cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.23065437.v1
title: Geographical, temporal variability and sexual size dimorphism of mandible in cave lion (<i>Panthera spelaea</i>) across Northern Eurasia

description: The mandible size variability including sexual size dimorphism (SSD) of the cave lion (<i>Panthera spelaea</i>) in the Pleistocene of Northern Eurasia time has been studied basing on the univariate and multivariate statistical analyses of 76 specimens from 43 localities. It has been confirmed that SSD in adult <i>P. spelaea</i>, as well as in extant <i>P. leo</i>, is the dominant form of group variability of mandible and, to somewhat lesser extent, of variability of cheek teeth. The lowest degree of SSD has been found in a relatively small Beringian subspecies, <i>P. spelaea vereshchagini</i>. The geographical variability of the cave lion from Western to Eastern Eurasia was not a cline at least in the Late Pleistocene. Our results confirm a decrease in overall mandible size from the Middle Pleistocene to the Late Pleistocene over a large part of the species’ range. We speculate that evolutionary changes in mandible size, lower canines or cheek teeth may have proceeded at different rates, allometry and probable heterochrony. Our results have added a new evidence to support the subspecies status of the Beringian lion (<i>P. spelaea vereshchagini</i>), but they are insufficient for other decisions on cave lion taxonomy at the subspecies level.
DOI: 10.6084/m9.figshare.23261047.v1
title: Flourishing chancelloriids from the Cambrian Kaili Biota of South China

description: Diverse chancelloriids from two sections of the Kaili Biota (Cambrian Wuliuan Stage) in Guizhou Province, China, are systematically described. A total of 25 complete individuals were collected from calcareous silty mudstones of the Cambrian Kaili Formation and are assigned to 3 genera and 6 species, including <i>Archiasterella anchoriformis</i> sp. nov., <i>Chancelloria zhaoi</i> sp. nov., <i>C. eros, Allonnia erjiensis, Al. phrixothrix</i>, and <i>Al</i>. sp. The new species <i>Ar. anchoriformis</i> with sclerites characterised by a large angle between two marginal-lateral rays and an obvious apical tuft represents the first unambiguous <i>Archiasterella</i> scleritome in South China. The <i>C. zhaoi</i> is dominated by a series of bilaterally symmetrical, rosette-like sclerites that composed of five or six lateral rays and a central ray. Moreover, based on a careful survey of the spatial-temporal distribution of chancelloriids (including both scleritome and isolated sclerite fossils) in South China, two flourishing ages, though may be related to preservational bias, of this metazoan group are recognised: 1) a significant diversification in the upper Stage 2 to Stage 3 and 2) a thriving in the Wuliuan Stage.
DOI: 10.6084/m9.figshare.23578625
title: The largest record of the minute beaver <i>Euroxenomys minutus</i> (Mammalia, Castoridae) from the early Late Miocene hominid locality Hammerschmiede (Bavaria, Southern Germany) and palaeoecological considerations

description: In this study, we describe the dental remains of a very minute beaver from the early Late Miocene locality Hammerschmiede (MN 7/8) located at the Northern Alpine Foreland Basin (Southern Germany, Bavaria). The finds represent the so far most comprehensive (&gt;1.000 dental specimens) collection of the trogontheriine castorid <i>Euroxenomys minutus</i>. Metrically and morphologically, the large data set demonstrates an extensive intraspecific variability of this beaver from Hammerschmiede that covers most finds of other European localities and confirms previous species assignments. The subspecies <i>Euroxenomys minutus rhenanus</i> from Dorn-Dürkheim (Germany), clearly isolates from this range of variation and can thus be validated. The performed age-frequency distributions for <i>Euroxenomys minutus</i> from the local stratigraphic levels HAM 5 (rivulet) and HAM 4 (river) correspond roughly and also resemble <i>Euroxenomys</i> from the swamp deposit Rudabánya (Hungary). Since previous mortality studies on the also occurring larger beaver <i>Steneofiber depereti</i> from Hammerschmiede demonstrated dominance of behavioural or internal factors, this cross-ecosystem similarity in mortality for the small beaver species is likely explained by external factors, such as predation. Supported by a taphonomic bone analysis, a multitude of predators are finally considered to prey on <i>Euroxenomys minutus</i> and indicate a predatory bone assemblage.
DOI: 10.6084/m9.figshare.23578625.v1
title: The largest record of the minute beaver <i>Euroxenomys minutus</i> (Mammalia, Castoridae) from the early Late Miocene hominid locality Hammerschmiede (Bavaria, Southern Germany) and palaeoecological considerations

description: In this study, we describe the dental remains of a very minute beaver from the early Late Miocene locality Hammerschmiede (MN 7/8) located at the Northern Alpine Foreland Basin (Southern Germany, Bavaria). The finds represent the so far most comprehensive (&gt;1.000 dental specimens) collection of the trogontheriine castorid <i>Euroxenomys minutus</i>. Metrically and morphologically, the large data set demonstrates an extensive intraspecific variability of this beaver from Hammerschmiede that covers most finds of other European localities and confirms previous species assignments. The subspecies <i>Euroxenomys minutus rhenanus</i> from Dorn-Dürkheim (Germany), clearly isolates from this range of variation and can thus be validated. The performed age-frequency distributions for <i>Euroxenomys minutus</i> from the local stratigraphic levels HAM 5 (rivulet) and HAM 4 (river) correspond roughly and also resemble <i>Euroxenomys</i> from the swamp deposit Rudabánya (Hungary). Since previous mortality studies on the also occurring larger beaver <i>Steneofiber depereti</i> from Hammerschmiede demonstrated dominance of behavioural or internal factors, this cross-ecosystem similarity in mortality for the small beaver species is likely explained by external factors, such as predation. Supported by a taphonomic bone analysis, a multitude of predators are finally considered to prey on <i>Euroxenomys minutus</i> and indicate a predatory bone assemblage.
DOI: 10.6084/m9.figshare.23261047
title: Flourishing chancelloriids from the Cambrian Kaili Biota of South China

description: Diverse chancelloriids from two sections of the Kaili Biota (Cambrian Wuliuan Stage) in Guizhou Province, China, are systematically described. A total of 25 complete individuals were collected from calcareous silty mudstones of the Cambrian Kaili Formation and are assigned to 3 genera and 6 species, including <i>Archiasterella anchoriformis</i> sp. nov., <i>Chancelloria zhaoi</i> sp. nov., <i>C. eros, Allonnia erjiensis, Al. phrixothrix</i>, and <i>Al</i>. sp. The new species <i>Ar. anchoriformis</i> with sclerites characterised by a large angle between two marginal-lateral rays and an obvious apical tuft represents the first unambiguous <i>Archiasterella</i> scleritome in South China. The <i>C. zhaoi</i> is dominated by a series of bilaterally symmetrical, rosette-like sclerites that composed of five or six lateral rays and a central ray. Moreover, based on a careful survey of the spatial-temporal distribution of chancelloriids (including both scleritome and isolated sclerite fossils) in South China, two flourishing ages, though may be related to preservational bias, of this metazoan group are recognised: 1) a significant diversification in the upper Stage 2 to Stage 3 and 2) a thriving in the Wuliuan Stage.
DOI: 10.6084/m9.figshare.24765236
title: LTN1 promotes RLR degradation to inhibit immune response to RNA virus through the ESCRT pathway

description: The excessive activation of immune responses will trigger autoimmune diseases or inflammatory injury. The endosomal sorting complexes required for transport (ESCRT) system can capture and mediate ubiquitinated protein degradation, which timely terminates signaling pathway hyperactivation. However, whether the ESCRT system participates in regulating RIGI-like receptor (RLR)-mediated antiviral responses remains unknown. In this study, we show that LTN1/listerin, a major component of RQC, can recruit E3 ubiquitin ligase TRIM27 to trigger K63-linked polyubiquitination of RIGI and IFIH1/MDA5. This K63-linked polyubiquitination facilitates the sorting and degradation of RIGI and IFIH1 proteins through the ESCRT-dependent pathway. Concordantly, LTN1 deficiency enhances the innate antiviral response to infection with RNA viruses. Thus, our work uncovers a new mechanism for RIGI and IFIH1 degradation and identifies the role of LTN1 in negatively regulating RLR-mediated antiviral innate immunity, which may provide new targets for the intervention of viral infection. <b>Abbreviation</b>: 5'-pppRNA: 5’ triphosphate double stranded RNA; ATG5: autophagy related 5; ATG7: autophagy related 7; BafA1: bafilomycin A<sub>1</sub>; ESCRT: endosomal sorting complexes required for transport; CHX: cycloheximide; IFIH1/MDA5: interferon induced with helicase C domain 1; IFN: interferon; PIK3C3/VPS34: phosphatidylinositol 3-kinase catalytic subunit type 3; RIGI: RNA sensor RIG-I; RLR: RIGI-like receptors; RQC: ribosome-associated protein quality control; SeV: Sendai virus; TRIM27: tripartite motif-containing 27; VSV: vesicular stomatitis virus; VPS4: vacuolar protein sorting 4.
DOI: 10.6084/m9.figshare.24765236.v1
title: LTN1 promotes RLR degradation to inhibit immune response to RNA virus through the ESCRT pathway

description: The excessive activation of immune responses will trigger autoimmune diseases or inflammatory injury. The endosomal sorting complexes required for transport (ESCRT) system can capture and mediate ubiquitinated protein degradation, which timely terminates signaling pathway hyperactivation. However, whether the ESCRT system participates in regulating RIGI-like receptor (RLR)-mediated antiviral responses remains unknown. In this study, we show that LTN1/listerin, a major component of RQC, can recruit E3 ubiquitin ligase TRIM27 to trigger K63-linked polyubiquitination of RIGI and IFIH1/MDA5. This K63-linked polyubiquitination facilitates the sorting and degradation of RIGI and IFIH1 proteins through the ESCRT-dependent pathway. Concordantly, LTN1 deficiency enhances the innate antiviral response to infection with RNA viruses. Thus, our work uncovers a new mechanism for RIGI and IFIH1 degradation and identifies the role of LTN1 in negatively regulating RLR-mediated antiviral innate immunity, which may provide new targets for the intervention of viral infection. <b>Abbreviation</b>: 5'-pppRNA: 5’ triphosphate double stranded RNA; ATG5: autophagy related 5; ATG7: autophagy related 7; BafA1: bafilomycin A<sub>1</sub>; ESCRT: endosomal sorting complexes required for transport; CHX: cycloheximide; IFIH1/MDA5: interferon induced with helicase C domain 1; IFN: interferon; PIK3C3/VPS34: phosphatidylinositol 3-kinase catalytic subunit type 3; RIGI: RNA sensor RIG-I; RLR: RIGI-like receptors; RQC: ribosome-associated protein quality control; SeV: Sendai virus; TRIM27: tripartite motif-containing 27; VSV: vesicular stomatitis virus; VPS4: vacuolar protein sorting 4.
DOI: 10.6084/m9.figshare.24793521.v1
title: Senecavirus a induces mitophagy to promote self-replication through direct interaction of 2C protein with K27-linked ubiquitinated TUFM catalyzed by RNF185

description: Senecavirus A (SVA) is a newly emerging picornavirus associated with swine vesicular lesions and neonatal mortality, threatening the global pig industry. Despite sustained efforts, the molecular mechanisms of SVA pathogenesis have not yet been fully elucidated. Here, we demonstrate for the first time that SVA infection can induce complete mitophagy in host cells, which depends on SVA replication. Mitophagy has been subsequently proven to promote SVA replication in host cells. Genome-wide screening of SVA proteins involved in inducing mitophagy showed that although VP2, VP3, 2C, and 3A proteins can independently induce mitophagy, only the 2C protein mediates mitophagy through direct interaction with TUFM (Tu translation elongation factor, mitochondrial). The glutamic acids at positions 196 and 211 of TUFM were shown to be two key sites for its interaction with 2C protein. Moreover, TUFM was discovered to interact directly with BECN1 and indirectly with the ATG12–ATG5 conjugate. Further experiments revealed that TUFM needs to undergo ubiquitination modification before being recognized by the macroautophagy/autophagy receptor protein SQSTM1/p62, and E3 ubiquitin ligase RNF185 catalyzes K27-linked polyubiquitination of TUFM through the interaction between RNF185’s transmembrane domain 1 and TUFM to initiate SVA-induced mitophagy. The ubiquitinated TUFM is recognized and bound by SQSTM1, which in turn interacts with MAP1LC3/LC3, thereby linking the 2C-anchored mitochondria to the phagophore for sequestration into mitophagosomes, which ultimately fuse with lysosomes to achieve complete mitophagy. Overall, our results elucidated the molecular mechanism by which SVA induces mitophagy to promote self-replication and provide new insights into SVA pathogenesis.
DOI: 10.6084/m9.figshare.24943071
title: Targeting cancer-associated fibroblast autophagy renders pancreatic cancer eradicable with immunochemotherapy by inhibiting adaptive immune resistance

description: Accumulating evidence suggests that cancer-associated fibroblast (CAF) macroautophagy/autophagy is crucial in tumor development and may be a therapeutic target for pancreatic ductal adenocarcinoma (PDAC). However, the role of CAF autophagy during immune surveillance and cancer immunotherapy is unclear. The present study revealed that the inhibition of CAF autophagy suppresses <i>in vivo</i> tumor development in immune-deficient xenografts. This deletion compromises anti-tumor immunity and anti-tumor efficacy both <i>in vitro</i> and <i>in vivo</i> by upregulating CD274/PDL1 levels in an immune-competent mouse model. A block in CAF autophagy reduced the production of IL6 (interleukin 6), disrupting high desmoplastic TME and decreasing USP14 expression at the transcription level in pancreatic cancer cells. We further identify USP14 as the post-translational factor responsible for downregulating CD274 expression by removing K63 linked-ubiquitination at the K280 residue. Finally, chloroquine diphosphate-loaded mesenchymal stem cell (MSC)-liposomes, by accurately targeting CAFs, inhibited CAF autophagy, improving the efficacy of immunochemotherapy to combat pancreatic cancer. <b>Abbreviation</b>: AIR: adaptive immune resistance; ATRA: all-trans-retinoicacid; CAF: cancer-associated fibroblast; CD274/PDL1: CD274 molecule; CM: conditioned medium; CQ: chloroquine diphosphate; CyTOF: Mass cytometry; FGF2/bFGF: fibroblast growth factor 2; ICB: immune checkpoint blockade; IF: immunofluorescence; IHC: immunohistochemistry; IP: immunoprecipitation; MS: mass spectrometer; MSC: mesenchymal stem cell; PDAC: pancreatic ductal adenocarcinoma; TEM: transmission electron microscopy; TILs: tumor infiltrating lymphocytes; TME: tumor microenvironment; USP14: ubiquitin specific peptidase 14.
DOI: 10.6084/m9.figshare.24943071.v1
title: Targeting cancer-associated fibroblast autophagy renders pancreatic cancer eradicable with immunochemotherapy by inhibiting adaptive immune resistance

description: Accumulating evidence suggests that cancer-associated fibroblast (CAF) macroautophagy/autophagy is crucial in tumor development and may be a therapeutic target for pancreatic ductal adenocarcinoma (PDAC). However, the role of CAF autophagy during immune surveillance and cancer immunotherapy is unclear. The present study revealed that the inhibition of CAF autophagy suppresses <i>in vivo</i> tumor development in immune-deficient xenografts. This deletion compromises anti-tumor immunity and anti-tumor efficacy both <i>in vitro</i> and <i>in vivo</i> by upregulating CD274/PDL1 levels in an immune-competent mouse model. A block in CAF autophagy reduced the production of IL6 (interleukin 6), disrupting high desmoplastic TME and decreasing USP14 expression at the transcription level in pancreatic cancer cells. We further identify USP14 as the post-translational factor responsible for downregulating CD274 expression by removing K63 linked-ubiquitination at the K280 residue. Finally, chloroquine diphosphate-loaded mesenchymal stem cell (MSC)-liposomes, by accurately targeting CAFs, inhibited CAF autophagy, improving the efficacy of immunochemotherapy to combat pancreatic cancer. <b>Abbreviation</b>: AIR: adaptive immune resistance; ATRA: all-trans-retinoicacid; CAF: cancer-associated fibroblast; CD274/PDL1: CD274 molecule; CM: conditioned medium; CQ: chloroquine diphosphate; CyTOF: Mass cytometry; FGF2/bFGF: fibroblast growth factor 2; ICB: immune checkpoint blockade; IF: immunofluorescence; IHC: immunohistochemistry; IP: immunoprecipitation; MS: mass spectrometer; MSC: mesenchymal stem cell; PDAC: pancreatic ductal adenocarcinoma; TEM: transmission electron microscopy; TILs: tumor infiltrating lymphocytes; TME: tumor microenvironment; USP14: ubiquitin specific peptidase 14.
DOI: 10.6084/m9.figshare.25459807
title: Foot-and-mouth disease virus VP1 degrades YTHDF2 through autophagy to regulate IRF3 activity for viral replication

description: Many viruses, including foot-and-mouth disease virus (FMDV), can promote the degradation of host proteins through macroautophagy/autophagy, thereby promoting viral replication. However, the regulatory mechanism between autophagy and innate immune responses is not fully understood during FMDV infection. Here, we found that the host GTPBP4/NOG1 (GTP binding protein 4) is a negative regulator of innate immune responses. GTPBP4 deficiency promotes the antiviral innate immune response, resulting in the ability of GTPBP4 to promote FMDV replication. Meanwhile, GTPBP4-deficient mice are more resistant to FMDV infection. To antagonize the host’s antiviral immunity, FMDV structural protein VP1 promotes the expression of GTPBP4, and the 209th site of VP1 is responsible for this effect. Mechanically, FMDV VP1 promotes autophagy during virus infection and interacts with and degrades YTHDF2 (YTH N6-methyladenosine RNA binding protein F2) in an AKT-MTOR-dependent autophagy pathway, resulting in an increase in <i>GTPBP4</i> mRNA and protein levels. Increased GTPBP4 inhibits IRF3 binding to the <i>Ifnb/Ifn-β</i> promoter, suppressing FMDV-induced type I interferon production. In conclusion, our study revealed an underlying mechanism of how VP1 negatively regulates innate immunity through the autophagy pathway, which would contribute to understanding the negative regulation of host innate immune responses and the function of GTPBP4 and YTHDF2 during FMDV infection. <b>Abbreviation:</b> 3-MA:3-methyladenine; ACTB: actin beta; ATG: autophagy related; ChIP:chromatin immunoprecipitation; CQ: chloroquine; DAPI:4’,6-diamidino-2-phenylindole; dpi: days post-infection; EV71:enterovirus 71; FMDV: foot-and-mouth disease virus; GTPBP4/NOG1: GTPbinding protein 4; HIF1A: hypoxia inducible factor 1 subunit alpha;hpt:hours post-transfection; IFNB/IFN-β:interferon beta; IRF3: interferon regulatory factor 3; MAP1LC3/LC3:microtubule associated protein 1 light chain 3; MAVS: mitochondriaantiviral signaling protein; MOI: multiplicity of infection; MTOR:mechanistic target of rapamycin kinase; m6A: N(6)-methyladenosine;qPCR:quantitativePCR; SIRT3:sirtuin 3; SQSTM1/p62: sequestosome 1; STING1: stimulator ofinterferon response cGAMP interactor 1; siRNA: small interfering RNA;TBK1: TANK binding kinase 1; TCID<sub>50</sub>:50% tissue culture infectious doses; ULK1: unc-51 like autophagyactivating kinase 1; UTR: untranslated region; WT: wild type; YTHDF2:YTH N6-methyladenosine RNA binding protein F2
DOI: 10.6084/m9.figshare.25459807.v1
title: Foot-and-mouth disease virus VP1 degrades YTHDF2 through autophagy to regulate IRF3 activity for viral replication

description: Many viruses, including foot-and-mouth disease virus (FMDV), can promote the degradation of host proteins through macroautophagy/autophagy, thereby promoting viral replication. However, the regulatory mechanism between autophagy and innate immune responses is not fully understood during FMDV infection. Here, we found that the host GTPBP4/NOG1 (GTP binding protein 4) is a negative regulator of innate immune responses. GTPBP4 deficiency promotes the antiviral innate immune response, resulting in the ability of GTPBP4 to promote FMDV replication. Meanwhile, GTPBP4-deficient mice are more resistant to FMDV infection. To antagonize the host’s antiviral immunity, FMDV structural protein VP1 promotes the expression of GTPBP4, and the 209th site of VP1 is responsible for this effect. Mechanically, FMDV VP1 promotes autophagy during virus infection and interacts with and degrades YTHDF2 (YTH N6-methyladenosine RNA binding protein F2) in an AKT-MTOR-dependent autophagy pathway, resulting in an increase in <i>GTPBP4</i> mRNA and protein levels. Increased GTPBP4 inhibits IRF3 binding to the <i>Ifnb/Ifn-β</i> promoter, suppressing FMDV-induced type I interferon production. In conclusion, our study revealed an underlying mechanism of how VP1 negatively regulates innate immunity through the autophagy pathway, which would contribute to understanding the negative regulation of host innate immune responses and the function of GTPBP4 and YTHDF2 during FMDV infection. <b>Abbreviation:</b> 3-MA:3-methyladenine; ACTB: actin beta; ATG: autophagy related; ChIP:chromatin immunoprecipitation; CQ: chloroquine; DAPI:4’,6-diamidino-2-phenylindole; dpi: days post-infection; EV71:enterovirus 71; FMDV: foot-and-mouth disease virus; GTPBP4/NOG1: GTPbinding protein 4; HIF1A: hypoxia inducible factor 1 subunit alpha;hpt:hours post-transfection; IFNB/IFN-β:interferon beta; IRF3: interferon regulatory factor 3; MAP1LC3/LC3:microtubule associated protein 1 light chain 3; MAVS: mitochondriaantiviral signaling protein; MOI: multiplicity of infection; MTOR:mechanistic target of rapamycin kinase; m6A: N(6)-methyladenosine;qPCR:quantitativePCR; SIRT3:sirtuin 3; SQSTM1/p62: sequestosome 1; STING1: stimulator ofinterferon response cGAMP interactor 1; siRNA: small interfering RNA;TBK1: TANK binding kinase 1; TCID<sub>50</sub>:50% tissue culture infectious doses; ULK1: unc-51 like autophagyactivating kinase 1; UTR: untranslated region; WT: wild type; YTHDF2:YTH N6-methyladenosine RNA binding protein F2
DOI: 10.6084/m9.figshare.25273312.v1
title: TRIM27 elicits protective immunity against tuberculosis by activating TFEB-mediated autophagy flux

description: Infectious diseases, such as <i>Mycobacterium tuberculosis</i> (Mtb)-caused tuberculosis (TB), remain a global threat exacerbated by increasing drug resistance. Host-directed therapy (HDT) is a promising strategy for infection treatment through targeting host immunity. However, the limited understanding of the function and regulatory mechanism of host factors involved in immune defense against infections has impeded HDT development. Here, we identify the ubiquitin ligase (E3) TRIM27 (tripartite motif-containing 27) as a host protective factor against Mtb by enhancing host macroautophagy/autophagy flux in an E3 ligase activity-independent manner. Mechanistically, upon Mtb infection, nuclear-localized TRIM27 increases and functions as a transcription activator of <i>TFEB</i> (transcription factor EB). Specifically, TRIM27 binds to the <i>TFEB</i> promoter and the TFEB transcription factor CREB1 (cAMP responsive element binding protein 1), thus enhancing CREB1-<i>TFEB</i> promoter binding affinity and promoting CREB1 transcription activity toward <i>TFEB</i>, eventually inducing autophagy-related gene expression as well as autophagy flux activation to clear the pathogen. Furthermore, TFEB activator 1 can rescue TRIM27 deficiency-caused decreased autophagy-related gene transcription and attenuated autophagy flux, and accordingly suppressed the intracellular survival of Mtb in cell and mouse models. Taken together, our data reveal that TRIM27 is a host defense factor against Mtb, and the TRIM27-CREB1-TFEB axis is a potential HDT-based TB target that can enhance host autophagy flux.