cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.9731051.v3
title: Comprehensive analysis of the lysine acetylome in <i>Aeromonas hydrophila</i> reveals cross-talk between lysine acetylation and succinylation in LuxS

description: Lysine acetylation and succinylation are both prevalent protein post-translational modifications (PTMs) in bacteria species, whereas the effect of the cross-talk between both PTMs on bacterial biological function remains largely unknown. Our previously study found lysine succinylated sites on proteins play important role on metabolic pathways in fish pathogenic <i>Aeromonas hydrophila</i>. A total of 3189 lysine-acetylation sites were further identified on 1013 proteins of this pathogen using LC-MS/MS in this study. Functional examination of these PTMs peptides showed associations with basal biological processes, especially metabolic pathways. Additionally, when comparing the obtained lysine acetylome to a previously obtained lysine succinylome, 1198 sites in a total of 547 proteins were found to be in common and associated with various metabolic pathways. As the autoinducer-2 (AI-2) synthase involved in quorum sensing of bacteria, the site-directed mutagenesis of LuxS at the K165 site was performed and revealed that the cross-talk between lysine acetylation and succinylation exerts an inverse influence on bacterial quorum sensing and on LuxS enzymatic activity. In summary, this study provides an in-depth <i>A. hydrophila</i> lysine acetylome profile and for the first time reveals the role of cross-talk between lysine acetylation and succinylation, and its potential impact on bacterial physiological functions.
DOI: 10.6084/m9.figshare.8186918
title: Single intranasal immunization with chimpanzee adenovirus-based vaccine induces sustained and protective immunity against MERS-CoV infection

description: The recently identified Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes severe and fatal acute respiratory illness in humans. However, no approved prophylactic and therapeutic interventions are currently available. The MERS-CoV envelope spike protein serves as a crucial target for neutralizing antibodies and vaccine development, as it plays a critical role in mediating viral entry through interactions with the cellular receptor, dipeptidyl peptidase 4 (DPP4). Here, we constructed a recombinant rare serotype of the chimpanzee adenovirus 68 (AdC68) that expresses full-length MERS-CoV S protein (AdC68-S). Single intranasal immunization with AdC68-S induced robust and sustained neutralizing antibody and T cell responses in BALB/c mice. In a human DPP4 knock-in (hDPP4-KI) mouse model, it completely protected against lethal challenge with a mouse-adapted MERS-CoV (MERS-CoV-MA). Passive transfer of immune sera to naïve hDPP4-KI mice also provided survival advantages from lethal MERS-CoV-MA challenge. Analysis of sera absorption and isolated monoclonal antibodies from immunized mice demonstrated that the potent and broad neutralizing activity was largely attributed to antibodies targeting the receptor binding domain (RBD) of the S protein. These results show that AdC68-S can induce protective immune responses in mice and represent a promising candidate for further development against MERS-CoV infection in both dromedaries and humans.
DOI: 10.6084/m9.figshare.8186918.v3
title: Single intranasal immunization with chimpanzee adenovirus-based vaccine induces sustained and protective immunity against MERS-CoV infection

description: The recently identified Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes severe and fatal acute respiratory illness in humans. However, no approved prophylactic and therapeutic interventions are currently available. The MERS-CoV envelope spike protein serves as a crucial target for neutralizing antibodies and vaccine development, as it plays a critical role in mediating viral entry through interactions with the cellular receptor, dipeptidyl peptidase 4 (DPP4). Here, we constructed a recombinant rare serotype of the chimpanzee adenovirus 68 (AdC68) that expresses full-length MERS-CoV S protein (AdC68-S). Single intranasal immunization with AdC68-S induced robust and sustained neutralizing antibody and T cell responses in BALB/c mice. In a human DPP4 knock-in (hDPP4-KI) mouse model, it completely protected against lethal challenge with a mouse-adapted MERS-CoV (MERS-CoV-MA). Passive transfer of immune sera to naïve hDPP4-KI mice also provided survival advantages from lethal MERS-CoV-MA challenge. Analysis of sera absorption and isolated monoclonal antibodies from immunized mice demonstrated that the potent and broad neutralizing activity was largely attributed to antibodies targeting the receptor binding domain (RBD) of the S protein. These results show that AdC68-S can induce protective immune responses in mice and represent a promising candidate for further development against MERS-CoV infection in both dromedaries and humans.
DOI: 10.6084/m9.figshare.8186918.v2
title: Single intranasal immunization with chimpanzee adenovirus-based vaccine induces sustained and protective immunity against MERS-CoV infection

description: The recently identified Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes severe and fatal acute respiratory illness in humans. However, no approved prophylactic and therapeutic interventions are currently available. The MERS-CoV envelope spike protein serves as a crucial target for neutralizing antibodies and vaccine development, as it plays a critical role in mediating viral entry through interactions with the cellular receptor, dipeptidyl peptidase 4 (DPP4). Here, we constructed a recombinant rare serotype of the chimpanzee adenovirus 68 (AdC68) that expresses full-length MERS-CoV S protein (AdC68-S). Single intranasal immunization with AdC68-S induced robust and sustained neutralizing antibody and T cell responses in BALB/c mice. In a human DPP4 knock-in (hDPP4-KI) mouse model, it completely protected against lethal challenge with a mouse-adapted MERS-CoV (MERS-CoV-MA). Passive transfer of immune sera to naïve hDPP4-KI mice also provided survival advantages from lethal MERS-CoV-MA challenge. Analysis of sera absorption and isolated monoclonal antibodies from immunized mice demonstrated that the potent and broad neutralizing activity was largely attributed to antibodies targeting the receptor binding domain (RBD) of the S protein. These results show that AdC68-S can induce protective immune responses in mice and represent a promising candidate for further development against MERS-CoV infection in both dromedaries and humans.
DOI: 10.6084/m9.figshare.8316326
title: The scrub typhus in mainland China: spatiotemporal expansion and risk prediction underpinned by complex factors

description: In mainland China, a geographic northward expansion of scrub typhus has been seen, highlighting the need to understand the factors and identify the risk for disease prevention. Incidence data from 1980 to 2013 were used. A Cox proportional hazard model was used to identify drivers for spatial spread, and a boosted regression tree (BRT) model was constructed to predict potential risk areas. Since the 1980s, an invasive expansion from South Natural Foci towards North Natural Foci was clearly identified, with the epidemiological heterogeneity observed between two regions, mainly in spatial distribution, seasonality, and demographic characteristics. Survival analysis disclosed significant factors contributing to the spatial expansion as following: being intersected by freeway (HR = 1.31, 95% CI: 1.11–1.54), coverage percentage of broadleaf forest (HR = 1.10, 95% CI: 1.06–1.15), and monthly average temperature (HR = 1.27, 95% CI: 1.25–1.30). The BRT models showed that precipitation, sunshine hour, temperature, crop field, and relative humidity contributed substantially to the spatial distribution of scrub typhus. A county-scale risk map was created to predict the regions with high probability of the disease. The current study enabled a comprehensive overview of epidemiological characteristics of scrub typhus in mainland China.
DOI: 10.6084/m9.figshare.8316326.v3
title: The scrub typhus in mainland China: spatiotemporal expansion and risk prediction underpinned by complex factors

description: In mainland China, a geographic northward expansion of scrub typhus has been seen, highlighting the need to understand the factors and identify the risk for disease prevention. Incidence data from 1980 to 2013 were used. A Cox proportional hazard model was used to identify drivers for spatial spread, and a boosted regression tree (BRT) model was constructed to predict potential risk areas. Since the 1980s, an invasive expansion from South Natural Foci towards North Natural Foci was clearly identified, with the epidemiological heterogeneity observed between two regions, mainly in spatial distribution, seasonality, and demographic characteristics. Survival analysis disclosed significant factors contributing to the spatial expansion as following: being intersected by freeway (HR = 1.31, 95% CI: 1.11–1.54), coverage percentage of broadleaf forest (HR = 1.10, 95% CI: 1.06–1.15), and monthly average temperature (HR = 1.27, 95% CI: 1.25–1.30). The BRT models showed that precipitation, sunshine hour, temperature, crop field, and relative humidity contributed substantially to the spatial distribution of scrub typhus. A county-scale risk map was created to predict the regions with high probability of the disease. The current study enabled a comprehensive overview of epidemiological characteristics of scrub typhus in mainland China.
DOI: 10.6084/m9.figshare.10007921.v3
title: The Nsp12-coding region of type 2 PRRSV is required for viral subgenomic mRNA synthesis

description: As one of many nonstructural proteins of porcine reproductive and respiratory syndrome virus (PRRSV), nonstructural protein 12 (Nsp12) has received relatively little attention, and its role in virus replication, if any, is essentially unknown. By the application of reverse genetic manipulation of an infectious PRRSV clone, the current study is the first to demonstrate that Nsp12 is a key component of PRRSV replication. In addition, the biochemical properties of Nsp12 were evaluated, revealing that Nsp12 forms dimers when exposed to oxidative conditions. Furthermore, we systemically analyzed the function of Nsp12 in PRRSV RNA synthesis using a strand-specific PCR method. To our surprise, Nsp12 was not found to be involved in minus-strand genomic RNA (-gRNA) synthesis; importantly, our results indicate that Nsp12 is involved in the synthesis of both plus- and minus-strand subgenomic mRNAs (+sgmRNA and -sgmRNA). Finally, we found that the combination of cysteine 35 and cysteine 79 in Nsp12 is required for sgmRNA synthesis. To our knowledge, we are the first to report the biological role of Nsp12 in the PRRSV lifecycle, and we conclude that Nsp12 is involved in the synthesis of both + sgRNA and -sgRNA.
DOI: 10.6084/m9.figshare.8015642
title: Avian influenza virus detection, temporality and co-infection in poultry in Cambodian border provinces, 2017–2018

description: Avian influenza virus detection, temporality and co-infection in poultry in Cambodian border provinces, 2017–2018
DOI: 10.6084/m9.figshare.8015642.v3
title: Avian influenza virus detection, temporality and co-infection in poultry in Cambodian border provinces, 2017–2018

description: Avian influenza virus detection, temporality and co-infection in poultry in Cambodian border provinces, 2017–2018
DOI: 10.6084/m9.figshare.8015642.v4
title: Avian influenza virus detection, temporality and co-infection in poultry in Cambodian border provinces, 2017–2018

description: Avian influenza virus detection, temporality and co-infection in poultry in Cambodian border provinces, 2017–2018
DOI: 10.6084/m9.figshare.8316326.v2
title: The scrub typhus in mainland China: spatiotemporal expansion and risk prediction underpinned by complex factors

description: In mainland China, a geographic northward expansion of scrub typhus has been seen, highlighting the need to understand the factors and identify the risk for disease prevention. Incidence data from 1980 to 2013 were used. A Cox proportional hazard model was used to identify drivers for spatial spread, and a boosted regression tree (BRT) model was constructed to predict potential risk areas. Since the 1980s, an invasive expansion from South Natural Foci towards North Natural Foci was clearly identified, with the epidemiological heterogeneity observed between two regions, mainly in spatial distribution, seasonality, and demographic characteristics. Survival analysis disclosed significant factors contributing to the spatial expansion as following: being intersected by freeway (HR = 1.31, 95% CI: 1.11–1.54), coverage percentage of broadleaf forest (HR = 1.10, 95% CI: 1.06–1.15), and monthly average temperature (HR = 1.27, 95% CI: 1.25–1.30). The BRT models showed that precipitation, sunshine hour, temperature, crop field, and relative humidity contributed substantially to the spatial distribution of scrub typhus. A county-scale risk map was created to predict the regions with high probability of the disease. The current study enabled a comprehensive overview of epidemiological characteristics of scrub typhus in mainland China.
DOI: 10.6084/m9.figshare.10007921
title: The Nsp12-coding region of type 2 PRRSV is required for viral subgenomic mRNA synthesis

description: As one of many nonstructural proteins of porcine reproductive and respiratory syndrome virus (PRRSV), nonstructural protein 12 (Nsp12) has received relatively little attention, and its role in virus replication, if any, is essentially unknown. By the application of reverse genetic manipulation of an infectious PRRSV clone, the current study is the first to demonstrate that Nsp12 is a key component of PRRSV replication. In addition, the biochemical properties of Nsp12 were evaluated, revealing that Nsp12 forms dimers when exposed to oxidative conditions. Furthermore, we systemically analyzed the function of Nsp12 in PRRSV RNA synthesis using a strand-specific PCR method. To our surprise, Nsp12 was not found to be involved in minus-strand genomic RNA (-gRNA) synthesis; importantly, our results indicate that Nsp12 is involved in the synthesis of both plus- and minus-strand subgenomic mRNAs (+sgmRNA and -sgmRNA). Finally, we found that the combination of cysteine 35 and cysteine 79 in Nsp12 is required for sgmRNA synthesis. To our knowledge, we are the first to report the biological role of Nsp12 in the PRRSV lifecycle, and we conclude that Nsp12 is involved in the synthesis of both + sgRNA and -sgRNA.
DOI: 10.6084/m9.figshare.10007921.v2
title: The Nsp12-coding region of type 2 PRRSV is required for viral subgenomic mRNA synthesis

description: As one of many nonstructural proteins of porcine reproductive and respiratory syndrome virus (PRRSV), nonstructural protein 12 (Nsp12) has received relatively little attention, and its role in virus replication, if any, is essentially unknown. By the application of reverse genetic manipulation of an infectious PRRSV clone, the current study is the first to demonstrate that Nsp12 is a key component of PRRSV replication. In addition, the biochemical properties of Nsp12 were evaluated, revealing that Nsp12 forms dimers when exposed to oxidative conditions. Furthermore, we systemically analyzed the function of Nsp12 in PRRSV RNA synthesis using a strand-specific PCR method. To our surprise, Nsp12 was not found to be involved in minus-strand genomic RNA (-gRNA) synthesis; importantly, our results indicate that Nsp12 is involved in the synthesis of both plus- and minus-strand subgenomic mRNAs (+sgmRNA and -sgmRNA). Finally, we found that the combination of cysteine 35 and cysteine 79 in Nsp12 is required for sgmRNA synthesis. To our knowledge, we are the first to report the biological role of Nsp12 in the PRRSV lifecycle, and we conclude that Nsp12 is involved in the synthesis of both + sgRNA and -sgRNA.
DOI: 10.6084/m9.figshare.10289597
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.10289597.v3
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.9198914
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.9198914.v4
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.