cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.1378748.v2
title: Design criteria for synthetic riboswitches acting on transcription

description: Riboswitches are RNA-based regulators of gene expression composed of a ligand-sensing aptamer domain followed by an overlapping expression platform. The regulation occurs at either the level of transcription (by formation of terminator or antiterminator structures) or translation (by presentation or sequestering of the ribosomal binding site). Due to a modular composition, these elements can be manipulated by combining different aptamers and expression platforms and therefore represent useful tools to regulate gene expression in synthetic biology. Using computationally designed theophylline-dependent riboswitches we show that 2 parameters, terminator hairpin stability and folding traps, have a major impact on the functionality of the designed constructs. These have to be considered very carefully during design phase. Furthermore, a combination of several copies of individual riboswitches leads to a much improved activation ratio between induced and uninduced gene activity and to a linear dose-dependent increase in reporter gene expression. Such serial arrangements of synthetic riboswitches closely resemble their natural counterparts and may form the basis for simple quantitative read out systems for the detection of specific target molecules in the cell.
DOI: 10.6084/m9.figshare.1378749.v3
title: RBM4-MEF2C network constitutes a feed-forward circuit that facilitates the differentiation of brown adipocytes

description: Myocyte enhancer factor 2c (MEF2C) is the MADS-box type transcription factor involved in the differentiation of cardiac and skeletal muscle and synaptic formation. Alternatively spliced transcripts of the <i>MEF2C</i> gene were proven to encode isoforms which exert distinct functions in transcriptional regulation. During the differentiation of brown adipocytes, upregulated RBM4 enhanced skipping of the <i>MEF2C</i>γ region which functions as a transcriptional repressor. The presence of an overexpressed MEF2Cγ- isoform in turn induced transcriptional activity of the <i>RBM4</i> promoter, constituting a positive feedback circuit in differentiating brown adipocytes. The RBM4-MEF2Cγ- network induced the expression of "myogenic" miR-1 to a greater extent than did <i>PRDM17, BMP7 C/EBP</i>β, or <i>UCP1</i> transcripts in C3H10T1/2 cells. Overexpression of miR-1 independently exerted the same activity as RBM4 and the MEF2Cγ- isoform of upregulating brown adipocyte-specific factors in C3H10T1/2 cells, which suggests a potential effect of miR-1 on brown adipocytes. These results indicated that the RBM4-MEF2C-miR-1 network constitutes a novel mechanism which programs the gene expression profile toward the development of brown adipocytes.
DOI: 10.6084/m9.figshare.1378748.v4
title: Design criteria for synthetic riboswitches acting on transcription

description: Riboswitches are RNA-based regulators of gene expression composed of a ligand-sensing aptamer domain followed by an overlapping expression platform. The regulation occurs at either the level of transcription (by formation of terminator or antiterminator structures) or translation (by presentation or sequestering of the ribosomal binding site). Due to a modular composition, these elements can be manipulated by combining different aptamers and expression platforms and therefore represent useful tools to regulate gene expression in synthetic biology. Using computationally designed theophylline-dependent riboswitches we show that 2 parameters, terminator hairpin stability and folding traps, have a major impact on the functionality of the designed constructs. These have to be considered very carefully during design phase. Furthermore, a combination of several copies of individual riboswitches leads to a much improved activation ratio between induced and uninduced gene activity and to a linear dose-dependent increase in reporter gene expression. Such serial arrangements of synthetic riboswitches closely resemble their natural counterparts and may form the basis for simple quantitative read out systems for the detection of specific target molecules in the cell.
DOI: 10.6084/m9.figshare.1378746.v1
title: Transcriptional profiling of <i>Bordetella pertussis</i> reveals requirement of RNA chaperone Hfq for Type III secretion system functionality

description: <i>Bordetella pertussis</i>, the causative agent of human whooping cough (pertussis) produces a complex array of virulence factors in order to establish efficient infection in the host. The RNA chaperone Hfq and small regulatory RNAs are key players in posttranscriptional regulation in bacteria and have been shown to play an essential role in virulence of a broad spectrum of bacterial pathogens. This study represents the first attempt to characterize the Hfq regulon of the human pathogen <i>B. pertussis</i> under laboratory conditions as well as upon passage in the host and indicates that loss of Hfq has a profound effect on gene expression in <i>B. pertussis</i>. Comparative transcriptional profiling revealed that Hfq is required for expression of several virulence factors in <i>B. pertussis</i> cells including the Type III secretion system (T3SS). In striking contrast to the wt strain, T3SS did not become operational in the <i>hfq</i> mutant passaged either through mice or macrophages thereby proving that Hfq is required for the functionality of the <i>B. pertussis</i> T3SS. Likewise, expression of virulence factors <i>vag8</i> and <i>tcfA</i> encoding autotransporter and tracheal colonization factor, respectively, was strongly reduced in the <i>hfq</i> mutant. Importantly, for the first time we demonstrate that <i>B. pertussis</i> T3SS can be activated upon contact with macrophage cells <i>in vitro</i>.
DOI: 10.6084/m9.figshare.1378745.v1
title: The VrrA sRNA controls a stationary phase survival factor Vrp of <i>Vibrio cholerae</i>

description: Small non-coding RNAs (sRNAs) are emerging regulatory elements in bacteria. The <i>Vibrio cholerae</i> sRNA VrrA has previously been shown to down-regulate outer membrane proteins (OmpA and OmpT) and biofilm matrix protein (RbmC) by base-pairing with the 5′ region of the corresponding mRNAs. In this study, we present an additional target of VrrA in <i>V. cholerae</i>, the mRNA coding for the ribosome binding protein Vrp. Vrp is homologous to ribosome-associated inhibitor A (RaiA) of <i>Escherichia coli</i> which facilitates stationary phase survival through ribosome hibernation. We show that VrrA down-regulates Vrp protein synthesis by base-pairing to the 5′ region of <i>vrp</i> mRNA and that the regulation requires the RNA chaperone protein, Hfq. We further demonstrate that Vrp is highly expressed during stationary phase growth and associates with the ribosome of <i>V. cholerae</i>. The effect of the Vrp protein in starvation survival is synergistic with that of the VC2530 protein, a homolog of the <i>E. coli</i> hibernation promoting factor HPF, suggesting a combined role for these proteins in ribosome hibernation in <i>V. cholerae</i>. Vrp and VC2530 are important for <i>V. cholerae</i> starvation survival under nutrient deficient conditions. While VC2530 is down-regulated in cells lacking <i>vrrA</i>, mutation of <i>vrp</i> results in VC2530 activation. This is the first report indicating a regulatory role for an sRNA, modulating stationary factors involved in bacterial ribosome hibernation.
DOI: 10.6084/m9.figshare.1378748.v3
title: Design criteria for synthetic riboswitches acting on transcription

description: Riboswitches are RNA-based regulators of gene expression composed of a ligand-sensing aptamer domain followed by an overlapping expression platform. The regulation occurs at either the level of transcription (by formation of terminator or antiterminator structures) or translation (by presentation or sequestering of the ribosomal binding site). Due to a modular composition, these elements can be manipulated by combining different aptamers and expression platforms and therefore represent useful tools to regulate gene expression in synthetic biology. Using computationally designed theophylline-dependent riboswitches we show that 2 parameters, terminator hairpin stability and folding traps, have a major impact on the functionality of the designed constructs. These have to be considered very carefully during design phase. Furthermore, a combination of several copies of individual riboswitches leads to a much improved activation ratio between induced and uninduced gene activity and to a linear dose-dependent increase in reporter gene expression. Such serial arrangements of synthetic riboswitches closely resemble their natural counterparts and may form the basis for simple quantitative read out systems for the detection of specific target molecules in the cell.
DOI: 10.6084/m9.figshare.1378746.v2
title: Transcriptional profiling of <i>Bordetella pertussis</i> reveals requirement of RNA chaperone Hfq for Type III secretion system functionality

description: <i>Bordetella pertussis</i>, the causative agent of human whooping cough (pertussis) produces a complex array of virulence factors in order to establish efficient infection in the host. The RNA chaperone Hfq and small regulatory RNAs are key players in posttranscriptional regulation in bacteria and have been shown to play an essential role in virulence of a broad spectrum of bacterial pathogens. This study represents the first attempt to characterize the Hfq regulon of the human pathogen <i>B. pertussis</i> under laboratory conditions as well as upon passage in the host and indicates that loss of Hfq has a profound effect on gene expression in <i>B. pertussis</i>. Comparative transcriptional profiling revealed that Hfq is required for expression of several virulence factors in <i>B. pertussis</i> cells including the Type III secretion system (T3SS). In striking contrast to the wt strain, T3SS did not become operational in the <i>hfq</i> mutant passaged either through mice or macrophages thereby proving that Hfq is required for the functionality of the <i>B. pertussis</i> T3SS. Likewise, expression of virulence factors <i>vag8</i> and <i>tcfA</i> encoding autotransporter and tracheal colonization factor, respectively, was strongly reduced in the <i>hfq</i> mutant. Importantly, for the first time we demonstrate that <i>B. pertussis</i> T3SS can be activated upon contact with macrophage cells <i>in vitro</i>.
DOI: 10.6084/m9.figshare.1378745.v2
title: The VrrA sRNA controls a stationary phase survival factor Vrp of <i>Vibrio cholerae</i>

description: Small non-coding RNAs (sRNAs) are emerging regulatory elements in bacteria. The <i>Vibrio cholerae</i> sRNA VrrA has previously been shown to down-regulate outer membrane proteins (OmpA and OmpT) and biofilm matrix protein (RbmC) by base-pairing with the 5′ region of the corresponding mRNAs. In this study, we present an additional target of VrrA in <i>V. cholerae</i>, the mRNA coding for the ribosome binding protein Vrp. Vrp is homologous to ribosome-associated inhibitor A (RaiA) of <i>Escherichia coli</i> which facilitates stationary phase survival through ribosome hibernation. We show that VrrA down-regulates Vrp protein synthesis by base-pairing to the 5′ region of <i>vrp</i> mRNA and that the regulation requires the RNA chaperone protein, Hfq. We further demonstrate that Vrp is highly expressed during stationary phase growth and associates with the ribosome of <i>V. cholerae</i>. The effect of the Vrp protein in starvation survival is synergistic with that of the VC2530 protein, a homolog of the <i>E. coli</i> hibernation promoting factor HPF, suggesting a combined role for these proteins in ribosome hibernation in <i>V. cholerae</i>. Vrp and VC2530 are important for <i>V. cholerae</i> starvation survival under nutrient deficient conditions. While VC2530 is down-regulated in cells lacking <i>vrrA</i>, mutation of <i>vrp</i> results in VC2530 activation. This is the first report indicating a regulatory role for an sRNA, modulating stationary factors involved in bacterial ribosome hibernation.
DOI: 10.6084/m9.figshare.1378746.v4
title: Transcriptional profiling of <i>Bordetella pertussis</i> reveals requirement of RNA chaperone Hfq for Type III secretion system functionality

description: <i>Bordetella pertussis</i>, the causative agent of human whooping cough (pertussis) produces a complex array of virulence factors in order to establish efficient infection in the host. The RNA chaperone Hfq and small regulatory RNAs are key players in posttranscriptional regulation in bacteria and have been shown to play an essential role in virulence of a broad spectrum of bacterial pathogens. This study represents the first attempt to characterize the Hfq regulon of the human pathogen <i>B. pertussis</i> under laboratory conditions as well as upon passage in the host and indicates that loss of Hfq has a profound effect on gene expression in <i>B. pertussis</i>. Comparative transcriptional profiling revealed that Hfq is required for expression of several virulence factors in <i>B. pertussis</i> cells including the Type III secretion system (T3SS). In striking contrast to the wt strain, T3SS did not become operational in the <i>hfq</i> mutant passaged either through mice or macrophages thereby proving that Hfq is required for the functionality of the <i>B. pertussis</i> T3SS. Likewise, expression of virulence factors <i>vag8</i> and <i>tcfA</i> encoding autotransporter and tracheal colonization factor, respectively, was strongly reduced in the <i>hfq</i> mutant. Importantly, for the first time we demonstrate that <i>B. pertussis</i> T3SS can be activated upon contact with macrophage cells <i>in vitro</i>.
DOI: 10.6084/m9.figshare.1378745.v4
title: The VrrA sRNA controls a stationary phase survival factor Vrp of <i>Vibrio cholerae</i>

description: Small non-coding RNAs (sRNAs) are emerging regulatory elements in bacteria. The <i>Vibrio cholerae</i> sRNA VrrA has previously been shown to down-regulate outer membrane proteins (OmpA and OmpT) and biofilm matrix protein (RbmC) by base-pairing with the 5′ region of the corresponding mRNAs. In this study, we present an additional target of VrrA in <i>V. cholerae</i>, the mRNA coding for the ribosome binding protein Vrp. Vrp is homologous to ribosome-associated inhibitor A (RaiA) of <i>Escherichia coli</i> which facilitates stationary phase survival through ribosome hibernation. We show that VrrA down-regulates Vrp protein synthesis by base-pairing to the 5′ region of <i>vrp</i> mRNA and that the regulation requires the RNA chaperone protein, Hfq. We further demonstrate that Vrp is highly expressed during stationary phase growth and associates with the ribosome of <i>V. cholerae</i>. The effect of the Vrp protein in starvation survival is synergistic with that of the VC2530 protein, a homolog of the <i>E. coli</i> hibernation promoting factor HPF, suggesting a combined role for these proteins in ribosome hibernation in <i>V. cholerae</i>. Vrp and VC2530 are important for <i>V. cholerae</i> starvation survival under nutrient deficient conditions. While VC2530 is down-regulated in cells lacking <i>vrrA</i>, mutation of <i>vrp</i> results in VC2530 activation. This is the first report indicating a regulatory role for an sRNA, modulating stationary factors involved in bacterial ribosome hibernation.
DOI: 10.6084/m9.figshare.1378746.v3
title: Transcriptional profiling of <i>Bordetella pertussis</i> reveals requirement of RNA chaperone Hfq for Type III secretion system functionality

description: <i>Bordetella pertussis</i>, the causative agent of human whooping cough (pertussis) produces a complex array of virulence factors in order to establish efficient infection in the host. The RNA chaperone Hfq and small regulatory RNAs are key players in posttranscriptional regulation in bacteria and have been shown to play an essential role in virulence of a broad spectrum of bacterial pathogens. This study represents the first attempt to characterize the Hfq regulon of the human pathogen <i>B. pertussis</i> under laboratory conditions as well as upon passage in the host and indicates that loss of Hfq has a profound effect on gene expression in <i>B. pertussis</i>. Comparative transcriptional profiling revealed that Hfq is required for expression of several virulence factors in <i>B. pertussis</i> cells including the Type III secretion system (T3SS). In striking contrast to the wt strain, T3SS did not become operational in the <i>hfq</i> mutant passaged either through mice or macrophages thereby proving that Hfq is required for the functionality of the <i>B. pertussis</i> T3SS. Likewise, expression of virulence factors <i>vag8</i> and <i>tcfA</i> encoding autotransporter and tracheal colonization factor, respectively, was strongly reduced in the <i>hfq</i> mutant. Importantly, for the first time we demonstrate that <i>B. pertussis</i> T3SS can be activated upon contact with macrophage cells <i>in vitro</i>.
DOI: 10.6084/m9.figshare.1378745.v3
title: The VrrA sRNA controls a stationary phase survival factor Vrp of <i>Vibrio cholerae</i>

description: Small non-coding RNAs (sRNAs) are emerging regulatory elements in bacteria. The <i>Vibrio cholerae</i> sRNA VrrA has previously been shown to down-regulate outer membrane proteins (OmpA and OmpT) and biofilm matrix protein (RbmC) by base-pairing with the 5′ region of the corresponding mRNAs. In this study, we present an additional target of VrrA in <i>V. cholerae</i>, the mRNA coding for the ribosome binding protein Vrp. Vrp is homologous to ribosome-associated inhibitor A (RaiA) of <i>Escherichia coli</i> which facilitates stationary phase survival through ribosome hibernation. We show that VrrA down-regulates Vrp protein synthesis by base-pairing to the 5′ region of <i>vrp</i> mRNA and that the regulation requires the RNA chaperone protein, Hfq. We further demonstrate that Vrp is highly expressed during stationary phase growth and associates with the ribosome of <i>V. cholerae</i>. The effect of the Vrp protein in starvation survival is synergistic with that of the VC2530 protein, a homolog of the <i>E. coli</i> hibernation promoting factor HPF, suggesting a combined role for these proteins in ribosome hibernation in <i>V. cholerae</i>. Vrp and VC2530 are important for <i>V. cholerae</i> starvation survival under nutrient deficient conditions. While VC2530 is down-regulated in cells lacking <i>vrrA</i>, mutation of <i>vrp</i> results in VC2530 activation. This is the first report indicating a regulatory role for an sRNA, modulating stationary factors involved in bacterial ribosome hibernation.
DOI: 10.6084/m9.figshare.1378727
title: Extended MaxT Tests of One-Sided Hypotheses

description: In many statistical applications of one-sided tests of multiple hypotheses researchers are often concerned not only with global tests of the intersection of individual hypotheses, but also with multiple tests of individual hypotheses. For example, in clinical trial studies researchers often need to find out the efficacy of a treatment, as well as the significance of each outcome measurement (endpoint) of the treatment. This article proposes MaxT type tests aiming at improving the global power of existing MaxT tests. Our extended MaxT tests are constructed by adding an extra component to the maximand set of existing MaxT tests. The added component is a weighted sum of other components. Some power properties relating to choices of weight are studied. Our simulation study shows that the proposed tests can considerably improve the global power of existing MaxT tests and can also outperform many other global tests under some alternatives and/or some nonnormal distributions. Furthermore, it is shown that such global power improvement may involve little loss of power on multiple testing. Two real data examples on clinical trial studies reported in the literature are reexamined. The results of our tests suggest stronger evidence on treatment effects over MaxT tests and likelihood ratio tests while changing little on the evidence concerning endpoint testing. Supplementary materials for this article are available online.
DOI: 10.6084/m9.figshare.1378727.v1
title: Extended MaxT Tests of One-Sided Hypotheses

description: In many statistical applications of one-sided tests of multiple hypotheses researchers are often concerned not only with global tests of the intersection of individual hypotheses, but also with multiple tests of individual hypotheses. For example, in clinical trial studies researchers often need to find out the efficacy of a treatment, as well as the significance of each outcome measurement (endpoint) of the treatment. This article proposes MaxT type tests aiming at improving the global power of existing MaxT tests. Our extended MaxT tests are constructed by adding an extra component to the maximand set of existing MaxT tests. The added component is a weighted sum of other components. Some power properties relating to choices of weight are studied. Our simulation study shows that the proposed tests can considerably improve the global power of existing MaxT tests and can also outperform many other global tests under some alternatives and/or some nonnormal distributions. Furthermore, it is shown that such global power improvement may involve little loss of power on multiple testing. Two real data examples on clinical trial studies reported in the literature are reexamined. The results of our tests suggest stronger evidence on treatment effects over MaxT tests and likelihood ratio tests while changing little on the evidence concerning endpoint testing. Supplementary materials for this article are available online.
DOI: 10.6084/m9.figshare.1378709
title: Sulfide intrusion and detoxification in the seagrass Zostera marina - dataset

description: Raw data for : Sulfide intrusion and detoxification in the seagrass Zostera marina
DOI: 10.6084/m9.figshare.1378709.v1
title: sulfide detox data

description: Raw data for : Sulfide intrusion and detoxification in the seagrass Zostera marina
DOI: 10.6084/m9.figshare.1378697
title: Deciphering the RNA landscape by RNAome sequencing

description: Current RNA expression profiling methods rely on enrichment steps for specific RNA classes, thereby not detecting all RNA species in an unperturbed manner. We report strand-specific RNAome sequencing that determines expression of small and large RNAs from rRNA-depleted total RNA in a single sequence run. Since current analysis pipelines cannot reliably analyze small and large RNAs simultaneously, we developed TRAP, Total Rna Analysis Pipeline, a robust interface that is also compatible with existing RNA sequencing protocols. RNAome sequencing quantitatively preserved all RNA classes, allowing cross-class comparisons that facilitates the identification of relationships between different RNA classes. We demonstrate the strength of RNAome sequencing in mouse embryonic stem cells treated with cisplatin. MicroRNA and mRNA expression in RNAome sequencing significantly correlated between replicates and was in concordance with both existing RNA sequencing methods and gene expression arrays generated from the same samples. Moreover, RNAome sequencing also detected additional RNA classes such as enhancer RNAs, anti-sense RNAs, novel RNA species and numerous differentially expressed RNAs undetectable by other methods. At the level of complete RNA classes, RNAome sequencing also identified a specific global repression of the microRNA and microRNA isoform classes after cisplatin treatment whereas all other classes such as mRNAs were unchanged. These characteristics of RNAome sequencing will significantly improve expression analysis as well as studies on RNA biology not covered by existing methods.
DOI: 10.6084/m9.figshare.1378709.v2
title: Sulfide intrusion and detoxification in the seagrass Zostera marina - dataset

description: Raw data for : Sulfide intrusion and detoxification in the seagrass Zostera marina
DOI: 10.6084/m9.figshare.1378695
title: Raw Data for Urban woodland & matrix

description: Raw bat activity data collected from surveying urban woodlands in Central Scotland in 2011.