea extradentata (formerly known as Baculum extradentatum) and demonstrated that most of the corresponding sequences are repetitive. Bisulfite sequencing of one of these fragments and of parts of conserved protein-coding genes revealed a methylcytosine content of 12.6%, mostly found at CpG, but also at CpT and CpA dinucleotides. Corresponding depletions of CpG and enrichments of TpG and CpA dinucleotides in some highly conserved protein-coding genes of Medauroidea reach a similar degree as in vertebrates and show that CpG methylation has occurred in the germline of these insects. Using four different methods, we demonstrate that the genome of Medauroidea extradentata is strongly methylated. Both repetitive DNA and coding genes appear to contain high levels of methylcytosines. These results argue for similar functions of DNA methylation in stick insects as those already known for vertebrates.

Stress Priming in Reading and the Selective Modulation of Lexical and Sub-Lexical Pathways:

Four experiments employed a priming methodology to investigate different mechanisms of stress assignment and how they are modulated by lexical and sub-lexical mechanisms in reading aloud in Italian. Lexical stress is unpredictable in Italian, and requires lexical look-up. The most frequent stress pattern (Dominant) is on the penultimate syllable [laVOro (work)], while stress on the antepenultimate syllable [MAcchina (car)] is relatively less frequent (non-Dominant). Word and pseudoword naming responses primed by words with non-dominant stress – which require whole-word knowledge to be read correctly – were compared to those primed by nonwords. Percentage of errors to words and percentage of dominant stress responses to nonwords were measured. In Experiments 1 and 2 stress errors increased for non-dominant stress words primed by nonwords, as compared to when they were primed by words. The results could be attributed to greater activation of sub-lexical codes, and an associated tendency to assign the dominant stress pattern by default in the nonword prime condition. Alternatively, they may have been the consequence of prosodic priming, inducing more errors on trials in which the stress pattern of primes and targets was not congruent. The two interpretations were investigated in Experiments 3 and 4. The results overall suggested a limited role of the default metrical pattern in word pronunciation, and showed clear effect of prosodic priming, but only when the sub-lexical mechanism prevailed.

The Brain Atlas Concordance Problem: Quantitative Comparison of Anatomical Parcellations:

Many neuroscientific reports reference discrete macro-anatomical regions of the brain which were delineated according to a brain atlas or parcellation protocol. Currently, however, no widely accepted standards exist for partitioning the cortex and subcortical structures, or for assigning labels to the resulting regions, and many procedures are being actively used. Previous attempts to reconcile neuroanatomical nomenclatures have been largely qualitative, focusing on the development of thesauri or simple semantic mappings between terms. Here we take a fundamentally different approach, discounting the names of regions and instead comparing their definitions as spatial entities in an effort to provide more precise quantitative mappings between anatomical entities as defined by different atlases. We develop an analytical framework for studying this brain atlas concordance problem, and apply these methods in a comparison of eight diverse labeling methods used by the neuroimaging community. These analyses result in conditional probabilities that enable mapping between regions across atlases, which also form the input to graph-based methods for extracting higher-order relationships between sets of regions and to procedures for assessing the global similarity between different parcellations of the same brain. At a global scale, the overall results demonstrate a considerable lack of concordance between available parcellation schemes, falling within chance levels for some atlas pairs. At a finer level, this study reveals spatial relationships between sets of defined regions that are not obviously apparent; these are of high potential interest to researchers faced with the challenge of comparing results that were based on these different anatomical models, particularly when coordinate-based data are not available. The complexity of the spatial overlap patterns revealed points to problems for attempts to reconcile anatomical parcellations and nomenclatures using strictly qualitative and/or categorical methods. Detailed results from this study are made available via an interactive web site at

Sustained Oscillations of NF-κB Produce Distinct Genome Scanning and Gene Expression Profiles:

NF-κB is a prototypic stress-responsive transcription factor that acts within a complex regulatory network. The signaling dynamics of endogenous NF-κB in single cells remain poorly understood. To examine real time dynamics in living cells, we monitored NF-κB activities at multiple timescales using GFP-p65 knock-in mouse embryonic fibroblasts. Oscillations in NF-κB were sustained in most cells, with several cycles of transient nuclear translocation after TNF-α stimulation. Mathematical modeling suggests that NF-κB oscillations are selected over other non-oscillatory dynamics by fine-tuning the relative strengths of feedback loops like IκBα. The ability of NF-κB to scan and interact with the genome in vivo remained remarkably constant from early to late cycles, as observed by fluorescence recovery after photobleaching (FRAP). Perturbation of long-term NF-κB oscillations interfered with its short-term interaction with chromatin and balanced transcriptional output, as predicted by the mathematical model. We propose that negative feedback loops do not simply terminate signaling, but rather promote oscillations of NF-κB in the nucleus, and these oscillations are functionally advantageous.

New Insights into the Diversity of Marine Picoeukaryotes:

Over the last decade, culture-independent surveys of marine picoeukaryotic diversity based on 18S ribosomal DNA clone libraries have unveiled numerous sequences of novel high-rank taxa. This newfound diversity has significantly altered our understanding of marine microbial food webs and the evolution of eukaryotes. However, the current picture of marine eukaryotic biodiversity may be significantly skewed by PCR amplification biases, occurrence of rDNA genes in multiple copies within a single cell, and the capacity of DNA to persist as extracellular material. In this study we performed an analysis of the metagenomic dataset from the Global Ocean Survey (GOS) expedition, seeking eukaryotic ribosomal signatures. This PCR-free approach revealed similar phylogenetic patterns to clone library surveys, suggesting that PCR steps do not impose major biases in the exploration of environmental DNA. The different cell size fractions within the GOS dataset, however, displayed a distinct picture. High protistan diversity in the <0.8 µm size fraction, in particular sequences from radiolarians and ciliates (and their absence in the 0.8-3 µm fraction), suggest that most of the DNA in this fraction comes from extracellular material from larger cells. In addition, we compared the phylogenetic patterns from rDNA and reverse transcribed rRNA 18S clone libraries from the same sample harvested in the Mediterranean Sea. The libraries revealed major differences, with taxa such as pelagophytes or picobiliphytes only detected in the 18S rRNA library. MAST (Marine Stramenopiles) appeared as potentially prominent grazers and we observed a significant decrease in the contribution of alveolate and radiolarian sequences, which overwhelmingly dominated rDNA libraries. The rRNA approach appears to be less affected by taxon-specific rDNA copy number and likely better depicts the biogeochemical significance of marine protists.

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