niryuu/sni-each-converted huggingface dataset:
The canine infectious respiratory disease complex (CIRDC) is an endemic worldwide syndrome involving multiple viral and bacterial pathogens. Traditionally, Bordetella bronchiseptica (Bb), canine adenovirus type 2 (CAV-2), canine distemper virus (CDV), canine herpesvirus (CHV) and canine parainfluenza virus (CPiV) were considered the major causative agents. Lately, new pathogens have been implicated in the development of CIRDC, namely canine influenza virus (CIV), canine respiratory coronavirus (CRCoV), canine pneumovirus (CnPnV), Mycoplasma cynos and Streptococcus equi subspecies zooepidemicus. To better understand the role of the different pathogens in the development of CIRDC and their epidemiological relevance in Europe, prevalence data were collected from peerreviewed publications and summarized. Evidence of exposure to Bb is frequently found in healthy and diseased dogs and client-owned dogs are as likely to be infected as kennelled dogs. Co-infections with viral pathogens are common. The findings confirm that Bb is an important cause of CIRDC in Europe. CAV-2 and CDV recovery rates from healthy and diseased dogs are low and the most likely explanation for this is control through vaccination. Seroconversion to CHV can be demonstrated following CIRDC outbreaks and CHV has been detected in the lower respiratory tract of diseased dogs. There is some evidence that CHV is not a primary cause of CIRDC, but opportunistically re-activates at the time of infection and exacerbates the disease. The currently available data suggest that CIV is, at present, neither a prevalent nor a significant pathogen in Europe. CPiV remains an important pathogen in CIRDC and facilitates co-infection with other viral and bacterial pathogens. CnPnV and CRCoV are important new elements in the aetiology of CIRDC and spread particularly well in multi-dog establishments. M. cynos is common in Europe and is more likely to occur in younger and kennelled dogs. This organism is frequently found together with other CIRDC pathogens and is significantly associated with more severe respiratory signs. S. zooepidemicus infection is not common and appears to be a particular problem in kennels. Protective immunity against respiratory diseases is rarely complete, and generally only a reduction in clinical signs and excretion of pathogen can be achieved through vaccination. However, even vaccines that only reduce and do not prevent infection carry epidemiological advantages. They reduce spread, increase herd immunity and decrease usage of antimicrobials. Recommending vaccination of dogs against pathogens of CIRDC will directly provide epidemiological advantages to the population and the individual dog.
Output: Aetiology of Canine Infectious Respiratory Disease Complex and Prevalence of its Pathogens in Europe-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). ScienceDirect
Mice infected with neurotropic strains of coronavirus develop acute encephalomyelitis and eliminate infectious virus. However, control of acute infection is incomplete resulting in persistence of viral RNA in the central nervous system (CNS) associated with ongoing primary demyelination. A high prevalence of virus specific CD8 and CD4 T cells within the CNS correlates with ex vivo cytolytic activity and IFN-7 secretion, which are both required for virus reduction during the acute infection. Although most infected cell types are susceptible to perforin mediated clearance, IFNq' is required for controlling infection of oligodendrocytes. Furthermore, by enhancing class I expression and inducing class II expression within resident CNS cells IFN-7 optimizes T cell receptor dependent functions. In addition to its direct anti viral activity, these multifactorial effects make IFN-y more essential than perforin for viral control. CD4 T cells enhance CD8 T cell expansion, survival and effectiveness. Although both CD8 and CD4 T cells are retained within the CNS during persistence, they cannot control viral recrudescence in the absence of humoral immunity. Demyelination can be mediated by either CD8 or CD4 T cells; however, although a variety of effector molecules have been excluded, a dominant common denominator remains elusive. Thus concerted efforts to control infection coincide with a variety of potential mechanisms causing chronic demyelinating disease.
Output: Chapter C4 THE ROLE OF T CELLS IN CORONA-VIRUS- INDUCED DEMYELINATION
Background: Despite advances in surveillance and prevention, pneumonia and influenza (P&I) remain among the leading causes of mortality in the United States. Elderly adults experience the most severe morbidity from influenza-associated diseases, and have the highest rates of seasonal migration within the U.S. compared to other subpopulations. The objective of this study is to assess spatiotemporal patterns in influenza-associated hospitalizations in the elderly, by time, geography, and intensity of P&I. Given the high seasonal migration of individuals to Florida, this state was examined more closely using harmonic regression to assess spatial and temporal patterns of P&I hospitalizations by state of residence. Methods: Data containing all Medicare-eligible hospitalizations in the United States for 1991-2006 with P&I (ICD-9-CM codes 480-487) were abstracted for the 65+ population. Hospitalizations were classified by state of residence, provider state, and date of admissions, specifically comparing those admitted between October and March to those admitted between April and September. We then compared the hospitalization profile data of Florida residents with that of out-of-state residents by state of primary residence and time of year (in-season or out-ofseason).
Output: Snowbirds and infection-new phenomena in pneumonia and influenza hospitalizations from winter migration of older adults: A spatiotemporal analysis
Background: Effective hand hygiene practice can reduce transmission of diseases such as respiratory tract infections (RTIs) and gastrointestinal infections, especially in young children. While hand hygiene has been widely promoted within Australia, primary care providers' (PCPs) and parents' understanding of hand hygiene importance, and their views on hand hygiene in reducing transmission of diseases in the community are unclear. Therefore, the aim of this study was to explore the views of PCPs and parents of young children on their knowledge and practice of hand hygiene in disease transmission. Methods: Using a cross-sectional qualitative research design, we conducted 30 in-depth interviews with PCPs and five focus groups with parents (n = 50) between June 2014 and July 2015 in Melbourne, Australia. Data were thematically analysed. Results: Participants agreed that hand hygiene practice was important in reducing disease transmissions. However, barriers such as variations of hand hygiene habits, relating visibility to transmission; concerns around young children being obsessed with washing hands; children already being 'too clean' and the need to build their immunity through exposure to dirt; and scepticism that hand hygiene practice was achievable in young children, all hindered participants' motivation to develop good hand hygiene behaviour in young children. Conclusion: Despite the established benefits of hand hygiene, sustained efforts are needed to ensure its uptake in routine care. To overcome the barriers identified in this study a multifaceted intervention is needed that includes teaching young children good hand hygiene habits, PCPs prompting parents and young children to practice hand hygiene when coming for an RTI consultation, reassuring parents that effective hand hygiene practice will not lead to abnormal psychological behaviour in their children, and community health promotion education campaigns.
Output: Visibility and transmission: complexities around promoting hand hygiene in young children -a qualitative study
| Over the past decade, a genomics revolution, made possible through the development of high-throughput sequencing, has triggered considerable progress in the study of ancient DNA , enabling complete genomes of past organisms to be reconstructed. A newly established branch of this field, ancient pathogen genomics, affords an in-depth view of microbial evolution by providing a molecular fossil record for a number of human-associated pathogens. Recent accomplishments include the confident identification of causative agents from past pandemics, the discovery of microbial lineages that are now extinct, the extrapolation of past emergence events on a chronological scale and the characterization of long-term evolutionary history of microorganisms that remain relevant to public health today. In this Review , we discuss methodological advancements, persistent challenges and novel revelations gained through the study of ancient pathogen genomes.
Output: Ancient pathogen genomics as an emerging tool for infectious disease research M I C R O B I A L G E N O M I C S 1500 CE 1000 BCE 500 BCE 0 CE
Many airborne infectious diseases can be transmitted via exhaled contaminants transported in the air. Direct exposure occurs when the exhaled jet from the infected person directly enters the breathing zone of the target person. Indirect exposure occurs when the contaminants disperse in the room and are inhaled by the target person. This paper presents a simple method for differentiating the direct and indirect exposure to exhaled contaminants in mechanically ventilated rooms. Experimental data for 191 cases were collected from the literature. After analyzing the data, a simple method was developed to differentiate direct and indirect exposure in mixing and displacement ventilated rooms. The proposed method correctly differentiated direct and indirect exposure for 120 out of the 133 mixing ventilation cases and 47 out of the 58 displacement ventilation cases. Therefore, the proposed method is suitable for use at the early design stage to quickly assess whether there will be direct exposure to exhaled contaminants in a mechanically ventilated room.
Output: A simple method for differentiating direct and indirect exposure to exhaled contaminants in mechanically ventilated rooms Article History
Heme oxygenase 1 (HO-1) is the first and rate-controlling enzyme in heme degradation. Bach1 is a mammalian transcriptional repressor of HO-1. To understand how zinc mesoporphyrin (ZnMP) induces the expression of HO-1, we investigated the effects of ZnMP on Bach1 mRNA and protein levels in human hepatoma Huh-7 cells by quantitative RT-PCR and Western blots. We found that ZnMP markedly up-regulated HO-1 mRNA and protein levels, and rapidly and significantly decreased Bach1 protein levels by increasing degradation of Bach1 protein [half life (t 1/2 ) from 19 h to 45 min], whereas ZnMP did not influence Bach1 mRNA levels. The proteasome inhibitors, epoxomicin and MG132, significantly inhibited degradation of Bach1 by ZnMP in a dose-dependent fashion, indicating the degradation of Bach1 by ZnMP is proteasome dependent. Purified Bach1 Cterminal fragment bound heme, but there was no evidence for binding of ZnMP to the heme-binding region of Bach1. In conclusion, ZnMP produces profound post-transcriptional down-regulation of Bach1 protein levels and transcriptional up-regulation of HO-1. Our results indicate that ZnMP upregulates HO-1 gene expression by markedly increasing Bach1 protein degradation in a proteasomedependent manner.
Output: Zinc Mesoporphyrin Induces Rapid and Marked Degradation of the Transcription Factor Bach1 and Up-regulates HO-1
Viral infections of the respiratory tract can be complicated by bacterial superinfection, resulting in a significantly longer duration of illness and even a fatal outcome. In this review, we focused on interactions between S. aureus and non-influenza viruses. Clinical data evidenced that rhinovirus infection may increase the S. aureus carriage load in humans and its spread. In children, respiratory syncytial virus infection is associated with S. aureus carriage. The mechanisms by which some non-influenza respiratory viruses predispose host cells to S. aureus superinfection can be summarized in three categories: i) modifying expression levels of cellular patterns involved in S. aureus adhesion and/or internalization, ii) inducing S. aureus invasion of epithelial cells due to the disruption of tight junctions, and iii) decreasing S. aureus clearance by altering the immune response. The comprehension of pathways involved in S. aureus-respiratory virus interactions may help developing new strategies of preventive and curative therapy. ARTICLE HISTORY
Output: Staphylococcus aureus colonization and non-influenza respiratory viruses: Interactions and synergism mechanisms
Kaye, H. S. (CDC, Atlanta, Ga. 30333), H. B. Marsh and W. R. Dowdle. Seroepidemiologic survey of coronavirus (strain OC 43) related infections in a children's population. Amer J Epid 94: 43-49, 1971.-Acute and convalescent serum pairs and control sera collected from subjects living in a children's home over a 7-year period (1960)(1961)(1962)(1963)(1964)(1965)(1966)(1967) were examined by hemagglutination-inhibition (HI) test witl coronavirus strain OC 43. Ninety-three serologic conversions were observed; 44 were associated with reported illnesses and 49 with no reported illnesses. In three distinct outbreaks during the winter and spring quarter of 1960-1961, 1964-1965, and 1966-1967, 67 conversions occurred. Seroconversions to strain OC 43 were associated with as much as 19% of the respiratory diseases in a single season. Over the 7-year period coronavirus strain OC 43 accounted for 3% of the total 1328 respiratory illnesses. Evidence of preexisting antibody was apparent in one-third of the children showing seroconversions. The j^ ( HI test was more sensitive for serodiagnosis than the complement-fixaticn test. The major presenting complaints of the children with respiratory disease associated with coronavirus strain OC 43 were sore throat, cough and coryza; the predominating symptoms were pharyngitis, coryza, fever and cervical adenitis.
Output: SEROEPIDEMIOLOGIC SURVEY OF CORONA VIRUS (STRAIN OC 43) RELATED INFECTIONS IN A CHILDREN'S POPULATION
In endemic countries such as Bangladesh, consequences of cholera place an enormous financial and social burden on patients and their families. Cholera vaccines not only provide health benefits to susceptible populations but also have effects on the earning capabilities and financial stability of the family. Community-based research and evaluations are necessary to understand perceptions about and practices of the community relating to cholera and oral cholera vaccines. This may help identify the ways in which such vaccines may be successfully introduced, and other preventive measures can be implemented. The present study assessed the knowledge of, attitudes toward, and preventive practices relating to cholera and oral cholera vaccine among an urban population residing in a high cholera-prone setting in Dhaka, Bangladesh. Methods: This cross-sectional study was conducted in an area of high cholera prevalence in 15 randomly-selected clusters in Mirpur, Dhaka city. A study team collected data through a survey and in-depth interviews during Results: Of 2,830 families included in the final analysis, 23% could recognize cholera as acute watery diarrhea and 16% had ever heard of oral cholera vaccine. About 54% of the respondents had poor knowledge about cholerarelated issues while 97% had a positive attitude toward cholera and oral cholera vaccine. One-third showed poor practice relating to the prevention of cholera. The findings showed a significant (p < 0.05) association between the respondents' knowledge and sex, education, occupation, monthly overall household expenditure, attitudes and practice. In the adjusted model, male sex, having a lower monthly overall household expenditure, and having a less positive attitude toward cholera were the significant predictors to having poor knowledge. Conclusions: The findings suggest the strengthening of health education activities to improve knowledge on cholera, its prevention and treatment and information on cholera vaccination among high-risk populations. The data also underscore the potential of mass cholera vaccination to prevent and control cholera.
Output: Knowledge of, attitudes toward, and preventive practices relating to cholera and oral cholera vaccine among urban high-risk groups: findings of a cross-sectional study in Dhaka, Bangladesh
The global vaccine market is diverse while facing a plethora of novel developments. Genetic modification (GM) techniques facilitate the design of 'smarter' vaccines. For many of the major infectious diseases of humans, like AIDS and malaria, but also for most human neoplastic disorders, still no vaccines are available. It may be speculated that novel GM technologies will significantly contribute to their development. While a promising number of studies is conducted on GM vaccines and GM vaccine technologies, the contribution of GM technology to newly introduced vaccines on the market is disappointingly limited. In this study, the field of vector-based GM vaccines is explored. Data on currently available, actually applied, and newly developed vectors is retrieved from various sources, synthesised and analysed, in order to provide an overview on the use of vector-based technology in the field of GM vaccine development. While still there are only two vector-based vaccines on the human vaccine market, there is ample activity in the fields of patenting, preclinical research, and different stages of clinical research. Results of this study revealed that vector-based vaccines comprise a significant part of all GM vaccines in the pipeline. This study further highlights that poxviruses and adenoviruses are among the most prominent vectors in GM vaccine development. After the approval of the first vectored human vaccine, based on a flavivirus vector, vaccine vector technology, especially based on poxviruses and adenoviruses, holds great promise for future vaccine development.
Output: Vector-based genetically modified vaccines: Exploiting Jenner's legacy
Background: Mice lacking the type I interferon receptor (IFNAR 2/2 mice) reproduce relevant aspects of Crimean-Congo hemorrhagic fever (CCHF) in humans, including liver damage. We aimed at characterizing the liver pathology in CCHF virusinfected IFNAR 2/2 mice by immunohistochemistry and employed the model to evaluate the antiviral efficacy of ribavirin, arbidol, and T-705 against CCHF virus. Methodology/Principal Findings: CCHF virus-infected IFNAR 2/2 mice died 2-6 days post infection with elevated aminotransferase levels and high virus titers in blood and organs. Main pathological alteration was acute hepatitis with extensive bridging necrosis, reactive hepatocyte proliferation, and mild to moderate inflammatory response with monocyte/macrophage activation. Virus-infected and apoptotic hepatocytes clustered in the necrotic areas. Ribavirin, arbidol, and T-705 suppressed virus replication in vitro by $3 log units (IC 50 0.6-2.8 mg/ml; IC 90 1.2-4.7 mg/ml). Ribavirin [100 mg/(kg6d)] did not increase the survival rate of IFNAR 2/2 mice, but prolonged the time to death (p,0.001) and reduced the aminotransferase levels and the virus titers. Arbidol [150 mg/(kg6d)] had no efficacy in vivo. Animals treated with T-705 at 1 h [15, 30, and 300 mg/(kg6d)] or up to 2 days [300 mg/(kg6d)] post infection survived, showed no signs of disease, and had no virus in blood and organs. Co-administration of ribavirin and T-705 yielded beneficial rather than adverse effects. Conclusions/Significance: Activated hepatic macrophages and monocyte-derived cells may play a role in the proinflammatory cytokine response in CCHF. Clustering of infected hepatocytes in necrotic areas without marked inflammation suggests viral cytopathic effects. T-705 is highly potent against CCHF virus in vitro and in vivo. Its in vivo efficacy exceeds that of the current standard drug for treatment of CCHF, ribavirin.
Output: Evaluation of Antiviral Efficacy of Ribavirin, Arbidol, and T-705 (Favipiravir) in a Mouse Model for Crimean-Congo Hemorrhagic Fever
Bunyaviruses are significant human pathogens, causing diseases ranging from hemorrhagic 26 fevers to encephalitis. Among these viruses, La Crosse virus (LACV), a member of the California 27 serogroup, circulates in the eastern and midwestern United States. While LACV infection is often 28 asymptomatic, dozens of cases of encephalitis are reported yearly. Unfortunately, no antivirals 29 have been approved to treat LACV infection. Here, we developed a method to rapidly test potential 30 antivirals against LACV infection. From this screen, we identified several potential antiviral 31 molecules, including known antivirals. Additionally, we identified many novel antivirals that 32 exhibited antiviral activity without affecting cellular viability. Valinomycin, a potassium ionophore, 33 was among our top targets. We found that valinomycin exhibited potent anti-LACV activity in 34 multiple cell types in a dose-dependent manner. Valinomycin did not affect particle stability or 35 infectivity, suggesting that it may preclude virus replication by altering cellular potassium ions, a 36 known determinant of LACV entry. We extended these results to other ionophores and found that 37 the antiviral activity of valinomycin extended to other viral families including bunyaviruses (Rift 38 Valley fever virus, Keystone virus), enteroviruses (Coxsackievirus, rhinovirus), flavirivuses (Zika), 39 and coronaviruses (229E and MERS-CoV). In all viral infections, we observed significant 40 reductions in virus titer in valinomycin-treated cells. In sum, we demonstrate the importance of 41 potassium ions to virus infection, suggesting a potential therapeutic target to disrupt virus 42 replication. 43 44 Importance 45 No antivirals are approved for the treatment of bunyavirus infection. The ability to rapidly screen 46 compounds and identify novel antivirals is one means to accelerate drug discovery for viruses 47 with no approved treatments. We used this approach to screen hundreds of compounds against 48 La Crosse virus, an emerging bunyavirus that causes significant disease, including encephalitis. 49 We identified several known and previously unidentified antivirals. We focused on a potassium 50 ionophore, valinomycin, due to its promising in vitro antiviral activity. We demonstrate that 51 valinomycin, as well as a selection of other ionophores, exhibits activity against La Crosse virus 52 as well as several other distantly related bunyaviruses. We finally observe that valinomycin has 53 activity against a wide array of human viral pathogens, suggesting that disrupting potassium ion 54 homeostasis with valinomycin may be a potent host pathway to target to quell virus infection.
Output: Novel ionophores active against La Crosse virus identified through rapid 1 antiviral screening 2 3
The metabolism of Epimedium-derived flavonoid glycosides (EF, with icariin as the main component) in rabbit intestinal flora and its inhibition by gluconolactone were investigated in this paper to help reveal the metabolic pathway of EF in rabbits and to identify the in vivo bioactive components of EF in the prevention of steroid-associated osteonecrosis. METHODS: EF were incubated at 37 °C anaerobically with rabbit intestinal flora, and then water-saturated ethyl acetate was used for sample extraction at different time points. Furthermore, gluconolactone was added at different concentrations (8, 12 and 16 mg·mL −1 ) to study its inhibition of the metabolism of EF in rabbit intestinal flora. The separation was performed on a ODS column by gradient elution with acetonitrile-water (including 0.1% formic acid respectively) as mobile phase at detection wavelength of 335 nm. RESULTS: EF were metabolized to icariside II in 2 h, and then to icaritin when incubated for 8 h; gluconolactone showed the inhibition of EF metabolism in rabbit intestinal flora in a concentration-dependent manner. CONCLUSION: EF were found to be metabolized rapidly by hydrolysis of rabbit intestinal flora to produce icariside II and icaritin; and the total inhibition was achieved by gluconolactone at a concentration of 16 mg·mL −1 . [KEY WORDS] Epimedium-derived flavonoid glycosides; Prevention of steroid-associated osteonecrosis; Metabolism in rabbit intestinal flora; Gluconolactone; Inhibition [CLC Number] R965 [Document code] A [Article ID] 1672-3651(2011)06-0461-05 [*Corresponding author] YAO Zhi-Hong: Associate Prof.,
Output: Chinese Journal of Natural Medicines Metabolism of Epimedium-derived Flavonoid Glycosides in Intestinal Flora of Rabbits and Its Inhibition by Gluconolactone
Plasmodium falciparum erythrocyte invasion is a multistep process that involves a spectrum of interactions that are not well characterized. We have characterized a 113-kDa immunogenic protein, PF3D7_1431400 (PF14_0293), that possesses coiled-coil structures. The protein is localized on the surfaces of both merozoites and gametocytes, hence the name Plasmodium falciparum surface-related antigen (PfSRA). The processed 32-kDa fragment of PfSRA binds normal human erythrocytes with different sensitivities to enzyme treatments. Temporal imaging from initial attachment to internalization of viable merozoites revealed that a fragment of PfSRA, along with PfMSP1 19, is internalized after invasion. Moreover, parasite growth inhibition assays showed that PfSRA P1 antibodies potently inhibited erythrocyte invasion of both sialic acid-dependent and -independent parasite strains. Also, immunoepidemiological studies show that malaria-infected populations have naturally acquired antibodies against PfSRA. Overall, the results demonstrate that PfSRA has the structural and functional characteristics of a very promising target for vaccine development.
Output: Functional Characterization of Plasmodium falciparum Surface-Related Antigen as a Potential Blood-Stage Vaccine Target The Journal of Infectious Diseases ® 2018;218:778-90
Many emerging arboviruses are not transmitted by traditional mosquito vectors, but by lesser-studied arthropods such as ticks, midges, and sand flies. Small RNA (sRNA) silencing pathways are the main antiviral defence mechanism for arthropods, which lack adaptive immunity. Non-retroviral integrated RNA virus sequences (NIRVS) are one potential source of sRNAs which comprise these pathways. NIRVS are remnants of past germline RNA viral infections, where viral cDNA integrates into the host genome and is vertically transmitted. In Aedes mosquitoes, NIRVS are widespread and produce PIWI-interacting RNAs (piRNAs). These are hypothesised to target incoming viral transcripts to modulate viral titre, perhaps rendering the organism a more efficient arbovirus vector. To explore the NIRVS landscape in alternative arbovirus vectors, we validated the NIRVS landscape in Aedes spp. and then identified novel NIRVS in six medically relevant arthropods and also in Drosophila melanogaster. We identified novel NIRVS in Phlebotomus papatasi, Culicoides sonorensis, Rhipicephalus microplus, Anopheles gambiae, Culex quinquefasciatus, and Ixodes scapularis. Due to their unexpected abundance, we further characterised NIRVS in the blacklegged tick I. scapularis (n = 143). Interestingly, NIRVS are not enriched in R. microplus, another hard tick, suggesting this is an Ixodes-specific adaptation. I. scapularis NIRVS are enriched in bunya-and orthomyxo-like sequences, reflecting that ticks are a dominant host for these virus groups. Unlike in mosquitoes, I. scapularis NIRVS are more commonly derived from the nonstructural region (replicase) of negative-sense viruses, as opposed to structural regions (e.g. glycoprotein). Like other arthropods, I. scapularis NIRVS preferentially integrate into genomic piRNA clusters, and serve as a template for primary piRNA production in the commonly used embryonic I. scapularis ISE6 cell line. Interestingly, we identified a two-fold enrichment of nonlong terminal repeat (non-LTR) retrotransposons, in genomic proximity to NIRVS, contrasting with studeis in Ae. aegypti, where LTR retrotransposons are instead associated with NIRVS formation. We characterised NIRVS phylogeny and integration patterns in the important vector, I. scapularis, revealing they are distinct from those in Aedes spp. Future studies will explore the possible antiviral mechanism conferred by NIRVS to I. scapularis,which may help the transmission of pathogenic arboviruses. Finally, this study explored NIRVS as an untapped wealth of viral diversity in arthropods.
Output: Novel insights into endogenous RNA viral elements in Ixodes scapularis and other arbovirus vector genomes
Most pandemics-eg, HIV/AIDS, severe acute respiratory syndrome, pandemic influenzaoriginate in animals, are caused by viruses, and are driven to emerge by ecological, behavioural, or socioeconomic changes. Despite their substantial effects on global public health and growing understanding of the process by which they emerge, no pandemic has been predicted before infecting human beings. We review what is known about the pathogens that emerge, the hosts that they originate in, and the factors that drive their emergence. We discuss challenges to their control and new efforts to predict pandemics, target surveillance to the most crucial interfaces, and identify prevention strategies. New mathematical modelling, diagnostic, communications, and informatics technologies can identify and report hitherto unknown microbes in other species, and thus new risk assessment approaches are needed to identify microbes most likely to cause human disease. We lay out a series of research and surveillance opportunities and goals that could help to overcome these challenges and move the global pandemic strategy from response to pre-emption.
Output: Prediction and prevention of the next pandemic zoonosis
Knowledge of the distribution and diversity of RNA viruses is still limited in spite of their possible environmental and epidemiological impacts because RNA virus-specific metagenomic methods have not yet been developed. We herein constructed an effective metagenomic method for RNA viruses by targeting long double-stranded (ds)RNA in cellular organisms, which is a hallmark of infection, or the replication of dsRNA and single-stranded (ss)RNA viruses, except for retroviruses. This novel dsRNA targeting metagenomic method is characterized by an extremely high recovery rate of viral RNA sequences, the retrieval of terminal sequences, and uniform read coverage, which has not previously been reported in other metagenomic methods targeting RNA viruses. This method revealed a previously unidentified viral RNA diversity of more than 20 complete RNA viral genomes including dsRNA and ssRNA viruses associated with an environmental diatom colony. Our approach will be a powerful tool for cataloging RNA viruses associated with organisms of interest.
Output: FLDS: A Comprehensive dsRNA Sequencing Method for Intracellular RNA Virus Surveillance
Rheumatoid arthritis (RA) is a chronic and genetically complex inflammatory disorder that leads to erosive destruction of peripheral joints 1-5 . The use of animal models mimicking RA, such as pristane-induced arthritis (PIA) in rats, should facilitate its genetic analysis. Pristane is a non-immunogenic synthetic oil that, after a single subcutaneous injection into DA rats, induces arthritis restricted to peripheral joints with a chronic relapsing disease course 6 . To identify genes involved in the control of chronic arthritis, we made crosses between susceptible DA rats and resistant E3 rats and analysed the progeny with microsatellite markers covering the entire rat genome. Our results show that different arthritis phenotypes are associated with different chromosomal loci. Loci on chromosomes 4 and 6 (Pia2 and Pia3) influence arthritis onset, whereas a locus on chromosome 12 (Pia4) is associated with severity and joint erosion. We found that chronicity is associated with a different set of loci, one on chromosome 4 and the other on chromosome 14 (Pia5, Pia6) . These findings demonstrate for the first time that different phases of a chronic self-perpetuative disease which mimics RA are associated with distinct sets of genes.
Output: Genetic control of arthritis onset, severity and chronicity in a model for rheumatoid arthritis in rats
The use of a live attenuated porcine reproductive and respiratory syndrome virus (PRRSV) vaccine in piglets has been associated with reproductive disorders in non-vaccinated sows. Vaccine-derived virus (VDV) has been isolated from foetuses, stillborn pigs, and dead piglets, indicating that the live vaccine spread from vaccinated piglets to non-vaccinated sows, and that the virus might be implicated in the severe reproductive problems observed. In the present study, one such VDV isolate was used to experimentally infect pregnant sows in the last trimester. The chosen isolate, which had more than 99.6% identity to the attenuated vaccine virus, originated from the lungs of a stillborn pig from a swine herd with a sudden high level of stillborn pigs and increased piglet mortality in the nursing period. Intranasal inoculation of sows with the virus isolate resulted in congenital infection, foetal death, and preweaning pig mortality. As such, the present study showed that vaccine-derived PRRSV can cause disease in swine consistent with PRRS. #
Output: Experimental inoculation of late term pregnant sows with a field isolate of porcine reproductive and respiratory syndrome vaccine-derived virus
Cancer is a multistep process involving genetic and epigenetic changes in the somatic genome. Genetic mutations as well as environmental factors lead to the initiation, promotion, and progression of cancer. Cancer progression ends in tumor metastasis to distant sites, and metastasis is the major reason for cancer patient deaths. Recent experimental evidence suggests the pivotal role of cancer stem cells. A tumor is heterogeneous and composed of different cell types. The cancer stem cells in the tumor have the capacity both to self-renew and differentiate to sustain the tumor. Features of cancer stem cells are described in this review, with an emphasis on the role that dietary phytochemicals may play in cancer chemoprevention. Ingredients in the diet can inhibit cancer cells and cancer stem cells. These compounds include curcumin from curry, epigallocatechin gallate from green tea, resveratrol from red wine, genistein from soy, sulforaphane from broccoli, and many others. Current research findings advocate the beneficial effects towards cancer chemoprevention via uptake of a combination of different dietary phytochemicals.
Output: Dietary Phytochemicals Target Cancer Stem Cells for Cancer Chemoprevention Cancer and Cancer Stem Cells Biology of Cancer
Tylophorine derivatives exhibit anti-cancer activities but their cellular targets remain unknown. We used a biotinylated tylophorine derivative to probe for the interacting cellular target(s) of tylophorine. Tylophorine directly binds to caprin-1 and consequently enhances the recruitment of G3BP1, c-Myc mRNA, and cyclin D2 mRNA to form a ribonucleoprotein complex. Subsequently, this tylophorine targeted ribonucleoprotein complex is sequestered to the polysomal fractions and the protein expressions of the associated mRNA-transcripts are repressed. Caprin-1 depleted carcinoma cells become more resistant to tylophorine, associated with decreased formation of the ribonucleoprotein complex targeted by tylophorine. Consequently, tylophorine downregulates c-Myc and cyclins D1/D2, causing hypophosphorylation of Rb and suppression of both processing-body formation and the Warburg effect. Gene expression profiling and gain-of-c-Myc-function experiments also revealed that the downregulated c-Myc contributes to the anti-oncogenic effects of tylophorine compounds. Furthermore, the potent tylophorine derivative dibenzoquinoline-33b elicited a similar effect, as c-Myc protein levels were also decreased in xenograft tumors treated with dibenzoquinoline-33b. Thus, tylophorine compounds exert anticancer activity predominantly by targeting and sequestering the caprin-1 protein and c-Myc mRNA associated ribonucleoprotein complex.
Output: Targeting a ribonucleoprotein complex containing the caprin-1 protein and the c-Myc mRNA suppresses tumor growth in mice: an identification of a novel oncotarget
Porcine transmissible gastroenteritis virus (TGEV) is the causative agent of acute diarrhea of newborn piglets that provokes high mortality rates in affected farms. In this study, specific immunoglobulin from egg yolk against TGEV was produced by immunization of White leghorn hens. Enzyme-linked immunosorbent assay (ELISA) and virus neutralization (VN) test revealed that the specific antibody titer started to increase on the tenth day post-immunization, reached its peak on the eighth week, and remained at a high level until the last week that we tested. The prophylactic and therapeutic effects of egg yolk immunoglobulin (IgY) was investigated in piglets. IgY was found effective to increase piglets survival rate significantly after challenge exposures in prophylactic efficacy analysis. The therapeutic effects test revealed that the mortality was dramatically reduced by orally administered IgY. All these results in our study indicated that IgY specific to TGEV could be an alternative prophylactic method like colostral antibodies against TGEV in piglets.
Output: Prophylactic and therapeutic effects of egg yolk immunoglobulin against porcine transmissible gastroenteritis virus in piglets
Npl4 is likely to be the most upstream factor recognizing Lys48-linked polyubiquitylated substrates in the proteasomal degradation pathway in yeast. Along with Ufd1, Npl4 forms a heterodimer (UN), and functions as a cofactor for the Cdc48 ATPase. Here, we report the crystal structures of yeast Npl4 in complex with Lys48-linked diubiquitin and with the Npl4binding motif of Ufd1. The distal and proximal ubiquitin moieties of Lys48-linked diubiquitin primarily interact with the C-terminal helix and N-terminal loop of the Npl4 C-terminal domain (CTD), respectively. Mutational analysis suggests that the CTD contributes to linkage selectivity and initial binding of ubiquitin chains. Ufd1 occupies a hydrophobic groove of the Mpr1/Pad1 N-terminal (MPN) domain of Npl4, which corresponds to the catalytic groove of the MPN domain of JAB1/MPN/Mov34 metalloenzyme (JAMM)-family deubiquitylating enzyme. This study provides important structural insights into the polyubiquitin chain recognition by the Cdc48-UN complex and its assembly.
Output: Structural insights into ubiquitin recognition and Ufd1 interaction of Npl4
This paper provides historical, theoretical, and empirical syntheses in understanding the rationality of investors, stock prices, and stock market efficiency behaviour in the theoretical lenses of behavioural finance paradigm. The inquiry is guided by multidisciplinary behaviouralrelated theories. The analyses employed a long span of Bursa Malaysia stock market data from 1977 to 2014 along the different phases of economic development and market states. The tests confirmed the presence of asymmetric dynamic behaviour of prices predictability as well as risk and return relationships across different market states, risk states and quantiles data segments. The efficiency tests show trends of an adaptive pattern of weak market efficiency across various economic phases and market states. Collectively, these evidences lend support to boundedadaptive rational of investors' behaviour, dynamic stock price behaviour, and accordingly forming bounded-adaptive market efficiency.
Output: Behavioural finance perspectives on Malaysian stock market efficiency-NC- ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
The primary intracellular protein degradation systems, including the ubiquitin-proteasome and the lysosome pathways, have been emerging as central regulators of viral infectivity, inflammation, and viral pathogenicity. Viral myocarditis is an inflammatory disease of the myocardium caused by virus infection in the heart. The disease progression of viral myocarditis occurs in three distinct stages: acute viral infection, immune cell infiltration, and cardiac remodelling. Growing evidence suggests a crucial role for host proteolytic machineries in the regulation of the pathogenesis and progression of viral myocarditis in all three stages. Cardiotropic viruses evolve different strategies to subvert host protein degradation systems to achieve successful viral replication. In addition, these proteolytic systems play important roles in the activation of innate and adaptive immune responses during viral infection. Recent evidence also suggests a key role for the ubiquitin-proteasome and lysosome systems as the primary effectors of protein quality control in the regulation of cardiac remodelling. This review summarizes the recent advances in understanding the direct interaction between cardiotropic viruses and host proteolytic systems, with an emphasis on coxsackievirus B3, one of the primary aetiological agents causing viral myocarditis, and highlights possible roles of the host degradation systems in the pathogenesis of viral myocarditis and its progression to dilated cardiomyopathy. ---
Output: SPOTLIGHT REVIEW Protein degradation systems in viral myocarditis leading to dilated cardiomyopathy
Since December 2019, the outbreak of a new coronavirus, named 2019-nCoV, has greatly threatened the public health in China and raised great concerns worldwide. No specific treatment for this infection is currently available. We previously reported that teicoplanin, a glycopeptide antibiotic which has routinely been used in the clinic to treat bacterial infection with low toxicity, significantly inhibits the invasion of cells by Ebola virus, SARS-CoV and MERS-CoV, via specifically inhibiting the activity of cathepsin L. Here, we tested the efficacy of teicoplanin against 2019-nCoV virus infection and found that teicoplanin potently prevents the entrance of 2019-nCoV-Spike-pseudoviruses into the cytoplasm, with an IC 50 of 1.66 μM. Although the inhibitory effect upon the replication of wildtype viruses ex vivo and in vivo remains to be determined, our preliminary result indicates that the potential antiviral activity of teicoplanin could be applied for the treatment of 2019-nCoV virus infection.
Output: Teicoplanin potently blocks the cell entry of 2019-nCoV
Following the outbreak of novel Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) or COVID-19 in Wuhan, China late 2019, different countries have put in place interventions such as travel ban, proper hygiene, and social distancing to slow the spread of this novel virus. We evaluated the effects of travel bans in the Australia context and projected the epidemic until May 2020. Our modelling results closely align with observed cases in Australia indicating the need for maintaining or improving on the control measures to slow down the virus.
Output: Delaying the COVID-19 epidemic in Australia: Evaluating the effectiveness of international travel bans
Influenza A virus (IAV) and human parainfluenza virus type 2 (hPIV2) are common pathogens that cause community-acquired respiratory disease in the same epidemic season, usually in winter. Both of these negative-stranded RNA viruses utilize sialic acids on the cell surface as a receptor, allowing them to target same cells. However, their biological properties are quite different. The IAV genome Abstract It has been reported that dual or multiple viruses can coinfect epithelial cells of the respiratory tract. However, little has been reported on in vitro interactions of coinfected viruses. To explore how coinfection of different viruses affects their biological property, we examined growth of influenza A virus (IAV) and human parainfluenza virus type 2 (hPIV2) during coinfection of Vero cells. We found that IAV growth was enhanced by coinfection with hPIV2. The enhanced growth of IAV was not reproduced by coinfection with an hPIV2 mutant with reduced cell fusion activity, or by ectopic expression of the V protein of hPIV2. In contrast, induction of cell fusion by ectopic expression of the hPIV2 HN and F proteins augments IAV growth. hPIV2 coinfection supported IAV growth in cells originated from the respiratory epithelium. The enhancement correlated closely with cell fusion ability of hPIV2 in those cells. These results indicate that cell fusion induced by hPIV2 infection is beneficial to IAV replication and that enhanced viral replication by coinfection with different viruses can modify their pathological consequences.
Output: Enhanced growth of influenza A virus by coinfection with human parainfluenza virus type 2
Hepatitis B virus (HBV) infection causes major public health problems worldwide. The clinical limitation of current antiviral drugs for HBV, such as lamivudine, is the emergence of drug-resistant viral strains during prolonged antiviral therapy. Cepharanthine hydrochloride (CH), a natural alkaloid-derived compound, has been reported to possess potent activity against various viruses. The present study was performed to evaluate the in vitro activity of CH against clinical wild-type and lamivudine-resistant HBV isolates in transiently transfected cells. HBV DNA was extracted from serum samples collected both before lamivudine therapy and at the time of viral breakthrough and was amplified by polymerase chain reaction (PCR). The amplicons were cloned into a novel expression vector, pHY106, which can initiate the intracellular HBV replication cycle after cell transfection. Following transfection of the cloned amplicon into HepG2 cells, a drug susceptibility assay was performed. The level of viral antigen, HBeAg, was determined by enzyme-linked immunosorbent assay (ELISA). Quantitative real-time PCR (Q-PCR) was used for determining the amount of intracellular HBV DNA. Heat stress cognate 70 (Hsc70), a host protein required for HBV replication, was also analyzed by reverse transcription PCR (RT-PCR) to explore the possible antiviral mechanism of CH. The results showed that CH inhibited replication and HBeAg production by either wild-type or lamivudine-resistant HBV clinical isolates in a dose-dependent manner. The Hsc70 mRNA was also downregulated significantly. In conclusion, CH is active against both wild-type and lamivudine-resistant HBV clinical isolates, and its activity may be associated with its inhibition of host Hsc70.
Output: In vitro activity of cepharanthine hydrochloride against clinical wild-type and lamivudine-resistant hepatitis B virus isolates
Objective: To investigate the clinical presentation of coronavirus disease 2019 , particularly the incidence of gastrointestinal tract symptoms. We enrolled adult COVID-19 patients from a mobile cabin hospital in Wuhan with a definitive diagnosis by SARS-CoV-2 nucleic acid testing. Face-to-face interviews were conducted in which the patient selected COVID-19-related symptoms and report the time of onset and duration of symptoms. Results: A total of 212 adults were enrolled in this study, of which 127 (59.9%) were females, mean age was 48.50 ±13.15 (range: 17-79) years, and mean disease course was 26.78±9.16 (3-60) days. Fever and cough were the most common and earliest clinical symptoms of COVID-19. All rights reserved. No reuse allowed without permission. author/funder, who has granted medRxiv a license to display the preprint in perpetuity. : medRxiv preprint Diarrhoea occurred in 43.8% (93/212) of patients, of which 86.0% (80/93) had mushy stools. Nausea and vomiting were also common (20.7%). Diarrhoea lasted for 4.00(2.00-8.85) days and mostly occurred 5.00(0.25-11.00) days after the emergence of the first symptoms. Multiple logistic regression analysis found that diarrhoea was significantly correlated with fatigue [OR2.900,), p<0.0001]. Conclusions: Gastrointestinal tract symptoms are common in COVID-19 and most occur during the middle stage of the disease and lasts for a short period of time. Clinicians need to pay greater attention to gastrointestinal tract symptoms of COVID-19.
Output: Gastrointestinal tract symptoms in coronavirus disease 2019: Analysis of clinical symptoms in adult patients