Genetic variation within populations depends on population size, spatial structuring, and environmental variation, but is also influenced by mating system. Mangroves are some of the most productive and threatened ecosystems on earth and harbor a large proportion of species with mixed-mating (self-fertilization and outcrossing). Understanding population structuring in mixed-mating species is critical for conserving and managing these complex ecosystems. Kryptolebias marmoratus is a unique mixed-mating vertebrate inhabiting mangrove swamps under highly variable tidal regimes and environmental conditions. We hypothesized that geographical isolation and ecological pressures influence outcrossing rates and genetic diversity, and ultimately determine the local population structuring of K. marmoratus. By comparing genetic variation at 32 microsatellites, diel fluctuations of environmental parameters, and parasite loads among four locations with different degrees of isolation, we found significant differences in genetic diversity and genotypic composition but little evidence of isolation by distance. Locations also differed in environmental diel fluctuation and parasite composition. Our results suggest that mating system, influenced by environmental instability and parasites, underpins local population structuring of K. marmoratus. More generally, we discuss how the conservation of selfing species inhabiting mangroves and other biodiversity hotspots may benefit from knowledge of mating strategies and population structuring at small spatial scales.

Waterfalls may affect fish distribution and genetic structure within drainage networks even to the extent of leading evolutionary events. Here, parallel evolution was studied by focusing on waterfall and the landlocked freshwater goby Rhinogobius sp. YB (YB), which evolved from amphidromous R. brunneus (BR). The fish fauna was surveyed at 30 sites in 11 rivers on Iriomote Island, Japan, the geography of which was characterized by terraces/tablelands with many waterfalls. We found that all YB individuals were distributed only above waterfalls (height 6.8-58.7 m), whereas BR, and other fishes, were mostly distributed below waterfalls. Mitochondrial DNA analysis showed that every YB local population above the waterfall was independently evolved from BR. In contrast, cluster analysis of nine morphological characters, such as fin color and body pattern, showed that the morphology of YB individuals held a similarity beyond the genetic divergence, suggesting parallel evolution has occurred relating to their morphology. Genetic distance between each YB local population and BR was significantly correlated with waterfall height (r(2) = 0.94), suggesting that the waterfalls have been heightened due to the constant geological erosion and that their height represents the isolation period of YB local populations from BR (ca. 11,000-88,000 years). Each local population of BR was once landlocked in upstream by waterfall formation, consequently evolving to YB in each site. Although the morphology of YB had a high degree of similarity among local populations, finer scale analysis showed that the morphology of YB was significantly correlated with the genetic distance from BR. Consequently, there could be simultaneous multiple phases of allopatric/parallel evolution of the goby due to variations in waterfall height on this small island.

The Black Tiger shrimp (Penaeus monodon) has a natural distribution range from East Africa to the South Pacific Islands. Although previous studies of Indo-Pacific P. monodon have found populations from the Indian Ocean and Australasia to differ genetically, their relatedness to South Pacific shrimp remains unknown. To address this, polymorphisms at eight shared microsatellite loci and haplotypes in a 418-bp mtDNA-CR (control region) sequence were examined across 682 P. monodon from locations spread widely across its natural range, including the South Pacific islands of Fiji, Palau, and Papua New Guinea (PNG). Observed microsatellite heterozygosities of 0.82-0.91, allele richness of 6.85-9.69, and significant mtDNA-CR haplotype variation indicated high levels of genetic diversity among the South Pacific shrimp. Analysis of microsatellite genotypes using a Bayesian STRUCTURE method segregated Indo-Pacific P. monodon into eight distinct clades, with Palau and PNG shrimp clustering among others from Southeast Asia and eastern Australia, respectively, and Fiji shrimp clustering as a distinct group. Phylogenetic analyses of mtDNA-CR haplotypes delineated shrimp into three groupings, with shrimp from Fiji again being distinct by sharing no haplotypes with other populations. Depending on regional location, the genetic structures and substructures identified from the genotyping and mtDNA-CR haplotype phylogeny could be explained by Metapopulation and/or Member-Vagrant type evolutionary processes. Neutrality tests of mutation-drift equilibrium and estimation of the time since population expansion supported a hypothesis that South Pacific P. monodon were colonized from Southeast Asia and eastern Australia during the Pleistocene period over 60,000 years ago when land bridges were more expansive and linked these regions more closely.

Temporal lobe epilepsy (TLE) is usually regarded as a polygenic and complex disorder. To understand its genetic component, numerous linkage analyses of familial forms and association studies of cases versus controls have been conducted since the middle of the nineties. The present paper lists genetic findings for TLE from the initial segregation analysis to the most recent results published in May 2011. To date, no genes have been clearly related to TLE despite many efforts to do so. However, it is vital to continue replication studies and collaborative attempts to find significant results and thus determine which gene variant combination plays a definitive role in the aetiology of TLE.

RecG is a DNA translocase that helps to maintain genomic integrity. Initial studies suggested a role in promoting recombination, a possibility consistent with synergism between recG and ruv null alleles and reinforced when the protein was shown to unwind Holliday junctions. In this article we describe novel suppressors of recG and show that the pathology seen without RecG is suppressed on reducing or eliminating PriB, a component of the PriA system for replisome assembly and replication restart. Suppression is conditional, depending on additional mutations that modify ribosomal subunit S6 or one of three subunits of RNA polymerase. The latter suppress phenotypes associated with deletion of priB, enabling the deletion to suppress recG. They include alleles likely to disrupt interactions with transcription anti-terminator, NusA. Deleting priB has a different effect in ruv strains. It provokes abortive recombination and compromises DNA repair in a manner consistent with PriB being required to limit exposure of recombinogenic ssDNA. This synergism is reduced by the RNA polymerase mutations identified. Taken together, the results reveal that RecG curbs a potentially negative effect of proteins that direct replication fork assembly at sites removed from the normal origin, a facility needed to resolve conflicts between replication and transcription.

Copyright and licensing of scientific data, internationally, are complex and present legal barriers to data sharing, integration and reuse, and therefore restrict the most efficient transfer and discovery of scientific knowledge. Much data are included within scientific journal articles, their published tables, additional files (supplementary material) and reference lists. However, these data are usually published under licenses which are not appropriate for data. Creative Commons CC0 is an appropriate and increasingly accepted method for dedicating data to the public domain, to enable data reuse with the minimum of restrictions. BioMed Central is committed to working towards implementation of open data-compliant licensing in its publications. Here we detail a protocol for implementing a combined Creative Commons Attribution license (for copyrightable material) and Creative Commons CC0 waiver (for data) agreement for content published in peer-reviewed open access journals. We explain the differences between legal requirements for attribution in copyright, and cultural requirements in scholarship for giving individuals credit for their work through citation. We argue that publishing data in scientific journals under CC0 will have numerous benefits for individuals and society, and yet will have minimal implications for authors and minimal impact on current publishing and research workflows. We provide practical examples and definitions of data types, such as XML and tabular data, and specific secondary use cases for published data, including text mining, reproducible research, and open bibliography. We believe this proposed change to the current copyright and licensing structure in science publishing will help clarify what users - people and machines - of the published literature can do, legally, with journal articles and make research using the published literature more efficient. We further believe this model could be adopted across multiple publishers, and invite comment on this article from all stakeholders in scientific research.

The availability of a large number of recently sequenced vertebrate genomes opens new avenues to integrate cytogenetics and genomics in comparative and evolutionary studies. Cytogenetic mapping can offer alternative means to identify conserved synteny shared by distinct genomes and also to define genome regions that are still not fine characterized even after wide-ranging nucleotide sequence efforts. An efficient way to perform comparative cytogenetic mapping is based on BAC clones mapping by fluorescence in situ hybridization. In this report, to address the knowledge gap on the genome evolution in cichlid fishes, BAC clones of an Oreochromis niloticus library covering the linkage groups (LG) 1, 3, 5, and 7 were mapped onto the chromosomes of 9 African cichlid species. The cytogenetic mapping data were also integrated with BAC-end sequences information of O. niloticus and comparatively analyzed against the genome of other fish species and vertebrates.

An appreciable volume of human clinical data supports increased dietary protein for greater gains from resistance training, but not all findings are in agreement. We recently proposed "protein spread theory" and "protein change theory" in an effort to explain discrepancies in the response to increased dietary protein in weight management interventions. The present review aimed to extend "protein spread theory" and "protein change theory" to studies examining the effects of protein on resistance training induced muscle and strength gains. Protein spread theory proposed that there must have been a sufficient spread or % difference in g/kg/day protein intake between groups during a protein intervention to see muscle and strength differences. Protein change theory postulated that for the higher protein group, there must be a sufficient change from baseline g/kg/day protein intake to during study g/kg/day protein intake to see muscle and strength benefits. Seventeen studies met inclusion criteria. In studies where a higher protein intervention was deemed successful there was, on average, a 66.1% g/kg/day between group intake spread versus a 10.2% g/kg/day spread in studies where a higher protein diet was no more effective than control. The average change in habitual protein intake in studies showing higher protein to be more effective than control was +59.5% compared to +6.5% when additional protein was no more effective than control. The magnitudes of difference between the mean spreads and changes of the present review are similar to our previous review on these theories in a weight management context. Providing sufficient deviation from habitual intake appears to be an important factor in determining the success of additional protein in enhancing muscle and strength gains from resistance training. An increase in dietary protein favorably effects muscle and strength during resistance training.

The Real-time PCR Array System is the ideal tool for analyzing the expression of a focused panel of genes. In this study, we will analyze the gene expression profile of pediatric acute myeloid leukemia with real-time PCR arrays.

Recently there has been a rapid increase in approaches to assess the effects of cigarette smoke in vitro. Despite a range of gravimetric and chemical methods, there is a requirement to identify simpler and more reliable methods to quantify in vitro whole smoke dose, to support extrapolation and comparisons to human/in vivo dose. We have previously characterised an in vitro exposure system using a Borgwaldt RM20S smoking machine and a chamber exposing cellular cultures to whole smoke at the air-liquid interface. In this study we demonstrate the utility of a quartz crystal microbalance (QCM), using this exposure system, to assess real-time cigarette smoke particulate deposition during a 30 minute smoke exposure. Smoke was generated at various dilutions (1:5-1:400, smoke:air) using two cigarette products, 3R4F Kentucky reference and 1 mg commercially available cigarettes. The QCM, integrated into the chamber, assessed particulate deposition and data generated were compared to traditional chemical spectrofluorometric analysis.

microRNAs (miRNAs) are shown to be involved in the regulation of circadian clock. However, it remains largely unknown whether miRNAs can regulate the core clock genes (Clock and Bmal1).

One hypothesis for the social deficits that characterize autism spectrum disorders (ASD) is diminished neural reward response to social interaction and attachment. Prior research using established monetary reward paradigms as a test of non-social reward to compare with social reward may involve confounds in the ability of individuals with ASD to utilize symbolic representation of money and the abstraction required to interpret monetary gains. Thus, a useful addition to our understanding of neural reward circuitry in ASD includes a characterization of the neural response to primary rewards.

Recent studies have demonstrated that photosynthetic cyanobacteria could be an excellent cell factory to produce renewable biofuels and chemicals due to their capability to utilize solar energy and CO2 as the sole energy and carbon sources. Biosynthesis of carbon-neutral biofuel alkanes with good chemical and physical properties has been proposed. However, to make the process economically feasible, one major hurdle to improve the low cell tolerance to alkanes needed to be overcome.

Monitoring neuronal electrical activity using fluorescent protein-based voltage sensors has been limited by small response magnitudes and slow kinetics of existing probes. Here we report the development of a fluorescent protein voltage sensor, named ArcLight, and derivative probes that exhibit large changes in fluorescence intensity in response to voltage changes. ArcLight consists of the voltage-sensing domain of Ciona intestinalis voltage-sensitive phosphatase and super ecliptic pHluorin that carries the point mutation A227D. The fluorescence intensity of ArcLight A242 decreases by 35% in response to a 100 mV depolarization when measured in HEK293 cells, which is more than five times larger than the signals from previously reported fluorescent protein voltage sensors. We show that the combination of signal size and response speed of these new probes allows the reliable detection of single action potentials and excitatory potentials in individual neurons and dendrites.

A fundamental question in developmental neuroscience is how a collection of progenitor cells proliferates and differentiates to create a brain of the appropriate size and cellular composition. To address this issue, we devised lineage-tracing assays in developing zebrafish embryos to reconstruct entire retinal lineage progressions in vivo and thereby provide a complete quantitative map of the generation of a vertebrate CNS tissue from individual progenitors. These lineage data are consistent with a simple model in which the retina is derived from a set of equipotent retinal progenitor cells (RPCs) that are subject to stochastic factors controlling lineage progression. Clone formation in mutant embryos reveals that the transcription factor Ath5 acts as a molecular link between fate choice and mode of cell division, giving insight into the elusive molecular mechanisms of histogenesis, the conserved temporal order by which neurons of different types exit the cell cycle.

The neurotransmitter glutamate mediates excitatory synaptic transmission by gating ionotropic glutamate receptors (iGluRs). AMPA receptors (AMPARs), a subtype of iGluR, are strongly implicated in synaptic plasticity, learning, and memory. We previously discovered two classes of AMPAR auxiliary proteins in C. elegans that modify receptor kinetics and thus change synaptic transmission. Here, we have identified another auxiliary protein, SOL-2, a CUB-domain protein that associates with both the related auxiliary subunit SOL-1 and with the GLR-1 AMPAR. In sol-2 mutants, behaviors dependent on glutamatergic transmission are disrupted, GLR-1-mediated currents are diminished, and GLR-1 desensitization and pharmacology are modified. Remarkably, a secreted variant of SOL-1 delivered in trans can rescue sol-1 mutants, and this rescue depends on in cis expression of SOL-2. Finally, we demonstrate that SOL-1 and SOL-2 have an ongoing role in the adult nervous system to control AMPAR-mediated currents.

Reference intervals (RIs) are ranges of upper and lower limits of a given analyte which are used for a laboratory test to determine whether a disease is present or absent or to know if the patient is at risk for future disease states. In Ethiopia, a country with highly diversified population groups and geographical sites, there are no established RIs to metabolic analytes including the liver function test (LFT) analytes for the pediatric population though it has been known that liver function assessment in this population is vital as a result of varied vulnerability to both endogenous and xenobiotic substances.

MicroRNAs (miRNAs) represent a class of small non-coding RNAs that regulate gene expression at the post-transcriptional levels. Recent studies show that miRNAs may function as oncogenes or tumor suppressor genes. In this study, we demonstrated that miR-518b was down-regulated in esophageal squamous cell carcinoma (ESCC) tissues and correlated with metastasis and survival. miR-518b suppressed the proliferation by inducing apoptosis and repressed the invasion in ESCC cells, but had no effect on the cell cycle. Furthermore, Rap1b was revealed to be directly regulated by miR-518b. These findings indicate that miR-518b may function as a tumor suppressor by targeting Rap1b in the development of ESCC and has important clinical and prognostic value.

To date, 68 loci have been associated with type 2 diabetes (T2D) or glucose homeostasis traits. We report here the results of experiments aimed at functionally characterizing the SNPs replicated for T2D and glucose traits. We sought to determine whether these loci were associated with transcript levels in adipose, muscle, liver, lymphocytes, and pancreatic β-cells. We found an excess of trans, rather than cis, associations among these SNPs in comparison to what was expected in adipose and muscle. Among transcripts differentially expressed (FDR < 0.05) between muscle or adipose cells of insulin-sensitive individuals and those of insulin-resistant individuals (matched on BMI), trans-regulated transcripts, in contrast to the cis-regulated ones, were enriched. The paucity of cis associations with transcripts was confirmed in a study of liver transcriptome and was further supported by an analysis of the most detailed transcriptome map of pancreatic β-cells. Relative to location- and allele-frequency-matched random SNPs, both the 68 loci and top T2D-associated SNPs from two large-scale genome-wide studies were enriched for trans eQTLs in adipose and muscle but not in lymphocytes. Our study suggests that T2D SNPs have broad-reaching and tissue-specific effects that often extend beyond local transcripts and raises the question of whether patterns of cis or trans transcript regulation are a key feature of the architecture of complex traits.

The extended Simes' test (known as GATES) and scaled chi-square test were proposed to combine a set of dependent genome-wide association signals at multiple single-nucleotide polymorphisms (SNPs) for assessing the overall significance of association at the gene or pathway levels. The two tests use different strategies to combine association p values and can outperform each other when the number of and linkage disequilibrium between SNPs vary. In this paper, we introduce a hybrid set-based test (HYST) combining the two tests for genome-wide association studies (GWASs). We describe how HYST can be used to evaluate statistical significance for association at the protein-protein interaction (PPI) level in order to increase power for detecting disease-susceptibility genes of moderate effect size. Computer simulations demonstrated that HYST had a reasonable type 1 error rate and was generally more powerful than its parents and other alternative tests to detect a PPI pair where both genes are associated with the disease of interest. We applied the method to three complex disease GWAS data sets in the public domain; the method detected a number of highly connected significant PPI pairs involving multiple confirmed disease-susceptibility genes not found in the SNP- and gene-based association analyses. These results indicate that HYST can be effectively used to examine a collection of predefined SNP sets based on prior biological knowledge for revealing additional disease-predisposing genes of modest effects in GWASs.