36 research outputs found

    Characterization of a fatal feline panleukopenia virus derived from giant panda with broad cell tropism and zoonotic potential

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    Represented by feline panleukopenia virus (FPV) and canine parvovirus (CPV), the species carnivore protoparvovirus 1 has a worldwide distribution through continuous ci13rculation in companion animals such as cats and dogs. Subsequently, both FPV and CPV had engaged in host-to-host transfer to other wild animal hosts of the order Carnivora. In the present study, we emphasized the significance of cross-species transmission of parvoviruses with the isolation and characterization of an FPV from giant panda displaying severe and fatal symptoms. The isolated virus, designated pFPV-sc, displayed similar morphology as FPV, while phylogenetic analysis indicated that the nucleotide sequence of pFPV-sc clades with Chinese FPV isolates. Despite pFPV-sc is seemingly an outcome of a spillover infection event from domestic cats to giant pandas, our study also provided serological evidence that FPV or other parvoviruses closely related to FPV could be already prevalent in giant pandas in 2011. Initiation of host transfer of pFPV-sc is likely with association to giant panda transferrin receptor (TfR), as TfR of giant panda shares high homology with feline TfR. Strikingly, our data also indicate that pFPV-sc can infect cell lines of other mammal species, including humans. To sum up, observations from this study shall promote future research of cross-host transmission and antiviral intervention of Carnivore protoparvovirus 1, and necessitate surveillance studies in thus far unacknowledged potential reservoirs

    Development and efficacy evaluation of remodeled canine parvovirus-like particles displaying major antigenic epitopes of a giant panda derived canine distemper virus

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    Canine parvovirus (CPV) and Canine distemper virus (CDV) can cause fatal diseases in giant panda (Ailuropoda melanoleuca). The main capsid protein of CPV VP2 can be self-assembled to form virus-like particles (VLPs) in vitro, which is of great significance for potential vaccine development. In the present study, we remodeled the VP2 protein of a giant panda-derived CPV, where the major CDV F and N epitopes were incorporated in the N-terminal and loop2 region in two combinations to form chimeric VLPs. The reactivity ability and morphology of the recombinant proteins were confirmed by Western blot, hemagglutination (HA) test and electron microscopy. Subsequently, the immunogenicity of the VLPs was examined in vivo. Antigen-specific antibodies and neutralizing activity were measured by ELISA, hemagglutination inhibition (HI) test and serum neutralization test (SNT), respectively. In addition, antigen specific T cell activation were determined in splenic lymphocytes. The results indicated that the VLPs displayed good reaction with CDV/CPV antibodies, and the heterologous epitopes do not hamper solubility or activity. The VLPs showed decent HA activity, and resembled round-shaped particles with a diameter of 22–26 nm, which is identical to natural virions. VLPs could induce high levels of specific antibodies to CPV and CDV, shown by the indication of neutralizing antibodies in both VP2N and VP2L VLPs group. In addition, splenic lymphocytes of mice immunized with VLPs could proliferate rapidly after stimulation by specific antigen. Taken together, the CPV VP2 VLPs or chimeric VLPs are highly immunogenic, and henceforth could function as CPV/CDV vaccine candidates for giant pandas

    The Mitochondrial Genome of Baylisascaris procyonis

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    BACKGROUND: Baylisascaris procyonis (Nematoda: Ascaridida), an intestinal nematode of raccoons, is emerging as an important helminthic zoonosis due to serious or fatal larval migrans in animals and humans. Despite its significant veterinary and public health impact, the epidemiology, molecular ecology and population genetics of this parasite remain largely unexplored. Mitochondrial (mt) genomes can provide a foundation for investigations in these areas and assist in the diagnosis and control of B. procyonis. In this study, the first complete mt genome sequence of B. procyonis was determined using a polymerase chain reaction (PCR)-based primer-walking strategy. METHODOLOGY/PRINCIPAL FINDINGS: The circular mt genome (14781 bp) of B. procyonis contained 12 protein-coding, 22 transfer RNA and 2 ribosomal RNA genes congruent with other chromadorean nematodes. Interestingly, the B. procyonis mtDNA featured an extremely long AT-rich region (1375 bp) and a high number of intergenic spacers (17), making it unique compared with other secernentean nematodes characterized to date. Additionally, the entire genome displayed notable levels of AT skew and GC skew. Based on pairwise comparisons and sliding window analysis of mt genes among the available 11 Ascaridida mtDNAs, new primer pairs were designed to amplify specific short fragments of the genes cytb (548 bp fragment) and rrnL (200 bp fragment) in the B. procyonis mtDNA, and tested as possible alternatives to existing mt molecular beacons for Ascaridida. Finally, phylogenetic analysis of mtDNAs provided novel estimates of the interrelationships of Baylisasaris and Ascaridida. CONCLUSIONS/SIGNIFICANCE: The complete mt genome sequence of B. procyonis sequenced here should contribute to molecular diagnostic methods, epidemiological investigations and ecological studies of B. procyonis and other related ascaridoids. The information will be important in refining the phylogenetic relationships within the order Ascaridida and enriching the resource of markers for systematic, population genetic and evolutionary biological studies of parasitic nematodes of socio-economic importance

    Vitamin D and cause-specific vascular disease and mortality:a Mendelian randomisation study involving 99,012 Chinese and 106,911 European adults

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    A 2.5-GS/s Four-Way-Interleaved Ringamp-Based Pipelined-SAR ADC with Digital Background Calibration in 28-nm CMOS

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    A 2.5-GS/s 12-bit four-way time-interleaved pipelined-SAR ADC is presented in 28-nm CMOS. A bias-enhanced ring amplifier is utilized as the residue amplifier to achieve high bandwidth and excellent power efficiency compared with a traditional operational amplifier. A high linearity front-end is proposed to alleviate the non-linearity of the diode for ESD protection in the input PAD. The embedded input buffer can suppress the kickback noise at high input frequencies. A blind background calibration based on digital-mixing is used to correct the mismatches between channels. Additionally, an optional neural network calibration is also provided. The prototype ADC achieves a low-frequency SNDR/SFDR of 51.0/68.0 dB, translating a competitive FoMw of 0.48 pJ/conv.-step at 250 MHz input running at 2.5 GS/s

    A 2.5-GS/s Four-Way-Interleaved Ringamp-Based Pipelined-SAR ADC with Digital Background Calibration in 28-nm CMOS

    No full text
    A 2.5-GS/s 12-bit four-way time-interleaved pipelined-SAR ADC is presented in 28-nm CMOS. A bias-enhanced ring amplifier is utilized as the residue amplifier to achieve high bandwidth and excellent power efficiency compared with a traditional operational amplifier. A high linearity front-end is proposed to alleviate the non-linearity of the diode for ESD protection in the input PAD. The embedded input buffer can suppress the kickback noise at high input frequencies. A blind background calibration based on digital-mixing is used to correct the mismatches between channels. Additionally, an optional neural network calibration is also provided. The prototype ADC achieves a low-frequency SNDR/SFDR of 51.0/68.0 dB, translating a competitive FoMw of 0.48 pJ/conv.-step at 250 MHz input running at 2.5 GS/s

    S-sulfhydration of SIRT3 combats BMSC senescence and ameliorates osteoporosis via stabilizing heterochromatic and mitochondrial homeostasis

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    Senescence of bone marrow mesenchymal stem cells (BMSCs) is one of the leading causes of osteoporosis. SIRT3, an essential NAD-dependent histone deacetylase, is highly correlated with BMSC senescence-mediated bone degradation and mitochondrial/heterochromatic disturbance. S-sulfhydration of cysteine residues favorably enhances SIRT3 activity by forming persulfides. Nevertheless, the underlying molecular mechanism of SIRT3 S-sulfhydration on mitochondrial/heterochromatic homeostasis involved in BMSC senescence remains unknown. Here, we demonstrated that CBS and CSE, endogenous hydrogen sulfide synthases, are downregulated with BMSC senescence. Exogenous H2S donor NaHS-mediated SIRT3 augmentation rescued the senescent phenotypes of BMSCs. Conversely, SIRT3 deletion accelerated oxidative stress-induced BMSC senescence through mitochondrial dysfunction and the detachment of the heterochromatic protein H3K9me3 from the nuclear envelope protein Lamin B1. H2S-mediated SIRT3 S-sulfhydration modification rescued the disorganized heterochromatin and fragmented mitochondria induced by the S-sulfhydration inhibitor dithiothreitol, thus leading to elevated osteogenic capacity and preventing BMSC senescence. The antisenescence effect of S-sulfhydration modification on BMSCs was abolished when the CXXC sites of the SIRT3 zinc finger motif were mutated. In vivo, aged mice-derived BMSCs pretreated with NaHS were orthotopically transplanted to the ovariectomy-induced osteoporotic mice, and we proved that SIRT3 ameliorates bone loss by inhibiting BMSC senescence. Overall, our study for the first time indicates a novel role of SIRT3 S-sulfhydration in stabilizing heterochromatin and mitochondrial homeostasis in counteracting BMSC senescence, providing a potential target for the treatment of degenerative bone diseases

    COVID-Scraper: An Open-Source Toolset for Automatically Scraping and Processing Global Multi-Scale Spatiotemporal COVID-19 Records

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    In 2019, COVID-19 quickly spread across the world, infecting billions of people and disrupting the normal lives of citizens in every country. Governments, organizations, and research institutions all over the world are dedicating vast resources to research effective strategies to fight this rapidly propagating virus. With virus testing, most countries publish the number of confirmed cases, dead cases, recovered cases, and locations routinely through various channels and forms. This important data source has enabled researchers worldwide to perform different COVID-19 scientific studies, such as modeling this virus’s spreading patterns, developing prevention strategies, and studying the impact of COVID-19 on other aspects of society. However, one major challenge is that there is no standardized, updated, and high-quality data product that covers COVID-19 cases data internationally. This is because different countries may publish their data in unique channels, formats, and time intervals, which hinders researchers from fetching necessary COVID-19 datasets effectively, especially for fine-scale studies. Although existing solutions such as John’s Hopkins COVID-19 Dashboard and 1point3acres COVID-19 tracker are widely used, it is difficult for users to access their original dataset and customize those data to meet specific requirements in categories, data structure, and data source selection. To address this challenge, we developed a toolset using cloud-based web scraping to extract, refine, unify, and store COVID-19 cases data at multiple scales for all available countries around the world automatically. The toolset then publishes the data for public access in an effective manner, which could offer users a real time COVID-19 dynamic dataset with a global view. Two case studies are presented about how to utilize the datasets. This toolset can also be easily extended to fulfill other purposes with its open-source nature
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