cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.3715272
title: Data and code to reproduce Dallas et al. 2016 "Ordination obscures the influence of environment on plankton metacommunity structure"

description: Code and data from:<br>&gt; Dallas, T., M. Zokan, A Kramer, and JM Drake. 2016. "Ordination obscures the influence of environment on plankton metacommunity structure" Limnology and Oceanography Letters. doi: (forthcoming)<br><br><br>
DOI: 10.6084/m9.figshare.3715272.v1
title: Data and code to reproduce Dallas et al. 2016 "Ordination obscures the influence of environment on plankton metacommunity structure"

description: Code and data from:<br>&gt; Dallas, T., M. Zokan, A Kramer, and JM Drake. 2016. "Ordination obscures the influence of environment on plankton metacommunity structure" Limnology and Oceanography Letters. doi: (forthcoming)<br><br><br>
DOI: 10.6084/m9.figshare.3708099
title: Data for "Positive Selection Linked with Generation of Novel Mammalian Dentition Patterns"

description: The data contained in them pretains to the manuscript"Positive Selection Linked with Generation of Novel Mammalian Dentition Patterns"<br>2 zip files:<br><b> 1) GENES.zip </b>- This file contains 236 folders with the genes used for evolutionary analysis:<br> ACHE/ ACLY/ ACVR1B/ ACVR2B/ ADAMTS2/ ADM/ AGPAT2/ ALKBH1/ ALPL/ AMBN/ AMTN/ ANKH/ ANKRD11/ ANTXR1/ APC/ AQP1/ AQP3/ AQP5/ AQP6/ ASPN/ ATR/ AXIN2/ BARX1/ BAX/ BAZ1B/ BCL11B/ BCL2L11/ BCOR/ BGLAP/ BMP2/ BMP4/ BMP7/ BMPR1A/ BRAF/ BSG/ CA2/ CBX2/ CCL2/ CCND1/ CD34/ CD86/ CDKN1A/ CDKN1B/ CDO1/ CDON/ CHUK/ CLCN5/ CLCN7/ COL10A1/ COL1A1/ COL1A2/ COL7A1/ CSF1/ CSF1R/ CSF2/ CSF3R/ CTNNA1/ CTNNB1/ CTSK/ DCN/ DIAP1/ DICER1/ DISP1/ DLL1/ DLX1/ DLX2/ DLX5/ DMP1/ DMRT3/ DSPP/ EDA/ EDAR/ EDARADD/ EDN1/ EDNRA/ ENAM/ ERBB2/ ERBB3/ ERBB4/ EVC/ FAM20A/ FAM20C/ FGF10/ FGF4/ FGF8/ FGFR1/ FGFR2/ FGFR3/ FMOD/ FOS/ FOXA2/ FST/ FUZ/ GALC/ GATA6/ GJA/ GLI2/ GLI3/ GTF2IRD1/ HAND1/ HAND2/ HDAC1/ HDAC2/ HOXB1/ HOXB8/ HRAS1/ ID3/ IDUA/ IFT88/ IL1R1/ INHBA/ INHBB/ IRF6/ ITGA11/ ITGA6/ JAG1/ JAG2/ KLK4/ LAMA3/ LAMA5/ LAMB1/ LEF1/ LHX8/ LMNA/ LPAR1/ LRP4/ LRP6/ LTBP1/ LTBP3/ MAP3K11/ MECOM/ MECP2/ MITF/ MMP14/ MMP20/ MSX1/ MSX2/ MTF2/ MYO5A/ NF2/ NFATC1/ NFE2L2/ NFIC/ NFKB1/ NFKB2/ NGFR/ NKX2-3/ NOS2/ NOTCH2/ NPHP3/ NPR2/ NR3C1/ ODAM/ OSR1/ OSR2/ OSTM1/ PAM/ PAPSS2/ PAX3/ PAX6/ PAX9/ PDGFRA/ PITX2/ PKD1/ PORCN/ POSTN/ POU1F1/ PPARA/ PRKCB/ PRRX2/ PRXX1/ PTCH1/ PTHLH/ PTPN9/ PVR1L/ PVRL3/ RAI1/ RBL1/ RBL2/ RSPO2/ RUNX2/ S100B/ SATB2/ SCN10A/ SCN5A/ SDC1/ SFPI1/ SH3PXD2B/ SHH/ SIM2/ SIRT6/ SLC39A13/ SLC4A2/ SLC4A4/ SLX4/ SMN1/ SMO/ SOSTDC1/ SOX3/ SP3/ SP6/ SPRY2/ SPRY4/ SRC/ STAG1/ SULF1/ SULF2/ TBX1/ TCF7L2/ TCFAP2A/ TCIRG1/ TFE3/ TGFB1/ TGFB2/ TGFB3/ TNC/ TNFRSF11A/ TNFRSF11B/ TNFRSF19/ TNFSF11/ TRAF6/ TRP53/ TRP63/ TUFT1/ UROS/ VAX1/ VEGFA/ WHSC1/ WLS/ WNT10A/ WNT6/ WNT7B/ ZIC3/ ZIC5/ ZMPSTE24/ ZNF22/<br> Each folder contains 5 sub-folders:<br> FASTA/ - Gene alingment GBLOCKS/ - 2 files: Gene full sequence (*.fas) Gene trimmed gene (*.fas-gb) MRAIC_GENE_TREE/ - Result tree from MrAIC applying the best evolutionary model obtained using BIC using the followin annotation: "GENE NAME".BIC-"BEST MODEL".tre GENE_TREE/ - Results of CODEML M0_7_8/ - Results of Model 0, 7 and 8 in a single file, M1_2/ - Results of Model 1 and 2 in a single file, M8a/ - Results of Model 8a SPECIES_TREE/ - Results of CODEML M0_7_8/ - Results of Model 0, 7 and 8 in a single file, M1_2/ - Results of Model 1 and 2 in a single file, M8a/ - Results of Model 8a<br> <b> 2) PARAMETERS.zip</b> - This file contains the used species tree, and 3 codeml parameter templates: Species_tree.nwk - Mammalian species tree used in CODEML codeml_M0_7_8.ctl - parameters file template for Models 0, 7 and 8a codeml_M1_2.ctl - parameters file template for Models 1 and 2 codeml_M8a.ctl - parameters file template for Model 8a
DOI: 10.17632/dkx728tns4.9
title: Data for: Engineering geology of residual soil derived from mudstone in Zimbabwe

description: The soil properties and supplementary materials are provided.
DOI: 10.6084/m9.figshare.3708099.v1
title: Data for "Positive Selection Linked with Generation of Novel Mammalian Dentition Patterns"

description: The data contained in them pretains to the manuscript"Positive Selection Linked with Generation of Novel Mammalian Dentition Patterns"<br>2 zip files:<br><b> 1) GENES.zip </b>- This file contains 236 folders with the genes used for evolutionary analysis:<br> ACHE/ ACLY/ ACVR1B/ ACVR2B/ ADAMTS2/ ADM/ AGPAT2/ ALKBH1/ ALPL/ AMBN/ AMTN/ ANKH/ ANKRD11/ ANTXR1/ APC/ AQP1/ AQP3/ AQP5/ AQP6/ ASPN/ ATR/ AXIN2/ BARX1/ BAX/ BAZ1B/ BCL11B/ BCL2L11/ BCOR/ BGLAP/ BMP2/ BMP4/ BMP7/ BMPR1A/ BRAF/ BSG/ CA2/ CBX2/ CCL2/ CCND1/ CD34/ CD86/ CDKN1A/ CDKN1B/ CDO1/ CDON/ CHUK/ CLCN5/ CLCN7/ COL10A1/ COL1A1/ COL1A2/ COL7A1/ CSF1/ CSF1R/ CSF2/ CSF3R/ CTNNA1/ CTNNB1/ CTSK/ DCN/ DIAP1/ DICER1/ DISP1/ DLL1/ DLX1/ DLX2/ DLX5/ DMP1/ DMRT3/ DSPP/ EDA/ EDAR/ EDARADD/ EDN1/ EDNRA/ ENAM/ ERBB2/ ERBB3/ ERBB4/ EVC/ FAM20A/ FAM20C/ FGF10/ FGF4/ FGF8/ FGFR1/ FGFR2/ FGFR3/ FMOD/ FOS/ FOXA2/ FST/ FUZ/ GALC/ GATA6/ GJA/ GLI2/ GLI3/ GTF2IRD1/ HAND1/ HAND2/ HDAC1/ HDAC2/ HOXB1/ HOXB8/ HRAS1/ ID3/ IDUA/ IFT88/ IL1R1/ INHBA/ INHBB/ IRF6/ ITGA11/ ITGA6/ JAG1/ JAG2/ KLK4/ LAMA3/ LAMA5/ LAMB1/ LEF1/ LHX8/ LMNA/ LPAR1/ LRP4/ LRP6/ LTBP1/ LTBP3/ MAP3K11/ MECOM/ MECP2/ MITF/ MMP14/ MMP20/ MSX1/ MSX2/ MTF2/ MYO5A/ NF2/ NFATC1/ NFE2L2/ NFIC/ NFKB1/ NFKB2/ NGFR/ NKX2-3/ NOS2/ NOTCH2/ NPHP3/ NPR2/ NR3C1/ ODAM/ OSR1/ OSR2/ OSTM1/ PAM/ PAPSS2/ PAX3/ PAX6/ PAX9/ PDGFRA/ PITX2/ PKD1/ PORCN/ POSTN/ POU1F1/ PPARA/ PRKCB/ PRRX2/ PRXX1/ PTCH1/ PTHLH/ PTPN9/ PVR1L/ PVRL3/ RAI1/ RBL1/ RBL2/ RSPO2/ RUNX2/ S100B/ SATB2/ SCN10A/ SCN5A/ SDC1/ SFPI1/ SH3PXD2B/ SHH/ SIM2/ SIRT6/ SLC39A13/ SLC4A2/ SLC4A4/ SLX4/ SMN1/ SMO/ SOSTDC1/ SOX3/ SP3/ SP6/ SPRY2/ SPRY4/ SRC/ STAG1/ SULF1/ SULF2/ TBX1/ TCF7L2/ TCFAP2A/ TCIRG1/ TFE3/ TGFB1/ TGFB2/ TGFB3/ TNC/ TNFRSF11A/ TNFRSF11B/ TNFRSF19/ TNFSF11/ TRAF6/ TRP53/ TRP63/ TUFT1/ UROS/ VAX1/ VEGFA/ WHSC1/ WLS/ WNT10A/ WNT6/ WNT7B/ ZIC3/ ZIC5/ ZMPSTE24/ ZNF22/<br> Each folder contains 5 sub-folders:<br> FASTA/ - Gene alingment GBLOCKS/ - 2 files: Gene full sequence (*.fas) Gene trimmed gene (*.fas-gb) MRAIC_GENE_TREE/ - Result tree from MrAIC applying the best evolutionary model obtained using BIC using the followin annotation: "GENE NAME".BIC-"BEST MODEL".tre GENE_TREE/ - Results of CODEML M0_7_8/ - Results of Model 0, 7 and 8 in a single file, M1_2/ - Results of Model 1 and 2 in a single file, M8a/ - Results of Model 8a SPECIES_TREE/ - Results of CODEML M0_7_8/ - Results of Model 0, 7 and 8 in a single file, M1_2/ - Results of Model 1 and 2 in a single file, M8a/ - Results of Model 8a<br> <b> 2) PARAMETERS.zip</b> - This file contains the used species tree, and 3 codeml parameter templates: Species_tree.nwk - Mammalian species tree used in CODEML codeml_M0_7_8.ctl - parameters file template for Models 0, 7 and 8a codeml_M1_2.ctl - parameters file template for Models 1 and 2 codeml_M8a.ctl - parameters file template for Model 8a
DOI: 10.6084/m9.figshare.3708099.v3
title: Data for "Positive Selection Linked with Generation of Novel Mammalian Dentition Patterns"

description: The data contained in them pretains to the manuscript"Positive Selection Linked with Generation of Novel Mammalian Dentition Patterns"<br>2 zip files:<br><b> 1) GENES.zip </b>- This file contains 236 folders with the genes used for evolutionary analysis:<br> ACHE/ ACLY/ ACVR1B/ ACVR2B/ ADAMTS2/ ADM/ AGPAT2/ ALKBH1/ ALPL/ AMBN/ AMTN/ ANKH/ ANKRD11/ ANTXR1/ APC/ AQP1/ AQP3/ AQP5/ AQP6/ ASPN/ ATR/ AXIN2/ BARX1/ BAX/ BAZ1B/ BCL11B/ BCL2L11/ BCOR/ BGLAP/ BMP2/ BMP4/ BMP7/ BMPR1A/ BRAF/ BSG/ CA2/ CBX2/ CCL2/ CCND1/ CD34/ CD86/ CDKN1A/ CDKN1B/ CDO1/ CDON/ CHUK/ CLCN5/ CLCN7/ COL10A1/ COL1A1/ COL1A2/ COL7A1/ CSF1/ CSF1R/ CSF2/ CSF3R/ CTNNA1/ CTNNB1/ CTSK/ DCN/ DIAP1/ DICER1/ DISP1/ DLL1/ DLX1/ DLX2/ DLX5/ DMP1/ DMRT3/ DSPP/ EDA/ EDAR/ EDARADD/ EDN1/ EDNRA/ ENAM/ ERBB2/ ERBB3/ ERBB4/ EVC/ FAM20A/ FAM20C/ FGF10/ FGF4/ FGF8/ FGFR1/ FGFR2/ FGFR3/ FMOD/ FOS/ FOXA2/ FST/ FUZ/ GALC/ GATA6/ GJA/ GLI2/ GLI3/ GTF2IRD1/ HAND1/ HAND2/ HDAC1/ HDAC2/ HOXB1/ HOXB8/ HRAS1/ ID3/ IDUA/ IFT88/ IL1R1/ INHBA/ INHBB/ IRF6/ ITGA11/ ITGA6/ JAG1/ JAG2/ KLK4/ LAMA3/ LAMA5/ LAMB1/ LEF1/ LHX8/ LMNA/ LPAR1/ LRP4/ LRP6/ LTBP1/ LTBP3/ MAP3K11/ MECOM/ MECP2/ MITF/ MMP14/ MMP20/ MSX1/ MSX2/ MTF2/ MYO5A/ NF2/ NFATC1/ NFE2L2/ NFIC/ NFKB1/ NFKB2/ NGFR/ NKX2-3/ NOS2/ NOTCH2/ NPHP3/ NPR2/ NR3C1/ ODAM/ OSR1/ OSR2/ OSTM1/ PAM/ PAPSS2/ PAX3/ PAX6/ PAX9/ PDGFRA/ PITX2/ PKD1/ PORCN/ POSTN/ POU1F1/ PPARA/ PRKCB/ PRRX2/ PRXX1/ PTCH1/ PTHLH/ PTPN9/ PVR1L/ PVRL3/ RAI1/ RBL1/ RBL2/ RSPO2/ RUNX2/ S100B/ SATB2/ SCN10A/ SCN5A/ SDC1/ SFPI1/ SH3PXD2B/ SHH/ SIM2/ SIRT6/ SLC39A13/ SLC4A2/ SLC4A4/ SLX4/ SMN1/ SMO/ SOSTDC1/ SOX3/ SP3/ SP6/ SPRY2/ SPRY4/ SRC/ STAG1/ SULF1/ SULF2/ TBX1/ TCF7L2/ TCFAP2A/ TCIRG1/ TFE3/ TGFB1/ TGFB2/ TGFB3/ TNC/ TNFRSF11A/ TNFRSF11B/ TNFRSF19/ TNFSF11/ TRAF6/ TRP53/ TRP63/ TUFT1/ UROS/ VAX1/ VEGFA/ WHSC1/ WLS/ WNT10A/ WNT6/ WNT7B/ ZIC3/ ZIC5/ ZMPSTE24/ ZNF22/<br> Each folder contains 5 sub-folders:<br> FASTA/ - Gene alingment GBLOCKS/ - 2 files: Gene full sequence (*.fas) Gene trimmed gene (*.fas-gb) MRAIC_GENE_TREE/ - Result tree from MrAIC applying the best evolutionary model obtained using BIC using the followin annotation: "GENE NAME".BIC-"BEST MODEL".tre GENE_TREE/ - Results of CODEML M0_7_8/ - Results of Model 0, 7 and 8 in a single file, M1_2/ - Results of Model 1 and 2 in a single file, M8a/ - Results of Model 8a SPECIES_TREE/ - Results of CODEML M0_7_8/ - Results of Model 0, 7 and 8 in a single file, M1_2/ - Results of Model 1 and 2 in a single file, M8a/ - Results of Model 8a<br> <b> 2) PARAMETERS.zip</b> - This file contains the used species tree, and 3 codeml parameter templates: Species_tree.nwk - Mammalian species tree used in CODEML codeml_M0_7_8.ctl - parameters file template for Models 0, 7 and 8a codeml_M1_2.ctl - parameters file template for Models 1 and 2 codeml_M8a.ctl - parameters file template for Model 8a
DOI: 10.6084/m9.figshare.3706665
title: Comparative analyses of ubiquitin-like <i>ATG8</i> and cysteine protease <i>ATG4</i> autophagy genes in the plant lineage and cross-kingdom processing of ATG8 by ATG4

description: Autophagy is important for degradation and recycling of intracellular components. In a diversity of genera and species, orthologs and paralogs of the yeast Atg4 and Atg8 proteins are crucial in the biogenesis of double-membrane autophagosomes that carry the cellular cargoes to vacuoles and lysosomes. Although many plant genome sequences are available, the <i>ATG4</i> and <i>ATG8</i> sequence analysis is limited to some model plants. We identified 28 <i>ATG4</i> and 116 <i>ATG8</i> genes from the available 18 different plant genome sequences. Gene structures and protein domain sequences of ATG4 and ATG8 are conserved in plant lineages. Phylogenetic analyses classified <i>ATG8</i>s into 3 subgroups suggesting divergence from the common ancestor. The <i>ATG8</i> expansion in plants might be attributed to whole genome duplication, segmental and dispersed duplication, and purifying selection. Our results revealed that the yeast Atg4 processes <i>Arabidopsis</i> ATG8 but not human LC3A (HsLC3A). In contrast, HsATG4B can process yeast and plant ATG8s <i>in vitro</i> but yeast and plant ATG4s cannot process HsLC3A. Interestingly, in <i>Nicotiana benthamiana</i> plants the yeast Atg8 is processed compared to HsLC3A. However, HsLC3A is processed when coexpressed with HsATG4B in plants. Molecular modeling indicates that lack of processing of HsLC3A by plant and yeast ATG4 is not due to lack of interaction with HsLC3A. Our in-depth analyses of <i>ATG4</i> and <i>ATG8</i> in the plant lineage combined with results of cross-kingdom ATG8 processing by ATG4 further support the evolutionarily conserved maturation of ATG8. Broad ATG8 processing by HsATG4B and lack of processing of HsLC3A by yeast and plant ATG4s suggest that the cross-kingdom ATG8 processing is determined by ATG8 sequence rather than ATG4.
DOI: 10.6084/m9.figshare.3706665.v1
title: Comparative analyses of ubiquitin-like <i>ATG8</i> and cysteine protease <i>ATG4</i> autophagy genes in the plant lineage and cross-kingdom processing of ATG8 by ATG4

description: Autophagy is important for degradation and recycling of intracellular components. In a diversity of genera and species, orthologs and paralogs of the yeast Atg4 and Atg8 proteins are crucial in the biogenesis of double-membrane autophagosomes that carry the cellular cargoes to vacuoles and lysosomes. Although many plant genome sequences are available, the <i>ATG4</i> and <i>ATG8</i> sequence analysis is limited to some model plants. We identified 28 <i>ATG4</i> and 116 <i>ATG8</i> genes from the available 18 different plant genome sequences. Gene structures and protein domain sequences of ATG4 and ATG8 are conserved in plant lineages. Phylogenetic analyses classified <i>ATG8</i>s into 3 subgroups suggesting divergence from the common ancestor. The <i>ATG8</i> expansion in plants might be attributed to whole genome duplication, segmental and dispersed duplication, and purifying selection. Our results revealed that the yeast Atg4 processes <i>Arabidopsis</i> ATG8 but not human LC3A (HsLC3A). In contrast, HsATG4B can process yeast and plant ATG8s <i>in vitro</i> but yeast and plant ATG4s cannot process HsLC3A. Interestingly, in <i>Nicotiana benthamiana</i> plants the yeast Atg8 is processed compared to HsLC3A. However, HsLC3A is processed when coexpressed with HsATG4B in plants. Molecular modeling indicates that lack of processing of HsLC3A by plant and yeast ATG4 is not due to lack of interaction with HsLC3A. Our in-depth analyses of <i>ATG4</i> and <i>ATG8</i> in the plant lineage combined with results of cross-kingdom ATG8 processing by ATG4 further support the evolutionarily conserved maturation of ATG8. Broad ATG8 processing by HsATG4B and lack of processing of HsLC3A by yeast and plant ATG4s suggest that the cross-kingdom ATG8 processing is determined by ATG8 sequence rather than ATG4.
DOI: 10.6084/m9.figshare.3706620
title: PEBP1, a RAF kinase inhibitory protein, negatively regulates starvation-induced autophagy by direct interaction with LC3

description: Autophagy plays a critical role in maintaining cell homeostasis in response to various stressors through protein conjugation and activation of lysosome-dependent degradation. MAP1LC3B/LC3B (microtubule- associated protein 1 light chain 3 β) is conjugated with phosphatidylethanolamine (PE) in the membranes and regulates initiation of autophagy through interaction with many autophagy-related proteins possessing an LC3-interacting region (LIR) motif, which is composed of 2 hydrophobic amino acids (tryptophan and leucine) separated by 2 non-conserved amino acids (WXXL). In this study, we identified a new putative LIR motif in PEBP1/RKIP (phosphatidylethanolamine binding protein 1) that was originally isolated as a PE-binding protein and also a cellular inhibitor of MAPK/ERK signaling. PEBP1 was specifically bound to PE-unconjugated LC3 in cells, and mutation (WXXL mutated to AXXA) of this LIR motif disrupted its interaction with LC3 proteins. Interestingly, overexpression of PEBP1 significantly inhibited starvation-induced autophagy by activating the AKT and MTORC1 (mechanistic target of rapamycin [serine/threonine kinase] complex 1) signaling pathway and consequently suppressing the ULK1 (unc-51 like autophagy activating kinase 1) activity. In contrast, ablation of PEBP1 expression dramatically promoted the autophagic process under starvation conditions. Furthermore, PEBP1 lacking the LIR motif highly stimulated starvation-induced autophagy through the AKT-MTORC1-dependent pathway. PEBP1 phosphorylation at Ser153 caused dissociation of LC3 from the PEBP1-LC3 complex for autophagy induction. PEBP1-dependent suppression of autophagy was not associated with the MAPK pathway. These findings suggest that PEBP1 can act as a negative mediator in autophagy through stimulation of the AKT-MTORC1 pathway and direct interaction with LC3.
DOI: 10.6084/m9.figshare.3706620.v1
title: PEBP1, a RAF kinase inhibitory protein, negatively regulates starvation-induced autophagy by direct interaction with LC3

description: Autophagy plays a critical role in maintaining cell homeostasis in response to various stressors through protein conjugation and activation of lysosome-dependent degradation. MAP1LC3B/LC3B (microtubule- associated protein 1 light chain 3 β) is conjugated with phosphatidylethanolamine (PE) in the membranes and regulates initiation of autophagy through interaction with many autophagy-related proteins possessing an LC3-interacting region (LIR) motif, which is composed of 2 hydrophobic amino acids (tryptophan and leucine) separated by 2 non-conserved amino acids (WXXL). In this study, we identified a new putative LIR motif in PEBP1/RKIP (phosphatidylethanolamine binding protein 1) that was originally isolated as a PE-binding protein and also a cellular inhibitor of MAPK/ERK signaling. PEBP1 was specifically bound to PE-unconjugated LC3 in cells, and mutation (WXXL mutated to AXXA) of this LIR motif disrupted its interaction with LC3 proteins. Interestingly, overexpression of PEBP1 significantly inhibited starvation-induced autophagy by activating the AKT and MTORC1 (mechanistic target of rapamycin [serine/threonine kinase] complex 1) signaling pathway and consequently suppressing the ULK1 (unc-51 like autophagy activating kinase 1) activity. In contrast, ablation of PEBP1 expression dramatically promoted the autophagic process under starvation conditions. Furthermore, PEBP1 lacking the LIR motif highly stimulated starvation-induced autophagy through the AKT-MTORC1-dependent pathway. PEBP1 phosphorylation at Ser153 caused dissociation of LC3 from the PEBP1-LC3 complex for autophagy induction. PEBP1-dependent suppression of autophagy was not associated with the MAPK pathway. These findings suggest that PEBP1 can act as a negative mediator in autophagy through stimulation of the AKT-MTORC1 pathway and direct interaction with LC3.
DOI: 10.6084/m9.figshare.3706302
title: <i>Ehrlichia</i> secretes Etf-1 to induce autophagy and capture nutrients for its growth through RAB5 and class III phosphatidylinositol 3-kinase

description: <i>Ehrlichia chaffeensis</i> is an obligatory intracellular bacterium that causes a potentially fatal emerging zoonosis, human monocytic ehrlichiosis. <i>E. chaffeensis</i> has a limited capacity for biosynthesis and metabolism and thus depends mostly on host-synthesized nutrients for growth. Although the host cell cytoplasm is rich with these nutrients, as <i>E. chaffeensis</i> is confined within the early endosome-like membrane-bound compartment, only host nutrients that enter the compartment can be used by this bacterium. How this occurs is unknown. We found that ehrlichial replication depended on autophagy induction involving class III phosphatidylinositol 3-kinase (PtdIns3K) activity, BECN1 (Beclin 1), and ATG5 (autophagy-related 5). <i>Ehrlichia</i> acquired host cell preincorporated amino acids in a class III PtdIns3K-dependent manner and ehrlichial growth was enhanced by treatment with rapamycin, an autophagy inducer. Moreover, ATG5 and RAB5A/B/C were routed to ehrlichial inclusions. <i>RAB5A/B/C</i> siRNA knockdown, or overexpression of a RAB5-specific GTPase-activating protein or dominant-negative RAB5A inhibited ehrlichial infection, indicating the critical role of GTP-bound RAB5 during infection. Both native and ectopically expressed ehrlichial type IV secretion effector protein, Etf-1, bound RAB5 and the autophagy-initiating class III PtdIns3K complex, PIK3C3/VPS34, and BECN1, and homed to ehrlichial inclusions. Ectopically expressed Etf-1 activated class III PtdIns3K as in <i>E. chaffeensis</i> infection and induced autophagosome formation, cleared an aggregation-prone mutant huntingtin protein in a class III PtdIns3K-dependent manner, and enhanced ehrlichial proliferation. These data support the notion that <i>E. chaffeensis</i> secretes Etf-1 to induce autophagy to repurpose the host cytoplasm and capture nutrients for its growth through RAB5 and class III PtdIns3K, while avoiding autolysosomal killing.
DOI: 10.6084/m9.figshare.3706302.v1
title: <i>Ehrlichia</i> secretes Etf-1 to induce autophagy and capture nutrients for its growth through RAB5 and class III phosphatidylinositol 3-kinase

description: <i>Ehrlichia chaffeensis</i> is an obligatory intracellular bacterium that causes a potentially fatal emerging zoonosis, human monocytic ehrlichiosis. <i>E. chaffeensis</i> has a limited capacity for biosynthesis and metabolism and thus depends mostly on host-synthesized nutrients for growth. Although the host cell cytoplasm is rich with these nutrients, as <i>E. chaffeensis</i> is confined within the early endosome-like membrane-bound compartment, only host nutrients that enter the compartment can be used by this bacterium. How this occurs is unknown. We found that ehrlichial replication depended on autophagy induction involving class III phosphatidylinositol 3-kinase (PtdIns3K) activity, BECN1 (Beclin 1), and ATG5 (autophagy-related 5). <i>Ehrlichia</i> acquired host cell preincorporated amino acids in a class III PtdIns3K-dependent manner and ehrlichial growth was enhanced by treatment with rapamycin, an autophagy inducer. Moreover, ATG5 and RAB5A/B/C were routed to ehrlichial inclusions. <i>RAB5A/B/C</i> siRNA knockdown, or overexpression of a RAB5-specific GTPase-activating protein or dominant-negative RAB5A inhibited ehrlichial infection, indicating the critical role of GTP-bound RAB5 during infection. Both native and ectopically expressed ehrlichial type IV secretion effector protein, Etf-1, bound RAB5 and the autophagy-initiating class III PtdIns3K complex, PIK3C3/VPS34, and BECN1, and homed to ehrlichial inclusions. Ectopically expressed Etf-1 activated class III PtdIns3K as in <i>E. chaffeensis</i> infection and induced autophagosome formation, cleared an aggregation-prone mutant huntingtin protein in a class III PtdIns3K-dependent manner, and enhanced ehrlichial proliferation. These data support the notion that <i>E. chaffeensis</i> secretes Etf-1 to induce autophagy to repurpose the host cytoplasm and capture nutrients for its growth through RAB5 and class III PtdIns3K, while avoiding autolysosomal killing.
DOI: 10.6084/m9.figshare.3706290
title: Impairment of chaperone-mediated autophagy induces dopaminergic neurodegeneration in rats

description: Chaperone-mediated autophagy (CMA) involves the selective lysosomal degradation of cytosolic proteins such as SNCA (synuclein α), a protein strongly implicated in Parkinson disease (PD) pathogenesis. However, the physiological role of CMA and the consequences of CMA failure in the living brain remain elusive. Here we show that CMA inhibition in the adult rat substantia nigra via adeno-associated virus-mediated delivery of short hairpin RNAs targeting the LAMP2A receptor, involved in CMA's rate limiting step, was accompanied by intracellular accumulation of SNCA-positive puncta, which were also positive for UBIQUITIN, and in accumulation of autophagic vacuoles within LAMP2A-deficient nigral neurons. Strikingly, LAMP2A downregulation resulted in progressive loss of nigral dopaminergic neurons, severe reduction in striatal dopamine levels/terminals, increased astro- and microgliosis and relevant motor deficits. Thus, this study highlights for the first time the importance of the CMA pathway in the dopaminergic system and suggests that CMA impairment may underlie PD pathogenesis.