niryuu/sni-each-converted huggingface dataset:
Objectives: To estimate the prevalence of acute respiratory tract infections (ARI) among 250 personnel serving in a Hajj medical mission, Al-Hada and Taif Armed Forces Hospitals, during the 2005 season and to determine the effectiveness of protective measures, including influenza vaccination, for these infections. Methods: This was a nested case-control study. A questionnaire was distributed to the study cohort two weeks after the Hajj period and was self-administered by all recruited subjects. In addition, the medical records of study subjects were reviewed at Al-Hada Hospital for the same period in order to document ARI. Results: The attack rate for ARI among study subjects during Hajj season or within two weeks of returning was 25.6% (64/250). Logistic regression analysis of factors related to acquiring ARI revealed that contact with pilgrims imposed an extremely high risk of infection (adjusted OR 13.2, 95% CI 1.5-117.6). Moreover, non-use of alcohol-based hand disinfection carried a more than 8-fold risk of acquiring ARI compared to those who always used alcohol for hand disinfection (adjusted OR 8.4, 95% CI 2.2-32.2). Smoking was also a predictor of ARI in our cohort and influenza vaccination was associated with a 30% reduction in ARI compared to unvaccinated subjects, although this finding was not statistically significant. Unexpectedly, the logistic regression model showed that Saudi nationals were three times more likely to acquire ARI than non-Saudis (adjusted OR 3.1, 95% CI 1.2-8.4). Conclusions: The common practice among pilgrims and medical personnel of using surgical facemasks to protect themselves against ARI should be discontinued and regular use of alcohol-based hand scrubs should be more vigorously encouraged. Further research is needed to evaluate the protective value of N95 facemasks against ARI during the Hajj period. #
Output: Acute respiratory tract infections among Hajj medical mission personnel, Saudi Arabia
A total of 84 nasopharyngeal swab specimens were collected from 84 patients. Viral nucleic acid was extracted by three automated extraction systems: QIAcube (Qiagen, Germany), EZ1 Advanced XL (Qiagen), and MICROLAB Nimbus IVD (Hamilton, USA). Fourteen RNA viruses and two DNA viruses were detected using the Anyplex II RV16 Detection kit (Seegene, Republic of Korea). The EZ1 Advanced XL system demonstrated the best analytical sensitivity for all the three viral strains. The nucleic acids extracted by EZ1 Advanced XL showed higher positive rates for virus detection than the others. Meanwhile, the MICROLAB Nimbus IVD system was comprised of fully automated steps from nucleic extraction to PCR setup function that could reduce human errors. For the nucleic acids recovered from nasopharyngeal swab specimens, the QIAcube system showed the fewest false negative results and the best concordance rate, and it may be more suitable for detecting various viruses including RNA and DNA virus strains. Each system showed different sensitivity and specificity for detection of certain viral pathogens and demonstrated different characteristics such as turnaround time and sample capacity. Therefore, these factors should be considered when new nucleic acid extraction systems are introduced to the laboratory.
Output: Evaluation of Three Automated Nucleic Acid Extraction Systems for Identification of Respiratory Viruses in Clinical Specimens by Multiplex Real-Time PCR
Surfactin has antiviral activity against various enveloped viruses by inhibiting viral membrane fusion. However, the potential utility of surfactin as an antiviral drug is limited by its cytotoxicity. In this study, 10 surfactin analogues were obtained by chemical synthesis and evaluated to determine their anti-PEDV activities, hemolytic activities, and critical micelle concentrations. The main goal of our study was to develop a safer drug; a surfactin analogue with high anti-PEDV activity and low hemolytic activity. Compared with surfactin, one of the analogues we developed, SLP5, has lower hemolytic activity, with the same antiviral activity. The selectivity index of SLP5 is 52, while the SI for surfactin is 4, in other words, the safe and effective concentration range of SLP5 is 12 times greater than that of surfactin. Like surfactin, SLP5 has a direct antiviral effect on PEDV. Structurally, SLP5 is a linear lipopeptide with three carboxyl groups. Surfactin derivatives similar to SLP5 could be obtained by lactone bond hydrolyzation of surfactin, as well as total synthesis.
Output: Synthetic surfactin analogues have improved anti-PEDV properties
Regulations are a part of life but who writes them, what is the basis on which they are written and when the regulations get it wrong, whose fault is it? Is it those who wrote the regulations, those enforcing the regulations, those being regulated or the science underpinning the regulations? In seeking answers to these questions, this paper explores the regulatory process and the contribution of science. It takes as examples the role of the Australian Pesticides and Veterinary Medicines Authority (APVMA) in regulating veterinary products, of the Security Sensitive Biological Agents regulations in managing the risks from specific pathogens, the Quarantine Act regulations as applied to containment facilities and the development of welfare standards. By dealing with products, pathogens, places and ''pets'' it provides a broad oversight of how regulations have been developed and applied from different perspectives and highlights the differing roles that science and research play both in developing policy and regulations. What is clear is that in the presence of good science it is usually possible to develop sound and defensible regulations e.g. those managed by APVMA, but when there is a lack of science to underpin the regulations, problems can arise e.g. in the case of animal welfare.
Output: Science delivering to regulators
Human herpesvirus type 6B (HHV-6B) is a strong inducer of IFN-alpha and has the capacity to promote Th1 responses and block Th2 responses in vitro. In this study we addressed whether inactivated HHV-6B can also induce IFN lambda responses and to what extent interferons alpha and lambda affect Th1/Th2 polarization. We show that inactivated HHV-6B induced IFN-lambda1 (IL-29) but not IFN-lambda2 (IL-28A) responses in plasmacytoid DC and that this induction was mediated through TLR9. We have previously shown that HHV-6B promotes Th1 responses and blocks Th2 responses in both humans and mice. We now show that neutralization of IFN-alpha but not IFN-lambda1 blocked the HHV-6B-induced enhancement of Th1 responses in MLR, but did not affect the HHV-6-induced dampening of Th2 responses. Similarly, blockage of TLR9 counteracted HHV-6Bs effects on the Th1/Th2 balance. In addition, IFN-alpha but not IFN-lambda1 promoted IFN-gamma production and blocked IL-5 and IL-13 production in purified CD4+ T-cells. The lack of effect of IFN-lambda1 correlated with the absence of the IFN-lambda receptor IL-28Ralfa chain on the cell surface of both resting and activated CD4+ T-cells. We conclude that inactivated HHV-6B is a strong inducer of IFN-lambda1 in plasmacytoid DC and that this induction is TLR9dependent. However, human CD4+ T-cells do not express the IFN-lambda receptor and are refractory to IFN-lambda1 treatment. The HHV-6B-induced alterations in the Th1/Th2 balance are instead mediated mainly through TLR9 and IFNalpha. Citation: Nordströ m I, Eriksson K (2012) HHV-6B Induces IFN-Lambda1 Responses in Cord Plasmacytoid Dendritic Cells through TLR9. PLoS ONE 7(6): e38683.
Output: HHV-6B Induces IFN-Lambda1 Responses in Cord Plasmacytoid Dendritic Cells through TLR9
The Golgi apparatus-complex (GA), is a key organelle involved in several posttranslational modifications of polypeptides destined for lysosomes, plasma membranes and secretion. As reported from this laboratory, certain astrocytes in rat brain contain cisternae of the GA not only in perikarya, but also in processes. In order to further investigate which type of astrocytes contain GA in processes we conducted the present study using primary cultures of rat astrocytes and organelle specific antibodies against the GA and the rough endoplasmic reticulum (RER). While the perikarya of all cells contained elements of the GA, only a single process of a subset of type I astrocytes, negative to antibodies A2B5 and HNK-1, contained GA. In contrast, elements of the RER were found within perikarya and all processes. In order to confirm that the immunostained structures in processes indeed represent the GA, we exposed cultures to Brefeldin A (BFA), a secretion blocker which disperses the GA and redistributes it to the RER. We observed that BFA disrupted the GA of both perikarya and processes. However, astrocytes were resistant to prolonged incubations with BFA, while a similar treatment killed cultured fibroblasts and PC-12 cells. Furthermore, in astrocytes exposed to BFA for several days, the delicate network of glial fibrillary acidic protein (GFAP), was replaced by large perinuclear masses of the protein. These observations demonstrate that a subset of type I astrocytes have a single process with elements of the GA. We suggest that this specialization of the GA may be related to yet unrecognized secretory or protein processing functions of these cells. The resistance of astrocytes to BFA and the striking changes in their cytoskeleton induced by the drug, may contribute to studies on the mechanism(s) of action of BFA.
Output: BRAIN RESEARCH Polarity of processes with Golgi apparatus in a subpopulation of type I astrocytes
Objective: This study was undertaken to evaluate the pregnancy and perinatal outcomes of pregnant women with severe acute respiratory syndrome (SARS). Study design: All pregnant women (12) who presented with SARS in Hong Kong between February 1 and July 31, 2003, were included. The pregnancy and perinatal outcomes were collected. Evidence of perinatal transmission of virus was assessed with the SARS-associated coronavirus reverse-transcriptase polymerase chain reaction on cord blood, placenta tissue, and subsequent follow-up of the neonate on serology. Results: Three deaths occurred among the 12 patients, giving a case fatality rate of 25%. Four of the 7 patients (57%) who presented in the first trimester had spontaneous miscarriage. Four of the 5 patients who presented after 24 weeks were delivered preterm. Two mothers recovered without delivery, but their ongoing pregnancies were complicated by intrauterine growth restriction. No newborn infant had clinical SARS and all investigations were negative for SARS. Conclusion: SARS during pregnancy is associated with high incidences of spontaneous miscarriage, preterm delivery, and intrauterine growth restriction. There is no evidence of perinatal SARS infection among infants born to these mothers.
Output: Pregnancy and perinatal outcomes of women with severe acute respiratory syndrome
Interleukin!01 activates natural killer cells and promotes the differentiation of Th0 CD3¦ cells^it is a critical factor in viral immunity[ IL!01 is secreted by antigen presenting cells including dendritic cells\ macrophages and astrocytes\ both in tissues and in secondary lymphoid organs[ Experimental studies have shown that administration of the cytokine rapidly activates both innate and speci_c immune responses^this results in enhanced host cellular responses and generally\ promotes clearance of virus and host recovery from infection[ The observations of many laboratories\ studying viral immunity to both RNA and DNA based pathogens\ are summarized[ Þ 0887 Elsevier Science Ltd[ All rights reserved[ Key words] Interleukin!01 = viral infection = signal transduction = innate immunity = acquired immunity[
Output: IL-12 and Viral Infections
Cholesterol present in the plasma membrane of target cells has been shown to be important for the infection by SARS-CoV. We show that cholesterol depletion by treatment with methyl-β-cyclodextrin (mβCD) affects infection by SARS-CoV to the same extent as infection by vesicular stomatitis virus-based pseudotypes containing the surface glycoprotein S of SARS-CoV (VSV-ΔG-S). Therefore, the role of cholesterol for SARS-CoV infection can be assigned to the S protein and is unaffected by other coronavirus proteins. There have been contradictory reports whether or not angiotensin-converting enzyme 2 (ACE2), the cellular receptor for SARS-CoV, is present in detergent-resistant membrane domains. We found that ACE2 of both Vero E6 and Caco-2 cells co-purifies with marker proteins of detergent-resistant membranes supporting the notion that cholesterol-rich microdomains provide a platform facilitating the efficient interaction of the S protein with the cellular receptor ACE2. To understand the involvement of cholesterol in the initial steps of the viral life cycle, we applied a cell-based binding assay with cells expressing the S protein and cells containing angiotensin-converting enzyme 2 (ACE2). Alternatively, we used a soluble S protein as interaction partner. Depletion of cholesterol from the ACE2-expressing cells reduced the binding of S-expressing cells by 50% whereas the binding of soluble S protein was not affected. This result suggests that optimal infection requires a multivalent interaction between viral attachment protein and cellular receptors.
Output: Importance of cholesterol-rich membrane microdomains in the interaction of the S protein of SARS-coronavirus with the cellular receptor angiotensin-converting enzyme 2
Background: Sepsis is a serious medical condition requiring timely administered, appropriate antibiotic therapy. Blood culture is regarded as the gold standard for aetiological diagnosis of sepsis, but it suffers from low sensitivity and long turnaround time. Thus, nucleic acid amplification tests (NAATs) have emerged to shorten the time to identification of causative microbes. The aim of the present study was to evaluate the clinical utility in everyday practice in the emergency department of two commercial NAATs in patients suspected with sepsis. Methods: During a six-week period, blood samples were collected consecutively from all adult patients admitted to the general emergency department for suspicion of a community-onset sepsis and treated with intravenous antibiotics. Along with conventional blood cultures, multiplex PCR (Magicplex™) was performed on whole blood specimens whereas portions from blood culture bottles were used for analysis by microarray-based assay (Prove-it™). The aetiological significance of identified organisms was determined by two infectious disease physicians based on clinical presentation and expected pathogenicity. Results: Among 382 episodes of suspected sepsis, clinically relevant microbes were detected by blood culture in 42 episodes (11%), by multiplex PCR in 37 episodes (9.7%), and by microarray in 32 episodes (8.4%). Although moderate agreement with blood culture (kappa 0.50), the multiplex PCR added diagnostic value by timely detection of 15 clinically relevant findings in blood culture-negative specimens. Results of the microarray corresponded very well to those of blood culture (kappa 0.90), but were available just marginally prior to blood culture results. Conclusions: The use of NAATs on whole blood specimens in adjunct to current culture-based methods provides a clinical add-on value by allowing for detection of organisms missed by blood culture. However, the aetiological significance of findings detected by NAATs should be interpreted with caution as the high analytical sensitivity may add findings that do not necessarily corroborate with the clinical diagnosis.
Output: Clinical evaluation of commercial nucleic acid amplification tests in patients with suspected sepsis
Background: Feline infectious peritonitis (FIP) is considered highly fatal in its naturally occurring form, although up to 36% of cats resist disease after experimental infection, suggesting that cats in nature may also resist development of FIP in the face of infection with FIP virus (FIPV). Previous experimental FIPV infection studies suggested a role for cellmediated immunity in resistance to development of FIP. This experimental FIPV infection study in specific pathogen free (SPF) kittens describes longitudinal antiviral T cell responses and clinical outcomes ranging from rapid progression, slow progression, and resistance to disease. Results: Differences in disease outcome provided an opportunity to investigate the role of T cell immunity to FIP determined by T cell subset proliferation after stimulation with different viral antigens. Reduced total white blood cell (WBC), lymphocyte and T cell counts in blood were observed during primary acute infection for all experimental groups including cats that survived without clinical FIP. Antiviral T cell responses during early primary infection were also similar between cats that developed FIP and cats remaining healthy. Recovery of antiviral T cell responses during the later phase of acute infection was observed in a subset of cats that survived longer or resisted disease compared to cats showing rapid disease progression. More robust T cell responses at terminal time points were observed in lymph nodes compared to blood in cats that developed FIP. Cats that survived primary infection were challenged a second time to pathogenic FIPV and tested for antiviral T cell responses over a four week period. Nine of ten rechallenged cats did not develop FIP or T cell depletion and all cats demonstrated antiviral T cell responses at multiple time points after rechallenge. Conclusions: In summary, definitive adaptive T cell responses predictive of disease outcome were not detected during the early phase of primary FIPV infection. However emergence of antiviral T cell responses after a second exposure to FIPV, implicated cellular immunity in the control of FIPV infection and disease progression. Virus host interactions during very early stages of FIPV infection warrant further investigation to elucidate host resistance to FIP.
Output: Characterization of antiviral T cell responses during primary and secondary challenge of laboratory cats with feline infectious peritonitis virus (FIPV)
The aim of the present study was to carry out molecular epidemiological investigation on enterotoxigenic Escherichia coli (ETEC) K99 and Salmonella spp. in diarrheic neonatal calves. Fecal samples were obtained from 220 diarrheic calves at 9 farms related to four governorates in central and northern Egypt. E. coli and Salmonella spp. isolates were examined for E. coli K99 and Salmonella spp. using PCR. ETEC K99 was recovered from 20 (10.36 %) out of 193 isolates, whereas Salmonella spp. was recovered from nine calves (4.09%). Multivariable logistic regression was used to evaluate the risk factors associated with both infections. ETEC K99 was significantly affected by age (P < 0.01; OR: 1.812; CI 95%: 0.566-1.769), colostrum feeding practice (P < 0.01; OR: 5.525; CI 95%: 2.025-15.076), rotavirus infection (P < 0.001; OR: 2.220; CI 95%: 0.273-1.251), vaccination of pregnant dams with combined vaccine against rotavirus, coronavirus and E. coli (K99) (P < 0.001; OR: 4.753; CI 95%: 2.124-10.641), and vitamin E and selenium administration to the pregnant dam (P < 0.01; OR: 3.933; CI 95%: 0.703-1.248). Infection with Salmonella spp. was found to be significantly affected by the animal age (P < 0.05; OR: 0.376; CI 95%: 0.511-1.369), Hygiene (P < 0.05; OR: 0.628; CI 95%: 1.729-5.612), and region (P < 0. 01; OR: 0.970; CI 95%: 0.841-1.624). The results of the present study indicate the importance of PCR as rapid, effective and reliable tool for screening of ETEC and Salmonella spp. when confronted with cases of undifferentiated calf diarrhea. Moreover, identification of the risk factors associated with the spreading of bacteria causing diarrhea may be helpful for construction of suitable methods for prevention and control.
Output: Molecular screening and risk factors of enterotoxigenic Escherichia coli and Salmonella spp. in diarrheic neonatal calves in Egypt
Four Massachusetts-type (Mass-type) strains of infectious bronchitis coronavirus (IBV) were compared genetically with the pathogenic M41 and H120 vaccine strains using the complete genomic sequences. The results revealed that strains ck/CH/LNM/091017 and ck/CH/LDL/101212 were closely related to the H120 vaccine, which suggests that they might represent re-isolations of vaccine strains or variants of vaccine strains that have resulted from the accumulated point mutations after several passages in chickens. In contrast, strains ck/CH/LHLJ/07VII and ck/CH/LHLJ/100902 had a close genetic relationship with the pathogenic M41 strain. In addition, molecular markers have been identified that distinguish between field and vaccine (or vaccine-like) Mass-type viruses, which may be able to differentiate between field and vaccine strains for diagnostic purposes. Phylogenetic analysis, and pairwise comparison of full-length genomes and the nine genes, identified the occurrence of recombination events in the genome of strain CK/VH/LHLJ/07VII, which suggests that this virus originated from recombination events between M41-and H120-like strains at the switch site located at the 3 0 end of the nucleocapsid (N) genes. To our knowledge, this is the first time that evidence for the evolution and natural recombination under field conditions between Mass-type pathogenic and vaccinal IBV strains has been documented. These findings provide insights into the emergence and evolution of the Mass-type IB coronaviruses and may help to explain the emergence of Mass-type IBV in chicken flocks all over the world.
Output: Comparative analysis of four Massachusetts type infectious bronchitis coronavirus genomes reveals a novel Massachusetts type strain and evidence of natural recombination in the genome
The accumulation of [3H]noradrenaline ([3H]NA) and its oxidation products was studied in primary cultures of cerebral astrocytes. Astroglial accumulation of radiolabeled catecholamine ([3H] NA and oxidation products) was enhanced by manganese or iron, but it was inhibited by unlabeled NA, dopamine or ascorbate. Tissue:medium ratios of radioactivity increased as extracellular [3H]NA was oxidized. When extracellular oxidation was prevented by ascorbate, as confirmed by high performance liquid chromatography with electrochemical detection, either ouabain pretreatment or nominally Na*-free incubation medium inhibited approximately one-half of specific [3H]NA accumulation by rat (but not mouse) astrocytes. These observations suggest that neurological responses to trace metals and ascorbate may arise from the effects of these agents on the clearance of extracellular catecholamines. Astrocytes can accumulate oxidation products of NA more rapidly than they take up NA itself, but ascorbate at physiological concentrations prevents the oxidation process in extracellular fluid. Furthermore, in the presence of ascorbate, Na+-dependent transport mediates a significant component of NA accumulation in rat astrocytes.
Output: Accumulation of Noradrenaline and Its Oxidation Products by Cultured Rodent Astrocytes
Seasonality is a complex force in nature that affects multiple processes in wild animal populations. In particular, seasonal variations in demographic processes may considerably affect the persistence of a pathogen in these populations. Furthermore, it has been long observed in computer simulations that under seasonal perturbations, a host-pathogen system can exhibit complex dynamics, including the transition to chaos, as the magnitude of the seasonal perturbation increases. In this paper, we develop a seasonally perturbed Susceptible-Infected-Recovered model of avian influenza in a seabird colony. Numerical simulations of the model give rise to chaotic recurrent epidemics for parameters that reflect the ecology of avian influenza in a seabird population, thereby providing a case study for chaos in a hostpathogen system. We give a computer-assisted exposition of the existence of chaos in the model using methods that are based on the concept of topological hyperbolicity. Our approach elucidates the geometry of the chaos in the phase space of the model, thereby offering a mechanism for the persistence of the infection. Finally, the methods described in this paper may be immediately extended to other infections and hosts, including humans.
Output: Mathematical Biology Chaos in a seasonally perturbed SIR model: avian influenza in a seabird colony as a paradigm
Background Pneumonia is the leading cause of death among children younger than 5 years. In this study, we estimated causes of pneumonia in young African and Asian children, using novel analytical methods applied to clinical and microbiological findings. We did a multi-site, international case-control study in nine study sites in seven countries: Bangladesh, The Gambia, Kenya, Mali, South Africa, Thailand, and Zambia. All sites enrolled in the study for 24 months. Cases were children aged 1-59 months admitted to hospital with severe pneumonia. Controls were age-group-matched children randomly selected from communities surrounding study sites. Nasopharyngeal and oropharyngeal (NP-OP), urine, blood, induced sputum, lung aspirate, pleural fluid, and gastric aspirates were tested with cultures, multiplex PCR, or both. Primary analyses were restricted to cases without HIV infection and with abnormal chest x-rays and to controls without HIV infection. We applied a Bayesian, partial latent class analysis to estimate probabilities of aetiological agents at the individual and population level, incorporating case and control data. Findings Between Aug 15, 2011, and Jan 30, 2014, we enrolled 4232 cases and 5119 community controls. The primary analysis group was comprised of 1769 (41·8% of 4232) cases without HIV infection and with positive chest x-rays and 5102 (99·7% of 5119) community controls without HIV infection. Wheezing was present in 555 (31·7%) of 1752 cases (range by site 10·6-97·3%). 30-day case-fatality ratio was 6·4% (114 of 1769 cases). Blood cultures were positive in 56 (3·2%) of 1749 cases, and Streptococcus pneumoniae was the most common bacteria isolated (19 [33·9%] of 56). Mycobacterium tuberculosis for 5·9% (3·9-8·3). Viruses were less common (54·5%, 95% CrI 47·4-61·5 vs 68·0%, 62·7-72·7) and bacteria more common (33·7%, 27·2-40·8 vs 22·8%, 18·3-27·6) in very severe pneumonia cases than in severe cases. RSV had the greatest aetiological fraction (31·1%, 95% CrI 28·4-34·2) of all pathogens. Human rhinovirus, human metapneumovirus A or B, human parainfluenza virus, S pneumoniae, M tuberculosis, and H influenzae each accounted for 5% or more of the aetiological distribution. We observed differences in aetiological fraction by age for Bordetella pertussis, parainfluenza types 1 and 3, parechovirus-enterovirus, P jirovecii, RSV, rhinovirus, Staphylococcus aureus, and S pneumoniae, and differences by severity for RSV, S aureus, S pneumoniae, and parainfluenza type 3. The leading ten pathogens of each site accounted for 79% or more of the site's aetiological fraction. Interpretation In our study, a small set of pathogens accounted for most cases of pneumonia requiring hospital admission. Preventing and treating a subset of pathogens could substantially affect childhood pneumonia outcomes.
Output: Causes of severe pneumonia requiring hospital admission in children without HIV infection from Africa and Asia: the PERCH multi-country case-control study The PERCH Study Group
The coronavirus avian Infectious bronchitis virus (IBV) poses economic threats to poultry farms worldwide, affecting the performance of both meat-type and egg-laying birds. To define the evolution of recent IBVs in Iran, a genetic analysis based on hypervariable nucleotide sequences of S1 gene was carried out. Tracheal swab samples were collected from 170 Broiler flocks during 2017. Ten tracheal swabs from each flock pooled. From a total number of 170 flocks tested, 84.71% found to be positive. Phylogenetic tree analysis revealed the presence of D274 as a first time in Iran. IS/1494/06 was showed to be dominant IBV type circulating in broiler farms with a significantly higher prevalence than other four genotypes. Considering fluctuations in QX-type prevalence in recent years, continuous monitoring is necessary to reduce economic consequences in layer and broiler farms. The findings highlight the importance of using modified vaccination strategies that are adapted to the changing disease scenario.
Output: Genotyping of avian infectious bronchitis virus in Iran: Detection of D274 and changing in the genotypes rate
Proteomic approaches can be a useful means of identifying targets for identifying and treating a variety of infectious agents. This is especially true for agents responsible for emerging infections or those important to biodefense. Keywords reverse-phase protein microarray; mass spectrometry; protein-protein interactions. Correspondence Viruses have developed numerous and elegant strategies to manipulate the host cell machinery to establish a productive infectious cycle. The interaction of viral proteins with host proteins plays an important role in infection and pathogenesis, often bypassing traditional host defenses such as the interferon response and apoptosis. Host-viral protein interactions can be studied using a variety of proteomic approaches ranging from genetic and biochemical to large-scale high-throughput technologies. Protein interactions between host and viral proteins are greatly influenced by host signal transduction pathways. In this review, we will focus on comparing proteomic information obtained through differing technologies and how their integration can be used to determine the functional aspect of the host response to infection. We will briefly review and evaluate techniques employed to elucidate viral-host interactions with a primary focus on Protein Microarrays (PMA) and Mass Spectrometry (MS) as potential tools in the discovery of novel therapeutic targets. As many potential molecular markers and targets are proteins, proteomic profiling is expected to yield both clearer and more direct answers to functional and pharmacologic questions.
Output: Proteomic strategies for the discovery of novel diagnostic and therapeutic targets for infectious diseases
Objectives of the present study were to characterize the dose dependency of an intravenous Escherichia coli O111:H8 challenge in colostrum-fed Jersey calves and to identify any biochemical markers indicative of septicemia. Eighteen 3-week old colostrum-fed Jersey calves were completely randomized to 1 of 6 doses of E. coli O111:H8. The challenge doses included 0, 1.5 × 10 5 , 1.5 × 10 6 , 1.5 × 10 7 , 1.5 × 10 8 , and 1.5 × 10 9 colony-forming units (CFU) given intravenously as a bolus in 5 mL of sterile isotonic saline. Peripheral blood samples were collected at 0, 2, 4, 8, 12, 24, and 48 h relative to the challenge for biochemical, total leukocyte count, and differential analyses. Rectal temperatures were collected via indwelling rectal temperature probes at 5-min intervals, and hourly averages calculated from 2 d prior to the challenge till 2 d after the challenge. All calves survived the 48 h observation period following the challenge. Calves given 1.5 × 10 8 and 1.5 × 10 9 CFU displayed sickness behaviors (P < 0.01) beginning 0.5 h after the challenge and returned to that of the control calves by 6 and 32 h for calves challenged with 1.5 × 10 8 and 1.5 × 10 9 CFU, respectively. There were treatment × time interactions (P < 0.01) on total leukocyte counts and plasma glucose and zinc concentrations. Calves administered 1.5 × 10 8 and 1.5 × 10 9 CFU had leucopenia beginning 2 h after the challenge and returning to counts similar to the control calves within 24 h. Additionally, those calves were hypoglycemic from 4 to 12 h after the challenge with the degree of hypoglycemia inversely related to the dose of the E. coli. All calves challenged with E. coli had decreased plasma zinc concentrations, and the magnitude was inversely proportional to the challenge dose. There were treatment × time interactions (P < 0.001) on rectal temperatures following the challenge. All calves challenged with E. coli developed a febrile response, but the intensity and duration of the response were dependent on the challenge dose. These data indicate that calves intravenously challenged with 1.5 × 10 8 and 1.5 × 10 9 CFU of the E. coli O111:H8 showed immediate clinical and biochemical signs indicative of septicemia. However, calves administered 1.5 × 10 7 or less of the E. coli had febrile responses, but did not develop septicemia. Blood glucose and zinc concentrations may be dose responsive indicators that could potentially differentiate between a septicemic versus non-septicemic calf.
Output: Effects of intravenous Escherichia coli dose on the pathophysiological response of colostrum-fed Jersey calves
Background: Wild birds are an important but to some extent under-studied reservoir for emerging pathogens. We used unbiased sequencing methods for virus discovery in shorebird samples from the Delaware Bay, USA; an important feeding ground for thousands of migratory birds. Findings: Analysis of shorebird fecal samples indicated the presence of a novel astrovirus and coronavirus. A sanderling sample yielded sequences with distant homology to avian nephritis virus 1, an astrovirus associated with acute nephritis in poultry. A ruddy turnstone sample yielded sequences with homology to deltacoronaviruses. Conclusions: Our findings highlight shorebirds as a virus reservoir and the need to closely monitor wild bird populations for the emergence of novel virus variants.
Output: Novel Coronavirus and Astrovirus in Delaware Bay Shorebirds
Serum and CSF specimens from clinically healthy Brown Norway (BN) rats inoculated intracerebrally with corona virus JHM were analysed with respect to the state of the blood-brain barrier (BBB) and the intrathecal synthesis and isoelectric distribution of immunoglobulins (Ig). Increased CSF/serum ratios for Ig in the context of an intact BBB were never seen in the absence of intrathecal synthesis of virus-specific antibodies. Affinity-mediated immunoblot analysis revealed a broad pattern of virus-specific antibodies with embedded clusters of restricted heterogeneity, but no signs of oligoclonal Ig production carrying non-viral specificity. From these data it was concluded that BN rats do control the intracerebral spread of JHM virus effectively by a strong local virus-specific antibody response, thereby preventing a clinically apparent disease.
Output: Analysis of the intrathecal humoral immune response in Brown Norway (BN) rats, infected with the murine coronavirus JHM
Background: Last-minute travellers (LMTs) present challenges for health care providers because they may have insufficient time for recommended vaccinations or pre-travel preparation. Our objective was to obtain a better understanding of LMTs in order to help travel medicine providers develop improved strategies to decrease the number of LMTs and potentially reduce travel-related morbidity. Methods: We defined LMTs as travellers with a departure date of 7 days or fewer from the medical encounter. We analysed the characteristics and health preparation of 12 494 LMTs who presented to a network of US clinical practices for pre-travel health advice between January 2009 and December 2015. Results: LMTs comprised 16% of all travellers. More LMTs than non-LMTs travelled for business or to visit friends and relatives (VFR) (26% vs 16% and 15% vs 8%, respectively; P < 0.0001). More LMTs also travelled for longer than 1 month (27% vs 21%; P < 0.0001) and visited only urban areas (40% vs 29%; P < 0.0001). At least one travel vaccine was deferred by 18% of LMTs because of insufficient time before departure. Vaccines that required multiple vaccinations, such as Japanese encephalitis and rabies, were the most likely to be deferred because of time constraints. Conclusion: Interventions to improve the timing of pre-travel health consultations should be developed, particularly for business and VFR travellers. Recently endorsed accelerated vaccine schedules for Japanese encephalitis and rabies may help some LMTs receive protection against these infections despite late presentation for pre-travel health care.
Output: Characteristics and preparation of the last-minute traveler: analysis of vaccine usage in the Global TravEpiNet Consortium
Background: International travel is rapidly increasing worldwide, and the greatest increases have occurred in tropical and subtropical areas. The aim of the survey was to investigate the pre-travel health-seeking practices of travelers to Asian destinations. Methods: A questionnaire-based survey was conducted at the Athens International Airport between the 1st of November 2011 and the 30th of April 2013. Results: A total of 1666 adult travelers participated in the study, and 69.7% were men. The mean age of the participants was 39 years. Previous travel to tropical countries was reported by 69% of the participants. The most frequent destination was the Indian subcontinent (45.0%). The main reasons for travel were visiting friends and relatives (VFRs; 36.5%) and business (32.4%). Most of the participants traveled for <1 month (51.4%). Only 24.5% pursued pre-travel consultations. Vaccinations were administered to 14.4% of the participants, and of those, 77%, 73%, and 32.5% received hepatitis A, tetanus/diphtheria, and typhoid vaccines, respectively. Malaria prophylaxis was given to 12.2% of the participants. Logistic regression analysis revealed that being male and unemployed, having an elementary level of education, traveling to visiting friends and relatives, and short durations of travel were significant determinants of not seeking pre-travel consultations. A. Pavli et al. Conclusion: Significant gaps were revealed in the vaccinations and malaria prophylaxes of travelers departing to Asia. Specific educational tools should be developed to improve the awareness of travelers to high-risk destinations.
Output: Vaccination and malaria prophylaxis among Greek international travelers to Asian destinations
and Golgi apparatus of the unicellular green alga, Micrasterias americana, is facilitated by 50-70 nm vesicles that form from part-rough, part-smooth transitional regions of the endoplasmic reticulum. In growing cells, the vesicles are present at the normal growth temperature of 23 ~ However, at 16 ~ vesicle accumulations occur. Golgi apparatus of non-growing cells exhibited both larger numbers of vesicles and larger dictyosomes at all temperatures. In non-growing cells, vesicle numbers also were increased at 16~ The 16 ~ block was reconstituted in a cell-free system using Golgi apparatusand endoplasmic reticulum-enriched fractions prepared from suspension cultures. When incubated in the presence of ATP and cytosol, transitional endoplasmic reticulum fragments of Micrasterias responded by formation of membrane blebs and vesicles resembling those seen in situ. When prepared from cells metabolically labeled with [3H]leucine, the isolated transition elements supported the transfer of radioactivity to Golgi apparatus preparations immobilized on nitrocellulose strips. The transfer was time-and temperaturedependent and stimulated by ATP. The ATP-dependent component of transfer expressed at 23 ~ was reduced or absent at temperatures of 16 ~ or below. This suggested that membrane transfer mediated by transition vesicles was the same rate-limiting step in endoplasmic reticulum to Golgi apparatus membrane trafficking both in situ and in the cell-free system. Growth, as evidenced by a progressively altered Micrasterias morphology, was slowed at low temperatures but showed no abrupt temperature transition as seen with_ the vesicular traffic between the endoplasmic reticulum and the Golgi apparatus.
Output: Pl ffDPI.ASMA Vesicular membrane transfer between endoplasmic reticulum and Golgi apparatus of a green alga, Micrasterias americana A 16 ~ block and reconstitution in a cell-free system
Severe cases after pH1N1 infection are consequence of interstitial pneumonia triggered by alveolar viral replication and an exacerbated host immune response, characterized by the up-regulation of pro-inflammatory cytokines and the influx of inflammatory leukocytes to the lungs. Different lung cell populations have been suggested as culprits in the unregulated innate immune responses observed in these cases. This study aims to clarify this question by studying the different induction of innate immune molecules by the distinct lung anatomic compartments (vascular, alveolar and bronchiolar) of ferrets intratracheally infected with a human pH1N1 viral isolate, by means of laser microdissection techniques. The obtained results were then analysed in relation to viral quantification in the different anatomic areas and the histopathological lesions observed. More severe lung lesions were observed at 24 h post infection (hpi) correlating with viral antigen detection in bronchiolar and alveolar epithelial cells. However, high levels of viral RNA were detected in all anatomic compartments throughout infection. Bronchiolar areas were the first source of IFN-α and most pro-inflammatory cytokines, through the activation of RIG-I. In contrast, vascular areas contributed with the highest induction of CCL2 and other pro-inflammatory cytokines, through the activation of TLR3. (2015) Hospitalization fatality risk of influenza A(H1N1)pdm09: a systematic review and meta-analysis. Am J Epidemiol 182:294-301 2.
Output: Involvement of the different lung compartments in the pathogenesis of pH1N1 influenza virus infection in ferrets
The influenza A nucleoprotein (NP) is an attractive target for avian flu vaccine development because of its high conversancy in the evolutionary chain of the virus. Here we identified two novel HLA-A*0201 restricted NP epitopes, named H5N1 NP373-381 AMDSNTLEL (NP373) and NP458-466 FQGRGVFEL (NP458), using computational bioinformatic analysis. The NP peptides showed a high binding affinity to HLA-A*0201 on T2 cells, and were able to induce the activation of the cytotoxic T cells in the human peripheral blood mononuclear cells. We examined the potential of using NP373 and NP458 peptide sequences supplemented with a single-chain trimer as potential DNA vaccine candidates in an HHD transgenic mouse model. A gene gun delivery system was used for administrating the vaccine candidates into the animals. The results from cytotoxicity and ELISPOT assays indicated that a significant amount of IFN-c was secreted by the T cells of the vaccinated mice, and the T cells were able to eliminate the corresponding peptide-loaded T2 cells. The discovery of these novel immunogenic NP peptides provides valuable information for avian flu vaccine design and construction. influenza A virus / H5N1 nucleoprotein / HLA-A*0201 T-cell epitope / single-chain trimer / HHD transgenic mouse model * Corresponding author: boyxie@ust.hk 1
Output: Two novel HLA-A*0201 T-cell epitopes in avian H5N1 viral nucleoprotein induced specific immune responses in HHD mice
Acute respiratory infections are a major cause of morbidity in children both in developed and developing countries. A wide range of respiratory viruses, including respiratory syncytial virus (RSV), influenza A and B viruses, parainfluenza viruses (PIVs), adenovirus, rhinovirus (HRV), have repeatedly been detected in acute lower respiratory tract infections (LRTI) in children in the past decades. However, in the last ten years thanks to progress in molecular technologies, newly discovered viruses have been identified including human Metapneumovirus (hMPV), coronaviruses NL63 (HcoV-NL63) and HKU1 (HcoV-HKU1), human Bocavirus (HBoV), new enterovirus (HEV), parechovirus (HpeV) and rhinovirus (HRV) strains, polyomaviruses WU (WUPyV) and KI (KIPyV) and the pandemic H1N1v influenza A virus. These discoveries have heavily modified previous knowledge on respiratory infections mainly highlighting that pediatric population is exposed to a variety of viruses with similar seasonal patterns. In this context establishing a causal link between a newly identified virus and the disease as well as an association between mixed infections and an increase in disease severity can be challenging. This review will present an overview of newly recognized as well as the main emerging respiratory viruses and seek to focus on the their contribution to infection and co-infection in LRTIs in childhood.
Output: The role of infections and coinfections with newly identified and emerging respiratory viruses in children
Synthetic biology is an emerging field, which, since its birth, has shown great value and potential in many fields including medicine, energy, environment and agriculture. It is also important for the study of the origin and evolution of life. Since the publication of the first synthetic cell in May, 2010, synthetic biology again attracts high attention and leads to extensive discussions all over the world. There have been a number of researches and achievements on synthetic biology in the United States and European countries. While in China, so far there is no systematic research on synthetic biology. In order to promote the development of this new discipline in China, we organized this review to systematically introduce the concept and research content of synthetic biology, summarize the achievements, and investigate the current situation in both China and abroad. We also analyzed the opportunities and challenges in synthetic biology, and looked forward to the future development of synthetic biology, especially its future development in China. synthetic cell, synthetic biology, minimal genome Zhang L Y, Chang S H, Wang J. Synthetic biology: From the first synthetic cell to see its current situation and future development.
Output: Invited Review Synthetic biology: From the first synthetic cell to see its current situation and future development
Severe acute respiratory syndrome coronavirus is the causative agent of a respiratory disease with a high case fatality rate. During the formation of the coronaviral replication/ transcription complex, essential steps include processing of the conserved polyprotein nsp7-10 region by the main protease M pro and subsequent complex formation of the released nsp's. Here, we analyzed processing of the coronavirus nsp7-10 region using native mass spectrometry showing consumption of substrate, rise and fall of intermediate products and complexation. Importantly, there is a clear order of cleavage efficiencies, which is influenced by the polyprotein tertiary structure. Furthermore, the predominant product is an nsp7+8(2 : 2) hetero-tetramer with nsp8 scaffold. In conclusion, native MS, opposed to other methods, can expose the processing dynamics of viral polyproteins and the landscape of protein interactions in one set of experiments. Thereby, new insights into protein interactions, essential for generation of viral progeny, were provided, with relevance for development of antivirals.
Output: Processing of the SARS-CoV pp1a/ab nsp7-10 region
Peste des petits ruminants virus (PPRV) causes a highly contagious disease, peste des petits ruminants (PPR), in sheep and goats which has been considered as a serious threat to the local economy in Africa and Asia. However, the in-depth evolutionary dynamics of PPRV during an epidemic is not well understood. We conducted phylogenetic analysis on genomic sequences of 25 PPRV strains from China 2013-2014 outbreaks. All these strains clustered into a novel clade in lineage 4. An evolutionary rate of 2.61 × 10 −6 nucleotide substitutions per site per day was estimated, dating the most recent common ancestor of PPRV China 2013-2014 strains to early August 2013. Transmission network analysis revealed that all the virus sequences could be grouped into five clusters of infection, suggesting long-distance animal transmission play an important role in the spread of PPRV in China. These results expanded our knowledge for PPRV evolution to achieve effective control measures.
Output: Evolutionary dynamics of recent peste des petits ruminants virus epidemic in China during 2013-2014