cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.10289597.v2
title: Structural basis of host ligand specificity change of GII porcine noroviruses from their closely related GII human noroviruses

description: Diverse noroviruses infect humans and animals via the recognition of host-specific glycan ligands. Genogroup II (GII) noroviruses consist of human noroviruses (huNoVs) that generally bind histo-blood group antigens (HBGAs) as host factors and three porcine norovirus (porNoV) genotypes (GII.11/18/19) that form a genetic lineage lacking HBGA-binding ability. Thus, these GII porNoVs provide an excellent model to study norovirus evolution with host ligand specificity changes. Here we solved the crystal structures of a native GII.11 porNoV P protein and a closely-related GII.3 huNoV P protein complexed with an HBGA, focusing on the HBGA-binding sites (HBSs) compared with the previously known ones to understand the structural basis of the host ligand specificity change. We found that the GII.3 huNoV binds HBGAs via a conventional GII HBS that uses an arginine instead of the conserved aromatic residue for the required Van der Waals interaction, while the GII.11 porNoV HBS loses its HBGA-binding function because of two mutations (Q355/V451). A mutant that reversed the two mutated residues back to the conventional A355/Y451 restored the HBGA-binding function of the GII.11 porNoV P protein, which validated our observations. Similar mutations are also found in GII.19 porNoVs and a GII.19 P protein mutant with double reverse mutations restored the HBS function. This is the first reconstruction of a functional HBS based on one with new host specificity back to its parental one. These data shed light on the molecular basis of structural adaptation of the GII porNoVs to the pig hosts through mutations at their HBSs.
DOI: 10.6084/m9.figshare.10297781
title: Identification of a novel RhlI/R-PrrH-LasI/Phzc/PhzD signalling cascade and its implication in <i>P. aeruginosa</i> virulence

description: Small regulatory RNAs (sRNAs) act as key regulators in many bacterial signalling cascades. However, in <i>P. aeruginosa</i>, the sRNAs involved in quorum sensing (QS) regulation and their function are still largely unknown. Here, we explored how the <i>prrH</i> locus sRNA influences <i>P. aeruginosa</i> virulence in the context of the QS regulatory network. First, gain- and loss-of-function studies showed that PrrH affects pyocyanin, elastase and rhamnolipid production; biofilm formation; and swimming and swarming motility and impaired the viability of <i>P. aeruginosa</i> in human whole blood. Next, our investigation disclosed that LasI and PhzC/D were directly repressed by PrrH. In addition, RhlI, the key member of the <i>rhl</i> QS system, diminished the expression of PrrH and enhanced the expression of downstream genes. Bioinformatics analysis found two binding sites of RhlR, the transcription factor of the <i>rhl</i> system, on the promoter region of <i>prrH</i>. Further β-galactosidase reporter and qPCR assays confirmed that PrrH was transcriptionally repressed by RhlR. Collectively, our data identified a novel RhlI/R-PrrH-LasI/PhzC/PhzD regulatory circuitry that may contribute to <i>P. aeruginosa</i> pathogenesis. Our findings indicate that PrrH is a quorum regulatory RNA (Qrr) in <i>P. aeruginosa</i> and provide new insight into PrrH’s function.
DOI: 10.6084/m9.figshare.10297781.v3
title: Identification of a novel RhlI/R-PrrH-LasI/Phzc/PhzD signalling cascade and its implication in <i>P. aeruginosa</i> virulence

description: Small regulatory RNAs (sRNAs) act as key regulators in many bacterial signalling cascades. However, in <i>P. aeruginosa</i>, the sRNAs involved in quorum sensing (QS) regulation and their function are still largely unknown. Here, we explored how the <i>prrH</i> locus sRNA influences <i>P. aeruginosa</i> virulence in the context of the QS regulatory network. First, gain- and loss-of-function studies showed that PrrH affects pyocyanin, elastase and rhamnolipid production; biofilm formation; and swimming and swarming motility and impaired the viability of <i>P. aeruginosa</i> in human whole blood. Next, our investigation disclosed that LasI and PhzC/D were directly repressed by PrrH. In addition, RhlI, the key member of the <i>rhl</i> QS system, diminished the expression of PrrH and enhanced the expression of downstream genes. Bioinformatics analysis found two binding sites of RhlR, the transcription factor of the <i>rhl</i> system, on the promoter region of <i>prrH</i>. Further β-galactosidase reporter and qPCR assays confirmed that PrrH was transcriptionally repressed by RhlR. Collectively, our data identified a novel RhlI/R-PrrH-LasI/PhzC/PhzD regulatory circuitry that may contribute to <i>P. aeruginosa</i> pathogenesis. Our findings indicate that PrrH is a quorum regulatory RNA (Qrr) in <i>P. aeruginosa</i> and provide new insight into PrrH’s function.
DOI: 10.6084/m9.figshare.9198914.v3
title: Mapping histoplasmosis in South East Asia – implications for diagnosis in AIDS

description: Histoplasmosis caused by the fungus <i>Histoplasma capsulatum</i> is often lethal in patients with AIDS. Urine antigen testing is highly sensitive and much quicker for diagnosis than culture. Histoplasmosis has a patchy and incompletely appreciated distribution around the world especially in South East Asia. We conducted a systematic literature review of cases of all disease forms of histoplasmosis in SE Asia, not including the Indian sub-continent. We also reviewed all histoplasmin skin test mapping studies to determine localities of exposure. We found a total of 407 cases contracted or likely to have been contracted in SE Asia. Numbers of cases by country varied: Thailand (233), Malaysia (76), Indonesia (48) and Singapore (21), with few or no cases reported in other countries. Most cases (255 (63%)) were disseminated histoplasmosis and 177 (43%) cases were HIV associated. Areas of high histoplasmin skin test sensitivity prevalence were found in Myanmar, the Philippines, Indonesia, Thailand and Vietnam - 86.4%, 26.0%, 63.6%, 36.0% and 33.7%, respectively. We have drawn maps of these data. Further study is required to ascertain the extent of histoplasmosis within SE Asia. Diagnostic capability for patients with HIV infection is urgently required in SE Asia, to reduce mortality and mis-diagnosis as tuberculosis.
DOI: 10.6084/m9.figshare.10297781.v2
title: Identification of a novel RhlI/R-PrrH-LasI/Phzc/PhzD signalling cascade and its implication in <i>P. aeruginosa</i> virulence

description: Small regulatory RNAs (sRNAs) act as key regulators in many bacterial signalling cascades. However, in <i>P. aeruginosa</i>, the sRNAs involved in quorum sensing (QS) regulation and their function are still largely unknown. Here, we explored how the <i>prrH</i> locus sRNA influences <i>P. aeruginosa</i> virulence in the context of the QS regulatory network. First, gain- and loss-of-function studies showed that PrrH affects pyocyanin, elastase and rhamnolipid production; biofilm formation; and swimming and swarming motility and impaired the viability of <i>P. aeruginosa</i> in human whole blood. Next, our investigation disclosed that LasI and PhzC/D were directly repressed by PrrH. In addition, RhlI, the key member of the <i>rhl</i> QS system, diminished the expression of PrrH and enhanced the expression of downstream genes. Bioinformatics analysis found two binding sites of RhlR, the transcription factor of the <i>rhl</i> system, on the promoter region of <i>prrH</i>. Further β-galactosidase reporter and qPCR assays confirmed that PrrH was transcriptionally repressed by RhlR. Collectively, our data identified a novel RhlI/R-PrrH-LasI/PhzC/PhzD regulatory circuitry that may contribute to <i>P. aeruginosa</i> pathogenesis. Our findings indicate that PrrH is a quorum regulatory RNA (Qrr) in <i>P. aeruginosa</i> and provide new insight into PrrH’s function.
DOI: 10.6084/m9.figshare.9878528
title: Chromatin remodelling factor BAF155 protects hepatitis B virus X protein (HBx) from ubiquitin-independent proteasomal degradation

description: HBx is a short-lived protein whose rapid turnover is mainly regulated by ubiquitin-dependent proteasomal degradation pathways. Our prior work identified BAF155 to be one of the HBx binding partners. Since BAF155 has been shown to stabilize other members of the SWI/SNF chromatin remodelling complex by attenuating their proteasomal degradation, we proposed that BAF155 might also contribute to stabilizing HBx protein in a proteasome-dependent manner. Here we report that BAF155 protected hepatitis B virus X protein (HBx) from ubiquitin-independent proteasomal degradation by competing with the 20S proteasome subunit PSMA7 to bind to HBx. BAF155 was found to directly interact with HBx via binding of its SANT domain to the HBx region between amino acid residues 81 and 120. Expression of either full-length BAF155 or SANT domain increased HBx protein levels whereas siRNA-mediated knockdown of endogenous BAF155 reduced HBx protein levels. Increased HBx stability and steady-state level by BAF155 were attributable to inhibition of ubiquitin-independent and PSMA7-mediated protein degradation. Consequently, overexpression of BAF155 enhanced the transcriptional transactivation function of HBx, activated protooncogene expression and inhibited hepatoma cell clonogenicity. These results suggest that BAF155 plays important roles in ubiquitin-independent degradation of HBx, which may be related to the pathogenesis and carcinogenesis of HBV-associated HCC.
DOI: 10.6084/m9.figshare.9878528.v3
title: Chromatin remodelling factor BAF155 protects hepatitis B virus X protein (HBx) from ubiquitin-independent proteasomal degradation

description: HBx is a short-lived protein whose rapid turnover is mainly regulated by ubiquitin-dependent proteasomal degradation pathways. Our prior work identified BAF155 to be one of the HBx binding partners. Since BAF155 has been shown to stabilize other members of the SWI/SNF chromatin remodelling complex by attenuating their proteasomal degradation, we proposed that BAF155 might also contribute to stabilizing HBx protein in a proteasome-dependent manner. Here we report that BAF155 protected hepatitis B virus X protein (HBx) from ubiquitin-independent proteasomal degradation by competing with the 20S proteasome subunit PSMA7 to bind to HBx. BAF155 was found to directly interact with HBx via binding of its SANT domain to the HBx region between amino acid residues 81 and 120. Expression of either full-length BAF155 or SANT domain increased HBx protein levels whereas siRNA-mediated knockdown of endogenous BAF155 reduced HBx protein levels. Increased HBx stability and steady-state level by BAF155 were attributable to inhibition of ubiquitin-independent and PSMA7-mediated protein degradation. Consequently, overexpression of BAF155 enhanced the transcriptional transactivation function of HBx, activated protooncogene expression and inhibited hepatoma cell clonogenicity. These results suggest that BAF155 plays important roles in ubiquitin-independent degradation of HBx, which may be related to the pathogenesis and carcinogenesis of HBV-associated HCC.
DOI: 10.6084/m9.figshare.8397356
title: The native European <i>Aedes geniculatus</i> mosquito species can transmit chikungunya virus

description: Europe is the world’s leading tourism destination and is receiving every year travellers from areas with active arbovirus transmission. There is thus a threat of mosquito-borne virus emergence in Europe due to the presence of the invasive mosquito vector <i>Aedes albopictus</i>. Little attention has been paid about the possible role of indigenous mosquito species as vectors of emerging arboviruses. Here, we assessed the vector competence dynamic of <i>Aedes geniculatus</i>, a European anthropophilic mosquito species, for chikungunya virus (CHIKV) in comparison with an European population of <i>Ae. albopictus</i>. We revealed that <i>Ae. geniculatus</i> is highly susceptible to CHIKV infection and could transmit the virus. By specifically exploring the vector competence dynamic in both mosquito species, we revealed that the cumulative distribution of CHIKV incubation period in <i>Ae. geniculatus</i> was delayed by several days as compared to <i>Ae. albopictus</i>. Our results strengthen the importance of considering indigenous species as potential vectors for emerging arboviruses. They also revealed the importance of considering variation in arbovirus dissemination or transmission dynamics in mosquitoes when performing vector competence assays. We will discuss the implications of our results on a CHIKV outbreak dynamic in a theoretical framework.
DOI: 10.6084/m9.figshare.8397356.v3
title: The native European <i>Aedes geniculatus</i> mosquito species can transmit chikungunya virus

description: Europe is the world’s leading tourism destination and is receiving every year travellers from areas with active arbovirus transmission. There is thus a threat of mosquito-borne virus emergence in Europe due to the presence of the invasive mosquito vector <i>Aedes albopictus</i>. Little attention has been paid about the possible role of indigenous mosquito species as vectors of emerging arboviruses. Here, we assessed the vector competence dynamic of <i>Aedes geniculatus</i>, a European anthropophilic mosquito species, for chikungunya virus (CHIKV) in comparison with an European population of <i>Ae. albopictus</i>. We revealed that <i>Ae. geniculatus</i> is highly susceptible to CHIKV infection and could transmit the virus. By specifically exploring the vector competence dynamic in both mosquito species, we revealed that the cumulative distribution of CHIKV incubation period in <i>Ae. geniculatus</i> was delayed by several days as compared to <i>Ae. albopictus</i>. Our results strengthen the importance of considering indigenous species as potential vectors for emerging arboviruses. They also revealed the importance of considering variation in arbovirus dissemination or transmission dynamics in mosquitoes when performing vector competence assays. We will discuss the implications of our results on a CHIKV outbreak dynamic in a theoretical framework.
DOI: 10.6084/m9.figshare.9378752
title: Carriage and potential long distance transmission of <i>Listeria monocytogenes</i> by migratory black-headed gulls in Dianchi Lake, Kunming

description: <i>Listeria monocytogenes</i> is a high risk pathogen which can cause invasive diseases in humans. We previously reported that black-headed gulls from Dianchi Lake of Kunming carrying <i>L. monocytogenes</i>, while the characteristics of these isolates and the relationship with habitats of migratory gulls have not been explored. In this study, we investigated the prevalence and molecular characteristics of <i>Listeria monocytogenes</i> from black-headed gulls in Dianchi Lake, and phylogenetic analysis based on core genome SNPs was used to determine the genetic relationship of the strains from Dianchi Lake and other regions. Occurrence of <i>L. monocytogenes</i> in black-headed gull feces in 2016, 2017 and 2018 was 1.0%, 1.0% and 0.6% respectively. The predominant serotype of 28 isolates was 4b, while the predominant sequence types were ST145 and ST201. Based on their prevalence and genomic relationships, ST5 and ST87 were likely to be sourced locally while ST145 and ST201 were likely to be non-local. <i>L. monocytogenes</i> may travel along the bird migration route leading to transmission over a large geographical span carried by black-headed gull. Although the prevalence of <i>L. monocytogenes</i> was low, its carriage by the migratory black-headed gulls poses potential public health risks in regions where the migratory birds passage and reside.
DOI: 10.6084/m9.figshare.9378752.v3
title: Carriage and potential long distance transmission of <i>Listeria monocytogenes</i> by migratory black-headed gulls in Dianchi Lake, Kunming

description: <i>Listeria monocytogenes</i> is a high risk pathogen which can cause invasive diseases in humans. We previously reported that black-headed gulls from Dianchi Lake of Kunming carrying <i>L. monocytogenes</i>, while the characteristics of these isolates and the relationship with habitats of migratory gulls have not been explored. In this study, we investigated the prevalence and molecular characteristics of <i>Listeria monocytogenes</i> from black-headed gulls in Dianchi Lake, and phylogenetic analysis based on core genome SNPs was used to determine the genetic relationship of the strains from Dianchi Lake and other regions. Occurrence of <i>L. monocytogenes</i> in black-headed gull feces in 2016, 2017 and 2018 was 1.0%, 1.0% and 0.6% respectively. The predominant serotype of 28 isolates was 4b, while the predominant sequence types were ST145 and ST201. Based on their prevalence and genomic relationships, ST5 and ST87 were likely to be sourced locally while ST145 and ST201 were likely to be non-local. <i>L. monocytogenes</i> may travel along the bird migration route leading to transmission over a large geographical span carried by black-headed gull. Although the prevalence of <i>L. monocytogenes</i> was low, its carriage by the migratory black-headed gulls poses potential public health risks in regions where the migratory birds passage and reside.
DOI: 10.6084/m9.figshare.9878528.v2
title: Chromatin remodelling factor BAF155 protects hepatitis B virus X protein (HBx) from ubiquitin-independent proteasomal degradation

description: HBx is a short-lived protein whose rapid turnover is mainly regulated by ubiquitin-dependent proteasomal degradation pathways. Our prior work identified BAF155 to be one of the HBx binding partners. Since BAF155 has been shown to stabilize other members of the SWI/SNF chromatin remodelling complex by attenuating their proteasomal degradation, we proposed that BAF155 might also contribute to stabilizing HBx protein in a proteasome-dependent manner. Here we report that BAF155 protected hepatitis B virus X protein (HBx) from ubiquitin-independent proteasomal degradation by competing with the 20S proteasome subunit PSMA7 to bind to HBx. BAF155 was found to directly interact with HBx via binding of its SANT domain to the HBx region between amino acid residues 81 and 120. Expression of either full-length BAF155 or SANT domain increased HBx protein levels whereas siRNA-mediated knockdown of endogenous BAF155 reduced HBx protein levels. Increased HBx stability and steady-state level by BAF155 were attributable to inhibition of ubiquitin-independent and PSMA7-mediated protein degradation. Consequently, overexpression of BAF155 enhanced the transcriptional transactivation function of HBx, activated protooncogene expression and inhibited hepatoma cell clonogenicity. These results suggest that BAF155 plays important roles in ubiquitin-independent degradation of HBx, which may be related to the pathogenesis and carcinogenesis of HBV-associated HCC.
DOI: 10.6084/m9.figshare.10620929
title: Dual activity of PNGM-1 pinpoints the evolutionary origin of subclass B3 metallo-<i>β</i>-lactamases: a molecular and evolutionary study

description: Resistance to <i>β</i>-lactams is one of the most serious problems associated with Gram-negative infections. <i>β</i>-Lactamases are able to hydrolyze <i>β</i>-lactams such as cephalosporins and/or carbapenems. Evolutionary origin of metallo-<i>β</i>-lactamases (MBLs), conferring critical antibiotic resistance threats, remains unknown. We discovered PNGM-1, the novel subclass B3 MBL, in deep-sea sediments that predate the antibiotic era. Here, our phylogenetic analysis suggests that PNGM-1 yields insights into the evolutionary origin of subclass B3 MBLs. We reveal the structural similarities between tRNase Zs and PNGM-1, and demonstrate that PNGM-1 has both MBL and tRNase Z activities, suggesting that PNGM-1 is thought to have evolved from a tRNase Z. We also show kinetic and structural comparisons between PNGM-1 and other proteins including subclass B3 MBLs and tRNase Zs. These comparisons revealed that the B3 MBL activity of PNGM-1 is a promiscuous activity and subclass B3 MBLs are thought to have evolved through PNGM-1 activity.
DOI: 10.6084/m9.figshare.10620929.v3
title: Dual activity of PNGM-1 pinpoints the evolutionary origin of subclass B3 metallo-<i>β</i>-lactamases: a molecular and evolutionary study

description: Resistance to <i>β</i>-lactams is one of the most serious problems associated with Gram-negative infections. <i>β</i>-Lactamases are able to hydrolyze <i>β</i>-lactams such as cephalosporins and/or carbapenems. Evolutionary origin of metallo-<i>β</i>-lactamases (MBLs), conferring critical antibiotic resistance threats, remains unknown. We discovered PNGM-1, the novel subclass B3 MBL, in deep-sea sediments that predate the antibiotic era. Here, our phylogenetic analysis suggests that PNGM-1 yields insights into the evolutionary origin of subclass B3 MBLs. We reveal the structural similarities between tRNase Zs and PNGM-1, and demonstrate that PNGM-1 has both MBL and tRNase Z activities, suggesting that PNGM-1 is thought to have evolved from a tRNase Z. We also show kinetic and structural comparisons between PNGM-1 and other proteins including subclass B3 MBLs and tRNase Zs. These comparisons revealed that the B3 MBL activity of PNGM-1 is a promiscuous activity and subclass B3 MBLs are thought to have evolved through PNGM-1 activity.
DOI: 10.6084/m9.figshare.8397356.v2
title: The native European <i>Aedes geniculatus</i> mosquito species can transmit chikungunya virus

description: Europe is the world’s leading tourism destination and is receiving every year travellers from areas with active arbovirus transmission. There is thus a threat of mosquito-borne virus emergence in Europe due to the presence of the invasive mosquito vector <i>Aedes albopictus</i>. Little attention has been paid about the possible role of indigenous mosquito species as vectors of emerging arboviruses. Here, we assessed the vector competence dynamic of <i>Aedes geniculatus</i>, a European anthropophilic mosquito species, for chikungunya virus (CHIKV) in comparison with an European population of <i>Ae. albopictus</i>. We revealed that <i>Ae. geniculatus</i> is highly susceptible to CHIKV infection and could transmit the virus. By specifically exploring the vector competence dynamic in both mosquito species, we revealed that the cumulative distribution of CHIKV incubation period in <i>Ae. geniculatus</i> was delayed by several days as compared to <i>Ae. albopictus</i>. Our results strengthen the importance of considering indigenous species as potential vectors for emerging arboviruses. They also revealed the importance of considering variation in arbovirus dissemination or transmission dynamics in mosquitoes when performing vector competence assays. We will discuss the implications of our results on a CHIKV outbreak dynamic in a theoretical framework.