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Biology, Volume 1, Issue 3 (December 2012), Pages 460-932

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Research

Jump to: Review

Open AccessArticle Bioinformatics Analysis of the FREM1 Gene—Evolutionary Development of the IL-1R1 Co-Receptor, TILRR
Biology 2012, 1(3), 484-494; doi:10.3390/biology1030484
Received: 23 July 2012 / Revised: 28 August 2012 / Accepted: 3 September 2012 / Published: 25 September 2012
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Abstract
The TLRs and IL-1 receptors have evolved to coordinate the innate immune response following pathogen invasion. Receptors and signalling intermediates of these systems are generally characterised by a high level of evolutionary conservation. The recently described IL-1R1 co-receptor TILRR is a transcriptional [...] Read more.
The TLRs and IL-1 receptors have evolved to coordinate the innate immune response following pathogen invasion. Receptors and signalling intermediates of these systems are generally characterised by a high level of evolutionary conservation. The recently described IL-1R1 co-receptor TILRR is a transcriptional variant of the FREM1 gene. Here we investigate whether innate co-receptor differences between teleosts and mammals extend to the expression of the TILRR isoform of FREM1. Bioinformatic and phylogenetic approaches were used to analyse the genome sequences of FREM1 from eukaryotic organisms including 37 tetrapods and five teleost fish. The TILRR consensus peptide sequence was present in the FREM1 gene of the tetrapods, but not in fish orthologs of FREM1, and neither FREM1 nor TILRR were present in invertebrates. The TILRR gene appears to have arisen via incorporation of adjacent non-coding DNA with a contiguous exonic sequence after the teleost divergence. Comparing co-receptors in other systems, points to their origin during the same stages of evolution. Our results show that modern teleost fish do not possess the IL-1RI co-receptor TILRR, but that this is maintained in tetrapods as early as amphibians. Further, they are consistent with data showing that co-receptors are recent additions to these regulatory systems and suggest this may underlie differences in innate immune responses between mammals and fish. Full article
Open AccessArticle Improved Cholinergic Transmission is Detrimental to Behavioural Plasticity in Honeybees (Apis mellifera)
Biology 2012, 1(3), 508-520; doi:10.3390/biology1030508
Received: 1 September 2012 / Revised: 21 September 2012 / Accepted: 27 September 2012 / Published: 16 October 2012
Cited by 1 | PDF Full-text (235 KB) | HTML Full-text | XML Full-text
Abstract
Unravelling the role of neuromessenger processes in learning and memory has long interested researchers. We investigated the effects of an acetylcholinesterase blocker, Methyl Parathion (MeP), on honeybee learning. We used visual and olfactory tasks to test whether MeP had a detrimental effect [...] Read more.
Unravelling the role of neuromessenger processes in learning and memory has long interested researchers. We investigated the effects of an acetylcholinesterase blocker, Methyl Parathion (MeP), on honeybee learning. We used visual and olfactory tasks to test whether MeP had a detrimental effect on the acquisition of new knowledge when this new knowledge contradicts previously acquired one. Our results indicate that treatment with MeP prior to conditioning was significantly detrimental to the acquisition of incongruous (but not irrelevant or congruous) new knowledge due to improved recall. The neurobiological and ecotoxicological consequences of these results are discussed. Full article
Open AccessArticle The Population Genomics of Sunflowers and Genomic Determinants of Protein Evolution Revealed by RNAseq
Biology 2012, 1(3), 575-596; doi:10.3390/biology1030575
Received: 30 August 2012 / Revised: 9 October 2012 / Accepted: 12 October 2012 / Published: 25 October 2012
Cited by 13 | PDF Full-text (911 KB) | HTML Full-text | XML Full-text
Abstract
Few studies have investigated the causes of evolutionary rate variation among plant nuclear genes, especially in recently diverged species still capable of hybridizing in the wild. The recent advent of Next Generation Sequencing (NGS) permits investigation of genome wide rates of protein [...] Read more.
Few studies have investigated the causes of evolutionary rate variation among plant nuclear genes, especially in recently diverged species still capable of hybridizing in the wild. The recent advent of Next Generation Sequencing (NGS) permits investigation of genome wide rates of protein evolution and the role of selection in generating and maintaining divergence. Here, we use individual whole-transcriptome sequencing (RNAseq) to refine our understanding of the population genomics of wild species of sunflowers (Helianthus spp.) and the factors that affect rates of protein evolution. We aligned 35 GB of transcriptome sequencing data and identified 433,257 polymorphic sites (SNPs) in a reference transcriptome comprising 16,312 genes. Using SNP markers, we identified strong population clustering largely corresponding to the three species analyzed here (Helianthus annuus, H. petiolaris, H. debilis), with one distinct early generation hybrid. Then, we calculated the proportions of adaptive substitution fixed by selection (alpha) and identified gene ontology categories with elevated values of alpha. The “response to biotic stimulus” category had the highest mean alpha across the three interspecific comparisons, implying that natural selection imposed by other organisms plays an important role in driving protein evolution in wild sunflowers. Finally, we examined the relationship between protein evolution (dN/dS ratio) and several genomic factors predicted to co-vary with protein evolution (gene expression level, divergence and specificity, genetic divergence [FST], and nucleotide diversity pi). We find that variation in rates of protein divergence was correlated with gene expression level and specificity, consistent with results from a broad range of taxa and timescales. This would in turn imply that these factors govern protein evolution both at a microevolutionary and macroevolutionary timescale. Our results contribute to a general understanding of the determinants of rates of protein evolution and the impact of selection on patterns of polymorphism and divergence. Full article
(This article belongs to the Special Issue Next Generation Sequencing Approaches in Biology)
Open AccessArticle Vulnerability to Climate Change of Mangroves: Assessment from Cameroon, Central Africa
Biology 2012, 1(3), 617-638; doi:10.3390/biology1030617
Received: 24 August 2012 / Revised: 28 September 2012 / Accepted: 31 October 2012 / Published: 6 November 2012
Cited by 9 | PDF Full-text (761 KB) | HTML Full-text | XML Full-text
Abstract
Intertidal mangrove ecosystems are sensitive to climate change impacts, particularly to associated relative sea level rise. Human stressors and low tidal range add to vulnerability, both characteristics of the Doula Estuary, Cameroon. To investigate vulnerability, spatial techniques were combined with ground surveys [...] Read more.
Intertidal mangrove ecosystems are sensitive to climate change impacts, particularly to associated relative sea level rise. Human stressors and low tidal range add to vulnerability, both characteristics of the Doula Estuary, Cameroon. To investigate vulnerability, spatial techniques were combined with ground surveys to map distributions of mangrove zones, and compare with historical spatial records to quantify change over the last few decades. Low technology techniques were used to establish the tidal range and relative elevation of the mapped mangrove area. Stratigraphic coring and palaeobiological reconstruction were used to show the longer term biological history of mangroves and net sedimentation rate, and oral history surveys of local communities were used to provide evidence of recent change and identify possible causes. Results showed that the seaward edge of mangroves had over two thirds of the shoreline experienced dieback at up to 3 m per year over the last three decades, and an offshore mangrove island had suffered 89% loss. Results also showed low net sedimentation rates under seaward edge mangroves, and restricted intertidal elevation habitats of all mangroves, and Avicennia and Laguncularia in particular. To reduce vulnerability, adaptation planning can be improved by reducing the non-climate stressors on the mangrove area, particularly those resulting from human impacts. Other priorities for adaptation planning in mangrove areas that are located in such low tidal range regions are to plan inland migration areas and strategic protected areas for mangroves, and to undertake management activities that enhance accretion within the mangroves. Full article
(This article belongs to the Special Issue Biological Implications of Climate Change)
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Open AccessArticle An Eco-Evolutionary Model for Demographic and Phenological Responses in Migratory Birds
Biology 2012, 1(3), 639-657; doi:10.3390/biology1030639
Received: 3 September 2012 / Revised: 26 October 2012 / Accepted: 6 November 2012 / Published: 14 November 2012
Cited by 4 | PDF Full-text (330 KB) | HTML Full-text | XML Full-text
Abstract
Many migratory birds have changed their timing of arrival at breeding grounds in response to recent climate change. Understanding the adaptive value and the demographic consequences of these shifts are key challenges. To address these questions we extend previous models of phenological [...] Read more.
Many migratory birds have changed their timing of arrival at breeding grounds in response to recent climate change. Understanding the adaptive value and the demographic consequences of these shifts are key challenges. To address these questions we extend previous models of phenological adaptation to climate change under territory competition to include feedback from population dynamics, winter survival and habitat productivity. We study effects of improved pre-breeding survival and of earlier food abundance peak. We show that phenological responses depend strongly on equilibrium population density via effects on territory competition. When density is high, improved pre-breeding survival affects selection pressures more than shifts of the resource peak. Under certain conditions, an advanced food peak can even select for later arrival due to competitive release. Improved pre-breeding survival has positive effects on population density that in many cases is stronger than negative effects of an advanced food peak. The fraction of young in the population decreases in all scenarios of change, but food peak shifts only affect population structure marginally unless population density is low. This work thus provides several missing links between phenological adaptation and demographic responses, and augments the toolbox for interpreting ongoing phenological shifts in migratory birds. We illustrate the utility of our model by explaining different patterns in demographic trends and phenological shifts in populations of Pied flycatchers (Ficedula hypoleuca) across Western Europe. Full article
(This article belongs to the Special Issue Biological Implications of Climate Change)
Open AccessArticle A Systematic Survey and Characterization of Enhancers that Regulate Sox3 in Neuro-Sensory Development in Comparison with Sox2 Enhancers
Biology 2012, 1(3), 714-735; doi:10.3390/biology1030714
Received: 17 October 2012 / Revised: 6 November 2012 / Accepted: 9 November 2012 / Published: 22 November 2012
Cited by 3 | PDF Full-text (1513 KB) | HTML Full-text | XML Full-text
Abstract
Development of neural and sensory primordia at the early stages of embryogenesis depends on the activity of two B1 Sox transcription factors, Sox2 and Sox3. The embryonic expression patterns of the Sox2 and Sox3 genes are similar, yet they show gene-unique features. [...] Read more.
Development of neural and sensory primordia at the early stages of embryogenesis depends on the activity of two B1 Sox transcription factors, Sox2 and Sox3. The embryonic expression patterns of the Sox2 and Sox3 genes are similar, yet they show gene-unique features. We screened for enhancers of the 231-kb genomic region encompassing Sox3 of chicken, and identified 13 new enhancers that showed activity in different domains of the neuro-sensory primordia. Combined with the three Sox3-proximal enhancers determined previously, at least 16 enhancers were involved in Sox3 regulation. Starting from the NP1 enhancer, more enhancers with different specificities are activated in sequence, resulting in complex overlapping patterns of enhancer activities. NP1 was activated in the caudal lateral epiblast adjacent to the posterior growing end of neural plate, and by the combined action of Wnt and Fgf signaling, similar to the Sox2 N1 enhancer involved in neural/mesodermal dichotomous cell lineage segregation. The Sox3 D5 enhancer and Sox2 N3 enhancer were also activated similarly in the diencephalon, optic vesicle and lens placode, suggesting analogies in their regulation. In general, however, the specificities of the enhancers were not identical between Sox3 and Sox2, including the cases of the NP1 and D5 enhancers. Full article
(This article belongs to the Special Issue Gene Expression and Regulation)
Open AccessArticle Will Climate Change, Genetic and Demographic Variation or Rat Predation Pose the Greatest Risk for Persistence of an Altitudinally Distributed Island Endemic?
Biology 2012, 1(3), 736-765; doi:10.3390/biology1030736
Received: 3 September 2012 / Revised: 29 October 2012 / Accepted: 16 November 2012 / Published: 23 November 2012
Cited by 2 | PDF Full-text (802 KB) | HTML Full-text | XML Full-text
Abstract
Species endemic to mountains on oceanic islands are subject to a number of existing threats (in particular, invasive species) along with the impacts of a rapidly changing climate. The Lord Howe Island endemic palm Hedyscepe canterburyana is restricted to two mountains above [...] Read more.
Species endemic to mountains on oceanic islands are subject to a number of existing threats (in particular, invasive species) along with the impacts of a rapidly changing climate. The Lord Howe Island endemic palm Hedyscepe canterburyana is restricted to two mountains above 300 m altitude. Predation by the introduced Black Rat (Rattus rattus) is known to significantly reduce seedling recruitment. We examined the variation in Hedyscepe in terms of genetic variation, morphology, reproductive output and demographic structure, across an altitudinal gradient. We used demographic data to model population persistence under climate change predictions of upward range contraction incorporating long-term climatic records for Lord Howe Island. We also accounted for alternative levels of rat predation into the model to reflect management options for control. We found that Lord Howe Island is getting warmer and drier and quantified the degree of temperature change with altitude (0.9 °C per 100 m). For H. canterburyana, differences in development rates, population structure, reproductive output and population growth rate were identified between altitudes. In contrast, genetic variation was high and did not vary with altitude. There is no evidence of an upward range contraction as was predicted and recruitment was greatest at lower altitudes. Our models predicted slow population decline in the species and that the highest altitude populations are under greatest threat of extinction. Removal of rat predation would significantly enhance future persistence of this species. Full article
(This article belongs to the Special Issue Biological Implications of Climate Change)
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Open AccessArticle Whole Genome Sequencing and a New Bioinformatics Platform Allow for Rapid Gene Identification in D. melanogaster EMS Screens
Biology 2012, 1(3), 766-777; doi:10.3390/biology1030766
Received: 5 October 2012 / Revised: 14 November 2012 / Accepted: 20 November 2012 / Published: 5 December 2012
Cited by 4 | PDF Full-text (414 KB) | HTML Full-text | XML Full-text
Abstract
Forward genetic screens in Drosophila melanogaster using ethyl methanesulfonate (EMS) mutagenesis are a powerful approach for identifying genes that modulate specific biological processes in an in vivo setting. The mapping of genes that contain randomly-induced point mutations has become more efficient in [...] Read more.
Forward genetic screens in Drosophila melanogaster using ethyl methanesulfonate (EMS) mutagenesis are a powerful approach for identifying genes that modulate specific biological processes in an in vivo setting. The mapping of genes that contain randomly-induced point mutations has become more efficient in Drosophila thanks to the maturation and availability of many types of genetic tools. However, classic approaches to gene mapping are relatively slow and ultimately require extensive Sanger sequencing of candidate chromosomal loci. With the advent of new high-throughput sequencing techniques, it is increasingly efficient to directly re-sequence the whole genome of model organisms. This approach, in combination with traditional chromosomal mapping, has the potential to greatly simplify and accelerate mutation identification in mutants generated in EMS screens. Here we show that next-generation sequencing (NGS) is an accurate and efficient tool for high-throughput sequencing and mutation discovery in Drosophila melanogaster. As a test case, mutant strains of Drosophila that exhibited long-term survival of severed peripheral axons were identified in a forward EMS mutagenesis. All mutants were recessive and fell into a single lethal complementation group, which suggested that a single gene was responsible for the protective axon degenerative phenotype. Whole genome sequencing of these genomes identified the underlying gene ect4. To improve the process of genome wide mutation identification, we developed Genomes Management Application (GEM.app, https://genomics.med.miami.edu), a graphical online user interface to a custom query framework. Using a custom GEM.app query, we were able to identify that each mutant carried a unique non-sense mutation in the gene ect4 (dSarm), which was recently shown by Osterloh et al. to be essential for the activation of axonal degeneration. Our results demonstrate the current advantages and limitations of NGS in Drosophila and we introduce GEM.app as a simple yet powerful genomics analysis tool for the Drosophila community. At a current cost of <$1,000 per genome, NGS should thus become a standard gene discovery tool in EMS induced genetic forward screens. Full article
(This article belongs to the Special Issue Next Generation Sequencing Approaches in Biology)
Open AccessArticle Using Natural Gradients to Infer a Potential Response to Climate Change: An Example on the Reproductive Performance of Dactylis Glomerata L.
Biology 2012, 1(3), 857-868; doi:10.3390/biology1030857
Received: 19 November 2012 / Revised: 5 December 2012 / Accepted: 6 December 2012 / Published: 13 December 2012
Cited by 2 | PDF Full-text (223 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
An understanding of the climate conditions governing spatial variation in the reproductive performance of plants can provide important information about the factors characterizing plant community structure, especially in the context of climate change. This study focuses on the effect of climate on [...] Read more.
An understanding of the climate conditions governing spatial variation in the reproductive performance of plants can provide important information about the factors characterizing plant community structure, especially in the context of climate change. This study focuses on the effect of climate on the sexual reproductive output of Dactylis glomerata L., a perennial grass species widely distributed throughout temperate regions. An indirect space-for-time substitution procedure was used. Sixty mountain populations of the same target species were surveyed along an elevation gradient, and then, a relevant climate model was used to infer a potential response to climate change over time. Within each population, information on the number of stems, seed number and seed mass were collected. Resource investment in reproduction (RIR) was quantified as seed number × seed mass. A clear variation was found in the reproductive performance of D. glomerata along the elevational gradient: RIR improved with increasing temperature. The best model included only one term: the maximum temperature of the warmest month. This study demonstrates that mountain ecosystems offer particularly good opportunities to study climate effects over relatively short distances and suggests that warming will enhance D. glomerata’s reproductive output throughout its elevational range. Furthermore, it can be hypothesized that a potential migration of D. glomerata toward higher altitudes may occur in response to accelerated climate change. Full article
(This article belongs to the Special Issue Biological Implications of Climate Change)
Open AccessArticle Climate Predictions Accelerate Decline for Threatened Macrozamia Cycads from Queensland, Australia
Biology 2012, 1(3), 880-894; doi:10.3390/biology1030880
Received: 3 October 2012 / Revised: 26 November 2012 / Accepted: 7 December 2012 / Published: 14 December 2012
Cited by 2 | PDF Full-text (671 KB) | HTML Full-text | XML Full-text
Abstract
Changes in the potential habitat of five allopatric species of threatened Macrozamia cycads under scenarios of increased ambient temperature were examined. A lack of seed dispersal, poor recruitment, low seedling survival, obligate pollinator mutualisms and continued habitat loss have led to extant [...] Read more.
Changes in the potential habitat of five allopatric species of threatened Macrozamia cycads under scenarios of increased ambient temperature were examined. A lack of seed dispersal, poor recruitment, low seedling survival, obligate pollinator mutualisms and continued habitat loss have led to extant populations being largely restricted to refugia. Models predict that the area of suitable habitat will further contract and move upslope, resulting in a reduced incidence within protected areas with increasing annual mean temperature. Areas of potential habitat for all five species are also predicted to become increasingly isolated from one another, further reducing the exchange between metapopulations and subpopulations, exacerbating existing threatening processes. Full article
(This article belongs to the Special Issue Biological Implications of Climate Change)
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Open AccessArticle FLEXBAR—Flexible Barcode and Adapter Processing for Next-Generation Sequencing Platforms
Biology 2012, 1(3), 895-905; doi:10.3390/biology1030895
Received: 28 August 2012 / Revised: 21 September 2012 / Accepted: 7 December 2012 / Published: 14 December 2012
Cited by 53 | PDF Full-text (261 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Quantitative and systems biology approaches benefit from the unprecedented depth of next-generation sequencing. A typical experiment yields millions of short reads, which oftentimes carry particular sequence tags. These tags may be: (a) specific to the sequencing platform and library construction method (e.g., [...] Read more.
Quantitative and systems biology approaches benefit from the unprecedented depth of next-generation sequencing. A typical experiment yields millions of short reads, which oftentimes carry particular sequence tags. These tags may be: (a) specific to the sequencing platform and library construction method (e.g., adapter sequences); (b) have been introduced by experimental design (e.g., sample barcodes); or (c) constitute some biological signal (e.g., splice leader sequences in nematodes). Our software FLEXBAR enables accurate recognition, sorting and trimming of sequence tags with maximal flexibility, based on exact overlap sequence alignment. The software supports data formats from all current sequencing platforms, including color-space reads. FLEXBAR maintains read pairings and processes separate barcode reads on demand. Our software facilitates the fine-grained adjustment of sequence tag detection parameters and search regions. FLEXBAR is a multi-threaded software and combines speed with precision. Even complex read processing scenarios might be executed with a single command line call. We demonstrate the utility of the software in terms of read mapping applications, library demultiplexing and splice leader detection. FLEXBAR and additional information is available for academic use from the website: http://sourceforge.net/projects/flexbar/. Full article
(This article belongs to the Special Issue Next Generation Sequencing Approaches in Biology)
Open AccessArticle Climate Change Impacts on the Tree of Life: Changes in Phylogenetic Diversity Illustrated for Acropora Corals
Biology 2012, 1(3), 906-932; doi:10.3390/biology1030906
Received: 19 September 2012 / Revised: 10 December 2012 / Accepted: 10 December 2012 / Published: 14 December 2012
Cited by 12 | PDF Full-text (519 KB) | HTML Full-text | XML Full-text
Abstract
The possible loss of whole branches from the tree of life is a dramatic, but under-studied, biological implication of climate change. The tree of life represents an evolutionary heritage providing both present and future benefits to humanity, often in unanticipated ways. Losses [...] Read more.
The possible loss of whole branches from the tree of life is a dramatic, but under-studied, biological implication of climate change. The tree of life represents an evolutionary heritage providing both present and future benefits to humanity, often in unanticipated ways. Losses in this evolutionary (evo) life-support system represent losses in “evosystem” services, and are quantified using the phylogenetic diversity (PD) measure. High species-level biodiversity losses may or may not correspond to high PD losses. If climate change impacts are clumped on the phylogeny, then loss of deeper phylogenetic branches can mean disproportionately large PD loss for a given degree of species loss. Over time, successive species extinctions within a clade each may imply only a moderate loss of PD, until the last species within that clade goes extinct, and PD drops precipitously. Emerging methods of “phylogenetic risk analysis” address such phylogenetic tipping points by adjusting conservation priorities to better reflect risk of such worst-case losses. We have further developed and explored this approach for one of the most threatened taxonomic groups, corals. Based on a phylogenetic tree for the corals genus Acropora, we identify cases where worst-case PD losses may be avoided by designing risk-averse conservation priorities. We also propose spatial heterogeneity measures changes to assess possible changes in the geographic distribution of corals PD. Full article
(This article belongs to the Special Issue Biological Implications of Climate Change)

Review

Jump to: Research

Open AccessReview Genotyping-by-Sequencing in Plants
Biology 2012, 1(3), 460-483; doi:10.3390/biology1030460
Received: 6 August 2012 / Revised: 7 August 2012 / Accepted: 13 September 2012 / Published: 25 September 2012
Cited by 40 | PDF Full-text (358 KB) | HTML Full-text | XML Full-text
Abstract
The advent of next-generation DNA sequencing (NGS) technologies has led to the development of rapid genome-wide Single Nucleotide Polymorphism (SNP) detection applications in various plant species. Recent improvements in sequencing throughput combined with an overall decrease in costs per gigabase of sequence [...] Read more.
The advent of next-generation DNA sequencing (NGS) technologies has led to the development of rapid genome-wide Single Nucleotide Polymorphism (SNP) detection applications in various plant species. Recent improvements in sequencing throughput combined with an overall decrease in costs per gigabase of sequence is allowing NGS to be applied to not only the evaluation of small subsets of parental inbred lines, but also the mapping and characterization of traits of interest in much larger populations. Such an approach, where sequences are used simultaneously to detect and score SNPs, therefore bypassing the entire marker assay development stage, is known as genotyping-by-sequencing (GBS). This review will summarize the current state of GBS in plants and the promises it holds as a genome-wide genotyping application. Full article
(This article belongs to the Special Issue Next Generation Sequencing Approaches in Biology)
Open AccessReview Genome Walking by Next Generation Sequencing Approaches
Biology 2012, 1(3), 495-507; doi:10.3390/biology1030495
Received: 1 August 2012 / Revised: 31 August 2012 / Accepted: 25 September 2012 / Published: 1 October 2012
Cited by 2 | PDF Full-text (274 KB) | HTML Full-text | XML Full-text
Abstract
Genome Walking (GW) comprises a number of PCR-based methods for the identification of nucleotide sequences flanking known regions. The different methods have been used for several purposes: from de novo sequencing, useful for the identification of unknown regions, to the characterization of [...] Read more.
Genome Walking (GW) comprises a number of PCR-based methods for the identification of nucleotide sequences flanking known regions. The different methods have been used for several purposes: from de novo sequencing, useful for the identification of unknown regions, to the characterization of insertion sites for viruses and transposons. In the latter cases Genome Walking methods have been recently boosted by coupling to Next Generation Sequencing technologies. This review will focus on the development of several protocols for the application of Next Generation Sequencing (NGS) technologies to GW, which have been developed in the course of analysis of insertional libraries. These analyses find broad application in protocols for functional genomics and gene therapy. Thanks to the application of NGS technologies, the original vision of GW as a procedure for walking along an unknown genome is now changing into the possibility of observing the parallel marching of hundreds of thousands of primers across the borders of inserted DNA molecules in host genomes. Full article
(This article belongs to the Special Issue Next Generation Sequencing Approaches in Biology)
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Open AccessReview Inhibitors of HIV-1 Reverse Transcriptase—Associated Ribonuclease H Activity
Biology 2012, 1(3), 521-541; doi:10.3390/biology1030521
Received: 18 August 2012 / Revised: 26 September 2012 / Accepted: 27 September 2012 / Published: 19 October 2012
Cited by 15 | PDF Full-text (656 KB) | HTML Full-text | XML Full-text
Abstract
HIV-1 enzyme reverse transcriptase (RT) is a major target for antiviral drug development, with over half of current FDA-approved therapeutics against HIV infection targeting the DNA polymerase activity of this enzyme. HIV-1 RT is a multifunctional enzyme that has RNA and DNA [...] Read more.
HIV-1 enzyme reverse transcriptase (RT) is a major target for antiviral drug development, with over half of current FDA-approved therapeutics against HIV infection targeting the DNA polymerase activity of this enzyme. HIV-1 RT is a multifunctional enzyme that has RNA and DNA dependent polymerase activity, along with ribonuclease H (RNase H) activity. The latter is responsible for degradation of the viral genomic RNA template during first strand DNA synthesis to allow completion of reverse transcription and the viral dsDNA. While the RNase H activity of RT has been shown to be essential for virus infectivity, all currently used drugs directed at RT inhibit the polymerase activity of the enzyme; none target RNase H. In the last decade, the increasing prevalence of HIV variants resistant to clinically used antiretrovirals has stimulated the search for inhibitors directed at stages of HIV replication different than those targeted by current drugs. HIV RNase H is one such novel target and, over the past few years, significant progress has been made in identifying and characterizing new RNase H inhibitor pharmacophores. In this review we focus mainly on the most potent low micromolar potency compounds, as these provide logical bases for further development. We also discuss why HIV RNase H has been a difficult target for antiretroviral drug development. Full article
(This article belongs to the Special Issue Structural and Molecular Biology of HIV)
Open AccessReview Recent Advances and Future Perspectives in Microbial Phototrophy in Antarctic Sea Ice
Biology 2012, 1(3), 542-556; doi:10.3390/biology1030542
Received: 17 September 2012 / Revised: 10 October 2012 / Accepted: 11 October 2012 / Published: 22 October 2012
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Abstract
Bacteria that utilize sunlight to supplement metabolic activity are now being described in a range of ecosystems. While it is likely that phototrophy provides an important competitive advantage, the contribution that these microorganisms make to the bioenergetics of polar marine ecosystems is [...] Read more.
Bacteria that utilize sunlight to supplement metabolic activity are now being described in a range of ecosystems. While it is likely that phototrophy provides an important competitive advantage, the contribution that these microorganisms make to the bioenergetics of polar marine ecosystems is unknown. In this minireview, we discuss recent advances in our understanding of phototrophic bacteria and highlight the need for future research. Full article
Open AccessReview Changes in Cis-regulatory Elements during Morphological Evolution
Biology 2012, 1(3), 557-574; doi:10.3390/biology1030557
Received: 9 July 2012 / Revised: 30 August 2012 / Accepted: 9 October 2012 / Published: 25 October 2012
Cited by 6 | PDF Full-text (333 KB) | HTML Full-text | XML Full-text
Abstract
How have animals evolved new body designs (morphological evolution)? This requires explanations both for simple morphological changes, such as differences in pigmentation and hair patterns between different Drosophila populations and species, and also for more complex changes, such as differences in the [...] Read more.
How have animals evolved new body designs (morphological evolution)? This requires explanations both for simple morphological changes, such as differences in pigmentation and hair patterns between different Drosophila populations and species, and also for more complex changes, such as differences in the forelimbs of mice and bats, and the necks of amphibians and reptiles. The genetic changes and pathways involved in these evolutionary steps require identification. Many, though not all, of these events occur by changes in cis-regulatory (enhancer) elements within developmental genes. Enhancers are modular, each affecting expression in only one or a few tissues. Therefore it is possible to add, remove or alter an enhancer without producing changes in multiple tissues, and thereby avoid widespread (pleiotropic) deleterious effects. Ideally, for a given step in morphological evolution it is necessary to identify (i) the change in phenotype, (ii) the changes in gene expression, (iii) the DNA region, enhancer or otherwise, affected, (iv) the mutation involved, (v) the nature of the transcription or other factors that bind to this site. In practice these data are incomplete for most of the published studies upon morphological evolution. Here, the investigations are categorized according to how far these analyses have proceeded. Full article
(This article belongs to the Special Issue Gene Expression and Regulation)
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Open AccessReview Climate Change, Sea-Level Rise and Implications for Coastal and Estuarine Shoreline Management with Particular Reference to the Ecology of Intertidal Benthic Macrofauna in NW Europe
Biology 2012, 1(3), 597-616; doi:10.3390/biology1030597
Received: 3 September 2012 / Revised: 11 October 2012 / Accepted: 31 October 2012 / Published: 5 November 2012
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Abstract
In many European estuaries, extensive areas of intertidal habitats consist of bare mudflats and sandflats that harbour a very high abundance and biomass of macrobenthic invertebrates. The high stocks of macrobenthos in turn provide important food sources for the higher trophic levels [...] Read more.
In many European estuaries, extensive areas of intertidal habitats consist of bare mudflats and sandflats that harbour a very high abundance and biomass of macrobenthic invertebrates. The high stocks of macrobenthos in turn provide important food sources for the higher trophic levels such as fish and shorebirds. Climate change and associated sea-level rise will have potential to cause changes in coastal and estuarine physical properties in a number of ways and thereby influence the ecology of estuarine dependent organisms. Although the mechanisms involved in biological responses resulting from such environmental changes are complex, the ecological effects are likely to be significant for the estuarine benthic macrofauna and hence the consumers they support. This paper reviews the utilisation patterns of estuarine intertidal habitats by shorebirds, fish and crustaceans, as well as factors affecting the distribution, abundance and biomass of estuarine macrobenthos that is known to be important food source for these estuarine predators. This study also provides simple conceptual models of the likely impacts of sea-level rise on the physical and biological elements of estuarine intertidal habitats, and implications of these results are discussed in the context of sustainable long term flood and coastal management in estuarine environments. Full article
(This article belongs to the Special Issue Biological Implications of Climate Change)
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Open AccessReview Methods, Challenges and Potentials of Single Cell RNA-seq
Biology 2012, 1(3), 658-667; doi:10.3390/biology1030658
Received: 24 October 2012 / Revised: 24 October 2012 / Accepted: 7 November 2012 / Published: 16 November 2012
Cited by 12 | PDF Full-text (221 KB) | HTML Full-text | XML Full-text
Abstract
RNA-sequencing (RNA-seq) has become the tool of choice for transcriptomics. Several recent studies demonstrate its successful adaption to single cell analysis. This allows new biological insights into cell differentiation, cell-to-cell variation and gene regulation, and how these aspects depend on each other. [...] Read more.
RNA-sequencing (RNA-seq) has become the tool of choice for transcriptomics. Several recent studies demonstrate its successful adaption to single cell analysis. This allows new biological insights into cell differentiation, cell-to-cell variation and gene regulation, and how these aspects depend on each other. Here, I review the current single cell RNA-seq (scRNA-seq) efforts and discuss experimental protocols, challenges and potentials. Full article
(This article belongs to the Special Issue Next Generation Sequencing Approaches in Biology)
Open AccessReview Strategies to Block HIV Transcription: Focus on Small Molecule Tat Inhibitors
Biology 2012, 1(3), 668-697; doi:10.3390/biology1030668
Received: 11 October 2012 / Revised: 6 November 2012 / Accepted: 7 November 2012 / Published: 19 November 2012
Cited by 5 | PDF Full-text (408 KB) | HTML Full-text | XML Full-text
Abstract
After entry into the target cell, the human immunodeficiency virus type I (HIV) integrates into the host genome and becomes a proviral eukaryotic transcriptional unit. Transcriptional regulation of provirus gene expression is critical for HIV replication. Basal transcription from the integrated HIV [...] Read more.
After entry into the target cell, the human immunodeficiency virus type I (HIV) integrates into the host genome and becomes a proviral eukaryotic transcriptional unit. Transcriptional regulation of provirus gene expression is critical for HIV replication. Basal transcription from the integrated HIV promoter is very low in the absence of the HIV transactivator of transcription (Tat) protein and is solely dependent on cellular transcription factors. The 5' terminal region (+1 to +59) of all HIV mRNAs forms an identical stem-bulge-loop structure called the Transactivation Responsive (TAR) element. Once Tat is made, it binds to TAR and drastically activates transcription from the HIV LTR promoter. Mutations in either the Tat protein or TAR sequence usually affect HIV replication, indicating a strong requirement for their conservation. The necessity of the Tat-mediated transactivation cascade for robust HIV replication renders Tat one of the most desirable targets for transcriptional therapy against HIV replication. Screening based on inhibition of the Tat-TAR interaction has identified a number of potential compounds, but none of them are currently used as therapeutics, partly because these agents are not easily delivered for an efficient therapy, emphasizing the need for small molecule compounds. Here we will give an overview of the different strategies used to inhibit HIV transcription and review the current repertoire of small molecular weight compounds that target HIV transcription. Full article
(This article belongs to the Special Issue Structural and Molecular Biology of HIV)
Open AccessReview The Role of DNA Methylation in Common Skeletal Disorders
Biology 2012, 1(3), 698-713; doi:10.3390/biology1030698
Received: 25 September 2012 / Revised: 31 October 2012 / Accepted: 16 November 2012 / Published: 22 November 2012
Cited by 3 | PDF Full-text (237 KB) | HTML Full-text | XML Full-text
Abstract
Bone is a complex connective tissue characterized by a calcified extracellular matrix. This mineralized matrix is constantly being formed and resorbed throughout life, allowing the bone to adapt to daily mechanical loads and maintain skeletal properties and composition. The imbalance between bone [...] Read more.
Bone is a complex connective tissue characterized by a calcified extracellular matrix. This mineralized matrix is constantly being formed and resorbed throughout life, allowing the bone to adapt to daily mechanical loads and maintain skeletal properties and composition. The imbalance between bone formation and bone resorption leads to changes in bone mass. This is the case of osteoporosis and osteoarthritis, two common skeletal disorders. While osteoporosis is characterized by a decreased bone mass and, consequently, higher susceptibly to fractures, bone mass tends to be higher in patients with osteoarthritis, especially in the subchondral bone region. It is known that these diseases are influenced by heritable factors. However, the DNA polymorphisms identified so far in GWAS explain less than 10% of the genetic risk, suggesting that other factors, and specifically epigenetic mechanisms, are involved in the pathogenesis of these disorders. This review summarizes current knowledge about the influence of epigenetic marks on bone homeostasis, paying special attention to the role of DNA methylation in the onset and progression of osteoporosis and osteoarthritis. Full article
(This article belongs to the Special Issue Gene Expression and Regulation)
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Open AccessReview Recruitment of Transcription Complexes to Enhancers and the Role of Enhancer Transcription
Biology 2012, 1(3), 778-793; doi:10.3390/biology1030778
Received: 1 November 2012 / Revised: 21 November 2012 / Accepted: 21 November 2012 / Published: 5 December 2012
Cited by 2 | PDF Full-text (847 KB) | HTML Full-text | XML Full-text
Abstract
Enhancer elements regulate the tissue- and developmental-stage-specific expression of genes. Recent estimates suggest that there are more than 50,000 enhancers in mammalian cells. At least a subset of enhancers has been shown to recruit RNA polymerase II transcription complexes and to generate [...] Read more.
Enhancer elements regulate the tissue- and developmental-stage-specific expression of genes. Recent estimates suggest that there are more than 50,000 enhancers in mammalian cells. At least a subset of enhancers has been shown to recruit RNA polymerase II transcription complexes and to generate enhancer transcripts. Here, we provide an overview of enhancer function and discuss how transcription of enhancers or enhancer-generated transcripts could contribute to the regulation of gene expression during development and differentiation. Full article
(This article belongs to the Special Issue Gene Expression and Regulation)
Open AccessReview Managing Artificially Drained Low-Gradient Agricultural Headwaters for Enhanced Ecosystem Functions
Biology 2012, 1(3), 794-856; doi:10.3390/biology1030794
Received: 24 October 2012 / Revised: 1 November 2012 / Accepted: 2 November 2012 / Published: 10 December 2012
Cited by 7 | PDF Full-text (1217 KB) | HTML Full-text | XML Full-text
Abstract
Large tracts of lowlands have been drained to expand extensive agriculture into areas that were historically categorized as wasteland. This expansion in agriculture necessarily coincided with changes in ecosystem structure, biodiversity, and nutrient cycling. These changes have impacted not only the landscapes [...] Read more.
Large tracts of lowlands have been drained to expand extensive agriculture into areas that were historically categorized as wasteland. This expansion in agriculture necessarily coincided with changes in ecosystem structure, biodiversity, and nutrient cycling. These changes have impacted not only the landscapes in which they occurred, but also larger water bodies receiving runoff from drained land. New approaches must append current efforts toward land conservation and restoration, as the continuing impacts to receiving waters is an issue of major environmental concern. One of these approaches is agricultural drainage management. This article reviews how this approach differs from traditional conservation efforts, the specific practices of drainage management and the current state of knowledge on the ecology of drainage ditches. A bottom-up approach is utilized, examining the effects of stochastic hydrology and anthropogenic disturbance on primary production and diversity of primary producers, with special regard given to how management can affect establishment of macrophytes and how macrophytes in agricultural landscapes alter their environment in ways that can serve to mitigate non-point source pollution and promote biodiversity in receiving waters. Full article
Open AccessReview Genetic and Epigenetic Regulation of CCR5 Transcription
Biology 2012, 1(3), 869-879; doi:10.3390/biology1030869
Received: 7 October 2012 / Revised: 27 November 2012 / Accepted: 3 December 2012 / Published: 13 December 2012
Cited by 2 | PDF Full-text (1025 KB) | HTML Full-text | XML Full-text
Abstract
The chemokine receptor CCR5 regulates trafficking of immune cells of the lymphoid and the myeloid lineage (such as monocytes, macrophages and immature dendritic cells) and microglia. Because of this, there is an increasing recognition of the important role of CCR5 in the [...] Read more.
The chemokine receptor CCR5 regulates trafficking of immune cells of the lymphoid and the myeloid lineage (such as monocytes, macrophages and immature dendritic cells) and microglia. Because of this, there is an increasing recognition of the important role of CCR5 in the pathology of (neuro-) inflammatory diseases such as atherosclerosis and multiple sclerosis. Expression of CCR5 is under the control of a complexly organized promoter region upstream of the gene. The transcription factor cAMP-responsive element binding protein 1 (CREB-1) transactivates the CCR5 P1 promoter. The cell-specific expression of CCR5 however is realized by using various epigenetic marks providing a multivalent chromatin state particularly in monocytes. Here we discuss the transcriptional regulation of CCR5 with a focus on the epigenetic peculiarities of CCR5 transcription. Full article
(This article belongs to the Special Issue Gene Expression and Regulation)

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