cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.1601913.v2
title: Atg41/Icy2 regulates autophagosome formation

description: Macroautophagy (hereafter autophagy) is one of the major degradation systems in eukaryotic cells, and its dysfunction may result in diseases ranging from neurodegeneration to cancer. Although most of the autophagy-related (Atg) proteins that function in this pathway were first identified in yeast, many were subsequently shown to have homologs in higher eukaryotes including humans, and the overall mechanism of autophagy is highly conserved. The most prominent feature of autophagy is the formation of a double-membrane sequestering compartment, the phagophore; this transient organelle surrounds part of the cytoplasm and matures into an autophagosome, which subsequently fuses with the vacuole or lysosome to allow degradation of the cargo. Much attention has focused on the process involved in phagophore nucleation and expansion, but many questions remain. Here, we identified the yeast protein Icy2, which we now name Atg41, as playing a role in autophagosome formation. Atg41 interacts with the transmembrane protein Atg9, a key component involved in autophagosome biogenesis, and both proteins display a similar localization profile. Under autophagy-inducing conditions the expression level of Atg41 increases dramatically and is regulated by the transcription factor Gcn4. This work provides further insight into the mechanism of Atg9 function and the dynamics of sequestering membrane formation during autophagy.
DOI: 10.6084/m9.figshare.1601911.v1
title: Autophagy positively regulates DNA damage recognition by nucleotide excision repair

description: Macroautophagy (hereafter autophagy) is a cellular catabolic process that is essential for maintaining tissue homeostasis and regulating various normal and pathologic processes in human diseases including cancer. One cancer-driving process is accumulation of genetic mutations due to impaired DNA damage repair, including nucleotide excision repair. Here we show that autophagy positively regulates nucleotide excision repair through enhancing DNA damage recognition by the DNA damage sensor proteins XPC and DDB2 <i>via</i> 2 pathways. First, autophagy deficiency downregulates the transcription of <i>XPC</i> through TWIST1-dependent activation of the transcription repressor complex E2F4-RBL2. Second, autophagy deficiency impairs the recruitment of DDB2 to ultraviolet radiation (UV)-induced DNA damage sites through TWIST1-mediated inhibition of EP300. In mice, the pharmacological autophagy inhibitor Spautin-1 promotes UVB-induced tumorigenesis, whereas the autophagy inducer rapamycin reduces UVB-induced tumorigenesis. These findings demonstrate the crucial role of autophagy in maintaining proper nucleotide excision repair in mammalian cells and suggest a previously unrecognized tumor-suppressive mechanism of autophagy in cancer.
DOI: 10.6084/m9.figshare.1601912.v2
title: Analysis of the native conformation of the LIR/AIM motif in the Atg8/LC3/GABARAP-binding proteins

description: The Atg8/LC3/GABARAP family of proteins, a group that has structural homology with ubiquitin, connects with a large set of binding partners to function in macroautophagy (hereafter autophagy). This interaction occurs primarily via a conserved motif termed the LC3-interacting region (LIR), or the Atg8-interacting motif (AIM). The consensus sequence for this motif, [W/F/Y]xx[L/I/V], can be found in many proteins, but only some of them are physiological partners containing a functional LIR/AIM. Because the structure of many full-length partners has not been, or cannot be, solved, the structural context of the LIR/AIM within the native protein conformation is not obvious. Here we suggest that the functional LIR/AIM is a short linear motif (SLiM) protein-binding module, arising from an intrinsically disordered region. This finding enables the rapid elimination of some false Atg8/LC3/GABARAP-binding proteins, and connects the exponentially growing knowledge on disordered SLiMs with autophagy.
DOI: 10.6084/m9.figshare.1601894
title: Individual_Hypertension_Diabetes.dta

description: Household survey exploring diagnostic and treatment pathways for people living with diabetes and hypertension in rural Cambodia.
DOI: 10.6084/m9.figshare.1601912.v1
title: Analysis of the native conformation of the LIR/AIM motif in the Atg8/LC3/GABARAP-binding proteins

description: The Atg8/LC3/GABARAP family of proteins, a group that has structural homology with ubiquitin, connects with a large set of binding partners to function in macroautophagy (hereafter autophagy). This interaction occurs primarily via a conserved motif termed the LC3-interacting region (LIR), or the Atg8-interacting motif (AIM). The consensus sequence for this motif, [W/F/Y]xx[L/I/V], can be found in many proteins, but only some of them are physiological partners containing a functional LIR/AIM. Because the structure of many full-length partners has not been, or cannot be, solved the structural context of the LIR/AIM within the native protein conformation is not obvious. Here we suggest that the functional LIR/AIM is a short linear motif (SLiM) protein-binding module, arising from an intrinsically disordered region. This finding enables the rapid elimination of some false Atg8/LC3/GABARAP-binding proteins, and connects the exponentially growing knowledge on disordered SLiMs with autophagy.
DOI: 10.6084/m9.figshare.1601913.v1
title: Atg41/Icy2 regulates autophagosome formation

description: Macroautophagy (hereafter autophagy) is one of the major degradation systems in eukaryotic cells, and its dysfunction may result in diseases ranging from neurodegeneration to cancer. Although many of the autophagy-related (Atg) proteins that function in this pathway were first identified in yeast, many were subsequently shown to have homologs in higher eukaryotes including humans, and the overall mechanism of autophagy is highly conserved. The most prominent feature of autophagy is the formation of a double-membrane sequestering compartment, the phagophore; this transient organelle surrounds part of the cytoplasm and matures into an autophagosome, which subsequently fuses with the vacuole or lysosome to allow degradation of the cargo. Much attention has focused on the process involved in phagophore nucleation and expansion, but many questions remain. Here, we identified the yeast protein Icy2, which we now name Atg41, as playing a role in autophagosome formation. Atg41 interacts with the transmembrane protein Atg9, a key component involved in autophagosome biogenesis, and both proteins display a similar localization profile. Under autophagy-inducing conditions the expression level of Atg41 increases dramatically and is regulated by the transcription factor Gcn4. This work provides further insight into the mechanism of Atg9 function and the dynamics of sequestering membrane formation during autophagy.
DOI: 10.6084/m9.figshare.1601915.v2
title: Reactivation of autophagy by spermidine ameliorates the myopathic defects of collagen VI-null mice

description: Autophagy is a self-degradative process responsible for the clearance of damaged or unnecessary cellular components. We have previously found that persistence of dysfunctional organelles due to autophagy failure is a key event in the pathogenesis of COL6/collagen VI-related myopathies, and have demonstrated that reactivation of a proper autophagic flux rescues the muscle defects of <i>Col6a1</i>-null (<i>col6a1</i><sup><i>−/−</i></sup>) mice. Here we show that treatment with spermidine, a naturally occurring nontoxic autophagy inducer, is beneficial for <i>col6a1</i><sup><i>−/−</i></sup> mice. Systemic administration of spermidine in <i>col6a1</i><sup><i>−/−</i></sup> mice reactivated autophagy in a dose-dependent manner, leading to a concurrent amelioration of the histological and ultrastructural muscle defects. The beneficial effects of spermidine, together with its being easy to administer and the lack of overt side effects, open the field for the design of novel nutraceutical strategies for the treatment of muscle diseases characterized by autophagy impairment.
DOI: 10.6084/m9.figshare.1601893
title: Household_Hypertension_Diabetes.dta

description: Household survey exploring diagnostic and treatment pathways for people living with diabetes and hypertension in rural Cambodia.
DOI: 10.6084/m9.figshare.1601915.v1
title: Reactivation of autophagy by spermidine ameliorates the myopathic defects of collagen VI-null mice

description: Autophagy is a self-degradative process responsible for the clearance of damaged or unnecessary cellular components. We have previously found that persistence of dysfunctional organelles due to autophagy failure is a key event in the pathogenesis of COL6/collagen VI-related myopathies, and have demonstrated that reactivation of a proper autophagic flux rescues the muscle defects of <i>Col6a1</i>-null (<i>col6a1</i><sup>−/−</sup>) mice. Here we show that treatment with spermidine, a naturally occurring nontoxic autophagy inducer, is beneficial for <i>col6a1</i><sup>−/−</sup> mice. Systemic administration of spermidine in <i>col6a1</i><sup>−/−</sup> mice reactivated autophagy in a dose-dependent manner, leading to a concurrent amelioration of the histological and ultrastructural muscle defects. The beneficial effects of spermidine, together with its being easy to administer and the lack of overt side effects, open the field for the design of novel nutraceutical strategies for the treatment of muscle diseases characterized by autophagy impairment.
DOI: 10.6084/m9.figshare.1601894.v1
title: Individual_Hypertension_Diabetes.dta

description: Household survey exploring diagnostic and treatment pathways for people living with diabetes and hypertension in rural Cambodia.
DOI: 10.6084/m9.figshare.1601893.v1
title: Household_Hypertension_Diabetes.dta

description: Household survey exploring diagnostic and treatment pathways for people living with diabetes and hypertension in rural Cambodia.
DOI: 10.6084/m9.figshare.1601910.v1
title: Tom August - Workflow number #1

description: In this workflow I demonstrate the powers of the ZOON R package
DOI: 10.6084/m9.figshare.1601890
title: Gaussian Job Archive for C7H13F3O5

description: Archive of work produced using the resources of the Imperial College High Performance Computing Service.
DOI: 10.6084/m9.figshare.1601891
title: Gaussian Job Archive for C6H16ClNO5

description: Archive of work produced using the resources of the Imperial College High Performance Computing Service.
DOI: 10.6084/m9.figshare.1601890.v1
title: Gaussian Job Archive for C7H13F3O5

description: Archive of work produced using the resources of the Imperial College High Performance Computing Service.
DOI: 10.6084/m9.figshare.1601887
title: Content analysis two internat

description: Content analysis two internat'l peer-reviewed journals from the point of view of a symbiosis of dialectological and formal theoretical approaches
DOI: 10.6084/m9.figshare.1601887.v1
title: Content analysis two internat

description: Content analysis two internat'l peer-reviewed journals from the point of view of a symbiosis of dialectological and formal theoretical approaches
DOI: 10.6084/m9.figshare.1601910.v2
title: Tom August - Workflow number #1

description: In this workflow I demonstrate the powers of the ZOON R package
DOI: 10.6084/m9.figshare.1601910.v4
title: Tom August - Workflow number #1

description: In this workflow I demonstrate the powers of the ZOON R package
DOI: 10.6084/m9.figshare.1601881
title: Contrasting the differences in the micro-environment of green and conventional roofs in Toronto, Canada.

description: Purpose: To see how temperature, soil moisture, and light availability differ between green and conventional rooftops at York University, Toronto. Hypothesis: Green roofs ameliorated the microclimate of a building by absorbing solar radiation, resulting in cooler temperatures and less evapotranspiration. To compare how green roofs may alter the temperature, evapotranspiration or solar radiation, we placed four sets of three Parrot Flower Power sensors in 6” pots filled with soil. Each set of pots and Flower Power sensors were be placed on two green roofs and two non-green roofs at York University. These four roofs were surveyed from September 16th to November 9th and data collected periodically. Soil moisture changes within the pots was used as a proxy for the evapotranspiration rate on top of the roofs. Data points were extracted for each day using the software Web Plot Digitizer. One set of loggers on a tradional roof did not record for the duration of the season.
DOI: 10.6084/m9.figshare.1601910.v3
title: Tom August - Workflow number #1

description: In this workflow I demonstrate the powers of the ZOON R package
DOI: 10.6084/m9.figshare.1601881.v1
title: Contrasting the differences in the micro-environment of green and conventional roofs in Toronto, Canada.

description: Purpose: To see how temperature, soil moisture, and light availability differ between green and conventional rooftops at York University, Toronto. Hypothesis: Green roofs ameliorated the microclimate of a building by absorbing solar radiation, resulting in cooler temperatures and less evapotranspiration. To compare how green roofs may alter the temperature, evapotranspiration or solar radiation, we placed four sets of three Parrot Flower Power sensors in 6” pots filled with soil. Each set of pots and Flower Power sensors were be placed on two green roofs and two non-green roofs at York University. These four roofs were surveyed from September 16th to November 9th and data collected periodically. Soil moisture changes within the pots was used as a proxy for the evapotranspiration rate on top of the roofs. Data points were extracted for each day using the software Web Plot Digitizer. One set of loggers on a tradional roof did not record for the duration of the season.
DOI: 10.6084/m9.figshare.1601868
title: Whole model empirical validation on a full-scale building

description: This paper describes an empirical validation study undertaken on two identical full-size buildings within the scope of the IEA ECB Annex 58 project. Details of the experimental configuration and monitoring are included, together with results from measurements and from predictions made by 21 modelling teams using commercial and research simulation programmes. The two-month, side-by-side experiment was undertaken on buildings with high levels of thermal mass and in a period with high solar gains. The detailed specification and associated measurement data provide a useful empirical validation dataset for programme testing. Results from the modelling demonstrate good agreement between measured data and predictions for a number of programmes, in both absolute predictions of temperatures and heat inputs as well as dynamic response. On the other hand, a significant number of user input errors resulted in poor agreement for other programmes, especially in the blind validation phase of the modelling methodology.
DOI: 10.6084/m9.figshare.1601868.v2
title: Whole model empirical validation on a full-scale building

description: This paper describes an empirical validation study undertaken on two identical full-size buildings within the scope of the IEA ECB Annex 58 project. Details of the experimental configuration and monitoring are included, together with results from measurements and from predictions made by 21 modelling teams using commercial and research simulation programmes. The two-month, side-by-side experiment was undertaken on buildings with high levels of thermal mass and in a period with high solar gains. The detailed specification and associated measurement data provide a useful empirical validation dataset for programme testing. Results from the modelling demonstrate good agreement between measured data and predictions for a number of programmes, in both absolute predictions of temperatures and heat inputs as well as dynamic response. On the other hand, a significant number of user input errors resulted in poor agreement for other programmes, especially in the blind validation phase of the modelling methodology.
DOI: 10.6084/m9.figshare.1601866
title: <i>In silico</i> exploratory study using structure–activity relationship models and metabolic information for prediction of mutagenicity based on the Ames test and rodent micronucleus assay

description: The mutagenic potential of chemicals is a cause of growing concern, due to the possible impact on human health. In this paper we have developed a knowledge-based approach, combining information from structure–activity relationship (SAR) and metabolic triggers generated from the metabolic fate of chemicals in biological systems for prediction of mutagenicity <i>in vitro</i> based on the Ames test and <i>in vivo</i> based on the rodent micronucleus assay. In the first part of the work, a model was developed, which comprises newly generated SAR rules and a set of metabolic triggers. These SAR rules and metabolic triggers were further externally validated to predict mutagenicity <i>in vitro</i>, with metabolic triggers being used only to predict mutagenicity of chemicals, which were predicted unknown, by SARpy. Hence, this model has a higher accuracy than the SAR model, with an accuracy of 89% for the training set and 75% for the external validation set. Subsequently, the results of the second part of this work enlist a set of metabolic triggers for prediction of mutagenicity <i>in vivo</i>, based on the rodent micronucleus assay. Finally, the results of the third part enlist a list of metabolic triggers to find similarities and differences in the mutagenic response of chemicals <i>in vitro</i> and <i>in vivo</i>.
DOI: 10.6084/m9.figshare.1601868.v1
title: Whole model empirical validation on a full-scale building

description: This paper describes an empirical validation study undertaken on two identical full-size buildings within the scope of the IEA ECB Annex 58 project. Details of the experimental configuration and monitoring are included, together with results from measurements and from predictions made by 21 modelling teams using commercial and research simulation programmes. The two-month, side-by-side experiment was undertaken on buildings with high levels of thermal mass and in a period with high solar gains. The detailed specification and associated measurement data provide a useful empirical validation dataset for programme testing. Results from the modelling demonstrate good agreement between measured data and predictions for a number of programmes, in both absolute predictions of temperatures and heat inputs as well as dynamic response. On the other hand, a significant number of user input errors resulted in poor agreement for other programmes, especially in the blind validation phase of the modelling methodology.
DOI: 10.6084/m9.figshare.1601869.v1
title: MIR517C inhibits autophagy and the epithelial-to-mesenchymal (-like) transition phenotype in human glioblastoma through KPNA2-dependent disruption of TP53 nuclear translocation

description: The epithelial-to-mesenchymal (-like) transition (EMT), a crucial embryonic development program, has been linked to the regulation of glioblastoma (GBM) progression and invasion. Here, we investigated the role of <i>MIR517C/miR-517c</i>, which belongs to the <i>C19MC</i> microRNA cluster identified in our preliminary studies, in the pathogenesis of GBM. We found that <i>MIR517C</i> was associated with improved prognosis in patients with GBM. Furthermore, following treatment with the autophagy inducer temozolomide (TMZ) and low glucose (LG), <i>MIR517C</i> degraded <i>KPNA2</i> (karyopherin alpha 2 [RAG cohort 1, importin alpha 1]) and subsequently disturbed the nuclear translocation of TP53 in the GBM cell line U87 in vitro. Interestingly, this microRNA could inhibit autophagy and reduce cell migration and infiltration in U87 cells harboring wild-type (WT) <i>TP53</i>, but not in U251 cells harboring mutant (MU) <i>TP53</i>. Moreover, the expression of epithelial markers (i.e., CDH13/T-cadherin and CLDN1 [claudin 1]) increased, while the expression of mesenchymal markers (i.e., CDH2/N-cadherin, SNAI1/Snail, and VIM [vimentin]) decreased, indicating that the EMT status was blocked by <i>MIR517C</i> in U87 cells. Compared with <i>MIR517C</i> overexpression, <i>MIR517C</i> knockdown promoted infiltration of U87 cells to the surrounding structures in nude mice in vivo. The above phenotypic changes were also observed in <i>TP53</i><sup><i>+/+</i></sup> and <i>TP53</i><sup><i>−/−</i></sup> HCT116 colon cancer cells. In summary, our study provided support for a link between autophagy and EMT status in WT <i>TP53</i> GBM cells and provided evidence for the signaling pathway (<i>MIR517C</i>-KPNA2-cytoplasmic TP53) involved in attenuating autophagy and eliminating the increased migration and invasion during the EMT.
DOI: 10.6084/m9.figshare.1601866.v1
title: <i>In silico</i> exploratory study using structure–activity relationship models and metabolic information for prediction of mutagenicity based on the Ames test and rodent micronucleus assay

description: The mutagenic potential of chemicals is a cause of growing concern, due to the possible impact on human health. In this paper we have developed a knowledge-based approach, combining information from structure–activity relationship (SAR) and metabolic triggers generated from the metabolic fate of chemicals in biological systems for prediction of mutagenicity <i>in vitro</i> based on the Ames test and <i>in vivo</i> based on the rodent micronucleus assay. In the first part of the work, a model was developed, which comprises newly generated SAR rules and a set of metabolic triggers. These SAR rules and metabolic triggers were further externally validated to predict mutagenicity <i>in vitro</i>, with metabolic triggers being used only to predict mutagenicity of chemicals, which were predicted unknown, by SARpy. Hence, this model has a higher accuracy than the SAR model, with an accuracy of 89% for the training set and 75% for the external validation set. Subsequently, the results of the second part of this work enlist a set of metabolic triggers for prediction of mutagenicity <i>in vivo</i>, based on the rodent micronucleus assay. Finally, the results of the third part enlist a list of metabolic triggers to find similarities and differences in the mutagenic response of chemicals <i>in vitro</i> and <i>in vivo</i>.