niryuu/sni-each-converted huggingface dataset:
Despite early attempts to control the spread of the disease, porcine reproductive and respiratory syndrome (PRRS) has now become endemic in many countries including Britain. The occurrence of subclinical herd infections, the prolonged circulation of virus within herds and probable aerogenic virus spread all mitigated against the success of control measures. Tile origin of tile disease is unknown but the causative agent has been shown to be an arterivirus with shared features to lactate dehydrogenase virus of mice. There is evidence of extreme genetic and antigenic variability between Mnerican and European isolates. PRRS virus has a predilection for alveolar macrophages and does not grow in most cell lines. In infected pigs, viraemia can persist for many weeks ill the face of circulating antibodies and little is known about the mechanisms by which immunity to infection develops. A wide spectrum of disease has been reported from the field, accompanied in some cases by heavy economic losses. Reproductive and perinatal losses were most prominent when the disease first appeared. In the endemic phase, PRRS may be more significan{ as a contributory factor to a post-weaning respiratory syndrome of young pigs of 3-8 weeks. On-farm techniques have been developed to reduce tile recycling of PRRS virus from older infected nursery pigs to the younger newly weaned pig. Vaccines are now marketed for the control of PRRS, but are not licensed for use in Britain. Improvements in knowledge of virion composition and antigenic stability and in the nature of the immune response of the pig should result in genetically engineered subunit vaccines becoming available. Diagnosis of PRRS is still difficult as many animals do not show clinical signs and may only be detected by serology and often only when other respiratory diseases are being investigated. Now that the infection is wide-0007-1935/96/020153-22/$12.00/0 © 1996 Bailli6re Tindall 154 BRITISH VETERINARY JOURNAL, 152, 2 spread, serological testing must be properly targeted and interpreted to give meaningful results about virus circulation. An increasing arsenal of diagnostic methods are becoming available to detect virus in both fresh and fixed specimens. The pathogenic mechanisms of PRRS remain poorly defined and more work is needed to reveal the nature of the interaction between PRRS virus and other factors in disease.
Output: REVIEW PORCINE REPRODUCTIVE AND RESPIRATORY SYNDROME (PRRS): A REVIEW, WITH EMPHASIS ON PATHOLOGICAL, VIROLOGICAL AND DIAGNOSTIC ASPECTS
Crystal structures of complexes of an antiviral lectin griffithsin (GRFT) with glucose and N-acetylglucosamine were solved and refined at high resolution. In both complexes, all six monosaccharide-binding sites of GRFT were occupied and the mode of binding was similar to that of mannose. In our previous attempts to obtain a complex with N-acetylglucosamine by soaking, only a single site was occupied; thus, cocrystallization was clearly superior despite lower concentration of the ligand. Isothermal titration calorimetric experiments with N-acetylglucosamine, glucose, and mannose provided enthalpic evidence of distinct binding differences between the three monosaccharides. A comparison of the mode of binding of different monosaccharides is discussed in the context of the antiviral activity of GRFT, based on specific binding to high-mannose-containing complex carbohydrates found on viral envelopes.
Output: Crystallographic studies of the complexes of antiviral protein griffithsin with glucose and N-acetylglucosamine
Acute lung injury (ALI), and its more severe form, acute respiratory distress syndrome (ARDS), are syndromes of acute hypoxemic respiratory failure resulting from a variety of direct and indirect injuries to the gas exchange parenchyma of the lungs. The clinical syndrome is characterized by critical hypoxemia (partial pressure of oxygen in arterial blood/fraction of inspired oxygen <300 for ALI and <200 for ARDS), bilateral pulmonary infiltrates suggesting edema, no clinical or measured evidence of cardiac failure, and no other explanation for these findings. Pulmonary or nonpulmonary infections with sepsis are the most common causes of ALI and ARDS, although gastric aspiration, massive transfusions, trauma, and other factors contribute. 1 The diversity of causes and the stereotyped physiologic and pathologic responses have made modeling human ALI and ARDS difficult, but new themes are evolving from experimental studies, some of which are reviewed in this article. Most of what is known about the pathology of ALI and ARDS comes from the studies of patients who have died, although a limited number of patients have undergone open lung biopsy (Fig. 1) . The pathologic changes include an early phase of diffuse alveolar damage, with an increase in endothelial permeability, evidence of intravascular thrombi, severe epithelial injury with denudation of alveolar wall basement membranes, accumulation of protein and fibrin-rich alveolar infiltrates in the airspaces, and abundant alveolar neutrophilic infiltrates. If patients survive, these changes progress for days to a repair phase, characterized by hyaline membrane formation, transition from neutrophilic to mononuclear infiltrates, and the appearance of intra-alveolar and
Output: Experimental Models and Emerging Hypotheses for Acute Lung Injury Lung injury Animal model Respiratory distress
Since 2012, MERS-CoV has caused up to 2220 cases and 790 deaths in 27 countries with Saudi Arabia being the most affected country with~83.1% of the cases and~38.8% local death rate. Current serological assays such as microneutralization (MN), plaque reduction neutralization, immunofluorescence, protein microarray or pseudoparticle neutralization assays rely on handling of live MERS-CoV in high containment laboratories or need for expensive and special equipment and reagents and highly trained personnel which represent a technical hurdle for most laboratories in resource-limited MERS-CoV endemic countries. Here, we developed, compared and evaluated three different indirect ELISAs based on MERS-CoV nucleocapsid protein (N), spike (S) ectodomain (amino acids 1-1297) and S1 subunit (amino acids 1-725) and compared them with MN assay. The developed ELISAs were evaluated using large number of confirmed seropositive (79 samples) and seronegative (274 samples) MERS-CoV human serum samples. Both rS1-and rS-ELISAs maintained high sensitivity and specificity (≥90%) across a wider range of OD values compared to rN-ELISA. Moreover, rS1-and rS-based ELISAs showed better agreement and correlation with MN assay in contrast to rN-ELISA. Collectively, our data demonstrate that rS1-ELISA and rS-ELISA are more reliable than rN-ELISA and represent a suitable choice for seroepidemiological testing and surveillance in MERS-CoV endemic regions. Several MERS-CoV serological assays have been developed and https://doi.
Output: Development and validation of different indirect ELISAs for MERS-CoV serological testing
Long noncoding RNAs (lncRNAs) have been shown to play important roles in immune cell development and immune responses through different mechanisms, such as dosage compensation, imprinting, enhancer function, and transcriptional regulation. Although the functions of most lncRNAs are unclear, some lncRNAs have been found to control transcriptional or post-transcriptional regulation of the innate and adaptive immune responses via new methods of protein-protein interactions or pairing with DNA and RNA. Interestingly, increasing evidence has elucidated the importance of lncRNAs in the interaction between hosts and pathogens. In this review, an overview of the lncRNAs modes of action, as well as the important and diversified roles of lncRNAs in immunity, are provided, and an emerging paradigm of lncRNAs in regulating innate immune responses is highlighted. Cellular & Molecular Immunology
Output: Long noncoding RNAs in innate immunity
e review aims to examine the emergence and reemergence of infectious diseases in Jordan, in parallel with the Syrian refugee crisis. Qualitative approach has been adopted for systematically examining the outcomes of the Syrian crisis, which resulted in emerging and reemerging infectious diseases. It has adhered that infectious diseases, including measles, tuberculosis, and cutaneous leishmaniasis, have hazardous effects on Syrian refugees along with the local population in Jordan. e threat of major infectious diseases is higher and alarming in Jordan. National health policies should be implemented to adhere the influence of infectious diseases as well as to reduce the extent of infectious diseases in Jordan. In the 21st century, Syrian conflict can be deliberated as one of the biggest humanitarian disasters. In this multifaceted emergency with devastating requirements and limitations, it has been found essential for dominant medical healthcare providers to develop medical strategies that are based on comprehensive understanding of the concerned context and the main medical requirements and susceptible groups.
Output: A Review on Emerging and Reemerging of Infectious Diseases in Jordan: The Aftermath of the Syrian Crises
Infl uenza epidemics occur regularly and prediction of their conversion to pandemics and their impact is diffi cult. Coordination of efforts on a global scale to control or reduce the impact is fraught with potential for under and overreaction. In light of the 1956 pandemic and more recently the SARS and H1N1 pandemics, the public health community took steps toward strengthening global surveillance and a coordinated response in keeping with the continuing memory of the tragedy seen in 1918. The scientifi c, professional, and technical resources of the 21 st century are now advanced far beyond those then available. The H1N1 pandemic which commenced in 2009 progressed differently than predicted; its course was diffi cult to predict with any degree of certainty. Public responses to national immunization programs against the H1N1 virus have been weak. International movement of diseases can lead to creation of new endemic areas and continuous spread such as that which happened with West Nile Fever and Chikungunya. The lessons learned and the public and political responses to each actual or threatened pandemic will serve public health well in dealing with future challenges.
Output: Infl uenza pandemics: past, present and future challenges
Coronavirus mouse hepatitis virus (MVH)-A59 causes a persistent, productive infection in primary glial cell cultures . Microbial Pathogenesis 1987 ; 3 : 79-86 . MHV-A59 causes a chronic demyelinating disease in mice which is accompanied by persistence of viral genome in white matter . As part of the investigation into the mechanism of viral persistence, infection of glial cells, probable targets for chronic infection, was studied by the use of mixed glial, enriched oligodendrocyte and enriched astrocyte cultures . Following MHV-A59 infection in vitro, approximately 10% of oligodendrocytes and 30% of astrocytes expressed viral antigens in the absence of overt cytopathic effect . All cultures released infectious virus for the lifetime of the cultures, for at least 45 days in the case of mixed glial cultures . Cultures derived from previously infected mice were similar to those infected in vitro with respect to percentage of cells expressing viral antigen and levels of infectious virus produced . These results show (1) that glial cells are early sites of infection in vivo as well as sites of infection in in vitro cultures, and (2) that glial cells support a non-lytic but productive infection in vitro and thus may contribute to viral persistence in vivo .
Output: Coronavirus mouse hepatitis virus (MHV)-A59 causes a persistent, productive infection in primary glial cell cultures
The family flaviviridae and alphaviridae contain a diverse group of pathogens that cause significant morbidity and mortality worldwide. Diagnosis of the virus responsible for disease is essential to ensure patients receive appropriate clinical management. Very few real-time RT-PCR based assays are able to detect the presence of all members of these families using a single primer and probe set. We have developed a novel chemistry, 3base, which simplifies the viral nucleic acids allowing the design of RT-PCR assays capable of pan-family identification. Synthetic constructs, viral nucleic acids, intact viral particles and characterised reference materials were used to determine the specificity and sensitivity of the assays. Synthetic constructs demonstrated the sensitivities of the pan-flavivirus detection component were in the range of 13 copies per PCR. The pan-alphavirus assay had a sensitivity range of 10-25 copies per reaction depending on the viral strain. Lower limit of detection studies using whole virus particles demonstrated that sensitivity for assays was in the range of 1-2 copies per reaction. No cross reactivity was observed with a number of commonly encountered viral strains. Proficiency panels showed 100% concordance with the expected results and the assays performed as well as, if not better than, other assays used in laboratories worldwide. After initial assay validation the pan-viral assays were then tested during the 2016-2017 Vanuatu dengue-2 outbreak. Positive results were detected in 116 positives from a total of 187 suspected dengue samples.
Output: Validation of the easyscreen flavivirus dengue alphavirus detection kit based on 3base amplification technology and its application to the 2016/17 Vanuatu dengue outbreak
Viruses depend on their hosts to complete their replication cycles; they exploit cellular receptors for entry and hijack cellular functions to replicate their genome, assemble progeny virions and spread. Recently, genome-scale CRISPR-Cas screens have been used to identify host factors that are required for virus replication, including the replication of clinically relevant viruses such as Zika virus, West Nile virus, dengue virus and hepatitis C virus. In this Review, we discuss the technical aspects of genome-scale knockout screens using CRISPR-Cas technology, and we compare these screens with alternative genetic screening technologies. The relative ease of use and reproducibility of CRISPR-Cas make it a powerful tool for probing virus-host interactions and for identifying new antiviral targets.
Output: A CRISPR toolbox to study virus-host interactions HHS Public Access
The Middle East respiratory syndrome (MERS) is a new human disease caused by a novel coronavirus (CoV). The disease is reported mainly in adults. Data in children are scarce. The disease caused by MERS-CoV in children presents with a wide range of clinical manifestations, and it is associated with a lower mortality rate compared with adults. Poor outcome is observed mainly in admitted patients with medical comorbidities. We report a new case of MERS-CoV infection in a 9-month-old child complicated by severe respiratory symptoms, multi-organ dysfunction, and death. We reviewed the literature in an attempt to characterize the mode of presentation, the risk factors, and outcome of MERS-CoV infection in the pediatric population.
Output: Middle East respiratory syndrome coronavirus in children ‫اجلديدة‬ ‫البشرية‬ ‫األمراض‬ ‫من‬ ‫التنفسية‬ ‫األوسط‬ ‫الشرق‬ ‫متالزمة‬ ‫تعد‬ ‫الفيروس‬ ‫هذا‬ ‫انتشر‬ ‫ولقد‬ ‫اجلديد.‬ ‫كورونا‬ ‫فيروس‬ ‫بها‬ ‫تسبب‬ ‫التي‬ ‫املعلومات‬ ‫كانت‬ ‫حني‬ ‫في‬ ‫املنشورة،‬ ‫التقارير‬ ‫حسب‬ ‫البالغني‬ ‫بني‬ ً ‫غالبا‬ ‫فيروس‬ ‫يظهر‬ ‫اآلن.‬ ‫حتى‬ ‫نادرة‬ ‫األطفال‬ ‫بني‬ ‫الفيروس‬ ‫هذا‬ ‫عن‬ ‫املنشورة‬ ‫أنه‬ ‫كما‬ ‫السريرية،‬ ‫املظاهر‬ ‫من‬ ‫كبيرة‬ ‫مبجموعة‬ ‫األطفال‬ ‫بني‬ ‫كورونا‬ ‫البالغني.‬ ‫بني‬ ‫عنها‬ ‫اإلبالغ‬ ‫مت‬ ‫التي‬ ‫تلك‬ ‫من‬ ‫أقل‬ ‫وفيات‬ ‫مبعدل‬ ‫مرتبط‬ ‫من‬ ‫يعانون‬ ‫الذين‬ ‫املرضى‬ ‫بني‬ ‫السيئة‬ ‫املرض‬ ‫نتائج‬ ‫ُالحظ‬ ‫ت‬ ‫ما‬ ً ‫وغالبا‬ ‫من‬ ‫يبلغ‬ ‫طفل‬ ‫حالة‬ ‫املقال‬ ‫هذا‬ ‫في‬ ‫نستعرض‬ ‫أخرى.‬ ‫صحية‬ ‫مشاكل‬ ‫أعراض‬ ‫إلى‬ ‫باإلضافة‬ ‫كورونا،‬ ‫بفيروس‬ ‫صيب‬ ُ ‫أ‬ ‫وقد‬ ‫أشهر،‬ 9 ‫العمر‬ ‫بالبحث‬ ‫قمنا‬ ‫لقد‬ ‫املوت.‬ ‫ثم‬ ‫ومن‬ ‫متعدد‬ ‫عضوي‬ ‫وفشل‬ ‫حادة‬ ‫تنفسية‬ ‫التي‬ ‫السريرية‬ ‫املظاهر‬ ‫وصف‬ ‫محاولة‬ ‫في‬ ‫وذلك‬ ‫العلمي‬ ‫األدب‬ ‫في‬ ‫بهذا‬ ‫اإلصابة‬ ‫خطر‬ ‫من‬ ‫تزيد‬ ‫التي‬ ‫والعوامل‬ ‫املرضى،‬ ‫هؤالء‬ ‫بها‬ ‫يظهر‬ ‫األطفال.‬ ‫بني‬ ‫املرض‬ ‫هذا‬ ‫ملثل‬ ‫املتوقعة‬ ‫النتائج‬ ‫وكذلك‬ ‫الفيروس،‬ Case Report
Background: Respiratory infections are the leading cause of childhood deaths in Bangladesh. Promoting respiratory hygiene may reduce infection transmission. This formative research explored community perceptions about respiratory infections. Methods: We conducted 34 in-depth interviews and 16 focus group discussions with community members and school children to explore respiratory hygiene related perceptions, practices, and social norms in an urban and a rural setting. We conducted unstructured observations on respiratory hygiene practices in public markets. Results: Informants were not familiar with the term "respiratory infection"; most named diseases that had no relation to respiratory dysfunction. Informants reported that their community identified a number of 'good behaviors' related to respiratory hygiene, but they also noted, and we observed, that very few people practiced these. All informants cited hot/cold weather changes or using cold water as causes for catching cold. They associated transmission of respiratory infections with close contact with a sick person's breath, cough droplets, or spit; sharing a sick person's utensils and food. Informants suggested that avoiding such contact was the most effective method to prevent respiratory infection. Although informants perceived that handwashing after coughing or sneezing might prevent illness, they felt this was not typically feasible or practical. Conclusion: Community perceptions of respiratory infections include both concerns with imbalances between hot and cold, and with person-to-person transmission. Many people were aware of measures that could prevent respiratory infection, but did not practice them. Interventions that leverage community understanding of personto-person transmission and that encourage the practice of their identified 'good behaviors' related to respiratory hygiene may reduce respiratory disease transmission.
Output: Understanding community perceptions, social norms and current practice related to respiratory infection in Bangladesh during 2009: a qualitative formative study
There are virtually no antiviral drugs available for the treatment of infections with RNA viruses. This is particularly worrisome since most of the highly pathogenic and emerging viruses are, and will likely continue to be, RNA viruses. These viruses can cause acute, severe illness, including severe respiratory disease, hemorrhagic fever and encephalitis, with a high case fatality rate. It is important to have potent and safe drugs at hand that can be used for the treatment or prophylaxis of such infections. Drugs approved for the treatment of RNA virus infections (other than HIV) are the influenza M2 channel inhibitors, amantadine and rimantadine; the influenza neuraminidase inhibitors, oseltamivir and zanamivir, and ribavirin for the treatment of infections with respiratory syncytial virus and hepatitis C virus. The molecular mechanism(s) by which ribavirin inhibits viral replication, such as depletion of intracellular GTP pools and induction of error catastrophe, may not readily allow the design of analogues that are more potent/selective than the parent drug. Highly pathogenic RNA viruses belong to a variety of virus families, each having a particular replication strategy, thus offering a wealth of potential targets to selectively inhibit viral replication. We here provide a non-exhaustive review of potential experimental strategies, using small molecules, to inhibit the replication of several RNA viruses. Other approaches, such as the use of interferon or other host-response modifiers, immune serum or neutralizing antibodies, are not addressed in this review.
Output: Molecular strategies to inhibit the replication of RNA viruses
The spike glycoprotein is a major neutralizing antigen of bovine coronavirus (BCV). Conformational neutralizing epitopes of group A and group B monoclonal antibodies (MAbs) have previously been mapped to two domains at amino acids 351 to 403 (domain I) and amino acids 517 to 621 (domain II). To further map antigenic sites, neutralization escape mutants of BCV were selected with a group A MAb which has both in vitro and in vivo virus-neutralizing ability. The escape mutants were demonstrated to be neutralization resistant to the selecting group A MAb and remained sensitive to neutralization by a group B MAb. In radioimmunoprecipitation assays, the spike proteins of neutralization escape mutants were shown to have lost their reactivities with the selecting group A MAb. Sequence analysis of the spike protein genes of the escape mutants identified a single nucleotide substitution of C to T at position 1583, resulting in the change of alanine to valine at amino acid position 528 (A528V). The mutation occurs in domain II and in a location which corresponds to the hypervariable region of the spike protein of the coronavirus mouse hepatitis virus. Experimental introduction of the A528V mutation into the wild-type spike protein resulted in the loss of MAb binding of the mutant protein, confirming that the single point mutation was responsible for the escape of BCV from immunological selective pressure.
Output: A Single Amino Acid Change within Antigenic Domain II of the Spike Protein of Bovine Coronavirus Confers Resistance to Virus Neutralization
Background: In the healthy central nervous system (CNS), microglia are found in a homeostatic state and peripheral macrophages are absent from the brain. Microglia play key roles in maintaining CNS homeostasis and acting as first responders to infection and inflammation, and peripheral macrophages infiltrate the CNS during neuroinflammation. Due to their distinct origins and functions, discrimination between these cell populations is essential to the comprehension of neuroinflammatory disorders. Studies comparing the gene profiles of microglia and peripheral macrophages, or macrophages in vitro-derived from bone marrow, under non-infectious conditions of the CNS, have revealed valuable microglial-specific genes. However, studies comparing gene profiles between CNS-infiltrating macrophages and microglia, when both are isolated from the CNS during viral-induced neuroinflammation, are lacking. Methods: We isolated, via flow cytometry, microglia and infiltrating macrophages from the brains of Theiler's murine encephalomyelitis virus-infected C57BL/6 J mice and used RNA-Seq, followed by validation with qPCR, to examine the differential transcriptional profiles of these cells. We utilized primary literature defining subcellular localization to determine whether or not particular proteins extracted from the transcriptional profiles were expressed at the cell surface. The surface expression and cellular specificity of triggering receptor expressed on myeloid cells 1 (TREM-1) protein were examined via flow cytometry. We also examined the immune response gene profile within the transcriptional profiles of these isolated microglia and infiltrating macrophages. We have identified and validated new microglial-and macrophage-specific genes, encoding cell surface proteins, expressed at the peak of neuroinflammation. TREM-1 protein was confirmed to be expressed by infiltrating macrophages, not microglia, at the peak of neuroinflammation. We also identified both unique and redundant immune functions, through examination of the immune response gene profiles, of microglia and infiltrating macrophages during neurotropic viral infection. The differential expression of cell surface-specific genes during neuroinflammation can potentially be used to discriminate between microglia and macrophages as well as provide a resource that can be further utilized to target and manipulate specific cell responses during neuroinflammation.
Output: Differential transcriptional profiles identify microglial-and macrophage-specific gene markers expressed during virus-induced neuroinflammation
This review provides a comparison of the theoretical issues and experimental findings for plasmid DNA and mRNA vaccine technologies. While both have been under development since the 1990s, in recent years, significant excitement has turned to mRNA despite the licensure of several veterinary DNA vaccines. Both have required efforts to increase their potency either via manipulating the plasmid DNA and the mRNA directly or through the addition of adjuvants or immunomodulators as well as delivery systems and formulations. The greater inherent inflammatory nature of the mRNA vaccines is discussed for both its potential immunological utility for vaccines and for the potential toxicity. The status of the clinical trials of mRNA vaccines is described along with a comparison to DNA vaccines, specifically the immunogenicity of both licensed veterinary DNA vaccines and select DNA vaccine candidates in human clinical trials.
Output: A Comparison of Plasmid DNA and mRNA as Vaccine Technologies
Human papilloma virus (HPV) is the primary etiological agent responsible for cervical cancer in women. Although in total 16 high-risk HPV strains have been identified so far. Currently available commercial vaccines are designed by targeting mainly HPV16 and HPV18 viral strains as these are the most common strains associated with cervical cancer. Because of the high level of antigenic specificity of HPV capsid antigens, the currently available vaccines are not suitable to provide cross-protection from all other high-risk HPV strains. Due to increasing reports of cervical cancer cases from other HPV high-risk strains other than HPV16 and 18, it is crucial to design vaccine that generate reasonable CD8? T-cell responses for possibly all the high-risk strains. With this aim, we have developed a computational workflow to identify conserved cross-clade CD8? T-cell HPV vaccine candidates by considering E1, E2, E6 and E7 proteins from all the highrisk HPV strains. We have identified a set of 14 immunogenic conserved peptide fragments that are supposed to provide protection against infection from any of the high-risk HPV strains across globe.
Output: Sequence-based approach for rapid identification of cross-clade CD8+ T-cell vaccine candidates from all high-risk HPV strains
Colibacillosis results from infection with avian pathogenic Escherichia coli bacteria. Healthy broilers are resistant to inhaled E. coli, but previous infection with vaccine or virulent strains of Infectious Bronchitis Virus (IBV) predisposes birds for severe colibacillosis. We investigated whether IBV affects recruitment and function of phagocytic cells and examined NO production, phagocytic and bactericidal activity, and kinetics of peripheral blood mononuclear cells (PBMC) and splenocytes. Moreover, we measured cytokine mRNA expression in lung and spleen samples. Broilers were inoculated with IBV H120 vaccine or virulent M41 and challenged 5 days later with E. coli 506. A PBS control and E. coli group without previous virus inoculation were also included. Birds were sacrificed at various time points after inoculation (h/dpi). Inoculation with IBV induced extended and more severe colibacillosis than with E. coli alone. At 4 dpi, the number of KUL-01 + PBMC in all E. coli-inoculated groups was significantly higher than in PBS-inoculated birds, which correlated with lesion scores. From 1 to 4 dpi, NO production by PBMC from all E. coliinoculated animals was elevated compared to PBS birds. Bactericidal activity of PBMC in IBV-inoculated animals at 7 dpi was lower than in PBS-and E. coli-inoculated birds, but phagocytic capacity and recruitment were not severely impaired. In spleen samples of IBV-infected animals reduced expression of IL-1b, IL-6, IL-8, IL-10, IL-18 and IFN-g mRNA was found 1 dpi. Our results suggest that enhanced colibacillosis after IBV infection or vaccination is caused at least by altered innate immunity and less by impairment of phagocytic cell function. #
Output: The role of phagocytic cells in enhanced susceptibility of broilers to colibacillosis after Infectious Bronchitis Virus infection
To investigate whether the presence of infections in C57BL/6 mice influences the metastatic ability of B16 melanoma (B16M) cells, we compared the susceptibility to metastasis development of pathogen-free mice with that of mice from a colony endemically infected with several mouse pathogens. We found that, compared to seronegative controls, mice that were seropositive at least to Mouse Hepatitis Virus (MHV) and Mycoplasma pulmonis: (i) exhibited a higher interindividual variability in all the parameters quantifying metastatic progression; (ii) had elevated serum levels of proinflammatory cytokines both before and at the end of the experiment; (iii) were more susceptible to hepatic metastasis. Interestingly, final levels of tumor necrosis factor (TNF)-a and interleukin (IL)-18 correlated with the extent of hepatic colonization by the melanoma cells. To confirm the metastasis-enhancing effect of MHV and M. pulmonis we measured the ability of B16M cells to metastasize in pathogen-free animals housed for increasing time-intervals in the vicinity of MHV + animals. Notably, susceptibility to metastasis was lower in animals seronegative to MHV than in MHV + mice, whereas the latter were less susceptible to metastasis than MHV + M. pulmonis + mice. Seropositive animals had increased levels of TNF-a and IL-18 suggesting that MHV and M. pulmonis enhance the metastatic ability of melanoma cells by inducing the release of proinflammatory cytokines. While our results highlight the importance of using pathogen-free animals in metastasis studies, they emphasize the need for a comprehensive health monitoring of the mice used in such studies, particularly in case of using facilities lacking appropriate containment measures. Abbreviations: B16M -B16 melanoma; ELISA -enzyme-linked immunosorbent assay; IL-18 -interleukin-18; i.p.intraperitoneal; LPS -lipopolysaccharide; MHV -Mouse Hepatitis Virus; TNF-a -tumor necrosis factor a
Output: Effect of asymptomatic natural infections due to common mouse pathogens on the metastatic progression of B16 murine melanoma in C57BL/6 mice
Objectives: To explore the epidemiological and clinical factors predictive of the case fatality rate (CFR) of Middle East respiratory syndrome-coronavirus (MERS-CoV) infection in an outbreak in Daejeon, the Republic of Korea. Methods: We reviewed the outbreak investigation reports and medical records of 1 index case and 25 additional MERS cases in hospitals A (14 cases) and B (11 cases), and conducted an in-depth interview with the index case. Results: The CFR in hospital B was higher than that in hospital A (63.6% vs. 28.6%, respectively). Higher MERS-CoV exposure conditions were also found in hospital B, including aggravated pneumonia in the index case and nebulizer use in a six-bed admission room. The host factors associated with high CFR were pre-existing pneumonia, smoking history, an incubation period of less than 5 days, leukocytosis, abnormal renal function at diagnosis, and respiratory symptoms such as sputum and dyspnea. Conclusions: The conditions surrounding MERS-CoV exposure and the underlying poor pulmonary function due to a smoking history or pre-existing pneumonia may explain the high CFR in hospital B. The clinical features described above may enable prediction of the prognosis of MERS cases.
Output: High fatality rates and associated factors in two hospital outbreaks of MERS in Daejeon, the Republic of Korea
Despite a 60-year history of discovery, trial and evaluation of scores of different compounds, there are no currently licensed effective antivirals for the common cold. The history of the development and abandonment of all potential compounds so far teaches us some important lessons for the continuation of our fight against colds. First, the common cold is a benign self-limiting condition, making the consumption of 'harmless' antivirals a requisite of prime importance for regulators. Second, the common cold is a syndrome caused by a myriad of known and unknown agents, which reduces the effectiveness of compounds that interfere with single specific agents or types of agents. The multifactorial nature of the genesis of colds makes it difficult for compounds showing in vitro efficacy to 'make the jump' to field effectiveness. Last, despite the heavy burden that the cold imposes on society, the vagueness and shortness of symptoms make it difficult for sufferers to present in time for physicians to prescribe antivirals, which are only effective if taken within a short time frame. Attention should be paid to the development of compounds with a non-virus-specific action.
Output: Antivirals for the common cold
Thirty Holstein calves were obtained from 2 dairy farms in central Iowa at birth and randomly assigned to 1 of 6 treatment groups: (1) colostrum deprived (CD), no vitamins; (2) colostrum replacer (CR), no vitamins; (3) CR, vitamin A; (4) CR, vitamin D 3 ; (5) CR, vitamin E; and (6) CR, vitamins A, D 3 , E, with 5 calves per treatment in a 14-d study. Calves were fed pasteurized whole milk (CD) or fractionated colostrum replacer (CR) at birth (d 0) and injected with vitamins according to treatment group. From d 1 through d 14 of the study, all calves were fed pasteurized whole milk (PWM) supplemented with vitamins as assigned. All calves were inoculated with Mycobacterium avium ssp. paratuberculosis on d 1 and 3 of age. Calves fed CR acquired IgG 1 and haptoglobin in serum within 24 h of birth, whereas CD calves did not. The CR-fed calves were 2.5 times less likely to develop scours, and CR calves supplemented with vitamins D 3 and E also demonstrated a decreased incidence of scours. Serum vitamin levels of A, D, and E increased within treatment group by d 7 and 14 of the study. Interestingly, synergistic effects of supplemental vitamins A, D 3 , and E on serum 25-(OH)-vitamin D were observed at d 7, resulting in higher levels than in calves administered vitamin D only. Further, vitamin D 3 deficiency was observed in CD and CR calves fed a basal diet of pasteurized whole milk and no supplemental vitamins. Colonization of tissues with Mycobacterium avium ssp. paratuberculosis was negligible and was not affected by colostrum feeding or vitamin supplementation. Results demonstrated passive transfer of haptoglobin to neonatal calves, and potential health benefits of supplemental vitamins D 3 and E to calves fed pasteurized whole milk.
Output: COLOSTRUM AND VITAMINS IN CALF HEALTH 2885 2886 KRUEGER ET AL
As the development of information and communication technology (ICT) and the affirmation of the importance of healthcare, using wireless sensor networks (WSNs) is a promising approach to assist modern medical practices. The transmission optimization of HWSNs is an issue worth studying deeply, which is facing challenges such as data diversity, real-time requirement, reliable transmission, dynamic environment and so on. This paper considers four kinds of transmission cost comprehensively, and adopts the stochastic differential game theory to discuss this issue. With the objective of minimizing the transmission cost, three kinds of game models are constructed, i.e., cooperative model, partial cooperative model and non-cooperative model. The optimal transmission strategies under different game modes are obtained for HWSNs. The numerical simulation compares three strategies and verifies the validity of the method present in this paper.
Output: Optimal Data Transmission Strategy for Healthcare- Based Wireless Sensor Networks: A Stochastic Differential Game Approach
The high case-fatality rate of confirmed MERS-CoV infections underlines the urgent need for an effective treatment to reduce the disease severity and mortality. REGN3051 and REGN3048 are two fully human neutralizing monoclonal antibodies (mAb) against MERS-CoV that reduced virus replication in mice expressing human DPP4 upon prophylactic and therapeutic treatment. Here, we evaluated the prophylactic and therapeutic efficacy of REGN3048 and REGN3051 in the common marmoset model of MERS-CoV infection. Intravenous administration of mAb resulted in high levels of MERS-CoV-neutralizing activity in circulating blood. When animals were treated with mAbs one day before challenge, respiratory disease was less severe and, in animals treated with both REGN3048 and REGN3051, viral loads in the lungs were reduced. However, therapeutic treatment on day one after challenge was less efficacious as it did not prevent the development of severe respiratory disease and all treated animals developed bronchointerstitial pneumonia of similar severity as the control animals. Thus, mAb administration may be more effective in a prophylactic treatment regimen rather than treatment of MERS.
Output: Prophylactic and therapeutic efficacy of mAb treatment against MERS-CoV in common marmosets
It is well known that mucosal tissues contain the largest surface area of the human body and are the front line of natural host defense against various pathogens. In fact, more than 80% of infectious disease pathogens probably gain entry into the susceptible human hosts through open mucosal surfaces. Human immunodeficiency virus type one (HIV-1), a mainly sexually transmitted virus, also primarily targets the vaginal and gastrointestinal mucosa as entry sites for viral transmission, seeding, replication and amplification. Since HIV-1 establishes its early replication in vaginal or rectal mucosal tissues, the induction of sufficient mucosal immunity at the initial site of HIV-1 transmission becomes essential for a protective vaccine. However, despite the fact that current conventional vaccine strategies have remained unsuccessful in preventing HIV-1 infection, sufficient financial support and resources have yet to be given to develop a vaccine able to elicit protective mucosal immunity against sexual transmissions. Interestingly, Chinese ancestors invented variolation through intranasal administration about one thousand years ago, which led to the discovery of a successful smallpox vaccine and the final eradication of the disease. It is the hope for all mankind that the development of a mucosal AIDS vaccine will ultimately help control the AIDS pandemic. In order to discover an effective mucosal AIDS vaccine, it is necessary to have a deep understanding of mucosal immunology and to test various mucosal vaccination strategies. Viruses 2010, 2 284
Output: The Development of an AIDS Mucosal Vaccine
H5N1 highly pathogenic avian influenza (HPAI) viruses have seriously affected the Asian poultry industry since their recurrence in 2003. The viruses pose a threat of emergence of a global pandemic influenza through point mutation or reassortment leading to a strain that can effectively transmit among humans. In this study, we present phylogenetic evidences for the interlineage reassortment among H5N1 HPAI viruses isolated from humans, cats, and birds in Indonesia, and identify the potential genetic parents of the reassorted genome segments. Parsimony analyses of viral phylogeography suggest that the reassortant viruses may have originated from greater Jakarta and surroundings, and subsequently spread to other regions in the West Java province. In addition, Bayesian methods were used to elucidate the genetic diversity dynamics of the reassortant strain and one of its genetic parents, which revealed a more rapid initial growth of genetic diversity in the reassortant viruses relative to their genetic parent. These results demonstrate that interlineage exchange of genetic information may play a pivotal role in determining viral genetic diversity in a focal population. Moreover, our study also revealed significantly stronger diversifying selection on the M1 and PB2 genes in the lineages preceding and subsequent to the emergence of the reassortant viruses, respectively. We discuss how the corresponding mutations might drive the adaptation and onward transmission of the newly formed reassortant viruses.
Output: Evolutionary and Transmission Dynamics of Reassortant H5N1 Influenza Virus in Indonesia
Background: Garcinia species contain bioactive compounds such as flavonoids, xanthones, triterpernoids, and benzophenones with antibacterial, antifungal, anti-inflammatory, and antioxidant activities. In addition, many of these compounds show interesting biological properties such as anti-human immunodeficiency virus activity. Garcinia parvifolia is used in traditional medicine. Currently, the antiviral activity of G. parvifolia is not known. Methods: This study was conducted to determine the effects of ethyl acetate (45 L Ea), ethanol (45 L Et), and hexane (45 L H) leaf extracts of G. parvifolia on the infectivity of pseudorabies virus (PrV) in Vero cells. The antiviral effects of the extracts were determined by cytopathic effect (CPE), inhibition, attachment, and virucidal assays. Results: The 50% cytotoxicity concentration (CC 50 ) values obtained were 237.5, 555.0, and < 1.25 μg/mL for 45 L Ea, 45 L Et, and 45 L H, respectively. The 45 L Ea showed the greatest viral inhibition potency of 75% at 125 μg/mL. Both 45 L Ea and 45 l Et caused 100% residual viral inhibition at 250 μg/mL. The selectivity index values for 45 L Ea, 45 L Et, and 45 L H were 2.65, 1.75, and 0.10 showing that 45 L Ea had the greatest antiviral activity among the three extracts. Conclusion: This study showed that ethyl acetate is the best solvent to be used to obtain extract from G. parvifolia leaves with potent antiviral activities.
Output: Virucidal activity of Garcinia parvifolia leaf extracts in animal cell culture
Post-translational modification of proteins and peptides by ubiquitin, a highly evolutionarily conserved 76 residue protein, and ubiquitin-like modifiers has emerged as a major regulatory mechanism in various cellular activities. Eukaryotic viruses are known to modulate protein ubiquitination to their advantage in various ways. At the same time, the evidence for the importance of deubiquitination as a viral target also is growing. This review centers on known viral interactions with protein deubiquitination, on viral enzymes for which deubiquitinating activities were recently demonstrated, and on the roles of viral ubiquitin-like sequences. Crown
Output: Minireview Deubiquitination in virus infection
Human populations worldwide are increasingly confronted with infectious diseases and antimicrobial resistance spreading faster and appearing more frequently. Knowledge regarding their occurrence and worldwide transmission is important to control outbreaks and prevent epidemics. Here, we performed shotgun sequencing of toilet waste from 18 international airplanes arriving in Copenhagen, Denmark, from nine cities in three world regions. An average of 18.6 Gb (14.8 to 25.7 Gb) of raw Illumina paired end sequence data was generated, cleaned, trimmed and mapped against reference sequence databases for bacteria and antimicrobial resistance genes. An average of 106,839 (0.06%) reads were assigned to resistance genes with genes encoding resistance to tetracycline, macrolide and beta-lactam resistance genes as the most abundant in all samples. We found significantly higher abundance and diversity of genes encoding antimicrobial resistance, including critical important resistance (e.g. bla CTX-M ) carried on airplanes from South Asia compared to North America. Presence of Salmonella enterica and norovirus were also detected in higher amounts from South Asia, whereas Clostridium difficile was most abundant in samples from North America. Our study provides a first step towards a potential novel strategy for global surveillance enabling simultaneous detection of multiple human health threatening genetic elements, infectious agents and resistance genes. Globally, infectious diseases are the cause of about 22% of all human deaths 1 . Due to increasing population density, increasing use of antimicrobial agents, disruption of wildlife habitats, and an increase in global travel and trade this number has been estimated to increase in coming years 2,3 . Rapid global surveillance systems for early detection of worldwide spread of zoonotic and human pathogens would enable outbreak control and epidemic prevention 4,5 . In addition to the direct severe consequences for human health, infectious diseases may cause an increased financial burden on health systems and may imply restriction on travel, trade, etc. Global spread of antimicrobial resistance in bacterial pathogens is another major threat against human health, yet we don't know much about how these genes travel and spread worldwide 6 . Current international disease surveillance system is mainly based on reports made by doctors after treatment of infected patients 7 . It has been attempted to establish regional and global networks, for the
Output: Meta-genomic analysis of toilet waste from long distance flights; a step towards global surveillance of infectious diseases and antimicrobial resistance OPEN
† Background Metallopeptidases of the M1 family are found in all phyla (except viruses) and are important in the cell cycle and normal growth and development. M1s often have spatiotemporal expression patterns which allow for strict regulation of activity. Mutations in the genes encoding M1s result in disease and are often lethal. This family of zinc metallopeptidases all share the catalytic region containing a signature amino acid exopeptidase (GXMXN) and a zinc binding (HEXXH[18X]E) motif. In addition, M1 aminopeptidases often also contain additional membrane association and/or protein interaction motifs. These protein interaction domains may function independently of M1 enzymatic activity and can contribute to multifunctionality of the proteins. † Scope A brief review of M1 metalloproteases in plants and animals and their roles in the cell cycle is presented. In animals, human puromycin-sensitive aminopeptidase (PSA) acts during mitosis and perhaps meiosis, while the insect homologue puromycin-sensitive aminopeptidase (PAM-1) is required for meiotic and mitotic exit; the remaining human M1 family members appear to play a direct or indirect role in mitosis/cell proliferation. In plants, meiotic prophase aminopeptidase 1 (MPA1) is essential for the first steps in meiosis, and aminopeptidase M1 (APM1) appears to be important in mitosis and cell division. † Conclusions M1 metalloprotease activity in the cell cycle is conserved across phyla. The activities of the multifunctional M1s, processing small peptides and peptide hormones and contributing to protein trafficking and signal transduction processes, either directly or indirectly impact on the cell cycle. Identification of peptide substrates and interacting protein partners is required to understand M1 function in fertility and normal growth and development in plants.
Output: REVIEW: PART OF A SPECIAL ISSUE ON THE PLANT CELL CYCLE The role of multifunctional M1 metallopeptidases in cell cycle progression