niryuu/sni-each-converted huggingface dataset:
or Actinomycin D (5nM) resulted in significantly decreased IE and pp65 mRNA and protein levels in human fibroblasts at early times post infection. This initially delayed replication was compensated for later during the replication process, at which stage it didn't significantly affect virus production. Pol I inhibition also reduced HSV-1 ICP0 and gB transcripts, suggesting that some herpesviruses engage Pol I for their early transcription. In contrast, inhibition of Pol I failed to affect MCMV transcription. Collectively, our results contribute to better understanding of the functional interplay between RNA Pol I-mediated nucleolar events and the Herpes viruses, particularly HCMV whose pathogenic impact ranges from congenital malformations and potentially deadly infections among immunosuppressed patients, up to HCMV's emerging oncomodulatory role in human tumors.
Output: Human cytomegalovirus and Herpes Simplex type I virus can engage RNA polymerase I for transcription of immediate early genes
The role of rhinovirus asymptomatic infections in the transmission among close contacts subjects is unknown. We tested health care workers, a pair of one child and a family member and immunocompromised patients (n =191). HRV were detected on 22.9% symptomatic and 3.6% asymptomatic cases suggesting lower transmission among contacts. Rhinovirus infections are among the most frequent causes of the common colds (18). It is the most common etiology of viral respiratory infections among diverse populations, including adults, children and more recent studies have linked HRVs to more severe lower respiratory illnesses in otherwise healthy young children (11-12), immunocompromised (4,6), and elderly patients. (5,13, 23). In Brazil, there are few HRV studies, Arruda et.al. (1991), realized the first Brazilian study detecting a 45.5% rate on symptomatic children in Fortaleza -CE. Another study realized in Salvador -BA also showed a high prevalence (48.5%) (Souza ,2003). The only study
Output: HUMAN RHINOVIRUS INFECTIONS IN SYMPTOMATIC AND ASYMPTOMATIC SUBJECTS
Since 1999 we have developed two computational mutation approaches to analyze the protein primary structure whose methodology and implications were reviewed in 2002. Our first approach is the calculation of predictable and unpredictable portions of amino-acid pairs in a protein, and the second is the calculation of amino-acid distribution rank in a protein. Both approaches provide quantitative measures to present a protein, which we have used to study a number of proteins with numerous mutations such as p53 proteins. More recently, we focussed our efforts on analyzing the proteins mutating frequently over time such as hemagglutinins of influenza A viruses. In this review we summarise our findings and their implications for hemagglutinin mutations in combination with some newly available data. Our approaches throw light on the true nature of genetic heterogeneity of influenza virus hemagglutinins; that is, the protein variability is highly relevant to its amino-acid construction. Using these approaches, we can monitor new mutations from influenza virus hemagglutinins and may predict their mutations in the future.
Output: Mutation trend of hemagglutinin of influenza A virus: a review from a computational mutation viewpoint
In this second part of the chapter on underutilized spices, nine spices are discussed briefl y. They are mango ginger, fragrant pandan, pink pepper, rue, sumac, savory and wasabi. Morphology, chemical composition, medicinal and culinary uses are given briefl y in each of these spices. In addition short notes on 12 lesser known spices are provided; these are blue fenugreek, boldo leaves, chameleon plant, cicely, cresses, epazote, fi nger root, gale, lemon myrtle, Mexican pepper leaf, Tasmanian pepper and water pepper.
Output: Other herbs and spices: mango ginger to wasabi
G-quadruplexes (G4s) are secondary structures of nucleic acids that epigenetically regulate cellular processes. In the human immunodeficiency lentivirus 1 (HIV-1), dynamic G4s are located in the unique viral LTR promoter. Folding of HIV-1 LTR G4s inhibits viral transcription; stabilization by G4 ligands intensifies this effect. Cellular proteins modulate viral transcription by inducing/unfolding LTR G4s. We here expanded our investigation on the presence of LTR G4s to all lentiviruses. G4s in the 5′-LTR U3 region were completely conserved in primate lentiviruses. A G4 was also present in a cattleinfecting lentivirus. All other non-primate lentiviruses displayed hints of less stable G4s. In primate lentiviruses, the possibility to fold into G4s was highly conserved among strains. LTR G4 sequences were very similar among phylogenetically related primate viruses, while they increasingly differed in viruses that diverged early from a common ancestor. A strong correlation between primate lentivirus LTR G4s and Sp1/NFκB binding sites was found. All LTR G4s folded: their complexity was assessed by polymerase stop assay. Our data support a role of the lentiviruses 5′-LTR G4 region as control centre of viral transcription, where folding/unfolding of G4s and multiple recruitment of factors based on both sequence and structure may take place.
Output: Conserved presence of G-quadruplex forming sequences in the Long Terminal Repeat Promoter of Lentiviruses
Background: Bronchiolitis is a common lower respiratory tract infection in infancy. The aim of this review is to present the clinical profi le of viral bronchiolitis, the different culprit viruses and the disease severity in relation to the viral etiology. Data sources: Databases including PubMed and Google Scholar were searched for articles about the clinical features of bronchiolitis and its viral etiology. The most relevant articles to the scope of this review were analyzed. Results: Currently there are two main definitions for bronchiolitis which are not identical, the European definition and the American one. The most common viral pathogen that causes bronchiolitis is respiratory syncytial virus which was identified in 1955; now many other viruses have been implicated in the etiology of bronchiolitis such as rhinovirus, adenovirus, metapneumovirus, and bocavirus. Several studies have attempted to investigate the correlation of bronchiolitis severity with the type of detected virus or viruses. However, the results were not consitent. Conclusions: For the time being, the diagnosis of bronchiolitis remains clinical. The isolation of the responsible respiratory pathogens does not seem to confer to the prognosis of the disease severity. World J Pediatr 2017;13(4):293-299
Output: Viral bronchiolitis in infancy Etiology and clinical features of viral bronchiolitis in infancy
The effects of cyclosporin A (CsA) on neuropathological lesions induced by a chronic viral infection have been tested in the experimental model of the mouse hepatitis virus 3 (MHV3) infection. Daily injections of CsA (50 mg/kg) inhibited the expression of the MHV3-induced ependymitis, meningitis. hydrocephalus and vasculitis, The effect was preserved even if CsA treatment was initiated 15 days after virus infection but was lost if CsA treatment was given later on or for a shorter period of time. Viral titers in brains of chronically infected mice were not affected by CsA treatment. During the first week following MHV3 infection, CsA treatment increased both the percentage of acute death (31 vs. 10%) and the viral titers in brain and liver of infected mice. In this model, the timing of CsA treatment appeared critical for the balance between its beneficial effect on CNS lesions and the risk of increased acute mortality.
Output: Effect of cyclosporin A on an experimental chronic viral infection of the central nervous system
Vaccination is the most effective strategy for prevention and control of influenza. Timely production and deployment of seasonal influenza vaccines is based on an understanding of the epidemiology of influenza and on global disease and virologic surveillance. Experience with seasonal influenza vaccines guided the initial development of pandemic influenza vaccines. A large investment in pandemic influenza vaccines in the last decade has resulted in much progress and a body of information that can now be applied to refine the established paradigm. Critical and complementary considerations for pandemic influenza vaccines include improved assessment of the pandemic potential of animal influenza viruses, proactive development and deployment of pandemic influenza vaccines, and application of novel platforms and strategies for vaccine production and administration.
Output: Refining the approach to vaccines against influenza A viruses with pandemic potential
Van Zaane, D., IJzerman, 3. and De Leeuw, P.W., 1986. Intestinal antibody response after vaccination and infection with rotavirus of calves fed colostrum with or without rotavirus antibody. Vet. Immunol. Immunopathol., 11:45-63. The intestinal and systemic antibody response of cah'es vaccinated and/or challenged with rotavirus was studied employing isotype-specific ELISAs for the detection of IgG1, IgG2, IgM and IgA antibodies to rotavirus. Monoclonal antibodies to bovine immunoglobulin isotypes of proven specificity were used as conjugated or catching antibody. Five days after oral inoculation (dpi) of a 5-day-old gnotobiotic calf with rotavirus, IgM rotavirus antibodies were excreted in faeces, followed 5 days later by IgA rotavirus antibodies. The increase in IgM rotavirus antibody titre coincided with the inability to detect further rotavirus excretion. Faeces IgM and IgA rotavirus antibody titres fell to low levels within 3 weeks post infection. IgG 1 and IgG 2 rotavirus antibodies were not detected in faecal samples. In serum, antibodies to rotavirus of all four isotypes were detected, starting with IgM at 5 dpi. Two SPF-calves, which were fed colostrum free of rotavirus antibodies, were vaccinated with a modified live rotavirus vaccine and challenged with virulent rotavirus 6 days later. Upon vaccination, the cah'es showed an antibody response similar to the response of the infected gnotobiotic calf. Intestinal IgM rotavirus antibodies were excreted before or on the day of challenge and appeared to be associated with protection against challenge infection with virulent virus and rotavirus-induced diarrhoea. In 3 control calves, which were challenged only, the antibody patterns also resembled that of the gnotobiotic calf and again the appearance of IgM rotavirus antibodies coincided with the end of the rotavirus detection period. Two other groups of :3 SPF-calves were treated similarly, but the calves were fed co]ostrum with rotavirus antibodies during the first 48 h of life. These calves excreted passively acquired IgG 1 and IgG 2 rotavirus antibodies in their faeces from 2 to 6 days after birth. After vaccination, no IgM or IgA antibody activity in serum or faeces was detectable. Upon challenge, all calves developed diarrhoea and excreted rotavirus. Seven to 10 days after challenge low levels of IgM rotavirus antibody were detected for a short period. These data indicate that the intestinal antibody response of young calves to an enteric viral infection is associated with the excretion of IgM antibodies, immediately followed by IgA antibodies. This response is absent or diminished in ealves with passively acquired specific antibodies which may explain the failure to induce a protective intestinal immune response by oral vaccination with modified live rotavirus of calves fed co]ostrum containing rotavirus antibodies.
Output: INTESTINAL ANTIBODY RESPONSE AFTER VACCINATION AND INFECTION WITH ROTAVIRUS OF CALVES FED COLOSTRUM WITH OR WITHOUT ROTAVIRUS ANTIBODY
Coronaviruses infect animals and humans causing a wide range of diseases. The diversity of coronaviruses in many mammalian species is contributed by relatively high mutation and recombination rates during replication. This dynamic nature of coronaviruses may facilitate cross-species transmission and shifts in tissue or cell tropism in a host, resulting in substantial change in virulence. Feline enteric coronavirus (FECV) causes inapparent or mild enteritis in cats, but a highly fatal disease, called feline infectious peritonitis (FIP), can arise through mutation of FECV to FIP virus (FIPV). The pathogenesis of FIP is intimately associated with immune responses and involves depletion of T cells, features shared by some other coronaviruses like Severe Acute Respiratory Syndrome Coronavirus. The increasing risks of highly virulent coronavirus infections in humans or animals call for effective antiviral drugs, but no such measures are yet available. Previously, we have reported the inhibitors that target 3C-like protease (3CLpro) with broad-spectrum activity against important human and animal coronaviruses. Here, we evaluated the therapeutic efficacy of our 3CLpro inhibitor in laboratory cats with FIP. Experimental FIP is 100% fatal once certain clinical and laboratory signs become apparent. We found that antiviral treatment led to full recovery of cats when treatment was started at a stage of disease that would be otherwise fatal if left untreated. Antiviral treatment was associated with a rapid improvement in fever, ascites, lymphopenia and gross signs of illness and cats returned to normal health within 20 days or less of treatment. Significant reduction in viral titers was also observed in cats. These results indicate that continuous virus replication is required for progression of immune-mediated inflammatory disease of FIP. These findings may provide important insights into devising therapeutic strategies and selection of antiviral compounds for further development for important coronaviruses in animals and humans.
Output: Reversal of the Progression of Fatal Coronavirus Infection in Cats by a Broad- Spectrum Coronavirus Protease Inhibitor
Background: Enteric outbreaks associated with child care centres (CCC) have been well documented internationally and in Canada. The current literature focuses on identifying potential risk factors for introduction and transmission of enteric disease, but does not examine why these risk factors happen, how the risk is understood and managed by the staff of CCCs, or what challenges they experience responding to enteric illness. The purpose of this study was to explore the understanding, knowledge and actions of CCC staff regarding enteric illness and outbreaks, and to identify challenges that staff encounter while managing them. Methods: Focus groups were conducted with staff of regulated CCCs in Southern Ontario. Five focus groups were held with 40 participants. An open ended style of interviewing was used. Data were analyzed using content analysis. Results: CCC staff play an important role in preventing and managing enteric illness. Staff used indepth knowledge of the children, the centre and their personal experiences to assist in making decisions related to enteric illness. The decisions and actions may differ from guidance provided by public health officials, particularly when faced with challenges related to time, money, staffing and parents. Conclusion: CCC staff relied on experience and judgment in coordination with public health information to assist decision-making in the management of enteric illness and outbreaks. Advice and guidance from public health officials to CCC staff needs to be consistent yet flexible so that it may be adapted in a variety of situations and meet regulatory and public health requirements. Research states that early childhood education and care is important for healthy child development [1] , and public health can be a primary partner and supporter in the delivery of early childhood programs in the community [2].
Output: BMC Public Health Gatekeepers of health: A qualitative assessment of child care centre staff's perspectives, practices and challenges to enteric illness prevention and management in child care centres
The analysis of T cell receptor diversity provides a clinically relevant and sensitive marker of repertoire loss, gain, or skewing. Spectratyping is a broadly utilized technique to measure global TCR diversity by the analysis of the lengths of CDR3 fragments in each Vβ family. However the common use of large numbers of T cells to obtain a global view of TCR Vβ CDR3 diversity has restricted spectratyping analyses when limited T-cell numbers are available in clinical setting, such as following transplant regimens. We here demonstrate that one hundred thousand T cells are sufficient to obtain a robust, highly reproducible measure of the global TCR Vβ repertoire diversity among twenty Vβ families in human peripheral blood. We also show that use of lower cell number results not in a dwindling of observed diversity but rather in non-reproducible patterns in replicate spectratypes. Finally, we report here a simple to use but sensitive method to quantify repertoire divergence in patient samples by comparison to a standard repertoire profile we generated from fifteen normal donors. We provide examples using this method to statistically evaluate the changes in the global TCR Vβ repertoire diversity that may take place during T subset immune reconstitution after hematopoietic stem cell transplantation or after immune modulating therapies. TCR Vβ CDR3 repertoire diversity in human peripheral blood; spectratype; immune reconstitution; hematopoietic stem cell transplantation Corresponding author: Sarfraz A. Memon, M.D., Experimental Transplantation and Immunology Branch,
Output: Quantitative Analysis of T Cell Receptor Diversity in Clinical Samples of Human Peripheral Blood
Life-threatening RNA viruses emerge regularly, and often in an unpredictable manner. Yet, the very few drugs available against known RNA viruses have sometimes required decades of research for development. Can we generate preparedness for outbreaks of the, as yet, unknown viruses? The VIZIER (VIral enZymes InvolvEd in Replication) (http://www.vizier-europe.org/) project has been set-up to develop the scientific foundations for countering this challenge to society. VIZIER studies the most conserved viral enzymes (that of the replication machinery, or replicases) that selected list of viruses in order to comprehensively cover the diversity of the RNA virus universe, and generate critical knowledge that could be efficiently utilized to jump-start research on any emerging RNA virus. VIZIER is a multidisciplinary project involving (i) bioinformatics to define functional domains, (ii) viral genomics to increase the number of characterized viral genomes and prepare defined targets, (iii) proteomics to express, purify, and characterize targets, (iv) structural biology to solve their crystal structures, and (v) pre-lead discovery to propose active scaffolds of antiviral molecules.
Output: The VIZIER project: Preparedness against pathogenic RNA viruses
In spite of significant advancements and success in antiretroviral therapies directed against HIV infection, there is no cure for HIV, which scan persist in a human body in its latent form and become reactivated under favorable conditions. Therefore, novel antiretroviral drugs with different modes of actions are still a major focus for researchers. In particular, novel lead structures are being sought from natural sources. So far, a number of compounds from marine organisms have been identified as promising therapeutics for HIV infection. Therefore, in this paper, we provide an overview of marine natural products that were first identified in the period between 2013 and 2018 that could be potentially used, or further optimized, as novel antiretroviral agents. This pipeline includes the systematization of antiretroviral activities for several categories of marine structures including chitosan and its derivatives, sulfated polysaccharides, lectins, bromotyrosine derivatives, peptides, alkaloids, diterpenes, phlorotannins, and xanthones as well as adjuvants to the HAART therapy such as fish oil. We critically discuss the structures and activities of the most promising new marine anti-HIV compounds.
Output: molecules Novel Antiretroviral Structures from Marine Organisms
Background: Although primary health care, and in particular, general practice will be at the frontline in the response to pandemic influenza, there are no frameworks to guide systematic planning for this task or to appraise available plans for their relevance to general practice. We aimed to develop a framework that will facilitate planning for general practice, and used it to appraise pandemic plans from Australia, England, USA, New Zealand and Canada. Methodology/Principal Findings: We adapted the Haddon matrix to develop the framework, populating its cells through a multi-method study that incorporated the peer-reviewed and grey literature, interviews with general practitioners, practice nurses and senior decision-makers, and desktop simulation exercises. We used the framework to analyse 89 publiclyavailable jurisdictional plans at similar managerial levels in the five countries. The framework identifies four functional domains: clinical care for influenza and other needs, public health responsibilities, the internal environment and the macroenvironment of general practice. No plan addressed all four domains. Most plans either ignored or were sketchy about noninfluenza clinical needs, and about the contribution of general practice to public health beyond surveillance. Collaborations between general practices were addressed in few plans, and inter-relationships with the broader health system, even less frequently. Conclusions: This is the first study to provide a framework to guide general practice planning for pandemic influenza. The framework helped identify critical shortcomings in available plans. Engaging general practice effectively in planning is challenging, particularly where governance structures for primary health care are weak. We identify implications for practice and for research.
Output: General Practice and Pandemic Influenza: A Framework for Planning and Comparison of Plans in Five Countries
LETTERS that the quantitative assessment of the effectiveness of public health intervention measures for SARS is a difficult task for modelers. To make models useful for assessing the effects of specific intervention measures and for predicting the future dynamics during an ongoing epidemic, we need improved knowledge on the transmission mechanisms, pathogenesis, and the epidemiologic determinants of the spread of the virus. Any retrospective analysis of the 2003 SARS epidemic that improves our knowledge of SARS epidemiology is welcome.
Output: SARS epi-demiology and cumulative case curve
The World Health Organisation has declared a pandemic caused by the newly discovered SARS-CoV-2. Due to growing demand for reagents used for SARS-CoV-2 RNA extraction for subsequent molecular diagnostics, there is a worldwide risk of kit-and/or reagent-shortages for extraction. With a detection sensitivity of 97.4% (95% CI=86.2-99.9%), we describe a simple, fast, alternative workflow for molecular detection of SARS-CoV-2, where samples are simply heat-processed for 5 minutes at 98˚C prior to the RT-qPCR reaction.
Output: Title: An alternative workflow for molecular detection of SARS-CoV-2 -escape from the NA
Understanding transcription factor (TF) mediated control of gene expression remains a major challenge at the interface of computational and experimental biology. Computational techniques predicting TF-binding site specificity are frequently unreliable. On the other hand, comprehensive experimental validation is difficult and time consuming. We introduce a simple strategy that dramatically improves robustness and accuracy of computational binding site prediction. First, we evaluate the rate of recurrence of computational TFBS predictions by commonly used sampling procedures. We find that the vast majority of results are biologically meaningless. However clustering results based on nucleotide position improves predictive power. Additionally, we find that positional clustering increases robustness to long or imperfectly selected input sequences. Positional clustering can also be used as a mechanism to integrate results from multiple sampling approaches for improvements in accuracy over each one alone. Finally, we predict and validate regulatory sequences partially responsible for transcriptional control of the mammalian type A g-aminobutyric acid receptor (GABA A R) subunit genes. Positional clustering is useful for improving computational binding site predictions, with potential application to improving our understanding of mammalian gene expression. In particular, predicted regulatory mechanisms in the mammalian GABA A R subunit gene family may open new avenues of research towards understanding this pharmacologically important neurotransmitter receptor system.
Output: Positional clustering improves computational binding site detection and identifies novel cis-regulatory sites in mammalian GABA A receptor subunit genes
Severe acute respiratory syndrome (SARS) is a significant emerging infectious disease. Humans infected with the etiological agent, SARS-associated coronavirus (SARS-CoV), primarily present with pneumonitis but may also develop hepatic, gastrointestinal, and renal pathology. We inoculated common marmosets (Callithrix jacchus) with the objective of developing a small nonhuman primate model of SARS. Two groups of C. jacchus were inoculated intratracheally with cell culture supernatant containing SARS-CoV. In a time course pathogenesis study, animals were evaluated at 2, 4, and 7 days after infection for morphological changes and evidence of viral replication. All animals developed a multifocal mononuclear cell interstitial pneumonitis, accompanied by multinucleated syncytial cells, edema, and bronchiolitis in most animals. Viral antigen localized primarily to infected alveolar macrophages and type-1 pneumocytes by immunohistochemistry. Viral RNA was detected in all animals from pulmonary tissue extracts obtained at necropsy. Viral RNA was also detected in tracheobronchial lymph node and myocardium, together with inflammatory changes, in some animals. Hepatic inflammation was observed in most animals, predominantly as a multifocal lymphocytic hepatitis accompanied by necrosis of individual hepatocytes. These findings identify the common marmoset as a promising nonhuman primate to study SARS-CoV pathogenesis. (Am J Pathol 2005, 167:455-463) 
Output: Immunopathology and Infectious Disease Pneumonitis and Multi-Organ System Disease in Common Marmosets (Callithrix jacchus) Infected with the Severe Acute Respiratory Syndrome-Associated Coronavirus
Findings by other authors indicate that exposure to chemical emissions from indoor paint is related to asthma symptoms in adults. In their first years of life children are receptive to obstructive airway diseases. The aim of this study was to investigate the influence of redecoration of the apartment on airway symptoms in infants during the first two years of life. The Leipzig Allergy Risk Children Study (LARS) is a birth cohort study with the following inclusion criteria: double positive family atopy anamnesis, cord blood IgE > 0.9 kU/l, or low birth weight between 1500 ± 2500 g. Within the context of LARS, 186 parents of risk children completed a questionnaire on the respiratory symptoms of their children and the redecoration of their apartment at the end of the first and second year of life. A total 22% of the children suffered from obstructive bronchitis once or more during their first year, and 11% experienced this condition during their second year of life. Redecoration of the apartment had a significant influence on the appearance of obstructive bronchitis in the first (OR 4.1 95%CI 1.4 ± 11.9) and in the second year of life (OR 4.2 95%CI 1.4 ± 12.9). (The OR are adjusted for cord blood-IgE > 0.9 kU/l, birth weight 2500 g, male sex and double positive parental atopy anamnesis, dampness, smoking or pet in the apartment). Simultaneous contamination from redecoration activities and additional exposures such as smoking, a pet or dampness in the apartment increased the risk for obstructive bronchitis in the first year (OR 9.1; 95% CI 2.3 ± 34.8) as well as in the second year (OR 5.1; 95%CI 1.6 ± 15.6). Our data suggest that redecoration of the apartment is associated with the development of acute inflammations, but not with a chronic influence on the airways in atopy risk infants. At an exposure to more than one environmental factor, pronounced effects were seen.
Output: International Journal of Hygiene and Environmental Health Redecoration of apartments promotes obstructive bronchitis in atopy risk infants ± Results of the LARS study
Copy Number Variations (CNVs) of regions of the human genome have been associated with multiple diseases. We present an algorithm which is mathematically sound and computationally efficient to accurately analyze CNV in a DNA sample utilizing a nanofluidic device, known as the digital array. This numerical algorithm is utilized to compute copy number variation and the associated statistical confidence interval and is based on results from probability theory and statistics. We also provide formulas which can be used as close approximations.
Output: Mathematical Analysis of Copy Number Variation in a DNA Sample Using Digital PCR on a Nanofluidic Device
Most emerging human infectious diseases have an animal origin. Yet, while zoonotic diseases originate from a primary reservoir, most theoretical studies have principally focused on single-host processes, either exclusively humans or exclusively animals, without considering the importance of animal to human transmission for understanding the dynamics of emerging infectious diseases. Here we aim to investigate the importance of spillover transmission for explaining the number and the size of outbreaks. We propose a simple stochastic Susceptible-Infected-Recovered model with a recurrent infection of an incidental host from a reservoir (e.g. humans by a zoonotic species), considering two
Output: Stochastic dynamics of an epidemics with recurrent spillovers from an endemic reservoir
Echinacea is one of the most commonly used herbal products, but controversy exists about its benefi t in the prevention and treatment of the common cold. Thus, we did a meta-analysis evaluating the eff ect of echinacea on the incidence and duration of the common cold. 14 unique studies were included in the meta-analysis. Incidence of the common cold was reported as an odds ratio (OR) with 95% CI, and duration of the common cold was reported as the weighted mean diff erence (WMD) with 95% CI. Weighted averages and mean diff erences were calculated by a random-eff ects model (DerSimonian-Laird methodology). Heterogeneity was assessed by the Q statistic and review of L'Abbé plots, and publication bias was assessed through the Egger weighted regression statistic and visual inspection of funnel plots. Echinacea decreased the odds of developing the common cold by 58% (OR 0·42; 95% CI 0·25-0·71; Q statistic p<0·001) and the duration of a cold by 1·4 days (WMD -1·44, -2·24 to -0·64; p=0·01). Similarly, signifi cant reductions were maintained in subgroup analyses limited to Echinaguard/Echinacin use, concomitant supplement use, method of cold exposure, Jadad scores less than 3, or use of a fi xed-eff ects model. Published evidence supports echinacea's benefi t in decreasing the incidence and duration of the common cold.
Output: Evaluation of echinacea for the prevention and treatment of the common cold: a meta-analysis
Since the outbreak of porcine epidemic diarrhea virus (PEDV) in May 2013, U.S. swine producers have lost almost five million baby pigs. In an attempt to understand the evolution of PEDV in the United States and possibly develop a control strategy, we compared the genome sequences of a PEDV strain isolated from an infected piglet against its in vitro adapted version. The original PEDV strain was grown in Vero cells and passed 10 times serially in a MARC145 cell line. The sequence analysis of the native PEDV strain and in vitro passaged virus shows that the cell culture adaptation specifically modifies PEDV spike protein whereas the open reading frame 1a/b (ORF1a/b)-encoded polyprotein, the nucleoprotein, NS3B (ORF3), and membrane and envelope proteins remain unchanged.
Output: Genome Sequences of Porcine Epidemic Diarrhea Virus: In Vivo and In Vitro Phenotypes
Respiratory Pathogen 13 Detection Kit (13× kit) is able to simultaneously detect 11 respiratory viruses, Mycoplasma pneumoniae (MP) and Chlamydia in a single reaction. Using 572 Nasopharyngeal aspirates collected from hospitalized children, the clinical performance of 13× kit for detecting 11 respiratory viruses was evaluated in comparison with a routinely used 2-tube multiplex reverse transcription PCR assay (2-tube assay) at provincial Centers for Disease Control and Prevention in China. The clinical performance of 13× kit for detecting MP and Chlamydia was evaluated by commercial real-time quantitative PCR (qPCR) kits or sequencing. For tested viruses, the assay concordance was 95.98% and the kappa coefficient was 0.89. All the MP and Chlamydia positive samples detected by 13× kit were confirmed as true positives. The utilization of the 13× kit in clinical settings will be helpful for doctors to assess clinical outcome according to virus type or multiple infections, and to limit the use of antibiotics.
Output: Clinical evaluation of a new single-tube multiplex reverse transcription PCR assay for simultaneous detection of 11 respiratory viruses, Mycoplasma pneumoniae and Chlamydia in hospitalized children with acute respiratory infections
Bovine herpesvirus 5 (BHV5) infection of young cattle is frequently associated with fatal neurological disease and, as such, represents an attractive model for studying the pathogenesis of viral-induced meningoencephalitis. Following replication in the nasal mucosa, BHV5 invades the central nervous system (CNS) mainly through the olfactory pathway. The innate immune response triggered by the host face to virus replication through the olfactory route is poorly understood. Recently, an upregulation of conserved pathogenassociated molecular pattern, as Toll-like receptors (TLRs), has been demonstrated in the CNS of BHV5 experimentally infected cows. A new perspective to understand hostpathogen interactions has emerged elucidating microRNAs (miRNAs) network that interact with innate immune response during neurotropic viral infections. In this study, we demonstrated a link between the expression of TLRs 3, 7, and 9 and miR-155 transcription in the olfactory bulbs (OB) of 16 cows suffering from acute BHV5-induced neurological disease. The OBs were analyzed for viral antigens and genome, miR-155 and TLR 3, 7, and 9 expression considering three major regions: olfactory receptor neurons (ORNs), glomerular layer (GL), and mitral cell layer (ML). BHV5 antigens and viral genomes, corresponding to glycol-C gene, were detected in all OBs regions by fluorescent antibody assay (FA) and PCR, respectively. TLR 3, 7, and 9 transcripts were upregulated in ORNs and ML, yet only ORN layers revealed a positive correlation between TLR3 and miR-155 transcription. In ML, miR-155 correlated positively with all TLRs studied. Herein, our results evidence miR-155 transcription in BHV5 infected OB tissue associated to TLRs expression specifically ORNs which may be a new window for further studies.
Output: Expression of miR-155 associated with Toll-like receptors 3, 7, and 9 transcription in the olfactory bulbs of cattle naturally infected with BHV5
Bats are natural reservoirs of coronaviruses and other viruses with zoonotic potential. Florida has indigenous non-migratory populations of Brazilian free-tailed bats (Tadarida brasiliensis) that mostly roost in colonies in artificial structures. Unlike their counterparts in Brazil and Mexico, the viruses harbored by the Florida bats have been underexplored. We report the detection of an alphacoronavirus RNA-dependent RNA polymerase (RdRp) gene sequence in the feces of two of 19 different T. brasiliensis that were capture/release bats that had been evaluated for overall health. The RdRp sequence is similar but not identical to previously detected sequences in the feces of two different species of bats (T. brasiliensis and Molossus molossus) in Brazil. In common with the experience of others doing similar work, attempts to isolate the virus in cell cultures were unsuccessful. We surmise that this and highly related alphacoronavirus are carried by Brazilian free-tailed bats living in a wide eco-spatial region. As various coronaviruses (CoVs) that affect humans emerged from bats, our study raises the question whether CoVs such as the one detected in our work are yet-to-be-detected pathogens of humans and animals other than bats.
Output: Detection of Alphacoronavirus vRNA in the Feces of Brazilian Free-Tailed Bats (Tadarida brasiliensis) from a Colony in Florida, USA
Objectives: The purpose of this study was to examine the change in health status of China's adult population between the years of 2003 and 2008 due to rapid economic growth and medical system improvement. Methods: Data from the third and fourth Chinese national health services surveys covering 141,927 residents in 2003 and 136,371 residents in 2008 who were aged .18 years were analyzed. Results: Chinese respondents in 2008 were more likely to report disease than in 2003. Smoking slightly decreased among men and women, and regular exercise showed much improvement. Stratified analyses revealed significant subpopulation disparities in rate ratios for 2008/2003 in the presence of chronic disease, with greater increases among women, elderly, the Han nationality, unmarried and widow, illiterate, rural, and regions east of China than other groups. Conclusions: Chinese adults in 2008 had worse health status than in 2003 in terms of presence of chronic disease. China's reform of health care will face more complex challenges in coming years from the deteriorating health status in Chinese adults.
Output: Changes of Adult Population Health Status in China from
Subtype specificity of influenza A virus (IAV) is determined by its two surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA). For HA, 16 distinct subtypes (H1-H16) exist, while nine exist for NA. The epidemic strains of H1N1 IAV change frequently and cause annual seasonal epidemics as well as occasional pandemics, such as the notorious 1918 influenza pandemic. The recent introduction of pandemic A/H1N1 IAV (H1N1pdm virus) into humans re-emphasizes the public health concern about H1N1 IAV. Several studies have identified conserved epitopes within specific HA subtypes that can be used for diagnostics. However, immune specific epitopes in H1N1 IAV have not been completely assessed. In this study, linear epitopes on the H1N1pdm viral HA protein were identified by peptide scanning using libraries of overlapping peptides against convalescent sera from H1N1pdm patients. One epitope, P5 (aa 58-72) was found to be immunodominant in patients and to evoke high titer antibodies in mice. Multiple sequence alignments and in silico coverage analysis showed that this epitope is highly conserved in influenza H1 HA [with a coverage of 91.6% (9,860/10,767)] and almost completely absent in other subtypes [with a coverage of 3.3% (792/23,895)]. This previously unidentified linear epitope is located outside the five well-recognized antigenic sites in HA. A peptide ELISA method based on this epitope was developed and showed high correlation (x 2 = 51.81, P,0.01, Pearson correlation coefficient R = 0.741) with a hemagglutination inhibition test. The highly conserved H1 subtype-specific immunodominant epitope may form the basis for developing novel assays for sero-diagnosis and active surveillance against H1N1 IAVs.
Output: Identification of a Highly Conserved H1 Subtype-Specific Epitope with Diagnostic Potential in the Hemagglutinin Protein of Influenza A Virus
The direct chemoselective differential functionalization of the ring-C hydroxyl groups present in the Amaryllidaceae alkaloid lycorine is described allowing for selective manipulation of the 1,2-hydroxyl groups. A mini-library comprised of synthetic and natural lycorane alkaloids was prepared and their apoptosis-inducing activity investigated in human leukemia (Jurkat) cells. Further insights into the nature of this interesting apoptosis-inducing pharmacophore are described, including the requirement of both free hydroxyl groups in ring-C.
Output: Structure-activity studies on the lycorine pharmacophore: A potent inducer of apoptosis in human leukemia cells
Background: The HIV-1 RNA genome has a biased nucleotide composition with a surplus of As. Several hypotheses have been put forward to explain this striking phenomenon, but the A-count of the HIV-1 genome has thus far not been systematically manipulated. The reason for this reservation is the likelihood that known and unknown sequence motifs will be affected by such a massive mutational approach, thus resulting in replication-impaired virus mutants. We present the first attempt to increase and decrease the A-count in a relatively small polymerase (pol) gene segment of HIV-1 RNA. To minimize the mutational impact, a new mutational approach was developed that is inspired by natural sequence variation as present in HIV-1 isolates. This phylogeny-instructed mutagenesis allowed us to create replication-competent HIV-1 mutants with a significantly increased or decreased local A-count. The local A-count of the wild-type (wt) virus (40.2%) was further increased to 46.9% or reduced to 31.7 and 26.3%. These HIV-1 variants replicate efficiently in vitro, despite the fact that the pol changes cause a quite profound move in HIV-SIV sequence space. Extrapolating these results to the complete 9 kb RNA genome, we may cautiously suggest that the A-rich signature does not have to be maintained. This survey also provided clues that silent codon changes, in particular from G-to-A, determine the subtype-specific sequence signatures.
Output: HIV-1 tolerates changes in A-count in a small segment of the pol gene
Background: Animal faeces comprise a community of many different microorganisms including bacteria and viruses. Only scarce information is available about the diversity of viruses present in the faeces of pigs. Here we describe a protocol, which was optimized for the purification of the total fraction of viral particles from pig faeces. The genomes of the purified DNA and RNA viruses were simultaneously amplified by PCR and subjected to deep sequencing followed by bioinformatic analyses. The efficiency of the method was monitored using a process control consisting of three bacteriophages (T4, M13 and MS2) with different morphology and genome types. Defined amounts of the bacteriophages were added to the sample and their abundance was assessed by quantitative PCR during the preparation procedure. Results: The procedure was applied to a pooled faecal sample of five pigs. From this sample, 69,613 sequence reads were generated. All of the added bacteriophages were identified by sequence analysis of the reads. In total, 7.7% of the reads showed significant sequence identities with published viral sequences. They mainly originated from bacteriophages (73.9%) and mammalian viruses (23.9%); 0.8% of the sequences showed identities to plant viruses. The most abundant detected porcine viruses were kobuvirus, rotavirus C, astrovirus, enterovirus B, sapovirus and picobirnavirus. In addition, sequences with identities to the chimpanzee stool-associated circular ssDNA virus were identified. Whole genome analysis indicates that this virus, tentatively designated as pig stool-associated circular ssDNA virus (PigSCV), represents a novel pig virus. The established protocol enables the simultaneous detection of DNA and RNA viruses in pig faeces including the identification of so far unknown viruses. It may be applied in studies investigating aetiology, epidemiology and ecology of diseases. The implemented process control serves as quality control, ensures comparability of the method and may be used for further method optimization.
Output: Simultaneous Identification of DNA and RNA Viruses Present in Pig Faeces Using Process-Controlled Deep Sequencing
Immune system factors including complement pathway activation are increasingly linked to the etiology and pathophysiology of schizophrenia. Complement protein, C1q, binds to and helps to clear immune complexes composed of immunoglobulins coupled to antigens. The antigenic stimuli for C1q activation in schizophrenia are not known. Food sensitivities characterized by elevated IgG antibodies to bovine milk caseins and wheat glutens have been reported in individuals with schizophrenia. Here, we examined the extent to which these food products might comprise the antigen component of complement C1q immune complexes in individuals with recent onset schizophrenia (n=38), non-recent onset schizophrenia (n=61) and non-psychiatric controls (n=63). C1q seropositivity was significantly associated with both schizophrenia groups (recent onset, odds ratio (OR)=8.02, p≤0.008; non-recent onset, OR=3.15, p≤0.03) compared to controls (logistic regression models corrected for age, sex, race and smoking status). Casein-and/ or gluten-IgG binding to C1q was significantly elevated in the non-recent onset group compared to controls (OR=4.36, p≤0.01). Significant amounts of C1q-casein/gluten-related immune complexes and C1q correlations with a marker for gastrointestinal inflammation in non-recent onset schizophrenia suggests a heightened rate of food antigens in the systemic circulation, perhaps via a disease-associated altered intestinal permeability. In individuals who are in the early stages of disease onset, C1q activation may reflect the formation of immune complexes with non-casein-or non-gluten-related antigens, the presence of C1q autoantibodies, and/or a dissociated state of immune complex components. In conclusion, complement activation may be a useful biomarker to diagnose schizophrenia early during the course of the disease. Future prospective studies should evaluate the impacts of casein-and gluten-free diets on C1q activation in schizophrenia.
Output: Complement C1q formation of immune complexes with milk caseins and wheat glutens in schizophrenia NIH Public Access Author Manuscript
There is an urgent need to develop effective vaccines against pneumonic plague, a highly lethal and contagious disease caused by the Gram-negative bacterium Yersinia pestis. Here we demonstrate that a novel DNA vaccine expressing a modified V antigen (LcrV) of Y. pestis, with a human tissue plasminogen activator (tPA) signal sequence, elicited strong V-specific antibody responses in BALB/c mice. This tPA-V DNA vaccine protected mice from intranasal challenge with lethal doses of Y. pestis. In comparison, a DNA vaccine expressing the wild type V antigen was much less effective. Only tPA-V formed oligomers spontaneously, and elicited a higher IgG2a anti-V antibody response in immunized mice, suggesting increased T H 1 type cellular immune response. Our data indicate that antigen engineering is effective in inducing high quality protective immune responses against conformationally sensitive antigens. These results support that optimized DNA vaccines have the potential to protect against bacterial pathogens than is generally recognized.
Output: A DNA vaccine producing LcrV antigen in oligomers is effective in protecting mice from lethal mucosal challenge of plague