cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.1304578.v1
title: Nuclear transcriptome profiling of induced pluripotent stem cells and embryonic stem cells identify non-coding loci resistant to reprogramming

description: ABSTRACTIdentification of functionally relevant differences between induced pluripotent stem cells (iPSC) and reference embryonic stem cells (ESC) remains a central question for therapeutic applications. Differences in gene expression between iPSC and ESC have been examined by microarray and more recently with RNA-SEQ technologies. We here report an in depth analyses of nuclear and cytoplasmic transcriptomes, using the CAGE (cap analysis of gene expression) technology, for five iPSC clones derived from mouse lymphocytes B and three ESC lines. This approach reveals nuclear transcriptomes significantly more complex in ESC than in iPSC. Hundreds of yet not annotated putative non-coding RNAs and enhancer-associated transcripts specifically transcribed in ESC have been detected and supported with epigenetic and chromatin-chromatin interactions data. We identified super-enhancers transcriptionally active specifically in ESC and associated with genes implicated in the maintenance of pluripotency. Similarly, we detected non-coding transcripts of yet unknown function being regulated by ESC specific super-enhancers. Taken together, these results demonstrate that current protocols of iPSC reprogramming do not trigger activation of numerous <i>cis</i>-regulatory regions. It thus reinforces the need for already suggested deeper monitoring of the non-coding transcriptome when characterizing iPSC clones. Such differences in regulatory transcript expression may indeed impact their potential for clinical applications.
DOI: 10.6084/m9.figshare.1304582.v3
title: Human Nek7-interactor RGS2 is required for mitotic spindle organization

description: The mitotic spindle apparatus is composed of microtubule (MT) networks attached to kinetochores organized from 2 centrosomes (a.k.a. spindle poles). In addition to this central spindle apparatus, astral MTs assemble at the mitotic spindle pole and attach to the cell cortex to ensure appropriate spindle orientation. We propose that cell cycle-related kinase, Nek7, and its novel interacting protein RGS2, are involved in mitosis regulation and spindle formation. We found that RGS2 localizes to the mitotic spindle in a Nek7-dependent manner, and along with Nek7 contributes to spindle morphology and mitotic spindle pole integrity. RGS2-depletion leads to a mitotic-delay and severe defects in the chromosomes alignment and congression. Importantly, RGS2 or Nek7 depletion or even overexpression of wild-type or kinase-dead Nek7, reduced γ-tubulin from the mitotic spindle poles. In addition to causing a mitotic delay, RGS2 depletion induced mitotic spindle misorientation coinciding with astral MT-reduction. We propose that these phenotypes directly contribute to a failure in mitotic spindle alignment to the substratum. In conclusion, we suggest a molecular mechanism whereupon Nek7 and RGS2 may act cooperatively to ensure proper mitotic spindle organization.
DOI: 10.6084/m9.figshare.1304582.v5
title: Human Nek7-interactor RGS2 is required for mitotic spindle organization

description: The mitotic spindle apparatus is composed of microtubule (MT) networks attached to kinetochores organized from 2 centrosomes (a.k.a. spindle poles). In addition to this central spindle apparatus, astral MTs assemble at the mitotic spindle pole and attach to the cell cortex to ensure appropriate spindle orientation. We propose that cell cycle-related kinase, Nek7, and its novel interacting protein RGS2, are involved in mitosis regulation and spindle formation. We found that RGS2 localizes to the mitotic spindle in a Nek7-dependent manner, and along with Nek7 contributes to spindle morphology and mitotic spindle pole integrity. RGS2-depletion leads to a mitotic-delay and severe defects in the chromosomes alignment and congression. Importantly, RGS2 or Nek7 depletion or even overexpression of wild-type or kinase-dead Nek7, reduced γ-tubulin from the mitotic spindle poles. In addition to causing a mitotic delay, RGS2 depletion induced mitotic spindle misorientation coinciding with astral MT-reduction. We propose that these phenotypes directly contribute to a failure in mitotic spindle alignment to the substratum. In conclusion, we suggest a molecular mechanism whereupon Nek7 and RGS2 may act cooperatively to ensure proper mitotic spindle organization.
DOI: 10.6084/m9.figshare.1304578.v2
title: Nuclear transcriptome profiling of induced pluripotent stem cells and embryonic stem cells identify non-coding loci resistant to reprogramming

description: Identification of functionally relevant differences between induced pluripotent stem cells (iPSC) and reference embryonic stem cells (ESC) remains a central question for therapeutic applications. Differences in gene expression between iPSC and ESC have been examined by microarray and more recently with RNA-SEQ technologies. We here report an in depth analyses of nuclear and cytoplasmic transcriptomes, using the CAGE (cap analysis of gene expression) technology, for 5 iPSC clones derived from mouse lymphocytes B and 3 ESC lines. This approach reveals nuclear transcriptomes significantly more complex in ESC than in iPSC. Hundreds of yet not annotated putative non-coding RNAs and enhancer-associated transcripts specifically transcribed in ESC have been detected and supported with epigenetic and chromatin-chromatin interactions data. We identified super-enhancers transcriptionally active specifically in ESC and associated with genes implicated in the maintenance of pluripotency. Similarly, we detected non-coding transcripts of yet unknown function being regulated by ESC specific super-enhancers. Taken together, these results demonstrate that current protocols of iPSC reprogramming do not trigger activation of numerous <i>cis</i>-regulatory regions. It thus reinforces the need for already suggested deeper monitoring of the non-coding transcriptome when characterizing iPSC clones. Such differences in regulatory transcript expression may indeed impact their potential for clinical applications.
DOI: 10.6084/m9.figshare.1304582.v4
title: Human Nek7-interactor RGS2 is required for mitotic spindle organization

description: The mitotic spindle apparatus is composed of microtubule (MT) networks attached to kinetochores organized from 2 centrosomes (a.k.a. spindle poles). In addition to this central spindle apparatus, astral MTs assemble at the mitotic spindle pole and attach to the cell cortex to ensure appropriate spindle orientation. We propose that cell cycle-related kinase, Nek7, and its novel interacting protein RGS2, are involved in mitosis regulation and spindle formation. We found that RGS2 localizes to the mitotic spindle in a Nek7-dependent manner, and along with Nek7 contributes to spindle morphology and mitotic spindle pole integrity. RGS2-depletion leads to a mitotic-delay and severe defects in the chromosomes alignment and congression. Importantly, RGS2 or Nek7 depletion or even overexpression of wild-type or kinase-dead Nek7, reduced γ-tubulin from the mitotic spindle poles. In addition to causing a mitotic delay, RGS2 depletion induced mitotic spindle misorientation coinciding with astral MT-reduction. We propose that these phenotypes directly contribute to a failure in mitotic spindle alignment to the substratum. In conclusion, we suggest a molecular mechanism whereupon Nek7 and RGS2 may act cooperatively to ensure proper mitotic spindle organization.
DOI: 10.6084/m9.figshare.1304578.v3
title: Nuclear transcriptome profiling of induced pluripotent stem cells and embryonic stem cells identify non-coding loci resistant to reprogramming

description: Identification of functionally relevant differences between induced pluripotent stem cells (iPSC) and reference embryonic stem cells (ESC) remains a central question for therapeutic applications. Differences in gene expression between iPSC and ESC have been examined by microarray and more recently with RNA-SEQ technologies. We here report an in depth analyses of nuclear and cytoplasmic transcriptomes, using the CAGE (cap analysis of gene expression) technology, for 5 iPSC clones derived from mouse lymphocytes B and 3 ESC lines. This approach reveals nuclear transcriptomes significantly more complex in ESC than in iPSC. Hundreds of yet not annotated putative non-coding RNAs and enhancer-associated transcripts specifically transcribed in ESC have been detected and supported with epigenetic and chromatin-chromatin interactions data. We identified super-enhancers transcriptionally active specifically in ESC and associated with genes implicated in the maintenance of pluripotency. Similarly, we detected non-coding transcripts of yet unknown function being regulated by ESC specific super-enhancers. Taken together, these results demonstrate that current protocols of iPSC reprogramming do not trigger activation of numerous <i>cis</i>-regulatory regions. It thus reinforces the need for already suggested deeper monitoring of the non-coding transcriptome when characterizing iPSC clones. Such differences in regulatory transcript expression may indeed impact their potential for clinical applications.
DOI: 10.6084/m9.figshare.1304573
title: Out-of-Position Rear Impact Tissue-Level Investigation Using Detailed Finite Element Neck Model

description: <b>Objective:</b> Whiplash injuries can occur in automotive crashes and may cause long-term health issues such as neck pain, headache, and visual and auditory disturbance. Evidence suggests that nonneutral head posture can significantly increase the potential for injury in a given impact scenario, but epidemiological and experimental data are limited and do not provide a quantitative assessment of the increased potential for injury. Although there have been some attempts to evaluate this important issue using finite element models, none to date have successfully addressed this complex problem. <b>Methods:</b> An existing detailed finite element neck model was evaluated in nonneutral positions and limitations were identified, including musculature implementation and attachment, upper cervical spine kinematics in axial rotation, prediction of ligament failure, and the need for repositioning the model while incorporating initial tissue strains. The model was enhanced to address these issues and an iterative procedure was used to determine the upper cervical spine ligament laxities. The neck model was revalidated using neutral position impacts and compared to an out-of-position cadaver experiment in the literature. The effects of nonneutral position (axial head rotation) coupled with muscle activation were studied at varying impact levels. <b>Results:</b> The laxities for the ligaments of the upper cervical spine were determined using 4 load cases and resulted in improved response and predicted failure loads relative to experimental data. The predicted head response from the model was similar to an experimental head-turned bench-top rear impact experiment. The parametric study identified specific ligaments with increased distractions due to an initial head-turned posture and the effect of active musculature leading to reduced ligament distractions. <b>Conclusions:</b> The incorporation of ligament laxity in the upper cervical spine was essential to predict range of motion and traumatic response, particularly for repositioning of the neck model prior to impact. The results of this study identify a higher potential for injury in out-of-position rear collisions and identified at-risk locations based on ligament distractions. The model predicted higher potential for injury by as much as 50% based on ligament distraction for the out-of-position posture and reduced potential for injury with muscle activation. Importantly, this study demonstrated that the location of injury or pain depends on the initial occupant posture, so that both the location of injury and kinematic threshold may vary when considering common head positions while driving.
DOI: 10.6084/m9.figshare.1304578.v4
title: Nuclear transcriptome profiling of induced pluripotent stem cells and embryonic stem cells identify non-coding loci resistant to reprogramming

description: Identification of functionally relevant differences between induced pluripotent stem cells (iPSC) and reference embryonic stem cells (ESC) remains a central question for therapeutic applications. Differences in gene expression between iPSC and ESC have been examined by microarray and more recently with RNA-SEQ technologies. We here report an in depth analyses of nuclear and cytoplasmic transcriptomes, using the CAGE (cap analysis of gene expression) technology, for 5 iPSC clones derived from mouse lymphocytes B and 3 ESC lines. This approach reveals nuclear transcriptomes significantly more complex in ESC than in iPSC. Hundreds of yet not annotated putative non-coding RNAs and enhancer-associated transcripts specifically transcribed in ESC have been detected and supported with epigenetic and chromatin-chromatin interactions data. We identified super-enhancers transcriptionally active specifically in ESC and associated with genes implicated in the maintenance of pluripotency. Similarly, we detected non-coding transcripts of yet unknown function being regulated by ESC specific super-enhancers. Taken together, these results demonstrate that current protocols of iPSC reprogramming do not trigger activation of numerous <i>cis</i>-regulatory regions. It thus reinforces the need for already suggested deeper monitoring of the non-coding transcriptome when characterizing iPSC clones. Such differences in regulatory transcript expression may indeed impact their potential for clinical applications.
DOI: 10.6084/m9.figshare.1304578.v6
title: Nuclear transcriptome profiling of induced pluripotent stem cells and embryonic stem cells identify non-coding loci resistant to reprogramming

description: Identification of functionally relevant differences between induced pluripotent stem cells (iPSC) and reference embryonic stem cells (ESC) remains a central question for therapeutic applications. Differences in gene expression between iPSC and ESC have been examined by microarray and more recently with RNA-SEQ technologies. We here report an in depth analyses of nuclear and cytoplasmic transcriptomes, using the CAGE (cap analysis of gene expression) technology, for 5 iPSC clones derived from mouse lymphocytes B and 3 ESC lines. This approach reveals nuclear transcriptomes significantly more complex in ESC than in iPSC. Hundreds of yet not annotated putative non-coding RNAs and enhancer-associated transcripts specifically transcribed in ESC have been detected and supported with epigenetic and chromatin-chromatin interactions data. We identified super-enhancers transcriptionally active specifically in ESC and associated with genes implicated in the maintenance of pluripotency. Similarly, we detected non-coding transcripts of yet unknown function being regulated by ESC specific super-enhancers. Taken together, these results demonstrate that current protocols of iPSC reprogramming do not trigger activation of numerous <i>cis</i>-regulatory regions. It thus reinforces the need for already suggested deeper monitoring of the non-coding transcriptome when characterizing iPSC clones. Such differences in regulatory transcript expression may indeed impact their potential for clinical applications.
DOI: 10.6084/m9.figshare.1304570
title: 50_T_T

description: Archive with graphs.
DOI: 10.6084/m9.figshare.1304569
title: Development of Equitable Algorithms for Road Funds Allocation in Developing Countries: A Case Study of Sub-Saharan Africa

description: PhD Thesis: Stage 2 E-Delphi panel completed questionnaires used in the development of equitable algorithms for road funds allocation in developing countries with particular emphasis on Sub-Saharan Africa
DOI: 10.6084/m9.figshare.1304570.v1
title: 50_T_T

description: Archive with graphs.
DOI: 10.6084/m9.figshare.1304578.v5
title: Nuclear transcriptome profiling of induced pluripotent stem cells and embryonic stem cells identify non-coding loci resistant to reprogramming

description: Identification of functionally relevant differences between induced pluripotent stem cells (iPSC) and reference embryonic stem cells (ESC) remains a central question for therapeutic applications. Differences in gene expression between iPSC and ESC have been examined by microarray and more recently with RNA-SEQ technologies. We here report an in depth analyses of nuclear and cytoplasmic transcriptomes, using the CAGE (cap analysis of gene expression) technology, for 5 iPSC clones derived from mouse lymphocytes B and 3 ESC lines. This approach reveals nuclear transcriptomes significantly more complex in ESC than in iPSC. Hundreds of yet not annotated putative non-coding RNAs and enhancer-associated transcripts specifically transcribed in ESC have been detected and supported with epigenetic and chromatin-chromatin interactions data. We identified super-enhancers transcriptionally active specifically in ESC and associated with genes implicated in the maintenance of pluripotency. Similarly, we detected non-coding transcripts of yet unknown function being regulated by ESC specific super-enhancers. Taken together, these results demonstrate that current protocols of iPSC reprogramming do not trigger activation of numerous <i>cis</i>-regulatory regions. It thus reinforces the need for already suggested deeper monitoring of the non-coding transcriptome when characterizing iPSC clones. Such differences in regulatory transcript expression may indeed impact their potential for clinical applications.
DOI: 10.6084/m9.figshare.1304569.v1
title: Development of Equitable Algorithms for Road Funds Allocation in Developing Countries: A Case Study of Sub-Saharan Africa

description: PhD Thesis: Stage 2 E-Delphi panel completed questionnaires used in the development of equitable algorithms for road funds allocation in developing countries with particular emphasis on Sub-Saharan Africa
DOI: 10.6084/m9.figshare.1304573.v1
title: Out-of-Position Rear Impact Tissue Level Investigation using Detailed Finite Element Neck Model

description: <b>Objective</b> Whiplash injuries can occur in automotive crashes and may cause long term health issues such as neck pain, headache, and visual and auditory disturbance. Evidence suggests that non-neutral head posture can significantly increase the potential for injury in a given impact scenario but epidemiological and experimental data is limited and does not provide a quantitative assessment of the increased potential for injury. Although there have been some attempts to evaluate this important issue using finite element models, none to date have successfully addressed this complex problem. <b>Methods</b> An existing detailed Finite Element neck model was evaluated in non-neutral positions and limitations were identified including musculature implementation and attachment, upper cervical spine kinematics in axial rotation, prediction of ligament failure, and the need for repositioning the model while incorporating initial tissue strains. The model was enhanced to address these issues and an iterative procedure was used to determine the upper cervical spine ligament laxities. The neck model was revalidated using neutral position impacts and compared to an out-of-position cadaver experiment in the literature. The effects of non-neutral position (axial head rotation) coupled with muscle activation were studied at varying impact levels. <b>Results</b> The laxities for the ligaments of the upper cervical spine were determined using four load cases and resulted in improved response and predicted failure loads relative to experimental data. The predicted head response from the model was similar to an experimental head-turned bench-top rear impact experiment. The parametric study identified specific ligaments with increased distractions due to an initial head-turned posture, and the effect of active musculature leading to reduced ligament distractions. <b>Conclusions</b> The incorporation of ligament laxity in the upper cervical spine was essential to predict range of motion and traumatic response, particularly for repositioning of the neck model prior to impact. The results of this study identify a higher potential for injury in out-of-position rear collisions and identified at-risk locations based on ligament distractions. The model predicted higher potential for injury by as much as 50% based on ligament distraction for the out-of-position posture and reduced potential for injury with muscle activation. Importantly, this study demonstrated that the location of injury or pain depends on the initial occupant posture, so that both the location of injury and kinematic threshold may vary when considering common head positions while driving.
DOI: 10.6084/m9.figshare.1304573.v3
title: Out-of-Position Rear Impact Tissue-Level Investigation Using Detailed Finite Element Neck Model

description: <b>Objective:</b> Whiplash injuries can occur in automotive crashes and may cause long-term health issues such as neck pain, headache, and visual and auditory disturbance. Evidence suggests that nonneutral head posture can significantly increase the potential for injury in a given impact scenario, but epidemiological and experimental data are limited and do not provide a quantitative assessment of the increased potential for injury. Although there have been some attempts to evaluate this important issue using finite element models, none to date have successfully addressed this complex problem. <b>Methods:</b> An existing detailed finite element neck model was evaluated in nonneutral positions and limitations were identified, including musculature implementation and attachment, upper cervical spine kinematics in axial rotation, prediction of ligament failure, and the need for repositioning the model while incorporating initial tissue strains. The model was enhanced to address these issues and an iterative procedure was used to determine the upper cervical spine ligament laxities. The neck model was revalidated using neutral position impacts and compared to an out-of-position cadaver experiment in the literature. The effects of nonneutral position (axial head rotation) coupled with muscle activation were studied at varying impact levels. <b>Results:</b> The laxities for the ligaments of the upper cervical spine were determined using 4 load cases and resulted in improved response and predicted failure loads relative to experimental data. The predicted head response from the model was similar to an experimental head-turned bench-top rear impact experiment. The parametric study identified specific ligaments with increased distractions due to an initial head-turned posture and the effect of active musculature leading to reduced ligament distractions. <b>Conclusions:</b> The incorporation of ligament laxity in the upper cervical spine was essential to predict range of motion and traumatic response, particularly for repositioning of the neck model prior to impact. The results of this study identify a higher potential for injury in out-of-position rear collisions and identified at-risk locations based on ligament distractions. The model predicted higher potential for injury by as much as 50% based on ligament distraction for the out-of-position posture and reduced potential for injury with muscle activation. Importantly, this study demonstrated that the location of injury or pain depends on the initial occupant posture, so that both the location of injury and kinematic threshold may vary when considering common head positions while driving.
DOI: 10.6084/m9.figshare.1304540
title: 25_T_T

description: Archive with graphs.
DOI: 10.6084/m9.figshare.1304541
title: 25_T_F

description: Archive with graphs.