cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.3830112
title: Suppressed translation and ULK1 degradation as potential mechanisms of autophagy limitation under prolonged starvation

description: Macroautophagy/autophagy is a well-organized process of intracellular degradation, which is rapidly activated under starvation conditions. Recent data demonstrate a transcriptional upregulation of several autophagy genes as a mechanism that controls autophagy in response to starvation. Here we report that despite the significant upregulation of mRNA of the essential autophagy initiation gene <i>ULK1</i>, its protein level is rapidly reduced under starvation. Although both autophagic and proteasomal systems contribute to the degradation of ULK1, under prolonged nitrogen deprivation, its level was still reduced in <i>ATG</i>7 knockout cells, and only initially stabilized in cells treated with the lysosomal or proteasomal inhibitors. We demonstrate that under starvation, protein translation is rapidly diminished and, similar to treatments with the proteosynthesis inhibitors cycloheximide or anisomycin, is associated with a significant reduction of ULK1. Furthermore, it was found that inhibition of the mitochondrial respiratory complexes or the mitochondrial ATP synthase function that could also take place in the absence of substrates, promote upregulation of <i>ULK1</i> mRNA and protein expression in an AMPK-dependent manner in U1810 lung cancer cells growing in complete culture medium. These inhibitors could also drastically increase the ULK1 protein in U1810 cells with knockout of <i>ATG13</i>, where the ULK1 expression is significantly diminished. However, such upregulation of ULK1 protein is negligible under starvation conditions, further signifying the contribution of translation and suggesting that transcriptional upregulation of ULK1 protein will be diminished under such conditions. Thus, we propose a model where inhibition of protein translation, together with the degradation systems, limit autophagy during starvation.
DOI: 10.7910/dvn/v1rjpf/uek2uj
title: mea20170624_03.txt.gz

description: :unav
DOI: 10.6084/m9.figshare.3830112.v1
title: Suppressed translation and ULK1 degradation as potential mechanisms of autophagy limitation under prolonged starvation

description: Macroautophagy/autophagy is a well-organized process of intracellular degradation, which is rapidly activated under starvation conditions. Recent data demonstrate a transcriptional upregulation of several autophagy genes as a mechanism that controls autophagy in response to starvation. Here we report that despite the significant upregulation of mRNA of the essential autophagy initiation gene <i>ULK1</i>, its protein level is rapidly reduced under starvation. Although both autophagic and proteasomal systems contribute to the degradation of ULK1, under prolonged nitrogen deprivation, its level was still reduced in <i>ATG</i>7 knockout cells, and only initially stabilized in cells treated with the lysosomal or proteasomal inhibitors. We demonstrate that under starvation, protein translation is rapidly diminished and, similar to treatments with the proteosynthesis inhibitors cycloheximide or anisomycin, is associated with a significant reduction of ULK1. Furthermore, it was found that inhibition of the mitochondrial respiratory complexes or the mitochondrial ATP synthase function that could also take place in the absence of substrates, promote upregulation of <i>ULK1</i> mRNA and protein expression in an AMPK-dependent manner in U1810 lung cancer cells growing in complete culture medium. These inhibitors could also drastically increase the ULK1 protein in U1810 cells with knockout of <i>ATG13</i>, where the ULK1 expression is significantly diminished. However, such upregulation of ULK1 protein is negligible under starvation conditions, further signifying the contribution of translation and suggesting that transcriptional upregulation of ULK1 protein will be diminished under such conditions. Thus, we propose a model where inhibition of protein translation, together with the degradation systems, limit autophagy during starvation.
DOI: 10.7910/dvn/v1rjpf/g41fwi
title: mea20170303_03.txt.gz

description: :unav
DOI: 10.7910/dvn/v1rjpf/gk4mhv
title: mea20170526_03.txt.gz

description: :unav
DOI: 10.7910/dvn/v1rjpf/74b7tg
title: mea20170506_03.txt.gz

description: :unav
DOI: 10.6084/m9.figshare.3830106
title: Intracellular <i>Staphylococcus aureus</i> eludes selective autophagy by activating a host cell kinase

description: Autophagy, a catabolic pathway of lysosomal degradation, acts not only as an efficient recycle and survival mechanism during cellular stress, but also as an anti-infective machinery. The human pathogen <i>Staphylococcus aureus</i> (<i>S. aureus</i>) was originally considered solely as an extracellular bacterium, but is now recognized additionally to invade host cells, which might be crucial for persistence. However, the intracellular fate of <i>S. aureus</i> is incompletely understood. Here, we show for the first time induction of selective autophagy by <i>S. aureus</i> infection, its escape from autophagosomes and proliferation in the cytoplasm using live cell imaging. After invasion, <i>S. aureus</i> becomes ubiquitinated and recognized by receptor proteins such as SQSTM1/p62 leading to phagophore recruitment. Yet, <i>S. aureus</i> evades phagophores and prevents further degradation by a MAPK14/p38α MAP kinase-mediated blockade of autophagy. Our study demonstrates a novel bacterial strategy to block autophagy and secure survival inside the host cell.
DOI: 10.7910/dvn/v1rjpf/m2etux
title: mea20171226_03.txt.gz

description: :unav
DOI: 10.6084/m9.figshare.3830103
title: A novel role for the 3′-5′ exoribonuclease Dis3L2 in controlling cell proliferation and tissue growth

description: In a complex organism, cell proliferation and apoptosis need to be precisely controlled in order for tissues to develop correctly. Excessive cell proliferation can lead to diseases such as cancer. We have shown that the exoribonuclease Dis3L2 is required for the correct regulation of proliferation in a natural tissue within the model organism <i>Drosophila melanogaster</i>. Dis3L2 is a member of a highly conserved family of exoribonucleases that degrade RNA in a 3′-5′ direction. We show that knockdown of <i>dis3L2</i> in the <i>Drosophila</i> wing imaginal discs results in substantial wing overgrowth due to increased cellular proliferation rather than an increase in cell size. Imaginal discs are specified in the embryo before proliferating and differentiating to form the adult structures of the fly. Using RNA-seq we identified a small set of mRNAs that are sensitive to Dis3L2 activity. Of the mRNAs which increase in levels and are therefore potential targets of Dis3L2, we identified 2 that change at the post-transcriptional level but not at the transcriptional level, namely <i>CG2678</i> (a transcription factor) and <i>pyrexia</i> (a TRP cation channel). We also demonstrate a compensatory effect between Dis3L2 and the 5′-3′ exoribonuclease Pacman demonstrating that these 2 exoribonucleases function to regulate opposing pathways within the developing tissue. This work provides the first description of the molecular and developmental consequences of Dis3L2 inactivation in a non-human animal model. The work is directly relevant to the understanding of human overgrowth syndromes such as Perlman syndrome.
DOI: 10.7910/dvn/v1rjpf/xr4pvl
title: mea20170707_03.txt.gz

description: :unav
DOI: 10.7910/dvn/v1rjpf/gi0i7p
title: mea20170121_03.txt.gz

description: :unav
DOI: 10.6084/m9.figshare.3830103.v1
title: A Novel Role for the 3′-5′ Exoribonuclease Dis3L2 in Controlling Cell Proliferation and Tissue Growth

description: In a complex organism, cell proliferation and apoptosis need to be precisely controlled in order for tissues to develop correctly. Excessive cell proliferation can lead to diseases such as cancer. We have shown that the exoribonuclease Dis3L2 is required for the correct regulation of proliferation in a natural tissue within the model organism <i>Drosophila melanogaster</i>. Dis3L2 is a member of a highly conserved family of exoribonucleases that degrade RNA in a 3′-5′ direction. We show that knockdown of <i>dis3L2</i> in the <i>Drosophila</i> wing imaginal discs results in substantial wing overgrowth due to increased cellular proliferation rather than an increase in cell size. Imaginal discs are specified in the embryo before proliferating and differentiating to form the adult structures of the fly. Using RNA-seq we identified a small set of mRNAs that are sensitive to Dis3L2 activity. Of the mRNAs which increase in levels and are therefore potential targets of Dis3L2, we identified two that change at the post-transcriptional level but not at the transcriptional level, namely <i>CG2678</i> (a transcription factor) and <i>pyrexia</i> (a TRP cation channel). We also demonstrate a compensatory effect between Dis3L2 and the 5′-3′ exoribonuclease Pacman demonstrating that these two exoribonucleases function to regulate opposing pathways within the developing tissue. This work provides the first description of the molecular and developmental consequences of Dis3L2 inactivation in a non-human animal model. The work is directly relevant to the understanding of human overgrowth syndromes such as Perlman syndrome.
DOI: 10.6084/m9.figshare.3830103.v3
title: A novel role for the 3′-5′ exoribonuclease Dis3L2 in controlling cell proliferation and tissue growth

description: In a complex organism, cell proliferation and apoptosis need to be precisely controlled in order for tissues to develop correctly. Excessive cell proliferation can lead to diseases such as cancer. We have shown that the exoribonuclease Dis3L2 is required for the correct regulation of proliferation in a natural tissue within the model organism <i>Drosophila melanogaster</i>. Dis3L2 is a member of a highly conserved family of exoribonucleases that degrade RNA in a 3′-5′ direction. We show that knockdown of <i>dis3L2</i> in the <i>Drosophila</i> wing imaginal discs results in substantial wing overgrowth due to increased cellular proliferation rather than an increase in cell size. Imaginal discs are specified in the embryo before proliferating and differentiating to form the adult structures of the fly. Using RNA-seq we identified a small set of mRNAs that are sensitive to Dis3L2 activity. Of the mRNAs which increase in levels and are therefore potential targets of Dis3L2, we identified 2 that change at the post-transcriptional level but not at the transcriptional level, namely <i>CG2678</i> (a transcription factor) and <i>pyrexia</i> (a TRP cation channel). We also demonstrate a compensatory effect between Dis3L2 and the 5′-3′ exoribonuclease Pacman demonstrating that these 2 exoribonucleases function to regulate opposing pathways within the developing tissue. This work provides the first description of the molecular and developmental consequences of Dis3L2 inactivation in a non-human animal model. The work is directly relevant to the understanding of human overgrowth syndromes such as Perlman syndrome.
DOI: 10.7910/dvn/v1rjpf/ovezk7
title: mea20170218_03.txt.gz

description: :unav
DOI: 10.7910/dvn/v1rjpf/0k3hne
title: mea20171112_03.txt.gz

description: :unav
DOI: 10.6084/m9.figshare.3830103.v2
title: A novel role for the 3′-5′ exoribonuclease Dis3L2 in controlling cell proliferation and tissue growth

description: In a complex organism, cell proliferation and apoptosis need to be precisely controlled in order for tissues to develop correctly. Excessive cell proliferation can lead to diseases such as cancer. We have shown that the exoribonuclease Dis3L2 is required for the correct regulation of proliferation in a natural tissue within the model organism <i>Drosophila melanogaster</i>. Dis3L2 is a member of a highly conserved family of exoribonucleases that degrade RNA in a 3′-5′ direction. We show that knockdown of <i>dis3L2</i> in the <i>Drosophila</i> wing imaginal discs results in substantial wing overgrowth due to increased cellular proliferation rather than an increase in cell size. Imaginal discs are specified in the embryo before proliferating and differentiating to form the adult structures of the fly. Using RNA-seq we identified a small set of mRNAs that are sensitive to Dis3L2 activity. Of the mRNAs which increase in levels and are therefore potential targets of Dis3L2, we identified 2 that change at the post-transcriptional level but not at the transcriptional level, namely <i>CG2678</i> (a transcription factor) and <i>pyrexia</i> (a TRP cation channel). We also demonstrate a compensatory effect between Dis3L2 and the 5′-3′ exoribonuclease Pacman demonstrating that these 2 exoribonucleases function to regulate opposing pathways within the developing tissue. This work provides the first description of the molecular and developmental consequences of Dis3L2 inactivation in a non-human animal model. The work is directly relevant to the understanding of human overgrowth syndromes such as Perlman syndrome.
DOI: 10.7910/dvn/v1rjpf/rg79hn
title: mea20170929_03.txt.gz

description: :unav
DOI: 10.6084/m9.figshare.3830100
title: PRNP/prion protein regulates the secretion of exosomes modulating CAV1/caveolin-1-suppressed autophagy

description: Prion protein modulates many cellular functions including the secretion of trophic factors by astrocytes. Some of these factors are found in exosomes, which are formed within multivesicular bodies (MVBs) and secreted into the extracellular space to modulate cell-cell communication. The mechanisms underlying exosome biogenesis were not completely deciphered. Here, we demonstrate that primary cultures of astrocytes and fibroblasts from prnp-null mice secreted lower levels of exosomes than wild-type cells. Furthermore, prnp-null astrocytes exhibited reduced MVB formation and increased autophagosome formation. The reconstitution of PRNP expression at the cell membrane restored exosome secretion in PRNP-deficient astrocytes, whereas macroautophagy/autophagy inhibition via BECN1 depletion reestablished exosome release in these cells. Moreover, the PRNP octapeptide repeat domain was necessary to promote exosome secretion and to impair the formation of the CAV1-dependent ATG12–ATG5 cytoplasmic complex that drives autophagosome formation. Accordingly, higher levels of CAV1 were found in lipid raft domains instead of in the cytoplasm in prnp-null cells. Collectively, these findings demonstrate that PRNP supports CAV1-suppressed autophagy to protect MVBs from sequestration into phagophores, thus facilitating exosome secretion.
DOI: 10.7910/dvn/v1rjpf/caqyte
title: mea20171212_03.txt.gz

description: :unav
DOI: 10.6084/m9.figshare.3830100.v1
title: PRNP/prion protein regulates the secretion of exosomes modulating CAV1/caveolin-1-suppressed autophagy

description: Prion protein modulates many cellular functions including the secretion of trophic factors by astrocytes. Some of these factors are found in exosomes, which are formed within multivesicular bodies (MVBs) and secreted into the extracellular space to modulate cell-cell communication. The mechanisms underlying exosome biogenesis were not completely deciphered. Here, we demonstrate that primary cultures of astrocytes and fibroblasts from prnp-null mice secreted lower levels of exosomes than wild-type cells. Furthermore, prnp-null astrocytes exhibited reduced MVB formation and increased autophagosome formation. The reconstitution of PRNP expression at the cell membrane restored exosome secretion in PRNP-deficient astrocytes, whereas macroautophagy/autophagy inhibition via BECN1 depletion reestablished exosome release in these cells. Moreover, the PRNP octapeptide repeat domain was necessary to promote exosome secretion and to impair the formation of the CAV1-dependent ATG12–ATG5 cytoplasmic complex that drives autophagosome formation. Accordingly, higher levels of CAV1 were found in lipid raft domains instead of in the cytoplasm in prnp-null cells. Collectively, these findings demonstrate that PRNP supports CAV1-suppressed autophagy to protect MVBs from sequestration into phagophores, thus facilitating exosome secretion.
DOI: 10.7910/dvn/v1rjpf/uknaqs
title: mea20170626_03.txt.gz

description: :unav
DOI: 10.6084/m9.figshare.3830097
title: data sheet representing gender and presence of denim pants

description: variables:<br>1. presence of denim pants regardless of colour , Y=yes N=no<br>2. sex, female=F and male=M <br>
DOI: 10.7910/dvn/v1rjpf/c4wnjf
title: mea20170826_03.txt.gz

description: :unav
DOI: 10.6084/m9.figshare.3830097.v1
title: data sheet representing gender and presence of denim pants

description: variables:<br>1. presence of denim pants regardless of colour , Y=yes N=no<br>2. sex, female=F and male=M <br>
DOI: 10.6084/m9.figshare.3830094
title: Investigating the Relationship between Instagram and Gender of User

description: A random sample of 20 York University students were surveyed. Two questions were asked: 1) for biological sex, and 2) whether or not they have opened an Instagram account, a social network sharing photos and videos through the Instagram app on mobile devices. Of the 20 students, 19 were asked inside Lumbers, a building with laboratories for multiple scientific disciplines.<br>In the collected data, "Gender" refers to biological sex of the participant. F stands for female and M stands for male. The second variable, "Opened an Instagram Account" records if the participant has ever registered for an Instagram account. The response to the second question was only "yes" or "no".
DOI: 10.7910/dvn/v1rjpf/pkbogi
title: mea20171025_03.txt.gz

description: :unav
DOI: 10.6084/m9.figshare.3830094.v1
title: Investigating the Relationship between Instagram and Gender of User

description: A random sample of 20 York University students were surveyed. Two questions were asked: 1) for biological sex, and 2) whether or not they have opened an Instagram account, a social network sharing photos and videos through the Instagram app on mobile devices. Of the 20 students, 19 were asked inside Lumbers, a building with laboratories for multiple scientific disciplines.<br>In the collected data, "Gender" refers to biological sex of the participant. F stands for female and M stands for male. The second variable, "Opened an Instagram Account" records if the participant has ever registered for an Instagram account. The response to the second question was only "yes" or "no".
DOI: 10.6084/m9.figshare.3830082
title: Car Analysis in Parking Lot 2016

description: Meta DataColour - description of paint job of the vehiclesCar Company - description of who made the vehicles<br>At designated school parking lot at York University <br>
DOI: 10.7910/dvn/v1rjpf/kbxnjq
title: mea20170708_03.txt.gz

description: :unav
DOI: 10.7910/dvn/v1rjpf/7u1y5d
title: mea20170914_03.txt.gz

description: :unav
DOI: 10.7910/dvn/v1rjpf/oxlvda
title: mea20170417_03.txt.gz

description: :unav
DOI: 10.7910/dvn/v1rjpf/lnxcwo
title: mea20170904_03.txt.gz

description: :unav
DOI: 10.7910/dvn/v1rjpf/slnb5o
title: mea20170320_03.txt.gz

description: :unav
DOI: 10.7910/dvn/v1rjpf/71d0pr
title: mea20170525_03.txt.gz

description: :unav
DOI: 10.7910/dvn/v1rjpf/98cseq
title: mea20171021_03.txt.gz

description: :unav
DOI: 10.7910/dvn/v1rjpf/cljy94
title: mea20170620_03.txt.gz

description: :unav
DOI: 10.7910/dvn/v1rjpf/gt4u2i
title: mea20170825_03.txt.gz

description: :unav
DOI: 10.7910/dvn/v1rjpf/rvhrgk
title: mea20170610_03.txt.gz

description: :unav
DOI: 10.6084/m9.figshare.3830061
title: SENSIBILIZAÇÃO DEPENDENTE DE TEMPO ENTRE LINHAGENS DE ZEBRAFISH (Danio rerio, Hamilton 1822)

description: Painel apresentado na VII Reunião Anual da IBNeC
DOI: 10.7910/dvn/v1rjpf/q5blaa
title: mea20171108_03.txt.gz

description: :unav
DOI: 10.6084/m9.figshare.3830061.v2
title: SENSIBILIZAÇÃO DEPENDENTE DE TEMPO ENTRE LINHAGENS DE ZEBRAFISH (Danio rerio, Hamilton 1822)

description: Painel apresentado na VII Reunião Anual da IBNeC
DOI: 10.7910/dvn/v1rjpf/dqln7g
title: mea20170605_03.txt.gz

description: :unav
DOI: 10.6084/m9.figshare.3830061.v1
title: SENSIBILIZAÇÃO DEPENDENTE DE TEMPO ENTRE LINHAGENS DE ZEBRAFISH (Danio rerio, Hamilton 1822)

description: Painel apresentado na VII Reunião Anual da IBNeC
DOI: 10.7910/dvn/v1rjpf/shjrce
title: mea20171031_03.txt.gz

description: :unav
DOI: 10.6084/m9.figshare.3830058
title: PAPEL DO SISTEMA SEROTONINÉRGICO NO COMPORTAMENTO AGRESSIVO EM DUAS LINHAGENS DE ZEBRAFISHES ADULTOS (DANIO RERIO HAMILTON 1822)

description: Painel apresentado na VII Reunião Anual da IBNeC
DOI: 10.7910/dvn/v1rjpf/kr4mba
title: mea20170410_03.txt.gz

description: :unav
DOI: 10.6084/m9.figshare.3830058.v2
title: PAPEL DO SISTEMA SEROTONINÉRGICO NO COMPORTAMENTO AGRESSIVO EM DUAS LINHAGENS DE ZEBRAFISHES ADULTOS (DANIO RERIO HAMILTON 1822)

description: Painel apresentado na VII Reunião Anual da IBNeC
DOI: 10.7910/dvn/v1rjpf/1xwtcq
title: mea20170606_03.txt.gz

description: :unav
DOI: 10.6084/m9.figshare.3830052
title: Lab Week 2

description: <b>Variable: Description:</b>Presence of Denim: Denim pants only regardless of colour or length (Y=Yes and N=No)<br>Sex: F=female and M=male
DOI: 10.6084/m9.figshare.3830052.v1
title: Lab Week 2

description: <b>Variable: Description:</b>Presence of Denim: Denim pants only regardless of colour or length (Y=Yes and N=No)<br>Sex: F=female and M=male
DOI: 10.7910/dvn/v1rjpf/mqc5ox
title: mea20170213_03.txt.gz

description: :unav
DOI: 10.6084/m9.figshare.3830043
title: EFEITO DO FGIN-1-27 E DO DIAZEPAM NA PREFERÊNCIA PELA ESCURIDÃO DO PAULISTINHA (Danio rerio)

description: Painel apresentado na VII Reunião Anual da IBNeC
DOI: 10.7910/dvn/v1rjpf/iuurzb
title: mea20170517_03.txt.gz

description: :unav
DOI: 10.7910/dvn/v1rjpf/sa6vja
title: mea20170311_03.txt.gz

description: :unav
DOI: 10.7910/dvn/v1rjpf/tfwkqp
title: mea20171213_03.txt.gz

description: :unav
DOI: 10.6084/m9.figshare.3830043.v3
title: EFEITO DO FGIN-1-27 E DO DIAZEPAM NA PREFERÊNCIA PELA ESCURIDÃO DO PAULISTINHA (Danio rerio)

description: Painel apresentado na VII Reunião Anual da IBNeC
DOI: 10.7910/dvn/v1rjpf/fy0nup
title: mea20170504_03.txt.gz

description: :unav
DOI: 10.6084/m9.figshare.3830043.v2
title: EFEITO DO FGIN-1-27 E DO DIAZEPAM NA PREFERÊNCIA PELA ESCURIDÃO DO PAULISTINHA (Danio rerio)

description: Painel apresentado na VII Reunião Anual da IBNeC
DOI: 10.6084/m9.figshare.3830037
title: REAÇÃO DE ALARME DO ZEBRAFISH (Danio rerio, Hamilton 1822) COMO MODELO DE TRANSTORNO DO PÂNICO: EFEITO DA FLUOXETINA

description: Painel apresentado na VII Reunião Anual da IBNeC
DOI: 10.7910/dvn/v1rjpf/6fcfn6
title: mea20171208_03.txt.gz

description: :unav
DOI: 10.7910/dvn/v1rjpf/elhhir
title: mea20170223_03.txt.gz

description: :unav
DOI: 10.7910/dvn/v1rjpf/3d84zh
title: mea20170716_03.txt.gz

description: :unav
DOI: 10.6084/m9.figshare.3830037.v3
title: REAÇÃO DE ALARME DO ZEBRAFISH (Danio rerio, Hamilton 1822) COMO MODELO DE TRANSTORNO DO PÂNICO: EFEITO DA FLUOXETINA

description: Painel apresentado na VII Reunião Anual da IBNeC
DOI: 10.6084/m9.figshare.3830037.v2
title: REAÇÃO DE ALARME DO ZEBRAFISH (Danio rerio, Hamilton 1822) COMO MODELO DE TRANSTORNO DO PÂNICO: EFEITO DA FLUOXETINA

description: Painel apresentado na VII Reunião Anual da IBNeC
DOI: 10.7910/dvn/v1rjpf/k9qdf9
title: iqa20151122_03.txt.gz

description: :unav
DOI: 10.6084/m9.figshare.3830031
title: scikit-learn species distribution dataset coverages.zip

description: Part of the species distribution dataset used in scikit-learn.
DOI: 10.7910/dvn/v1rjpf/opkxux
title: iqa20151104_03.txt.gz

description: :unav
DOI: 10.6084/m9.figshare.3830031.v2
title: scikit-learn species distribution dataset coverages.zip

description: Part of the species distribution dataset used in scikit-learn.
DOI: 10.7910/dvn/v1rjpf/xmngnm
title: iqa20151208_03.txt.gz

description: :unav
DOI: 10.6084/m9.figshare.3830031.v1
title: coverages.zip

description: Part of the species distribution dataset used in scikit-learn.
DOI: 10.7910/dvn/v1rjpf/n4qfv8
title: iqa20150605_03.txt.gz

description: :unav
DOI: 10.6084/m9.figshare.3830028
title: scikit-learn species distribution dataset samples.zip

description: Part of the species distribution dataset used in scikit-learn.