Category Archives: PLoS

Another Tuesday night, another embarrassment of riches on PLoS ONE (yeah, yeah, I work there, OK). There are 35 new articles published today and it is hard for me to pick and choose as so many are interesting to me, including a couple I may have to write separate posts about (and test the new BPR3 icon). If any of these, or any of older ONE articles (or any of yet-to-be-published articles – ask me by e-mail) are in your area of interest/expertise and you would like to volunteer your group (research lab group, graduate seminar, honors class, whatever counts as a “group” of scientists) for a future Journal Club, let me know. In the meantime, you know what you need to do: read the papers, rate them, annotate them, post comments, blog about them and send trackbacks. Here are my picks for this week:
The LARK RNA-Binding Protein Selectively Regulates the Circadian Eclosion Rhythm by Controlling E74 Protein Expression:

Despite substantial progress in defining central components of the circadian pacemaker, the output pathways coupling the clock to rhythmic physiological events remain elusive. We previously showed that LARK is a Drosophila RNA-binding protein which functions downstream of the clock to mediate behavioral outputs. To better understand the roles of LARK in the circadian system, we sought to identify RNA molecules associated with it, in vivo, using a three-part strategy to (1) capture RNA ligands by immunoprecipitation, (2) visualize the captured RNAs using whole-genome microarrays, and (3) identify functionally relevant targets through genetic screens. We found that LARK is associated with a large number of RNAs, in vivo, consistent with its broad expression pattern. Overexpression of LARK increases protein abundance for certain targets without affecting RNA level, suggesting a translational regulatory role for the RNA-binding protein. Phenotypic screens of target-gene mutants have identified several with rhythm-specific circadian defects, indicative of effects on clock output pathways. In particular, a hypomorphic mutation in the E74 gene, E74BG01805, was found to confer an early-eclosion phenotype reminiscent of that displayed by a mutant with decreased LARK gene dosage. Molecular analyses demonstrate that E74A protein shows diurnal changes in abundance, similar to LARK. In addition, the E74BG01805 allele enhances the lethal phenotype associated with a lark null mutation, whereas overexpression of LARK suppresses the early eclosion phenotype of E74BG01805, consistent with the idea that E74 is a target, in vivo. Our results suggest a model wherein LARK mediates the transfer of temporal information from the molecular oscillator to different output pathways by interacting with distinct RNA targets.

Chemical Magnetoreception: Bird Cryptochrome 1a Is Excited by Blue Light and Forms Long-Lived Radical-Pairs:

Cryptochromes (Cry) have been suggested to form the basis of light-dependent magnetic compass orientation in birds. However, to function as magnetic compass sensors, the cryptochromes of migratory birds must possess a number of key biophysical characteristics. Most importantly, absorption of blue light must produce radical pairs with lifetimes longer than about a microsecond. Cryptochrome 1a (gwCry1a) and the photolyase-homology-region of Cry1 (gwCry1-PHR) from the migratory garden warbler were recombinantly expressed and purified from a baculovirus/Sf9 cell expression system. Transient absorption measurements show that these flavoproteins are indeed excited by light in the blue spectral range leading to the formation of radicals with millisecond lifetimes. These biophysical characteristics suggest that gwCry1a is ideally suited as a primary light-mediated, radical-pair-based magnetic compass receptor.

Exceptionally Preserved Jellyfishes from the Middle Cambrian:

Cnidarians are a group of animals including corals, jellyfish and sea anemones. Due to the early emergence of this group, it may provide important clues for understanding animal evolution. The authors of this paper describe cnidarian fossils from Utah believed to be approximately 505 million years old. These fossils have very well preserved soft tissue, which the authors interpret as evidence that representatives of modern jellyfish existed by the middle Cambrian period.

Underestimation of Species Richness in Neotropical Frogs Revealed by mtDNA Analyses:

Previously unknown amphibian species are being discovered every year as a result of increased exploration in poorly surveyed tropical areas. However, this group is also experiencing high rates of extinction. The authors of this paper analyze rDNA sequences from 60 frog species in South America to estimate the number of undescribed species in this region. The results indicate that more than half the frog species in the Amazonian part of the Guianas are as yet undiscovered, suggesting that the global decline of amphibians may be more serious than previously thought.

Selection at the Y Chromosome of the African Buffalo Driven by Rainfall:

Selection coefficients at the mammalian Y chromosome typically do not deviate strongly from neutrality. Here we show that strong balancing selection, maintaining intermediate frequencies of DNA sequence variants, acts on the Y chromosome in two populations of African buffalo (Syncerus caffer). Significant correlations exist between sequence variant frequencies and annual rainfall in the years before conception, with five- to eightfold frequency changes over short time periods. Annual rainfall variation drives the balancing of sequence variant frequencies, probably by affecting parental condition. We conclude that sequence variants confer improved male reproductive success after either dry or wet years, making the population composition and dynamics very sensitive to climate change. The mammalian Y chromosome, interacting with ecological processes, may affect male reproductive success much more strongly than previously thought.

How Emotion Strengthens the Recollective Experience: A Time-Dependent Hippocampal Process:

Emotion significantly strengthens the subjective recollective experience even when objective accuracy of the memory is not improved. Here, we examine if this modulation is related to the effect of emotion on hippocampal-dependent memory consolidation. Two critical predictions follow from this hypothesis. First, since consolidation is assumed to take time, the enhancement in the recollective experience for emotional compared to neutral memories should become more apparent following a delay. Second, if the emotion advantage is critically dependent on the hippocampus, then the effects should be reduced in amnesic patients with hippocampal damage. To test these predictions we examined the recollective experience for emotional and neutral photos at two retention intervals (Experiment 1), and in amnesics and controls (Experiment 2). Emotional memories were associated with an enhancement in the recollective experience that was greatest after a delay, whereas familiarity was not influenced by emotion. In amnesics with hippocampal damage the emotion effect on recollective experience was reduced. Surprisingly, however, these patients still showed a general memory advantage for emotional compared to neutral items, but this effect was manifest primarily as a facilitation of familiarity. The results support the consolidation hypothesis of recollective experience, but suggest that the effects of emotion on episodic memory are not exclusively hippocampally mediated. Rather, emotion may enhance recognition by facilitating familiarity when recollection is impaired due to hippocampal damage.

A Step Towards Seascape Scale Conservation: Using Vessel Monitoring Systems (VMS) to Map Fishing Activity:

Conservation of marine ecosystems will require a holistic understanding of fisheries with concurrent spatial patterns of biodiversity. Using data from the UK Government Vessel Monitoring System (VMS) deployed on UK-registered large fishing vessels we investigate patterns of fisheries activity on annual and seasonal scales. Analysis of VMS data shows that regions of the UK European continental shelf (i.e. Western Channel and Celtic Sea, Northern North Sea and the Goban Spur) receive consistently greater fisheries pressure than the rest of the UK continental shelf fishing zone. VMS provides a unique and independent method from which to derive patterns of spatially and temporally explicit fisheries activity. Such information may feed into ecosystem management plans seeking to achieve sustainable fisheries while minimising putative risk to non-target species (e.g. cetaceans, seabirds and elasmobranchs) and habitats of conservation concern. With multilateral collaboration VMS technologies may offer an important solution to quantifying and managing ecosystem disturbance, particularly on the high-seas.

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As always on Fridays, there are new papers published in PLoS Genetics, PLoS Pathogens and PLoS Computational Biology. I like to take my own picks, and today I pick this pre-publication (there is a provisional PDF online) in my own field:
Meta-analysis of Drosophila Circadian Microarray Studies Identifies a Novel Set of Rhythmically Expressed Genes:

Five independent groups have reported microarray studies that identify dozens of rhythmically expressed genes in the fruit fly Drosophila melanogaster. Limited overlap among the lists of discovered genes makes it difficult to determine which, if any, exhibit truly rhythmic patterns of expression. We reanalyzed data from all five reports and found two sources for the observed discrepancies, the use of different expression pattern detection algorithms and underlying variation among the data sets. To improve upon the methods originally employed, we developed a new analysis that involves compilation of all existing data, application of identical transformation and standardization procedures followed by ANOVA based statistical pre-screening, and three separate classes of post-hoc analysis: cross-correlation to various cycling waveforms, autocorrelation, and a previously described Fast Fourier Transform (FFT) based technique [1-3]. Permutation based statistical tests were used to derive significance measures for all post-hoc tests. We find application of our method, most significantly the ANOVA prescreening procedure, to significantly reduce the false discovery rate (FDR) relative to that observed among the results of the original five reports while maintaining desirable statistical power. We identify a set of 81 cycling transcripts previously found in one or more of the original reports as well as a novel set of 133 not found in any of the original studies. We introduce a novel analysis method that compensates for variability observed among the original five Drosophila circadian array reports. We identify a set of previously found cycling transcripts as well as a set of novel ones. Based on the statistical fidelity of our meta-analysis results, and the results of our initial validation experiments (quantitative RT-PCR), we predict many of our newly found genes to be bona fide cyclers, and suggest that they may lead to new insights into the pathways through which clock mechanisms regulate behavioral rhythms.

The other one I chose is this one, as it is related to some stuff I published way back when I was still in the lab:
Food Deprivation Attenuates Seizures through CaMKII and EAG K+ Channels:

Accumulated research has demonstrated the beneficial effects of dietary restriction on extending lifespan and increasing cellular stress resistance. However, reducing nutrient intake has also been shown to direct animal behaviors toward food acquisition. Under food-limiting conditions, behavioral changes suggest that neuronal and muscle activities in circuits that are not involved in nutrient acquisition are down-regulated. These dietary-regulated mechanisms, if understood better, might provide an approach to compensate for defects in molecules that regulate cell excitability. We previously reported that a neuromuscular circuit used in Caenorhabditis elegans male mating behavior is attenuated under food-limiting conditions. During periods between matings, sex-specific muscles that control movements of the male’s copulatory spicules are kept inactive by UNC-103 ether-a-go-go-related gene (ERG)-like K+ channels. Deletion of unc-103 causes ∼30%-40% of virgin males to display sex-muscle seizures; however, when food is deprived from males, the incidence of spontaneous muscle contractions drops to 9%-11%. In this work, we used genetics and pharmacology to address the mechanisms that act parallel with UNC-103 to suppress muscle seizures in males that lack ERG-like K+ channel function. We identify calcium/calmodulin-dependent protein kinase II as a regulator that uses different mechanisms in food and nonfood conditions to compensate for reduced ERG-like K+ channel activity. We found that in food-deprived conditions, calcium/calmodulin-dependent protein kinase II acts cell-autonomously with ether-a-go-go K+ channels to inhibit spontaneous muscle contractions. Our work suggests that upregulating mechanisms used by food deprivation can suppress muscle seizures.

Holy Cow! Every Tuesday night I like to link to 5-6 of the brand new papers on PLoS ONE that I find personally most intriguing. But today, it is so difficult to choose – I want to highlight something like 20 out of today’s 39. So, here are a few and you definitely go and see the whole list for yourself (and you know the drill, as I parrot it every week: read, rate, comment):
Impedance-Matching Hearing in Paleozoic Reptiles: Evidence of Advanced Sensory Perception at an Early Stage of Amniote Evolution

Insights into the onset of evolutionary novelties are key to the understanding of amniote origins and diversification. The possession of an impedance-matching tympanic middle ear is characteristic of all terrestrial vertebrates with a sophisticated hearing sense and an adaptively important feature of many modern terrestrial vertebrates. Whereas tympanic ears seem to have evolved multiple times within tetrapods, especially among crown-group members such as frogs, mammals, squamates, turtles, crocodiles, and birds, the presence of true tympanic ears has never been recorded in a Paleozoic amniote, suggesting they evolved fairly recently in amniote history.
In the present study, we performed a morphological examination and a phylogenetic analysis of poorly known parareptiles from the Middle Permian of the Mezen River Basin in Russia. We recovered a well-supported clade that is characterized by a unique cheek morphology indicative of a tympanum stretching across large parts of the temporal region to an extent not seen in other amniotes, fossil or extant, and a braincase specialized in showing modifications clearly related to an increase in auditory function, unlike the braincase of any other Paleozoic tetrapod. In addition, we estimated the ratio of the tympanum area relative to the stapedial footplate for the basalmost taxon of the clade, which, at 23:1, is in close correspondence to that of modern amniotes capable of efficient impedance-matching hearing.
Using modern amniotes as analogues, the possession of an impedance-matching middle ear in these parareptiles suggests unique ecological adaptations potentially related to living in dim-light environments. More importantly, our results demonstrate that already at an early stage of amniote diversification, and prior to the Permo-Triassic extinction event, the complexity of terrestrial vertebrate ecosystems had reached a level that proved advanced sensory perception to be of notable adaptive significance.

Chimpanzees Share Forbidden Fruit:

It is common for chimpanzee communities that engage in hunting to use meat as a “social tool” for nurturing alliances and social bonds; however the sharing of wild plant foods is rare. As part of a study directly observing adult chimpanzees in West Africa, Hockings and colleagues found that cultivated plant foods were shared more frequently than wild plant foods. The results suggest that the challenge of crop-raiding provides adult male chimpanzees with food that may be considered highly desirable to the opposite sex.

Sleep in the Human Hippocampus: A Stereo-EEG Study

Our data imply that cortical slow oscillation is attenuated in the hippocampal structures during NREM sleep. The most peculiar feature of hippocampal sleep is the increased synchronization of the EEG rhythms during REM periods. This state of resonance may have a supportive role for the processing/consolidation of memory.

Successful Biological Invasion despite a Severe Genetic Load

Through population genetic analysis of neutral microsatellite markers and a gene experiencing balancing selection, we demonstrate that the solitary bee Lasioglossum leucozonium experienced a single and severe bottleneck during its introduction from Europe. Paradoxically, the success of L. leucozonium in its introduced range occurred despite the severe genetic load caused by single-locus complementary sex-determination that still turns 30% of female-destined eggs into sterile diploid males, thereby substantially limiting the growth potential of the introduced population. Using stochastic modeling, we show that L. leucozonium invaded North America through the introduction of a very small number of propagules, most likely a singly-mated female. Our results suggest that chance events and ecological traits of invaders are more important than propagule pressure in determining invasion success, and that the vigilance required to prevent invasions may be considerably greater than has been previously considered.

Self-Referential Cognition and Empathy in Autism

Individuals with autism spectrum conditions (ASC) are known to have difficulties empathizing with others, but this study shows them to have lesser self awareness as well. Thirty individuals with Asperger Syndrome or high-functioning autism were compared to matched controls in a number of standard tests. Individuals with ASC had broad impairments in both self-referential cognition and empathy, suggesting specific dysfunctions within brain areas such as the medial prefrontal cortex.

Ubx Regulates Differential Enlargement and Diversification of Insect Hind Legs

In many insect groups, such as in grasshoppers and crickets, there has been an evolutionary trend over time towards the development of larger hind legs. The actual processes responsible for this trend are still to be determined. This paper examines the molecular basis of hind leg enlargement in the house cricket and the milkweed bug. The results show that the gene Ultrabithorax (Ubx) regulates the differential growth and enlargement of the hind leg, suggesting that the diversity of insect hind leg size can result from alterations in the timing and duration of expression of a single gene.

Crown Plasticity and Competition for Canopy Space: A New Spatially Implicit Model Parameterized for 250 North American Tree Species

We introduce a new, simple and rapidly-implemented model-the Ideal Tree Distribution, ITD-with tree form (height allometry and crown shape), growth plasticity, and space-filling, at its core. The ITD predicts the canopy status (in or out of canopy), crown depth, and total and exposed crown area of the trees in a stand, given their species, sizes and potential crown shapes. We use maximum likelihood methods, in conjunction with data from over 100,000 trees taken from forests across the coterminous US, to estimate ITD model parameters for 250 North American tree species. With only two free parameters per species-one aggregate parameter to describe crown shape, and one parameter to set the so-called depth bias-the model captures between-species patterns in average canopy status, crown radius, and crown depth, and within-species means of these metrics vs stem diameter. The model also predicts much of the variation in these metrics for a tree of a given species and size, resulting solely from deterministic responses to variation in stand structure.

Retinal Encoding of Ultrabrief Shape Recognition Cues

Shape encoding mechanisms can be probed by the sequential brief display of dots that mark the boundary of the shape, and delays of less that a millisecond between successive dots can impair recognition. It is not entirely clear whether this is accomplished by preserving stimulus timing in the signal being sent to the brain, or calls for a retinal binding mechanism. Two experiments manipulated the degree of simultaneity among and within dot pairs, requiring also that the pair members be in the same half of the visual field or on opposite halves, i.e., across the midline from one another. Recognition performance was impaired the same for these two conditions. The results make it likely that simultaneity of cues is being registered within the retina. A potential mechanism is suggested, calling for linkage of stimulated sites through activation of PA1 cells. A third experiment confirmed a prior finding that the overall level of recognition deficit is partly a function of display-set size, and affirmed submillisecond resolution in binding dot pairs into effective shape-recognition cues.

Nonassociative Learning Promotes Respiratory Entrainment to Mechanical Ventilation

Patient-ventilator synchrony is a major concern in critical care and is influenced by phasic lung-volume feedback control of the respiratory rhythm. Routine clinical application of positive end-expiratory pressure (PEEP) introduces a tonic input which, if unopposed, might disrupt respiratory-ventilator entrainment through sustained activation of the vagally-mediated Hering-Breuer reflex. We suggest that this potential adverse effect may be averted by two differentiator forms of nonassociative learning (habituation and desensitization) of the Hering-Breuer reflex via pontomedullary pathways.

Declining Rates in Male Circumcision amidst Increasing Evidence of its Public Health Benefit

Male circumcision was common among men seeking STD services in San Francisco but has declined substantially in recent decades. Male circumcision rates differed by race/ethnicity and sexual orientation. Given recent studies suggesting the public health benefits of male circumcision, a reconsideration of national male circumcision policy is needed to respond to current trends.

Degeneration of the Olfactory Guanylyl Cyclase D Gene during Primate Evolution

The mammalian olfactory system consists of several subsystems that detect specific sets of chemical cues and underlie a variety of behavioral responses. ———— These data suggest that signaling through GC-D-expressing cells was probably compromised more than 40 million years ago, prior to the divergence of New World monkeys from Old World monkeys and apes, and thus cannot be involved in chemosensation in most primates.

No Language-Specific Activation during Linguistic Processing of Observed Actions

These results show that linguistic tasks do not only share common neural representations but essentially activate a subset of the action observation network if identical stimuli are used. Our findings strongly support the evolutionary hypothesis that fronto-parietal systems matching action execution and observation were co-opted for language, a process known as exaptation.

Age- and Sex-Specific Mortality Patterns in an Emerging Wildlife Epidemic: The Phocine Distemper in European Harbour Seals

Analyses of the dynamics of diseases in wild populations typically assume all individuals to be identical. However, profound effects on the long-term impact on the host population can be expected if the disease has age and sex dependent dynamics. The Phocine Distemper Virus (PDV) caused two mass mortalities in European harbour seals in 1988 and in 2002. We show the mortality patterns were highly age specific on both occasions, where young of the year and adult (>4 yrs) animals suffered extremely high mortality, and sub-adult seals (1-3 yrs) of both sexes experienced low mortality. Consequently, genetic differences cannot have played a main role explaining why some seals survived and some did not in the study region, since parents had higher mortality levels than their progeny. Furthermore, there was a conspicuous absence of animals older than 14 years among the victims in 2002, which strongly indicates that the survivors from the previous disease outbreak in 1988 had acquired and maintained immunity to PDV. These specific mortality patterns imply that contact rates and susceptibility to the disease are strongly age and sex dependent variables, underlining the need for structured epidemic models for wildlife diseases. Detailed data can thus provide crucial information about a number of vital parameters such as functional herd immunity. One of many future challenges in understanding the epidemiology of the PDV and other wildlife diseases is to reveal how immune system responses differ among animals in different stages during their life cycle. The influence of such underlying mechanisms may also explain the limited evidence for abrupt disease thresholds in wild populations.

A Fully Automated Robotic System for Microinjection of Zebrafish Embryos

As an important embodiment of biomanipulation, injection of foreign materials (e.g., DNA, RNAi, sperm, protein, and drug compounds) into individual cells has significant implications in genetics, transgenics, assisted reproduction, and drug discovery. This paper presents a microrobotic system for fully automated zebrafish embryo injection, which overcomes the problems inherent in manual operation, such as human fatigue and large variations in success rates due to poor reproducibility. Based on computer vision and motion control, the microrobotic system performs injection at a speed of 15 zebrafish embryos (chorion unremoved) per minute, with a survival rate of 98% (n = 350 embryos), a success rate of 99% (n = 350 embryos), and a phenotypic rate of 98.5% (n = 210 embryos). The sample immobilization technique and microrobotic control method are applicable to other biological injection applications such as the injection of mouse oocytes/embryos and Drosophila embryos to enable high-throughput biological and pharmaceutical research.

Evidence for Paternal Leakage in Hybrid Periodical Cicadas (Hemiptera: Magicicada spp.)

Mitochondrial inheritance is generally assumed to be maternal. However, there is increasing evidence of exceptions to this rule, especially in hybrid crosses. In these cases, mitochondria are also inherited paternally, so “paternal leakage” of mitochondria occurs. It is important to understand these exceptions better, since they potentially complicate or invalidate studies that make use of mitochondrial markers. We surveyed F1 offspring of experimental hybrid crosses of the 17-year periodical cicadas Magicicada septendecim, M. septendecula, and M. cassini for the presence of paternal mitochondrial markers at various times during development (1-day eggs; 3-, 6-, 9-week eggs; 16-month old 1st and 2nd instar nymphs). We found evidence of paternal leakage in both reciprocal hybrid crosses in all of these samples. The relative difficulty of detecting paternal mtDNA in the youngest eggs and ease of detecting leakage in older eggs and in nymphs suggests that paternal mitochondria proliferate as the eggs develop. Our data support recent theoretical predictions that paternal leakage may be more common than previously estimated.