niryuu/sni-each-converted huggingface dataset:
Acute otitis media (AOM) is an inflammatory response to microbes in the middle ear, sometimes associated with rupture of the tympanic membrane. Human leukocytes produce different patterns of inflammatory mediators in vitro when stimulated with Gram-positive and Gram-negative bacteria, respectively. Here, we investigated the cytokine and prostaglandin E 2 (PGE 2 ) responses in middle ear fluids (MEFs) from children with spontaneously perforated AOM, and related the mediator levels to the presence of pathogens detected by culture (live) or PCR (live or dead). Furthermore, the in vivo cytokine pattern was compared with that induced in leukocytes stimulated by dead bacteria in vitro. MEFs with culturable pathogenic bacteria contained more interleukin (IL)-1b (median: 110 lg/L vs. <7.5 lg/L), tumour necrosis factor (TNF) (6.3 lg/L vs. <2.5 lg/L), IL-8 (410 lg/L vs. 38 lg/L) and IL-10 (0.48 lg/L vs. <0.30 lg/L) than culture-negative fluids, irrespective of PCR findings. IL-6 and PGE 2 were equally abundant (69-110 lg/L) in effusions with live, dead or undetectable bacteria. Cytokine levels were unrelated to bacterial species and to the presence or absence of virus. Similar levels of TNF and IL-6 as found in the MEFs were obtained by in vitro stimulation of leukocytes, whereas 11 times more IL-1b and 3.5 times more IL-8 were produced in vivo, and 22 times more IL-10 was produced in vitro. Vigorous production of proinflammatory cytokines accompanies AOM with membrane rupture, regardless of the causative agent, but the production seems to cease rapidly once the bacteria are killed and fragmented. IL-6 and PGE 2 , however, remain after bacterial disintegration, and may play a role in the resolution phase.
Output: High cytokine levels in perforated acute otitis media exudates containing live bacteria
Hepatitis E virus (HEV) is a viral pathogen transmitted primarily via fecal-oral route. In humans, HEV mainly causes acute hepatitis and is responsible for large outbreaks of hepatitis across the world. The case fatality rate of HEV-induced hepatitis ranges from 0.5 to 3% in young adults and up to 30% in infected pregnant women. HEV strains infecting humans are classified into four genotypes. HEV strains from genotypes 3 and 4 are zoonotic, whereas those from genotypes 1 and 2 have no known animal reservoirs. Recently, notable progress has been accomplished for better understanding of HEV biology and infection, such as chronic HEV infection, in vitro cell culture system, quasienveloped HEV virions, functions of the HEV proteins, mechanism of HEV antagonizing host innate immunity, HEV pathogenesis and vaccine development. However, further investigation on the cross-species HEV infection, host tropism, vaccine efficacy, and HEV-specific antiviral strategy is still needed. This review mainly focuses on molecular biology and infection of HEV and offers perspective new insight of this enigmatic virus.
Output: Molecular Biology and Infection of Hepatitis E Virus
SARS coronavirus (SCoV) nonstructural protein (nsp) 1, a potent inhibitor of host gene expression, possesses a unique mode of action: it binds to 40S ribosomes to inactivate their translation functions and induces host mRNA degradation. Our previous study demonstrated that nsp1 induces RNA modification near the 59-end of a reporter mRNA having a short 59 untranslated region and RNA cleavage in the encephalomyocarditis virus internal ribosome entry site (IRES) region of a dicistronic RNA template, but not in those IRES elements from hepatitis C or cricket paralysis viruses. By using primarily cellfree, in vitro translation systems, the present study revealed that the nsp1 induced endonucleolytic RNA cleavage mainly near the 59 untranslated region of capped mRNA templates. Experiments using dicistronic mRNAs carrying different IRESes showed that nsp1 induced endonucleolytic RNA cleavage within the ribosome loading region of type I and type II picornavirus IRES elements, but not that of classical swine fever virus IRES, which is characterized as a hepatitis C virus-like IRES. The nsp1-induced RNA cleavage of template mRNAs exhibited no apparent preference for a specific nucleotide sequence at the RNA cleavage sites. Remarkably, SCoV mRNAs, which have a 59 cap structure and 39 poly A tail like those of typical host mRNAs, were not susceptible to nsp1-mediated RNA cleavage and importantly, the presence of the 59-end leader sequence protected the SCoV mRNAs from nsp1-induced endonucleolytic RNA cleavage. The escape of viral mRNAs from nsp1-induced RNA cleavage may be an important strategy by which the virus circumvents the action of nsp1 leading to the efficient accumulation of viral mRNAs and viral proteins during infection. Citation: Huang C, Lokugamage KG, Rozovics JM, Narayanan K, Semler BL, et al. (2011) SARS Coronavirus nsp1 Protein Induces Template-Dependent Endonucleolytic Cleavage of mRNAs: Viral mRNAs Are Resistant to nsp1-Induced RNA Cleavage. PLoS Pathog 7(12): e1002433.
Output: SARS Coronavirus nsp1 Protein Induces Template- Dependent Endonucleolytic Cleavage of mRNAs: Viral mRNAs Are Resistant to nsp1-Induced RNA Cleavage
A facile one-pot two-enzyme chemoenzymatic approach has been established for gram (Neu4,5Ac 2 α3Lac, 1.33 g) and preparative-scale (Neu4,5Ac 2 α3LNnT) synthesis of monotreme milk oligosaccharides. Other O-acetyl-5-N-acetylneuraminic acid (Neu4,5Ac 2 )-or 4-O-acetyl-5-N-glycolylneuraminic acid (Neu4Ac5Gc)-containing α2-3-sialosides have also been synthesized in preparative scale. Used as an effective probe, Neu4,5Ac 2 α3GalβpNP was found to be a suitable substrate by human influenza A viruses but not bacterial sialidases. One-pot multienzyme (OPME) synthesis: Monotreme milk oligosaccharides and other sialosides containing a 4-O-acetyl-sialic acid were synthesized in gram (1.33 g for Neu4,5Ac 2 α3Lac) or preparative (10-56 mg) scales using a one-pot two-enzyme (OP2E) sialylation system containing a bacterial cytidine 5′-monophosphate (CMP)-sialic acid synthetase and Pasteurella multocida sialyltransferase 3 (PmST3). Neu4,5Ac 2 α3Galβ4GlcNAcβ3Galβ4GlcβProN 3 (34)-20 mg, yield 81%; white solid. 1 H NMR (800 MHz, D 2 O) δ 4.93 (m, 1H), 4.67 (d, J = 8.0 Hz, 1H), 4.54 (d, J = 8.0 Hz, 1H), 4.47 (d, J = 8.0 Hz, 1H), 4.41 (d, J = 8.0 Hz, 1H), 4.14 (d, J = 3.2 Hz, 1H), 4.11 (dd, J = 9.6 and 3.2 Hz, 1H), 4.07 (t, J = 10.4 Hz, 1H), 3.98-3.54 (m, 28H), 3.44 (t, J = 6.4 Yu et al.
Output: Effective one-pot multienzyme (OPME) synthesis of monotreme milk oligosaccharides and other sialosides containing a 4-O- acetyl sialic acid † HHS Public Access Author manuscript
Abstraet--A preliminary study was conducted to compare the regional intestinal immune responses of neonatal calves inoculated with virulent or attenuated bovine coronavirus (BCV) to determine the cause of reported vaccine failures. A group of 9 newborn, colostrum-deprived calves was used; two calves were inoculated with attenuated virus, four calves were infected with virulent virus (including one naturally infected calf), and three calves were uninfected controls. Calves inoculated with virulent virus produced higher titers of BCV antibodies in the intestines than those inoculated with the attenuated virus. The failure of the calves to respond to the attenuated virus was apparently due to the inability of the virus to replicate to high titers. Spiral colon, ileum, and jejunum were found to be immunologically distinct; the highest anti-BCV antibody responses were detected in spiral colon, the primary site of infection, and involved all four isotypes of bovine immunoglobulins. The antibody response in ileum was lower than in spiral colon. The immune responses developed slowly in jejunum and were associated primarily with the lgG subtypes.
Output: ~ Pergamon ANTIBODY RESPONSES IN SPIRAL COLON, ILEUM, AND JEJUNUM OF BOVINE CORONAVIRUS-INFECTED NEONATAL CALVES
is not known whether they edit RNA genomes through cytidine deamination. Here, we investigated APOBEC3-mediated restriction of Coronaviridae. In experiments in vitro, three human APOBEC3 proteins (A3C, A3F and A3H) inhibited HCoV-NL63 infection and limited production of progeny virus, but did not cause hypermutation of the coronaviral genome. APOBEC3-mediated restriction was partially dependent on enzyme activity, and was reduced by the use of enzymatically inactive APOBEC3. Moreover, APOBEC3 proteins bound to the coronaviral nucleoprotein, and this interaction also affected viral replication. Although the precise molecular mechanism of deaminasedependent inhibition of coronavirus replication remains elusive, our results further our understanding of APOBEC-mediated restriction of RNA virus infections. Apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like type 3 (APOBEC3) proteins are Zn 2+dependent cytidine deaminases that belong to the APOBEC superfamily. APOBEC3 enzymes are considered to be part of the intrinsic defense system in eukaryotic cells, and can inhibit replication of some viruses and restrict mobile genetic elements. All APOBEC3 proteins share a cytidine-deaminase domain, which is identifiable by the primary amino acid motif His-Xaa-Glu-Xaa 23-28 -Pro-Cys-Xaa 2-4 -Cys, in which Zn 2+ is coordinated. Deamination of cytidine results in its conversion to uridine. During this process, the ammonium group on C 4 of cytidine undergoes nucleophilic attack by an activated water molecule and the APOBEC3 glutamate residue. A single copy of a gene encoding APOBEC3 is found in the genomes of rodents, cats, pigs and sheeps, with two genes in the genomes of cows, three the genomes of dogs and horses and seven genes in the human genome, encoding A3A, A3B, A3C, A3D, A3F, A3G and A3H 1 . The mechanisms and selective pressures that led to the APOBEC3 gene expansion in humans are unclear, but it is believed that all the genes originated from duplication of a single-copy primordial APOBEC3 gene. This multiplication may have provided protection from genomic instability caused by human endogenous retroviruses and retrotransposons 2 . The best-studied protein within the human APOBEC3 family is A3G. Its function as an antiviral factor was discovered in 2002 through cDNA-transfer experiments that were designed to identify a cellular suppressor of an HIV-1 accessory protein, the virion infectivity factor (Vif). The primary antiretroviral activity of A3G requires its encapsidation into HIV-1 particles, and involves cytidine deamination of the reverse-transcribed first viral DNA strand, with mutations becoming fixed as G to A changes upon second-strand synthesis. Mutational frequencies can exceed 10% of all G residues (hypermutation), and may result in inhibition of viral replication. This activity is blocked by Vif protein, which specifically binds to and ubiquitinates A3G, directing it for degradation in the Published: xx xx xxxx OPEN www.nature.com/scientificreports/ 2 ScIentIFIc REPORts | (2018) 8:5960 |
Output: APOBEC3-mediated restriction of RNA virus replication OPEN
Tulane virus (TV) is a cultivable calicivirus isolated from rhesus monkeys. In this study, we characterized the substrate specificity of TV protease in trans using recombinant proteases and TV polyprotein fragments containing the predicted proteolytic cleavage sites. Cleavage products have been obtained from 4 of the 5 fragments containing 573 Q-S 574 between the helicase and 3A-like protein, 712 E-A 713 between the 3A-like protein and Vpg, 802 E-G 803 between Vpg and the protease, and 976 E-G 977 between the protease and RdRp. We also characterized the enzymatic activities of the recombinant proteases of TV and Norwalk virus using synthetic fluorogenic peptide substrates. Under optimal conditions for enzymatic assays, partial cross-reactivities on reciprocal substrates were observed between TV and Norwalk virus proteases. The apparently shared substrate specificities between TV and Norwalk virus proteases suggested that the cultivable TV could be used as a model for in vivo evaluation of lead candidates of protease inhibitors for human norovirus.
Output: Substrate specificity of Tulane virus protease
Ubiquitin-specific proteases (USPs) represent the largest family of deubiquitinating enzymes (DUB). These proteases cleave the isopeptide bond between ubiquitin and a lysine residue of a ubiquitin-modified protein. USP18 is a special member of the USP family as it only deconjugates the ubiquitin-like protein ISG15 (interferon-stimulated gene (ISG) 15) from target proteins but is not active towards ubiquitin. Independent of its protease activity, USP18 functions as a major negative regulator of the type I interferon response showing that USP18 is -at least -a bifunctional protein. In this review, we summarise our current knowledge of protease-dependent and -independent functions of USP18 and discuss the structural basis of its dual activity.
Output: USP18 -a multifunctional component in the interferon response
Background: DC-SIGNR (also called CD209L) has been extensively studied on its role in host genetic predisposition to viral infection. In particular, variable number tandem repeat (VNTR) of the neck-region of DC-SIGNR is highly polymorphic and the polymorphism has been investigated for genetic predisposition to various infectious diseases, though conflicting results had been reported. As infection is a major cause of human death and a mechanism of natural selection, we hypothesized that VNTR polymorphism of DC-SIGNR might have an effect on human life span. Here we collected 361 peri-centenarian individuals (age ≥94 for female and age ≥90 for male) and 342 geographically matched controls (age 22-53, mean 35.0 ± 12.0) from Han Chinese. The VNTR polymorphism of the neck region was determined by PCR and genotype was called by separating the PCR products in agarose gel. Results: A total of 11 genotypes and 5 alleles were found in our population. The genotype distribution, allele frequencies and homozygote proportion did not show a significant difference between peri-centenarian and control group. As gender differences in lifespan are ubiquitously observed throughout the animal kingdom, we then stratified the samples by gender. There was more 6/7 genotypes in female peri-centenarian group than that in female control group, at a marginal level of significance (5.56 vs. 1.28%, p = 0.041). The difference was not significant after correction by Bonferroni method. It suggests a possible differential effect of DC-SIGNR VNTR genotypes between sexes. Further studies are warranted to confirm our preliminary findings and investigate the mechanisms of the underlying functions. Our study indicated that there was absence of association between the neck region polymorphism of DC-SIGNR and longevity in Han Chinese population. But the question of whether the DC-SIGNR could affect longevity in a gender-specific pattern remains open.
Output: BMC Medical Genetics The neck-region polymorphism of DC-SIGNR in peri-centenarian from Han Chinese Population
Immune reactivity in the retina can be critically important in inflammation and infections, but regulation of this response is essential. The retinal pigment epithelial (RPE), a unique retinal cell, displays a number of essential functions to support the health of the retina. In this review, we highlight how the RPE cell plays a pivotal role in immune defense. The RPE cell orchestrates both innate and adaptive immunity since it expresses TLRs, complement components, MHC class I and II molecules, and serves as an antigen presenting cell. Moreover, both of these immune responses result in the production of a plethora of cytokines, mainly proinflammatory. In order to counteract these inflammatory factors and silence unwanted immune reactivity, the RPE cell also generates suppressive molecules. Recently, chronic immune reactivity has been implicated in a number of retinal diseases, such as age-related macular degeneration (AMD). Current evidence suggests that the generation of excessive retinal inflammation may be the consequence of a loss of RPE immunosuppressive factors. Herein, we summarize the varied interactions of the RPE cell with the immune response and highlight how the RPE cell survives and participates in this dynamic environment.
Output: Immune regulation in the retina
Swine influenza is an acute respiratory disease in pigs caused by swine influenza virus (SIV). Highly virulent SIV strains cause mortality of up to 10%. Importantly, pigs have long been considered ''mixing vessels'' that generate novel influenza viruses with pandemic potential, a constant threat to public health. Since its emergence in 2009 and subsequent pandemic spread, the pandemic (H1N1) 2009 (H1N1pdm) has been detected in pig farms, creating the risk of generating new reassortants and their possible infection of humans. Pathogenesis in SIV or H1N1pdm-infected pigs remains poorly characterized. Proinflammatory and antiviral cytokine responses are considered correlated with the intensity of clinical signs, and swine macrophages are found to be indispensible in effective clearance of SIV from pig lungs. In this study, we report a unique pattern of cytokine responses in swine macrophages infected with H1N1pdm. The roles of mitogen-activated protein (MAP) kinases in the regulation of the host responses were examined. We found that proinflammatory cytokines IL-6, IL-8, IL-10, and TNF-a were significantly induced and their induction was ERK1/2-dependent. IFN-b and IFN-inducible antiviral Mx and 2959-OAS were sharply induced, but the inductions were effectively abolished when ERK1/2 was inhibited. Induction of CCL5 (RANTES) was completely inhibited by inhibitors of ERK1/2 and JNK1/2, which appeared also to regulate FasL and TNF-a, critical for apoptosis in pig macrophages. We found that NFkB was activated in H1N1pdm-infected cells, but the activation was suppressed when ERK1/2 was inhibited, indicating there is cross-talk between MAP kinase and NFkB responses in pig macrophages. Our data suggest that MAP kinase may activate NFkB through the induction of RIG-1, which leads to the induction of IFN-b in swine macrophages. Understanding host responses and their underlying mechanisms may help identify venues for effective control of SIV and assist in prevention of future influenza pandemics.
Output: Distinct Regulation of Host Responses by ERK and JNK MAP Kinases in Swine Macrophages Infected with Pandemic (H1N1) 2009 Influenza Virus
Advances in free radical research show that reactive oxygen and nitrogen oxide species, for example superoxide, nitric oxide (NO) and peroxynitrite, play an important role in the pathogenesis of different viral infections, including dengue virus. The pathogenic mechanism of dengue haemorrhagic fever (DHF) is complicated and is not clearly understood. The hallmarks of the dengue disease, the antibody-dependent enhancement, the shift from T-helper type 1 (Th1) to Th2 cytokine response and the cytokine tsunami resulting in vascular leakage can now be explained much better with the knowledge gained about NO and peroxynitrite. This paper makes an effort to present a synthesis of the current opinions to explain the pathogenesis of DHF/shock syndrome with NO on centre stage.
Output: Nitric oxide in dengue and dengue haemorrhagic fever: necessity or nuisance?
A Actual pension amount (APA), 1732e1733 and artificial income concept, 1733e1734 old-age dependency ratio, 1743 for specific year, 1733 Adjustment factor (AF), 1746e1747 ADLI. See Agriculture development led-industrialization AEEI. See Autonomous energy efficiency improvement AEZ. See Agro-ecological zone AF. See Adjustment factor AGE analysis, global. See Global applied general equilibrium analysis Agent-based modeling, 1378 AgLU model, 860e861 Agricultural incentives, distortions to, 903e904 national NRAs, 904e906 nominal rates of assistance, 906f, 907e908, 907f RRA calculation, 904 RRA mapped on income, 905f Agricultural price distortions, 880e881 Agriculture development led-industrialization (ADLI), 935e936 Agriculture towards 2050, 960 baseline robustness agricultural growth importance, 977 agricultural price elasticity, 976t, 977 distributional assumptions, 976, 976t ENVISAGE and LEITAP, 971e972, 971t ENVISAGE land supply function, 970 LEITAP model, 970 nested CET function, 970e971 price variability across crops, 974t, 975 sensitivity analysis, 972e973, 973t demand-side assumptions, 965e967 global implications agricultural growth in baseline, 969e970 average global producer price, 967e968, 967f land supply and price growth, 969, 969t productivity growth, 968e969, 968f global stock-to-use ratios, 961e962, 962f multiple structural factors, 961, 961f supply-side assumptions average productivity increase, 964t, 965 LEI group, 963 segments land, 963, 963t
Output: INDEX-VOLUME 1B
Many viruses that replicate in the cytoplasm compartmentalize their genome replication and transcription in organelle-like structures that enhance replication efficiency and protection from host defenses. In particular, recent studies with diverse positive-strand RNA viruses have further elucidated the ultrastructure of membrane-bound RNA replication complexes and how these complexes function in close coordination with virion assembly and budding. The structure, function, and assembly of some positive-strand RNA virus replication complexes have parallels and potential evolutionary links with the replicative cores of doublestrand RNA virus and retrovirus virions and more general similarities with the replication factories of cytoplasmic DNA viruses. . In vivo self-interaction of nodavirus RNA replicase protein a revealed by fluorescence resonance energy transfer. J. Virol. 79, 8909-8919. Egger, D., and Bienz, K. (2002) . Recombination of poliovirus RNA proceeds in mixed replication complexes originating from distinct replication start sites. J. Virol. 76, 10960-10971. Egger, D., Teterina, N., Ehrenfeld, E., and Bienz, K. (2000). Formation of the poliovirus replication complex requires coupled viral translation, vesicle production, and viral RNA synthesis. J. Virol. 74, 6570-6580. Froshauer, S., Kartenbeck, J., and Helenius, A. (1988). Alphavirus RNA replicase is located on the cytoplasmic surface of endosomes and lysosomes.
Output: Cell Host & Microbe Review Cytoplasmic Viral Replication Complexes
China. In the current study we investigated the genetic diversity of RVAs in fecal samples from 87 straw-colored fruit bats living in close contact with humans in Cameroon using viral metagenomics. Five (near) complete RVA genomes were obtained. A single RVA strain showed a partial relationship with the Kenyan bat RVA strain, whereas the other strains were completely novel. Only the VP7 and VP4 genes showed significant variability, indicating the occurrence of frequent reassortment events. Comparing these bat RVA strains with currently used human RVA screening primers indicated that most of the novel VP7 and VP4 segments would not be detected in routine epidemiological screening studies. Therefore, novel consensus screening primers were developed and used to screen samples from infants with gastroenteritis living in close proximity with the studied bat population. Although RVA infections were identified in 36% of the infants, there was no evidence of zoonosis. This study identified multiple novel bat RVA strains, but further epidemiological studies in humans will have to assess if these viruses have the potential to cause gastroenteritis in humans. Rotaviruses (RVs) are major enteric pathogens causing severe dehydrating diarrhea mostly in juvenile humans and animals worldwide 1 . RVs belong to the family Reoviridae and the genus Rotavirus consists of eight species (A-H) 2 . Recently, a distinct canine RV species has been identified and tentatively named Rotavirus I (RVI), although ratification by the International Committee on Taxonomy of Viruses (ICTV) is pending 3 . Group A rotaviruses (RVAs) are the most common of all rotavirus species and infect a wide range of animals including humans 4 . The rotavirus genome consists of 11 double-stranded RNA segments encoding 6 structural viral proteins (VP1-VP4, VP6, and VP7) and 6 nonstructural proteins (NSP1-NSP6). In 2008, a uniform classification system was proposed for each of the 11 gene segments resulting in G-, P-, I-, R-, C-, M-, A-, N-, T-,
Output: Novel highly divergent reassortant bat rotaviruses in Cameroon, without evidence of zoonosis
Intake of colostrum by neonatal calves and early transition to calf starter are two important factors in successful calf programs. Thirty-one Holstein calves were used to determine health and performance of calves that were 1) allowed to remain with their dams for 3 d and suckle (suckled calves) or were removed from their dams and fed colostrum only by bottle (bottle calves); and were 2) fed ground, pelleted, or textured starters, formulated to be isonitrogenous. Bottle calves were removed from their dams at birth, fed 2.84 L of colostrum, placed in individual hutches, and fed 1.89 L of colostrum 12 h after the first feeding. Suckled calves were removed from their dams after 3 d and placed in individual hutches. Once calves were housed in hutches, they were fed 2 L of whole milk twice daily and were provided starters and water beginning on d 3. Calves were weighed at birth and weekly for 6 wk. Blood samples were obtained at birth, 24 h, and weekly for serum protein determination. Starter intake, fecal scores, and electrolyte treatments were recorded daily. Weaning began when calves had consumed 0.68 kg starter for 2 d consecutively. There were no differences in treatment means between suckled and bottle calves for total gain, grain consumption, days with fecal scores >2, or electrolyte treatments per calf. Average days to weaning was greater for bottle calves compared with suckled calves. Mean serum protein concentration at 24 h was greater for bottle (6.0 g/dl) compared with suckled calves (5.8 g/dl) and only 2 of 15 bottle calves had serum protein concentrations <5.0 g/dl compared with 6 of 16 suckled calves. For starter treatments, calves fed textured starter consumed more total grain, were weaned earlier, and weighed more at 6 wk of age than calves fed pelleted starter. Based on 24-h serum
Output: Health and Performance of Holstein Calves that Suckled or Were Hand-Fed Colostrum and Were Fed One of Three Physical Forms of Starter 1
Oral administration of immunoglobulin prepared from the egg yolk of hens immunized with porcine transmissible gastroenteritis virus (TGEV) has been demonstrated to reduce piglets mortality significantly in our previous studies. In the present study, we investigated the stability of chicken yolk immunoglobulin (IgY) specific to TGEV by measuring the remaining activity by ELISA. The results showed that the IgY was stable between pH 4 and pH 11. In the incubation with pepsin at pH 4 and pH 6, about 90% and 100% of the IgY activity remained, respectively. IgY activity could remain approximately 80% at 60°C for 30 min, suggesting that pasteurization can be applied to sterilizing the product. The stability of IgY at 25°C and freezing-thawing treatment indicated that the IgY was easy to be conserved. These results highlight the attractive potential application of IgY as the antibodies of oral administration for treatment of TGEV infections.
Output: Preparation and physicochemical property of chicken yolk immunoglobulin (IgY) against porcine transmissible gastroenteritis virus (TGEV)
Porcine reproductive and respiratory syndrome virus (PRRSV), an arterivirus that causes significant losses in the pig industry, is one of the most important animal pathogens of global significance. Since the discovery of the virus, significant progress has been made in understanding its epidemiology and transmission, but no adequate control measures are yet available to eliminate infection with this pathogen. The genome replication of PRRSV is required to reproduce, within a few hours of infection, the millions of progeny virions that establish, disseminate, and maintain infection. Replication of the viral RNA genome is a multistep process involving a replication complex that is formed not only from components of viral and cellular origin but also from the viral genomic RNA template; this replication complex is embedded within particular virus-induced membrane vesicles. PRRSV RNA replication is directed by at least 14 replicase proteins that have both common enzymatic activities, including viral RNA polymerase, and also unusual and poorly understood RNAprocessing functions. In this review, we summarize our current understanding of PRRSV replication, which is important for developing a successful strategy for the prevention and control of this pathogen. : porcine reproductive and respiratory syndrome virus, RNA replication, viral gene expression, arterivirus Pensaert, M.B. 1999. Entry of porcine reproductive and respiratory syndrome virus into porcine alveolar macrophages via receptor-mediated endocytosis. . 2010. Arterivirus Nsp1 modulates the accumulation of minus-strand templates to control the relative abundance of viral mRNAs. PLoS Pathog. 6, e1000772. Nedialkova, D.D., Ulferts, R., van den Born, E., Lauber, C., Gorbalenya, A.E., Ziebuhr, J., and Snijder, E.J. 2009. Biochemical characterization of arterivirus nonstructural protein 11 reveals the nidovirus-wide conservation of a replicative endoribonuclease. J. Virol. 83, 5671-5682. Nelsen, C.J., Murtaugh, M.P., and Faaberg, K.S. 1999. Porcine reproductive and respiratory syndrome virus comparison: divergent evolution on two continents. . 1993. Differentiation of U.S. and European isolates of porcine reproductive and respiratory syndrome virus by monoclonal antibodies.
Output: Overview: Replication of Porcine Reproductive and Respiratory Syndrome Virus
Background: Transmission of respiratory infections poses a major public health challenge during the Hajj and Umrah in the Kingdom of Saudi Arabia. Acquisition of Streptococcus pneumoniae during Hajj has been studied in the past and recommendations for vaccination against S. pneumoniae have been made for high risk groups. Methods: The purpose of this study was to assess the knowledge and attitudes of French Hajj pilgrims towards pneumococcal vaccination. Adult pilgrims departing from Marseille, France to Mecca for the 2014 Hajj season were administered a face-to-face questionnaire to ascertain their knowledge and attitudes towards pneumococcal vaccination before departing for Hajj. Results: A total of 300 participants took part. Their overall knowledge about the severity of pneumonia and the existence of the vaccine was very low. Out of 101 participants who had an indication for pneumococcal vaccination, irrespective of their travel status, only 7% were advised to have the vaccine by their general practitioner. Conclusions: These results reinforce the need for better dissemination of information either before or during the pre-travel counselling. The visit to the travel clinic for receiving the * Corresponding author. þ33 (0) 4 91 96 35 35, þ33 (0) 4 91 96 35 36; fax: þ33 (0) 4 91 96 89 38. Travel Medicine and Infectious Disease (2015) 13, 251e255 mandatory meningococcal vaccination for Hajj is a good opportunity to update routine immunizations, including pneumococcal vaccination. ª
Output: French Hajj pilgrims' experience with pneumococcal infection and vaccination: A knowledge, attitudes and practice (KAP) evaluation
To assess the economic impact of bovine coronavirus (BCV) and bovine respiratory syncytial virus (BRSV) infections, accurate estimates of their associated effects on animal performance are needed. This study aimed to quantify the variation in individual test-day milk yield and somatic cell count, risk of reproductive failure after first service of dairy cows, and risk of death of calves and heifers according to the BCV and BRSV status of the herd. Three types of status were defined for BCV and BRSV infections, based on 1) the dynamics over a 7-mo period of BCV-and BRSV-specific antibody levels in pooled milk of primiparous cows; 2) the possible occurrence of presumably BCV-and BRSV-related clinical outbreaks; and 3) the combination of both pieces of information. A total of 36,184 test days, 2,716 cows with a first service, and 4,104 calves and heifers in 65 Swedish herds were included in the analyses. Animal performance associated with BCV and BRSV infections was quantified using hierarchical mixed generalized and survival models, after adjustment for covariates known to influence the performance under study. A significant reduction in milk yield was observed for cows in presumably BRSV recently infected herds, as well as in herds having a presumably BRSV-related clinical outbreak (of 0.57 and 0.91 kg/d, respectively), compared with cows in presumably infection-free herds. There was also a significant increase in somatic cell count (of 12,000 cells/mL) for cows located in herds with a BRSV outbreak. The risk of failure after first service, as well as the risk of death in calf and heifer, was numerically higher in BRSV-infected herds, although this was not statistically significant. In contrast, BCV infection herd status, as defined in the present study, was not significantly associated with any production losses in animals from infected herds compared with those in infection-free herds.
Output: Associations between bovine coronavirus and bovine respiratory syncytial virus infections and animal performance in Swedish dairy herds
Background: Data on the etiologies of pneumonia among children are inadequate, especially in developing countries. The principal objective is to undertake a multicenter incident case-control study of <5-year-old children hospitalized with pneumonia in developing and emerging countries, aiming to identify the causative agents involved in pneumonia while assessing individual and microbial factors associated with the risk of severe pneumonia. Methods/design: A multicenter case-control study, based on the GABRIEL network, is ongoing. Ten study sites are located in 9 countries over 3 continents: Brazil, and Paraguay. At least 1,000 incident cases and 1,000 controls will be enrolled and matched for age and date. Cases are hospitalized children <5 years with radiologically confirmed pneumonia, and the controls are children without any features suggestive of pneumonia. Respiratory specimens are collected from all enrolled subjects to identify 19 viruses and 5 bacteria. Whole blood from pneumonia cases is being tested for 3 major bacteria. S. pneumoniae-positive specimens are serotyped. Urine samples from cases only are tested for detection of antimicrobial activity. The association between procalcitonin, C-reactive protein and pathogens is being evaluated. A discovery platform will enable pathogen identification in undiagnosed samples. Discussion: This multicenter study will provide descriptive results for better understanding of pathogens responsible for pneumonia among children in developing countries. The identification of determinants related to microorganisms associated with pneumonia and its severity should facilitate treatment and prevention.
Output: Multicenter case-control study protocol of pneumonia etiology in children: Global Approach to Biological Research, Infectious diseases and Epidemics in Low-income countries (GABRIEL network)
Estimating the case-fatality risk (CFR)-the probability that a person dies from an infection given that they are a case-is a high priority in epidemiologic investigation of newly emerging infectious diseases and sometimes in new outbreaks of known infectious diseases. The data available to estimate the overall CFR are often gathered for other purposes (e.g., surveillance) in challenging circumstances. We describe two forms of bias that may affect the estimation of the overall CFR-preferential ascertainment of severe cases and bias from reporting delays-and review solutions that have been proposed and implemented in past epidemics. Also of interest is the estimation of the causal impact of specific interventions (e.g., hospitalization, or hospitalization at a particular hospital) on survival, which can be estimated as a relative CFR for two or more groups. When observational data are used for this purpose, three more sources of bias may arise: confounding, survivorship bias, and selection due to preferential inclusion in surveillance datasets of those who are hospitalized and/or die. We illustrate these biases and caution against causal interpretation of differential CFR among those receiving different interventions in observational datasets. Again, we discuss ways to reduce these biases, particularly by estimating outcomes in smaller but more systematically defined cohorts ascertained before the onset of symptoms, such as those identified by forward contact tracing. Finally, we discuss the circumstances in which these biases may affect non-causal interpretation of risk factors for death among cases. PLOS Neglected Tropical Diseases |
Output: Potential Biases in Estimating Absolute and Relative Case-Fatality Risks during Outbreaks
Nanomaterial, due to its unique physical, chemical and biological properties compared to its bulk counterparts, has the potential to provide a product superior to its bulk predecessor. In this study, a novel alumina nanofiber filter was assessed for its removal and retention capability for MS2 aerosol. Its physical removal efficiency in the 10-400 nm range was 94.35%, while its viable removal efficiency was 98.87%, which was slightly lower than three conventional HEPA filters tested. However, its pressure drop was much lower than HEPA filters, yielding a higher filter quality than HEPA filters. The average extracted fraction from the nanofiber filter was 8.64×10 −2 ± 7.00×10 −2 , which is three orders lower than other HEPA filters, demonstrating that the viruses were effectively retained in the nanofiber filter. Furthermore, the performance of the nanofiber filter showed no dependence on relative humidity. In conclusion, this novel alumina nanofiber filter presents advantageous potential for removal and retention of viral aerosol agents.
Output: Removal and retention of viral aerosols by a novel alumina nanofiber filter
Heightened surveillance of acute febrile illness in China since 2004 led to the identification of a severe fever with thrombocytopenia syndrome (SFTS) with unknown etiology. Sporadic patients hospitalized with SFTS in 2009 and 2010 were identified and serum samples were collected. Sequence from a novel species of phlebovirus was identified by sequence independent single primer amplification (SISPA) from the serum of a patient with SFTS. The virus was isolated in Vero cell culture and its complete genome sequence was determined, only distantly related to other known phleboviruses. Electron microscopic analysis revealed a virion morphologically characteristic of phleboviruses. The virus was named as SFTS virus. The viral RNA and/or specific antibodies were detected from the blood of patients with SFTS. Serological assays demonstrated a virus-specific immune response in pairs of sera collected from patients at acute and convalescent phases. The pathogenic mechanisms of thrombocytopenia in human SFTS disease was resembled in a mouse model. The results had been collected to demonstrate that SFTS virus was etiologically associated with an acute and novel infectious disease, SFTS in humans.
Output: The Discovery Process of SFTS in China
Background: Lactoferrin (Lf) is an 80 kDa iron-binding glycoprotein of the transferrin family. It is abundant in milk and in most biological fluids and is a cell-secreted molecule that bridges innate and adaptive immune function in mammals. Its protective effects range from anticancer, anti-inflammatory and immune modulator activities to antimicrobial activities against a large number of microorganisms. This wide range of activities is made possible by mechanisms of action involving not only the capacity of Lf to bind iron but also interactions of Lf with molecular and cellular components of both hosts and pathogens. Scope of review: This review summarizes the activities of Lf, its regulation and potential applications. Major conclusions: The extensive uses of Lf in the treatment of various infectious diseases in animals and humans has been the driving force in Lf research however, a lot of work is required to obtain a better understanding of its activity. General significance: The large potential applications of Lf have led scientists to develop this nutraceutical protein for use in feed, food and pharmaceutical applications. This article is part of a Special Issue entitled Molecular Mechanisms of Iron Transport and Disorders. j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / b b a g e n primates, 7 even-toed ungulates, 1 pig, 1 cat, and 1 mouse. Pairwise sequence identities ranged from a minimum of~78% to nearly 100%. The main outliers in this group were Lfs from primates, in which human and chimpanzee are quite similar (95-98%) when compared to orangutan (79%). On the other hand, horse and camel; pig, cow, yak, water buffalo, bull, and goat Lfs share 81 and 78% of sequence identity respectively when compared to human Lf as outgroup. The sequence relationships given above show that the Lfs form a highly conserved sequence family, and also sequence identity between Lfs and other Tfs is relatively high at 60-65% [19] . A characteristic feature of Lfs is their highly basic character, with a pI typically greater than 9; this property is typically predictable from their sequence. Structurally, the feature that most readily distinguishes Lfs from Tfs is the peptide linker between the two lobes, thought to have evolved from an ancient duplication event [20] , which also contains several proline residues. Lf is an 80 kDa glycosylated protein of~700 amino acids, with a high homology among species. It is comprised of a simple polypeptide chain folded into two symmetrical lobes (the N-lobe and C-lobe), which are highly homologous with one another (33-41% homology). The two lobes are connected via a hinge region containing parts of an α-helix between amino acids 333 and 343 in human Lf (hLf) [7] , which confers flexibility to the molecule [6, 7, 21] . The polypeptide chain includes amino acids 1-332, comprising the N-lobe, and 344-703, comprising the C-lobe, and it is made up of α-helix and β-pleated sheet structures that create two domains within each lobe (domains I and II) [22] . Each lobe can bind a metal atom in synergy with the carbonate ion (CO 3 −2
Output: Lactoferrin a multiple bioactive protein: An overview ☆
This paper uses multivariate GARCH techniques to study volatility spillovers between the Chinese non-deliverable forward market and seven of its Asia-Pacific counterparts over the period January 1998 to March 2005. To account for the time-variability of conditional correlation, a dynamic correlation structure is included in the volatility model specification. The empirical results demonstrate that the renminbi non-deliverable forward (NDF) has been a driver of various Asian currency markets but that such co-movements exhibit a substantial degree of heterogeneity. As to the determinants of the magnitude of these co-movements, we test the relevance of potential factors and find that it is the degree of real and financial integration, in particular, that exerts the largest influence on volatility transmission.
Output: Volatility transmissions between renminbi and Asia-Pacific on-shore and off-shore U.S. dollar futures
Inhalation of Saccharopolyspora rectivirgula causes "farmer's lung" disease, a classic example of hypersensitivity pneumonitis (HP). Monocyte chemoattractant protein-1 (MCP-1) is increased in the bronchoalveolar lavage fluid of mice challenged with S rectivirgula, and S rectivirgula induces MCP-1 secretion by alveolar macrophages. We tested the hypothesis that MCP-1 and its receptor CC chemokine receptor-2 (CCR2) are essential to the development of experimental HP by treating mice with MCP-1 antibody and using CCR2 ؊/؊ mice. Administration of anti-MCP-1 did not change the response to intratracheally administered S rectivirgula. CCR2 ؊/؊ animals responded in a fashion similar to that of wild-type animals to intratracheally administered.S rectivirgula. To determine the influence of the MCP-1-CCR2 interaction in vitro, we transferred S rectivirgula-cultured spleen cells from S rectivirgulasensitized mice, to naïve recipients. Later, challenge of the recipients with intratracheal S rectivirgula and examination of both lung histology and bronchoalveolar lavage fluid characteristics were used to determine whether adoptive transfer had occurred. We found that cultured cells from CCR2 ؊/؊ animals were fully capable of adoptive transfer. We conclude that interaction of MCP-1 with CCR2 is not necessary for the development of pulmonary inflammation in response to intratracheally administered S rectivirgula or cells able to adoptively transfer experimental HP. (J Lab Clin Med 2003;142:187-95) Abbreviations: ANOVA ϭ analysis of variance; BALF ϭ bronchoalveolar lavage fluid; CCR2 ϭ CC chemokine receptor-2; EHP ϭ experimental hypersensitivity pneumonitis; FLD ϭ "farmer's lung" disease; HEPA ϭ high-efficiency particulate air; HP ϭ hypersensitivity pneumonitis; HSD ϭ honestly significant difference; IFN-␥ ϭ interferon-␥; IL ϭ interleukin; MCP ϭ monocyte chemoattractant protein; MIP-1␣ ϭ macrophage inflammatory protein-1␣; SEM ϭ standard error of the mean; Th ϭ T-helper; TNF ϭ tumor necrosis factor
Output: Experimental hypersensitivity pneumonitis: Role of MCP-1
Human longevity is a complex phenotype with a strong genetic predisposition. Increasing evidence has revealed the genetic antecedents of human longevity. This article aims to review the data of various case/control association studies that examine the difference in genetic polymorphisms between long-lived people and younger subjects across different human populations. There are more than 100 candidate genes potentially involved in human longevity; this article particularly focuses on genes of the insulin/IGF-1 pathway, FOXO3A, FOXO1A, lipoprotein metabolism (e.g., APOE and PON1), and cell-cycle regulators (e.g., TP53 and P21). Since the confirmed genetic components for human longevity are few to date, further precise assessment of the genetic contributions is required. Gaining a better understanding of the contribution of genetics to human longevity may assist in the design of improved treatment methods for age-related diseases, delay the aging process, and, ultimately, prolong the human lifespan.
Output: The role of genetic variants in human longevity
Immune sera from convalescent patients have been shown to be effective in the treatment of patients infected with Severe Acute Respiratory Syndrome Virus (SARS-CoV) making passive immune therapy with human monoclonal antibodies an attractive treatment strategy for SARS. Previously, using Xenomouse (Amgen British Columbia Inc), we produced a panel of neutralizing Human monoclonal antibodies (HmAbs) that could specifically bind to the ectodomain of the SARS-CoV spike (S) glycoprotein. Some of the HmAbs were S1 domain specific, while some were not. In this study, we describe non-S1 binding neutralizing HmAbs that can specifically bind to the conserved S2 domain of the S protein. However, unlike the S1 specific HmAbs, the S2 specific HmAbs can neutralize pseudotyped viruses expressing different S proteins containing receptor binding domain sequences of various clinical isolates. These data indicate that HmAbs which bind to conserved regions of the S protein are more suitable for conferring protection against a wide range of SARS-CoV variants and have implications for generating therapeutic antibodies or subunit vaccines against other enveloped viruses. Citation: Elshabrawy HA, Coughlin MM, Baker SC, Prabhakar BS (2012) Human Monoclonal Antibodies against Highly Conserved HR1 and HR2 Domains of the SARS-CoV Spike Protein Are More Broadly Neutralizing. PLoS ONE 7(11): e50366.
Output: Human Monoclonal Antibodies against Highly Conserved HR1 and HR2 Domains of the SARS-CoV Spike Protein Are More Broadly Neutralizing