cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.10608305
title: Inactivation of Mdm2 restores apoptosis proficiency of cooperativity mutant p53 in vivo

description: <i>TP53</i> mutations are found in 50% of all cancers and mutated <i>TP53</i> status is considered poor for treatment. However, some <i>TP53</i> mutations exhibit only partial loss-of-function (LOF), meaning they retain residual transcriptional and non-transcriptional activities that are potentially beneficial for therapy. Earlier we have characterized a knock-in mouse model for the partial LOF mutant <i>Trp53<sup>E177R</sup></i> (p53RR). Reduced DNA binding cooperativity of this mutant led to the loss of p53-dependent apoptosis, while p53 functions in cell cycle control, senescence, metabolism, and antioxidant defense remained intact. Concomitantly, tumor suppression was evident but strongly compromised compared to wild-type mice. Here we used the <i>Trp53<sup>E177R</sup></i> mouse as a model to investigate whether residual functions of mutant p53 can be engaged to induce cell death, which is considered the most desirable outcome of tumor therapy. We made use of <i>Mdm2</i> knock-out in developing embryos as a sensitive tool for detecting remaining p53 activities. Genetic ablation of <i>Mdm2</i> led to embryonic lethality in <i>Trp53<sup>E177R/E177R</sup></i> homozygotes at days 9.5–11.5. This effect was not rescued by concomitant p21-knockout, indicating its independence of p21-mediated cell cycle arrest. Instead, immunohistochemical analysis showed widespread apoptosis in tissues of defective embryos accompanied by persistent accumulation of p53RR protein. This led to partial restoration of the mutant’s proficiency in transcriptional induction of the pro-apoptotic genes <i>Bbc3</i> (Puma) and <i>Bax</i>. These data indicate that increased quantity can compensate for qualitative defects of p53 mutants and suggest that Mdm2-targeting (potentially in combination with other drugs) might be effective against cells bearing p53 partial LOF mutants.
DOI: 10.6084/m9.figshare.10921601
title: DNA damage responses in murine Pre-B cells with genetic deficiencies in damage response genes

description: DNA damage can be generated in multiple ways from genotoxic and physiologic sources. Genotoxic damage is known to disrupt cellular functions and is lethal if not repaired properly. We compare the transcriptional programs activated in response to genotoxic DNA damage induced by ionizing radiation (IR) in abl pre-B cells from mice deficient in DNA damage response (DDR) genes <i>Atm, Mre11, Mdc1, H2ax, 53bp1</i>, and <i>DNA-PKcs</i>. We identified a core IR-specific transcriptional response that occurs in abl pre-B cells from WT mice and compared the response of the other genotypes to the WT response. We also identified genotype specific responses and compared those to each other. The WT response includes many processes involved in lymphocyte development and immune response, as well as responses associated with the molecular mechanisms of cancer, such as TP53 signaling. As expected, there is a range of similarity in transcriptional profiles in comparison to WT cells, with <i>Atm</i>-/- cells being the most different from the core WT DDR and <i>Mre11</i> hypomorph (<i>Mre11<sup>A/A</sup></i>) cells also very dissimilar to WT and other genotypes. For example, NF-kB-related signaling and CD40 signaling are deficient in both <i>Atm</i>-/- and <i>Mre11<sup>A/A</sup></i> cells, but present in all other genotypes. In contrast, IR-induced TP53 signaling is seen in the <i>Mre11<sup>A/A</sup></i> cells, while these responses are not seen in the <i>Atm</i>-/- cells. By examining the similarities and differences in the signaling pathways in response to IR when specific genes are absent, our results further illustrate the contribution of each gene to the DDR. The microarray gene expression data discussed in this paper have been deposited in NCBI’s Gene Expression Omnibus (GEO) (http://www.ncbi.nlm.nih.gov/geo/) and are accessible under accession number GSE116388.
DOI: 10.6084/m9.figshare.10608305.v1
title: Inactivation of Mdm2 restores apoptosis proficiency of cooperativity mutant p53 in vivo

description: <i>TP53</i> mutations are found in 50% of all cancers and mutated <i>TP53</i> status is considered poor for treatment. However, some <i>TP53</i> mutations exhibit only partial loss-of-function (LOF), meaning they retain residual transcriptional and non-transcriptional activities that are potentially beneficial for therapy. Earlier we have characterized a knock-in mouse model for the partial LOF mutant <i>Trp53<sup>E177R</sup></i> (p53RR). Reduced DNA binding cooperativity of this mutant led to the loss of p53-dependent apoptosis, while p53 functions in cell cycle control, senescence, metabolism, and antioxidant defense remained intact. Concomitantly, tumor suppression was evident but strongly compromised compared to wild-type mice. Here we used the <i>Trp53<sup>E177R</sup></i> mouse as a model to investigate whether residual functions of mutant p53 can be engaged to induce cell death, which is considered the most desirable outcome of tumor therapy. We made use of <i>Mdm2</i> knock-out in developing embryos as a sensitive tool for detecting remaining p53 activities. Genetic ablation of <i>Mdm2</i> led to embryonic lethality in <i>Trp53<sup>E177R/E177R</sup></i> homozygotes at days 9.5–11.5. This effect was not rescued by concomitant p21-knockout, indicating its independence of p21-mediated cell cycle arrest. Instead, immunohistochemical analysis showed widespread apoptosis in tissues of defective embryos accompanied by persistent accumulation of p53RR protein. This led to partial restoration of the mutant’s proficiency in transcriptional induction of the pro-apoptotic genes <i>Bbc3</i> (Puma) and <i>Bax</i>. These data indicate that increased quantity can compensate for qualitative defects of p53 mutants and suggest that Mdm2-targeting (potentially in combination with other drugs) might be effective against cells bearing p53 partial LOF mutants.
DOI: 10.6084/m9.figshare.11558883.v1
title: METTL3-mediated m<sup>6</sup>A is required for murine oocyte maturation and maternal-to-zygotic transition

description: N<sup>6</sup>-methyladenosine (m<sup>6</sup>A) is the most prevalent epigenetic modification of messenger RNA (mRNA) in higher eukaryotes; this modification is mainly catalyzed by a methyltransferase complex including methyltransferase-like 3 (METTL3) as a key factor. Although m<sup>6</sup>A modification has been proven to play an essential role in diverse biological processes, our knowledge of <i>Mettl3</i> is still limited because <i>Mettl3</i> mutations are lethal to embryos in both mammals and plants. In this study, we knocked down <i>Mettl3</i> by microinjection of its specific short interfering RNAs (siRNAs) or morpholino into fully grown germinal vesicle (GV) oocytes. As a result, we demonstrated that knocking down <i>Mettl3</i> in female germ cells severely inhibited oocyte maturation by decreasing mRNA translation efficiency and led to defects in the maternal-to-zygotic transition, probably due to its interference in disrupting mRNA degradation. The discovery from this study suggests that the reversible m<sup>6</sup>A modification has vital functions in mammalian oocyte maturation and pre-implantation embryonic development processes.
DOI: 10.6084/m9.figshare.11667309.v1
title: The microtubule targeting agents eribulin and paclitaxel activate similar signaling pathways and induce cell death predominantly in a caspase-independent manner

description: Microtubule-targeting agents (MTAs) are the most effective chemotherapeutics used in cancer therapy to date, but their clinical use is often hampered by the acquisition of resistance. Thereby, elucidation of the molecular signaling pathways activated by novel FDA-approved MTAs such as eribulin is important for future therapeutic applications. In contrast to several reports, we show here that regardless of the presence of caspase-3, clinically relevant concentrations of eribulin and the classical MTA paclitaxel predominantly induce caspase-independent cell death in MCF-7 breast carcinoma cells. On the molecular level, several key proteins involved in apoptosis such as p53, Plk1, caspase-2, and Bim as well as the two MAPKs ERK and JNK were activated by both compounds to a similar extent. However, none of them proved to be important for eribulin- and paclitaxel-induced cytotoxicity, as their siRNA-mediated knockdown or inactivation by small molecule inhibitors did not alter cell death rates. In contrast, knockdown of the anti-apoptotic Bcl-2 protein, which becomes heavily phosphorylated at Ser70 during MTA treatment, resulted surprisingly in a reduction of MTA-mediated cell death. This phenomenon can be most likely explained by our observation that the absence of Bcl-2 slowed down cell cycle progression resulting in fewer cells entering mitosis, thereby delaying the mitotic capability of these MTAs to induce cell death. Taken together, although eribulin and paclitaxel disturb the mitotic spindle differently, they exhibit no functional differences in downstream molecular cell death signaling in MCF-7 breast cancer cells.
DOI: 10.6084/m9.figshare.11667909
title: WIP1 dephosphorylation of p27<sup>Kip1</sup> Serine 140 destabilizes p27<sup>Kip1</sup> and reverses anti-proliferative effects of ATM phosphorylation

description: The phosphoinositide-3-kinase like kinases (PIKK) such as ATM and ATR play a key role in initiating the cellular DNA damage response (DDR). One key ATM target is the cyclin-dependent kinase inhibitor p27<sup>Kip1</sup> that promotes G1 arrest. ATM activates p27<sup>Kip1</sup>-induced arrest in part through phosphorylation of p27<sup>Kip1</sup> at Serine 140. Here we show that this site is dephosphorylated by the type 2C serine/threonine phosphatase, WIP1 (Wildtype p53-Induced Phosphatase-1), encoded by the <i>PPM1D</i> gene. WIP1 has been shown to dephosphorylate numerous ATM target sites in DDR proteins, and its overexpression and/or mutation has often been associated with oncogenesis. We demonstrate that wildtype, but not phosphatase-dead WIP1, efficiently dephosphorylates p27<sup>Kip1</sup> Ser140 both in vitro and in cells and that this dephosphorylation is sensitive to the WIP1-specific inhibitor GSK 2830371. Increased expression of wildtype WIP1 reduces stability of p27<sup>Kip1</sup> while increased expression of similar amounts of phosphatase-dead WIP1 has no effect on p27<sup>Kip1</sup> protein stability. Overexpression of wildtype p27<sup>Kip1</sup> reduces cell proliferation and colony forming capability relative to the S140A (constitutively non-phosphorylated) form of p27. Thus, WIP1 plays a significant role in homeostatic modulation of p27<sup>Kip1</sup> activity following activation by ATM.
DOI: 10.6084/m9.figshare.11667909.v1
title: WIP1 dephosphorylation of p27<sup>Kip1</sup> Serine 140 destabilizes p27<sup>Kip1</sup> and reverses anti-proliferative effects of ATM phosphorylation

description: The phosphoinositide-3-kinase like kinases (PIKK) such as ATM and ATR play a key role in initiating the cellular DNA damage response (DDR). One key ATM target is the cyclin-dependent kinase inhibitor p27<sup>Kip1</sup> that promotes G1 arrest. ATM activates p27<sup>Kip1</sup>-induced arrest in part through phosphorylation of p27<sup>Kip1</sup> at Serine 140. Here we show that this site is dephosphorylated by the type 2C serine/threonine phosphatase, WIP1 (Wildtype p53-Induced Phosphatase-1), encoded by the <i>PPM1D</i> gene. WIP1 has been shown to dephosphorylate numerous ATM target sites in DDR proteins, and its overexpression and/or mutation has often been associated with oncogenesis. We demonstrate that wildtype, but not phosphatase-dead WIP1, efficiently dephosphorylates p27<sup>Kip1</sup> Ser140 both in vitro and in cells and that this dephosphorylation is sensitive to the WIP1-specific inhibitor GSK 2830371. Increased expression of wildtype WIP1 reduces stability of p27<sup>Kip1</sup> while increased expression of similar amounts of phosphatase-dead WIP1 has no effect on p27<sup>Kip1</sup> protein stability. Overexpression of wildtype p27<sup>Kip1</sup> reduces cell proliferation and colony forming capability relative to the S140A (constitutively non-phosphorylated) form of p27. Thus, WIP1 plays a significant role in homeostatic modulation of p27<sup>Kip1</sup> activity following activation by ATM.
DOI: 10.6084/m9.figshare.11558883
title: METTL3-mediated m<sup>6</sup>A is required for murine oocyte maturation and maternal-to-zygotic transition

description: N<sup>6</sup>-methyladenosine (m<sup>6</sup>A) is the most prevalent epigenetic modification of messenger RNA (mRNA) in higher eukaryotes; this modification is mainly catalyzed by a methyltransferase complex including methyltransferase-like 3 (METTL3) as a key factor. Although m<sup>6</sup>A modification has been proven to play an essential role in diverse biological processes, our knowledge of <i>Mettl3</i> is still limited because <i>Mettl3</i> mutations are lethal to embryos in both mammals and plants. In this study, we knocked down <i>Mettl3</i> by microinjection of its specific short interfering RNAs (siRNAs) or morpholino into fully grown germinal vesicle (GV) oocytes. As a result, we demonstrated that knocking down <i>Mettl3</i> in female germ cells severely inhibited oocyte maturation by decreasing mRNA translation efficiency and led to defects in the maternal-to-zygotic transition, probably due to its interference in disrupting mRNA degradation. The discovery from this study suggests that the reversible m<sup>6</sup>A modification has vital functions in mammalian oocyte maturation and pre-implantation embryonic development processes.
DOI: 10.6084/m9.figshare.11667309
title: The microtubule targeting agents eribulin and paclitaxel activate similar signaling pathways and induce cell death predominantly in a caspase-independent manner

description: Microtubule-targeting agents (MTAs) are the most effective chemotherapeutics used in cancer therapy to date, but their clinical use is often hampered by the acquisition of resistance. Thereby, elucidation of the molecular signaling pathways activated by novel FDA-approved MTAs such as eribulin is important for future therapeutic applications. In contrast to several reports, we show here that regardless of the presence of caspase-3, clinically relevant concentrations of eribulin and the classical MTA paclitaxel predominantly induce caspase-independent cell death in MCF-7 breast carcinoma cells. On the molecular level, several key proteins involved in apoptosis such as p53, Plk1, caspase-2, and Bim as well as the two MAPKs ERK and JNK were activated by both compounds to a similar extent. However, none of them proved to be important for eribulin- and paclitaxel-induced cytotoxicity, as their siRNA-mediated knockdown or inactivation by small molecule inhibitors did not alter cell death rates. In contrast, knockdown of the anti-apoptotic Bcl-2 protein, which becomes heavily phosphorylated at Ser70 during MTA treatment, resulted surprisingly in a reduction of MTA-mediated cell death. This phenomenon can be most likely explained by our observation that the absence of Bcl-2 slowed down cell cycle progression resulting in fewer cells entering mitosis, thereby delaying the mitotic capability of these MTAs to induce cell death. Taken together, although eribulin and paclitaxel disturb the mitotic spindle differently, they exhibit no functional differences in downstream molecular cell death signaling in MCF-7 breast cancer cells.
DOI: 10.5287/bodleian:j1vv56vjq
title: MSP COHORT GDM SCREEN
DOI: 10.6084/m9.figshare.19375355.v1
title: Gene Trees

description: Gene trees of PD Machinery components in our surveyed taxa
DOI: 10.6084/m9.figshare.19375355
title: Gene Trees

description: Gene trees of PD Machinery components in our surveyed taxa
DOI: 10.6084/m9.figshare.19375358
title: OrthoFinder Results

description: Raw OrthoFinder results
DOI: 10.6084/m9.figshare.19375358.v1
title: OrthoFinder Results

description: Raw OrthoFinder results
DOI: 10.5281/zenodo.6359001
title: What energy infrastructure to support 1.5°C scenarios? - Scenario data

description: This excel file summarizes the main assumptions considered for the analysis " What energy infrastructure to support 1.5°C scenarios?", prepared by Artelys on behalf of the European Climate Foundation in 2020. The report is available here: https://www.artelys.com/wp-content/uploads/2020/12/Artelys-2050EnergyInfrastructureNeeds.pdf
DOI: 10.5281/zenodo.6359000
title: What energy infrastructure to support 1.5°C scenarios? - Scenario data

description: This excel file summarizes the main assumptions considered for the analysis " What energy infrastructure to support 1.5°C scenarios?", prepared by Artelys on behalf of the European Climate Foundation in 2020. The report is available here: https://www.artelys.com/wp-content/uploads/2020/12/Artelys-2050EnergyInfrastructureNeeds.pdf
DOI: 10.34740/kaggle/dsv/3313378
title: UNET Lung Segmentation Weights for Chest X Rays
DOI: 10.5286/isis.e.rb2210278
title: Spectroscopic Neutron Imaging to Resolve Electrolyte Degradation in Operando Fast-Charging Li-Ion Batteries

description: In this experiment, we will further develop time-of-flight neutron imaging (ToF-NI) as a spectroscopic method to investigate the physical and chemical state of the electrolyte in Li-ion batteries (LIBs) after failure due to fast-charging protocols and under the influence of external temperature variations. This will allow: 1) to track the effects of temperature gradients in LIB electrolytes without invasive probes, 2) to correlate the effects of fast charging (up to 5C) to electrochemical performance, electrolyte health, and cycle life in LIBs, and 3) to correlate the variations of 1H neutron cross-sections (1HCS) to chemical changes due to degradation processes in the electrolytes. This experiment is a follow up of our latest findings, where we use ToF-NI to differentiate between CHn bonds in liquid organic molecules by calculating their 1HCS.
DOI: 10.5286/isis.e.rb2210278-1
title: Spectroscopic Neutron Imaging to Resolve Electrolyte Degradation in Operando Fast-Charging Li-Ion Batteries

description: In this experiment, we will further develop time-of-flight neutron imaging (ToF-NI) as a spectroscopic method to investigate the physical and chemical state of the electrolyte in Li-ion batteries (LIBs) after failure due to fast-charging protocols and under the influence of external temperature variations. This will allow: 1) to track the effects of temperature gradients in LIB electrolytes without invasive probes, 2) to correlate the effects of fast charging (up to 5C) to electrochemical performance, electrolyte health, and cycle life in LIBs, and 3) to correlate the variations of 1H neutron cross-sections (1HCS) to chemical changes due to degradation processes in the electrolytes. This experiment is a follow up of our latest findings, where we use ToF-NI to differentiate between CHn bonds in liquid organic molecules by calculating their 1HCS.
DOI: 10.6084/m9.figshare.19375493
title: Updated data extraction sheet COVID vaccine 18.12.2021.xlsx

description: Extracted data from vaccine safety studies
DOI: 10.6084/m9.figshare.19375328.v1
title: Untitled Item

description: This is the online appendix we intend to publish as supplementary material to the literature review paper. It shows our selection criteria for the papers, our quality assessment criteria, and the complete analysis of papers reviewed.
DOI: 10.6084/m9.figshare.19375328
title: Systematic Literature Review Supplementary Material

description: This is the online appendix we intend to publish as supplementary material to the literature review paper. It shows our selection criteria for the papers, our quality assessment criteria, and the complete analysis of papers reviewed.
DOI: 10.6084/m9.figshare.19375328.v3
title: Systematic Literature Review Supplementary Material

description: This is the online appendix we intend to publish as supplementary material to the literature review paper. It shows our selection criteria for the papers, our quality assessment criteria, and the complete analysis of papers reviewed.
DOI: 10.6084/m9.figshare.19375328.v2
title: Systematic Literature Review Supplementary Material

description: This is the online appendix we intend to publish as supplementary material to the literature review paper. It shows our selection criteria for the papers, our quality assessment criteria, and the complete analysis of papers reviewed.
DOI: 10.25403/upresearchdata.12702326
title: Cochlear dimensions

description: The document provides a complete table of typical cochlear dimensions compiled from the literature and the corresponding dimensions measured on 28 cochleae of South African origin.
DOI: 10.25403/upresearchdata.12702326.v1
title: Cochlear dimensions

description: The document provides a complete table of typical cochlear dimensions compiled from the literature and the corresponding dimensions measured on 28 cochleae of South African origin.
DOI: 10.26165/juelich-data/fbzrvo
title: Replication Data for the studies on HCl discrepancy and on total reactive nitrogen redistribution

description: This data repository provides access to the model data of the study by Grooß et al. (2018) and Ziereis et al. (2022). Grooß et al. investigate the discrepancy between HCl observations in the early Antarctic winter stratosphere and simulations by 3 different models. Ziereis et al use the simulations of the model CLaMS for the investigation of Redistribution of total reactive nitrogen in the lowermost Arctic stratosphere in comparison with aircraft observations.
DOI: 10.6084/m9.figshare.12336275.v1
title: List of the image queries

description: The image queries were used in the following studies:<br>* Y. Bitirim, S. Bitirim, D. Ç. Ertuğrul and Ö. Toygar, “An Evaluation of Reverse Image Search Performance of Google”, <i>2020 IEEE 44th Annual Computer Software and Applications Conference (COMPSAC)</i>, pp. 1368-1372, IEEE, Madrid, Spain, July 2020. (DOI: 10.1109/COMPSAC48688.2020.00-65)<br>** Y. Bitirim, “Retrieval Effectiveness of Google on Reverse Image Search”,<i> Journal of Imaging Science and Technology</i>, Vol. 66, No. 1, pp. 010505-1-010505-6, January 2022. (DOI: 10.2352/J.ImagingSci.Technol.2022.66.1.010505)
DOI: 10.6084/m9.figshare.12336275
title: List of the image queries

description: The image queries were used in the following studies:<br>* Y. Bitirim, S. Bitirim, D. Ç. Ertuğrul and Ö. Toygar, “An Evaluation of Reverse Image Search Performance of Google”, <i>2020 IEEE 44th Annual Computer Software and Applications Conference (COMPSAC)</i>, pp. 1368-1372, IEEE, Madrid, Spain, July 2020. (DOI: 10.1109/COMPSAC48688.2020.00-65)<br>** Y. Bitirim, “Retrieval Effectiveness of Google on Reverse Image Search”,<i> Journal of Imaging Science and Technology</i>, Vol. 66, No. 1, pp. 010505-1-010505-6, January 2022. (DOI: 10.2352/J.ImagingSci.Technol.2022.66.1.010505)
DOI: 10.6084/m9.figshare.11932743
title: TNBDroid Test APK

description: Open-source apps from F-droid used for the evaluation of the tool TNBDroid. We only use the apps for research.<br>Commercial apps from google play used for the evaluation of the tool TNBDroid. We only use the apps for research.<br>
DOI: 10.6084/m9.figshare.11932743.v8
title: TNBDroid Test APK

description: Open-source apps from F-droid used for the evaluation of the tool TNBDroid. We only use the apps for research.<br>Commercial apps from google play used for the evaluation of the tool TNBDroid. We only use the apps for research.<br>
DOI: 10.6084/m9.figshare.11932743.v7
title: TNBDroid Test APK

description: Open-source apps from F-droid used for the evaluation of the tool TNBDroid. We only use the apps for research.<br>Commercial apps from google play used for the evaluation of the tool TNBDroid. We only use the apps for research.<br>