cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.1263577.v4
title: Transcriptome-wide N<sup>6</sup>-methyladenosine profiling of rice callus and leaf reveals the presence of tissue-specific competitors involved in selective mRNA modification

description: <i>N</i><sup>6</sup>-methyladenosine (m<sup>6</sup>A) is the most prevalent internal modification present in mRNAs of all higher eukaryotes. With the development of MeRIP-seq technique, in-depth identification of mRNAs with m<sup>6</sup>A modification becomes feasible. Here we present a transcriptome-wide m<sup>6</sup>A modification profiling effort for rice transcriptomes of differentiated callus and leaf, which yields 8,138 and 14,253 m<sup>6</sup>A-modified genes, respectively. The m<sup>6</sup>A peak (m<sup>6</sup>A-modified nucleotide position on mRNAs) distribution exhibits preference toward both translation termination and initiation sites. The m<sup>6</sup>A peak enrichment is negatively correlated with gene expression and weakly positively correlated with certain gene features, such as exon length and number. By comparing m<sup>6</sup>A-modified genes between the 2 samples, we define 1,792 and 6,508 tissue-specific m<sup>6</sup>A-modified genes (TSMGs) in callus and leaf, respectively. Among which, 626 and 5,509 TSMGs are actively expressed in both tissues but are selectively m<sup>6</sup>A-modified (SMGs) only in one of the 2 tissues. Further analyses reveal characteristics of SMGs: (1) Most SMGs are differentially expressed between callus and leaf. (2) Two conserved RNA-binding motifs, predicted to be recognized by PUM and RNP4F, are significantly over-represented in SMGs. (3) GO enrichment analysis shows that SMGs in callus mainly participate in transcription regulator/factor activity whereas SMGs in leaf are mainly involved in plastid and thylakoid. Our results suggest the presence of tissue-specific competitors involved in SMGs. These findings provide a resource for plant RNA epitranscriptomic studies and further enlarge our knowledge on the function of RNA m<sup>6</sup>A modification.
DOI: 10.6084/m9.figshare.1263577.v3
title: Transcriptome-wide N<sup>6</sup>-methyladenosine profiling of rice callus and leaf reveals the presence of tissue-specific competitors involved in selective mRNA modification

description: <i>N</i><sup>6</sup>-methyladenosine (m<sup>6</sup>A) is the most prevalent internal modification present in mRNAs of all higher eukaryotes. With the development of MeRIP-seq technique, in-depth identification of mRNAs with m<sup>6</sup>A modification becomes feasible. Here we present a transcriptome-wide m<sup>6</sup>A modification profiling effort for rice transcriptomes of differentiated callus and leaf, which yields 8,138 and 14,253 m<sup>6</sup>A-modified genes, respectively. The m<sup>6</sup>A peak (m<sup>6</sup>A-modified nucleotide position on mRNAs) distribution exhibits preference toward both translation termination and initiation sites. The m<sup>6</sup>A peak enrichment is negatively correlated with gene expression and weakly positively correlated with certain gene features, such as exon length and number. By comparing m<sup>6</sup>A-modified genes between the 2 samples, we define 1,792 and 6,508 tissue-specific m<sup>6</sup>A-modified genes (TSMGs) in callus and leaf, respectively. Among which, 626 and 5,509 TSMGs are actively expressed in both tissues but are selectively m<sup>6</sup>A-modified (SMGs) only in one of the 2 tissues. Further analyses reveal characteristics of SMGs: (1) Most SMGs are differentially expressed between callus and leaf. (2) Two conserved RNA-binding motifs, predicted to be recognized by PUM and RNP4F, are significantly over-represented in SMGs. (3) GO enrichment analysis shows that SMGs in callus mainly participate in transcription regulator/factor activity whereas SMGs in leaf are mainly involved in plastid and thylakoid. Our results suggest the presence of tissue-specific competitors involved in SMGs. These findings provide a resource for plant RNA epitranscriptomic studies and further enlarge our knowledge on the function of RNA m<sup>6</sup>A modification.
DOI: 10.6084/m9.figshare.1266492
title: Regulation of Greatwall kinase by protein stabilization and nuclear localization

description: Greatwall (Gwl) functions as an essential mitotic kinase by antagonizing protein phosphatase 2A. In this study we identified Hsp90, Cdc37 and members of the importin α and β families as the major binding partners of Gwl. Both Hsp90/Cdc37 chaperone and importin complexes associated with the N-terminal kinase domain of Gwl, whereas an intact glycine-rich loop at the N-terminus of Gwl was essential for binding of Hsp90/Cdc37 but not importins. We found that Hsp90 inhibition led to destabilization of Gwl, a mechanism that may partially contribute to the emerging role of Hsp90 in cell cycle progression and the anti-proliferative potential of Hsp90 inhibition. Moreover, in agreement with its importin association, Gwl exhibited nuclear localization in interphase Xenopus S3 cells, and dynamic nucleocytoplasmic distribution during mitosis. We identified KR456/457 as the locus of importin binding and the functional NLS of Gwl. Mutation of this site resulted in exclusion of Gwl from the nucleus. Finally, we showed that the Gwl nuclear localization is indispensable for the biochemical function of Gwl in promoting mitotic entry.
DOI: 10.6084/m9.figshare.1266492.v1
title: Regulation of Greatwall kinase by protein stabilization and nuclear localization

description: Greatwall (Gwl) functions as an essential mitotic kinase by antagonizing protein phosphatase 2A. In this study we identified Hsp90, Cdc37 and members of the importin α and β families as the major binding partners of Gwl. Both Hsp90/Cdc37 chaperone and importin complexes associated with the N-terminal kinase domain of Gwl, whereas an intact glycine-rich loop at the N-terminus of Gwl was essential for binding of Hsp90/Cdc37 but not importins. We found that Hsp90 inhibition led to destabilization of Gwl, a mechanism that may partially contribute to the emerging role of Hsp90 in cell cycle progression and the anti-proliferative potential of Hsp90 inhibition. Moreover, in agreement with its importin association, Gwl exhibited nuclear localization in interphase Xenopus S3 cells, and dynamic nucleocytoplasmic distribution during mitosis. We identified KR456/457 as the locus of importin binding and the functional NLS of Gwl. Mutation of this site resulted in exclusion of Gwl from the nucleus. Finally, we showed that the Gwl nuclear localization is indispensable for the biochemical function of Gwl in promoting mitotic entry.
DOI: 10.6084/m9.figshare.1266492.v2
title: Regulation of Greatwall kinase by protein stabilization and nuclear localization

description: Greatwall (Gwl) functions as an essential mitotic kinase by antagonizing protein phosphatase 2A. In this study we identified Hsp90, Cdc37 and members of the importin α and β families as the major binding partners of Gwl. Both Hsp90/Cdc37 chaperone and importin complexes associated with the N-terminal kinase domain of Gwl, whereas an intact glycine-rich loop at the N-terminus of Gwl was essential for binding of Hsp90/Cdc37 but not importins. We found that Hsp90 inhibition led to destabilization of Gwl, a mechanism that may partially contribute to the emerging role of Hsp90 in cell cycle progression and the anti-proliferative potential of Hsp90 inhibition. Moreover, in agreement with its importin association, Gwl exhibited nuclear localization in interphase Xenopus S3 cells, and dynamic nucleocytoplasmic distribution during mitosis. We identified KR456/457 as the locus of importin binding and the functional NLS of Gwl. Mutation of this site resulted in exclusion of Gwl from the nucleus. Finally, we showed that the Gwl nuclear localization is indispensable for the biochemical function of Gwl in promoting mitotic entry.
DOI: 10.6084/m9.figshare.1266492.v3
title: Regulation of Greatwall kinase by protein stabilization and nuclear localization

description: Greatwall (Gwl) functions as an essential mitotic kinase by antagonizing protein phosphatase 2A. In this study we identified Hsp90, Cdc37 and members of the importin α and β families as the major binding partners of Gwl. Both Hsp90/Cdc37 chaperone and importin complexes associated with the N-terminal kinase domain of Gwl, whereas an intact glycine-rich loop at the N-terminus of Gwl was essential for binding of Hsp90/Cdc37 but not importins. We found that Hsp90 inhibition led to destabilization of Gwl, a mechanism that may partially contribute to the emerging role of Hsp90 in cell cycle progression and the anti-proliferative potential of Hsp90 inhibition. Moreover, in agreement with its importin association, Gwl exhibited nuclear localization in interphase Xenopus S3 cells, and dynamic nucleocytoplasmic distribution during mitosis. We identified KR456/457 as the locus of importin binding and the functional NLS of Gwl. Mutation of this site resulted in exclusion of Gwl from the nucleus. Finally, we showed that the Gwl nuclear localization is indispensable for the biochemical function of Gwl in promoting mitotic entry.
DOI: 10.6084/m9.figshare.1266494
title: Identification of DNA methylation changes at <i>cis</i>-regulatory elements during early steps of HSC differentiation using tagmentation-based whole genome bisulfite sequencing

description: Epigenetic alterations during cellular differentiation are a key molecular mechanism which both instructs and reinforces the process of lineage commitment. Within the haematopoietic system, progressive changes in the DNA methylome of haematopoietic stem cells (HSCs) are essential for the effective production of mature blood cells. Inhibition or loss of function of the cellular DNA methylation machinery has been shown to lead to a severe perturbation in blood production and is also an important driver of malignant transformation. HSCs constitute a very rare cell population in the bone marrow, capable of life-long self-renewal and multi-lineage differentiation. The low abundance of HSCs has been a major technological barrier to the global analysis of the CpG methylation status within both HSCs and their immediate progeny, the multipotent progenitors (MPPs). Within this Extra View article, we review the current understanding of how the DNA methylome regulates normal and malignant hematopoiesis. We also discuss the current methodologies that are available for interrogating the DNA methylation status of HSCs and MPPs and describe a new data set that was generated using tagmentation-based whole genome bisulfite sequencing (TWGBS) in order to comprehensively map methylated cytosines using the limited amount of genomic DNA that can be harvested from rare cell populations. Extended analysis of this data set clearly demonstrates the added value of genome-wide sequencing of methylated cytosines and identifies novel important <i>cis</i>-acting regulatory regions that are dynamically remodeled during the first steps of haematopoietic differentiation.
DOI: 10.6084/m9.figshare.1266494.v1
title: Identification of DNA methylation changes at <i>cis</i>-regulatory elements during early steps of HSC differentiation using tagmentation-based whole genome bisulfite sequencing

description: Epigenetic alterations during cellular differentiation are a key molecular mechanism which both instructs and reinforces the process of lineage commitment. Within the haematopoietic system, progressive changes in the DNA methylome of haematopoietic stem cells (HSCs) are essential for the effective production of mature blood cells. Inhibition or loss of function of the cellular DNA methylation machinery has been shown to lead to a severe perturbation in blood production and is also an important driver of malignant transformation. HSCs constitute a very rare cell population in the bone marrow, capable of life-long self-renewal and multi-lineage differentiation. The low abundance of HSCs has been a major technological barrier to the global analysis of the CpG methylation status within both HSCs and their immediate progeny, the multipotent progenitors (MPPs). Within this Extra View article, we review the current understanding of how the DNA methylome regulates normal and malignant hematopoiesis. We also discuss the current methodologies that are available for interrogating the DNA methylation status of HSCs and MPPs and describe a new data set that was generated using tagmentation-based whole genome bisulfite sequencing (TWGBS) in order to comprehensively map methylated cytosines using the limited amount of genomic DNA that can be harvested from rare cell populations. Extended analysis of this data set clearly demonstrates the added value of genome-wide sequencing of methylated cytosines and identifies novel important <i>cis</i>-acting regulatory regions that are dynamically remodeled during the first steps of haematopoietic differentiation.
DOI: 10.6084/m9.figshare.1266494.v2
title: Identification of DNA methylation changes at <i>cis</i>-regulatory elements during early steps of HSC differentiation using tagmentation-based whole genome bisulfite sequencing

description: Epigenetic alterations during cellular differentiation are a key molecular mechanism which both instructs and reinforces the process of lineage commitment. Within the haematopoietic system, progressive changes in the DNA methylome of haematopoietic stem cells (HSCs) are essential for the effective production of mature blood cells. Inhibition or loss of function of the cellular DNA methylation machinery has been shown to lead to a severe perturbation in blood production and is also an important driver of malignant transformation. HSCs constitute a very rare cell population in the bone marrow, capable of life-long self-renewal and multi-lineage differentiation. The low abundance of HSCs has been a major technological barrier to the global analysis of the CpG methylation status within both HSCs and their immediate progeny, the multipotent progenitors (MPPs). Within this Extra View article, we review the current understanding of how the DNA methylome regulates normal and malignant hematopoiesis. We also discuss the current methodologies that are available for interrogating the DNA methylation status of HSCs and MPPs and describe a new data set that was generated using tagmentation-based whole genome bisulfite sequencing (TWGBS) in order to comprehensively map methylated cytosines using the limited amount of genomic DNA that can be harvested from rare cell populations. Extended analysis of this data set clearly demonstrates the added value of genome-wide sequencing of methylated cytosines and identifies novel important <i>cis</i>-acting regulatory regions that are dynamically remodeled during the first steps of haematopoietic differentiation.
DOI: 10.6084/m9.figshare.1266494.v3
title: Identification of DNA methylation changes at <i>cis</i>-regulatory elements during early steps of HSC differentiation using tagmentation-based whole genome bisulfite sequencing

description: Epigenetic alterations during cellular differentiation are a key molecular mechanism which both instructs and reinforces the process of lineage commitment. Within the haematopoietic system, progressive changes in the DNA methylome of haematopoietic stem cells (HSCs) are essential for the effective production of mature blood cells. Inhibition or loss of function of the cellular DNA methylation machinery has been shown to lead to a severe perturbation in blood production and is also an important driver of malignant transformation. HSCs constitute a very rare cell population in the bone marrow, capable of life-long self-renewal and multi-lineage differentiation. The low abundance of HSCs has been a major technological barrier to the global analysis of the CpG methylation status within both HSCs and their immediate progeny, the multipotent progenitors (MPPs). Within this Extra View article, we review the current understanding of how the DNA methylome regulates normal and malignant hematopoiesis. We also discuss the current methodologies that are available for interrogating the DNA methylation status of HSCs and MPPs and describe a new data set that was generated using tagmentation-based whole genome bisulfite sequencing (TWGBS) in order to comprehensively map methylated cytosines using the limited amount of genomic DNA that can be harvested from rare cell populations. Extended analysis of this data set clearly demonstrates the added value of genome-wide sequencing of methylated cytosines and identifies novel important <i>cis</i>-acting regulatory regions that are dynamically remodeled during the first steps of haematopoietic differentiation.
DOI: 10.6084/m9.figshare.1266501
title: Semiparametric Estimation of Gamma Processes for Deteriorating Products

description: This article investigates the semiparametric inference of the simple Gamma-process model and a random-effects variant. Maximum likelihood estimates of the parameters are obtained through the EM algorithm. The bootstrap is used to construct confidence intervals. A simulation study reveals that an estimation based on the full likelihood method is more efficient than the pseudo likelihood method. In addition, a score test is developed to examine the existence of random effects under the semiparametric scenario. A comparison study using a fatigue-crack growth dataset shows that performance of a semiparametric estimation is comparable to the parametric counterpart. This article has supplementary material online.
DOI: 10.6084/m9.figshare.1266501.v2
title: Semiparametric Estimation of Gamma Processes for Deteriorating Products

description: This article investigates the semiparametric inference of the simple Gamma-process model and a random-effects variant. Maximum likelihood estimates of the parameters are obtained through the EM algorithm. The bootstrap is used to construct confidence intervals. A simulation study reveals that an estimation based on the full likelihood method is more efficient than the pseudo likelihood method. In addition, a score test is developed to examine the existence of random effects under the semiparametric scenario. A comparison study using a fatigue-crack growth dataset shows that performance of a semiparametric estimation is comparable to the parametric counterpart. This article has supplementary material online.
DOI: 10.6084/m9.figshare.1266501.v1
title: Semiparametric Estimation of Gamma Processes for Deteriorating Products

description: This article investigates the semiparametric inference of the simple Gamma-process model and a random-effects variant. Maximum likelihood estimates of the parameters are obtained through the EM algorithm. The bootstrap is used to construct confidence intervals. A simulation study reveals that an estimation based on the full likelihood method is more efficient than the pseudo likelihood method. In addition, a score test is developed to examine the existence of random effects under the semiparametric scenario. A comparison study using a fatigue-crack growth dataset shows that performance of a semiparametric estimation is comparable to the parametric counterpart. This article has supplementary material online.
DOI: 10.6084/m9.figshare.1266505
title: A D-Optimal Design for Estimation of Parameters of an Exponential-Linear Growth Curve of Nanostructures

description: We consider the problem of determining an optimal experimental design for estimation of parameters of a class of complex curves characterizing nanowire growth that is partially exponential and partially linear. Locally D-optimal designs for some of the models belonging to this class are obtained by using a geometric approach. Further, a Bayesian sequential algorithm is proposed for obtaining D-optimal designs for models with a closed-form solution, and for obtaining efficient designs in situations where theoretical results cannot be obtained. The advantages of the proposed algorithm over traditional approaches adopted in recently reported nanoexperiments are demonstrated using Monte Carlo simulations. The computer code implementing the sequential algorithm is available as supplementary materials.
DOI: 10.6084/m9.figshare.1266505.v1
title: A D-Optimal Design for Estimation of Parameters of an Exponential-Linear Growth Curve of Nanostructures

description: We consider the problem of determining an optimal experimental design for estimation of parameters of a class of complex curves characterizing nanowire growth that is partially exponential and partially linear. Locally D-optimal designs for some of the models belonging to this class are obtained by using a geometric approach. Further, a Bayesian sequential algorithm is proposed for obtaining D-optimal designs for models with a closed-form solution, and for obtaining efficient designs in situations where theoretical results cannot be obtained. The advantages of the proposed algorithm over traditional approaches adopted in recently reported nanoexperiments are demonstrated using Monte Carlo simulations. The computer code implementing the sequential algorithm is available as supplementary materials.
DOI: 10.6084/m9.figshare.1266505.v2
title: A D-Optimal Design for Estimation of Parameters of an Exponential-Linear Growth Curve of Nanostructures

description: We consider the problem of determining an optimal experimental design for estimation of parameters of a class of complex curves characterizing nanowire growth that is partially exponential and partially linear. Locally D-optimal designs for some of the models belonging to this class are obtained by using a geometric approach. Further, a Bayesian sequential algorithm is proposed for obtaining D-optimal designs for models with a closed-form solution, and for obtaining efficient designs in situations where theoretical results cannot be obtained. The advantages of the proposed algorithm over traditional approaches adopted in recently reported nanoexperiments are demonstrated using Monte Carlo simulations. The computer code implementing the sequential algorithm is available as supplementary materials.
DOI: 10.6084/m9.figshare.1270351
title: VDR regulation of microRNA differs across prostate cell models suggesting extremely flexible control of transcription

description: The Vitamin D Receptor (VDR) is a member of the nuclear receptor superfamily and is of therapeutic interest in cancer and other settings. Regulation of microRNA (miRNA) by the VDR appears to be important to mediate its actions, for example, to control cell growth. To identify if and to what extent VDR-regulated miRNA patterns change in prostate cancer progression, we undertook miRNA microarray analyses in 7 cell models representing non-malignant and malignant prostate cells (RWPE-1, RWPE-2, HPr1, HPr1AR, LNCaP, LNCaP-C4–2, and PC-3). To focus on primary VDR regulatory events, we undertook expression analyses after 30 minutes treatment with 1α,25(OH)<sub>2</sub>D<sub>3</sub>. Across all models, 111 miRNAs were significantly modulated by 1α,25(OH)<sub>2</sub>D<sub>3</sub> treatment. Of these, only 5 miRNAs were modulated in more than one cell model, and of these, only 3 miRNAs were modulated in the same direction. The patterns of miRNA regulation, and the networks they targeted, significantly distinguished the different cell types. Integration of 1α,25(OH)<sub>2</sub>D<sub>3</sub>-regulated miRNAs with published VDR ChIP-seq data showed significant enrichment of VDR peaks in flanking regions of miRNAs. Furthermore, mRNA and miRNA expression analyses in non-malignant RWPE-1 cells revealed patterns of miRNA and mRNA co-regulation; specifically, 13 significant reciprocal patterns were identified and these patterns were also observed in TCGA prostate cancer data. Lastly, motif search analysis revealed differential motif enrichment within VDR peaks flanking mRNA compared to miRNA genes. Together, this study revealed that miRNAs are rapidly regulated in a highly cell-type specific manner, and are significantly co-integrated with mRNA regulation.