title: Evaluation of a Commercially Available Human Serum Amyloid A (SAA) Turbidimetric Immunoassay for Determination of Feline SAA Concentration

text: Serum amyloid A (SAA) is an acute-phase protein in cats likely to be useful for diagnosing and monitoring inflammatory diseases, especially if rapid, reliable and automated assays can be made available. A commercially available automated human SAA turbidimetric immunoassay (SAA-TIA) was evaluated for determination of SAA in cats. Intra-assay and inter-assay imprecisions were in the ranges 2.1–9.9% and 7.0–12.5%, respectively, and without significant inaccuracy. Eighty-eight cats were divided into groups according to (A) the presence or absence of an acute-phase response (APR) (n = 23 and 65, respectively) and (B) clinical diagnosis (clinically healthy cats, cats diagnosed with inflammatory/infectious diseases, endocrine/metabolic diseases, neoplastic diseases, and miscellaneous disorders (n=43, 13, 8, 4 and 20, respectively)). The observed SAA concentrations were, as expected, different for (A) cats with and without an APR and (B) cats with inflammatory/infectious diseases compared to other diagnostic groups, except neoplastic diseases. In conclusion, the SAA concentration in cats could be measured reliably using the commercially available TIA designed for measuring human SAA, which should facilitate implementation of the parameter for routine diagnostic purposes.


title: Sortilin as a Regulator of Lipoprotein Metabolism

text: Elevated low-density lipoprotein cholesterol (LDL-C) is associated with increased risk of atherosclerotic cardiovascular disease (ASCVD) and myocardial infarction (MI). Much of the insight into LDL metabolism has been gained through the study of Mendelian disorders of lipid metabolism. Genome-wide associations studies (GWAS) are now being used to identify novel genes and loci that contribute to variations in LDL-C levels, and they have identified the SORT1 gene as an important modulator of LDL-C levels and ASCVD risk. Mechanistic studies in mice and cell culture also suggest that the SORT1 gene is an important regulator of lipoprotein metabolism; however, these studies disagree on the directionality of the effect of Sort1 expression on plasma lipids and the mechanism for the lipid changes. Here we review the identification of the SORT1 locus as a modulator of LDL-C levels and ASCVD risk and the first mechanistic studies that explore the role of Sortilin in lipid metabolism.


title: Alterations in cell cycle dynamics in human endothelium cell culture infected with influenza virus

text: The cell cycle of endothelium EAhy 926 cell culture infected with influenza virus has been studied. Cytometric analysis of cell culture synchronized by contact inhibition revealed the elongation of the S phase of the cell cycle in EAhy 926 cells under the influence of influenza virus. This result was shown in an EAhy 926 culture infected with influenza virus and treated with nocodazole. Comparison of a lung carcinoma A549 cell line in which influenza virus causes G(0)/G(1) arrest and of an endothelial EAhy 926 cell line in which the same infection leads to S-phase elongation allows it to be suggested that different effects of influenza virus on cell cycle dynamics depend on the origin of infected cells.


title: Transcriptome profiling indicating canine parvovirus type 2a as a potential immune activator

text: Canine parvovirus type 2a (CPV-2a) is a variant of CPV-2, which is a highly contagious pathogen causing severe gastroenteritis and death in young dogs. However, how CPV-2 participates in cell regulation and immune response remains unknown. In this study, persistently infected MDCK cells were generated through culture passage of the CPV-2a-infected cells for ten generations. Our study showed that CPV-2a induces cell proliferation arrest and cell morphology alternation before the fourth generation, whereas, the cell morphology returns to normal after five times of passages. PCR detection of viral VP2 gene demonstrated that CPV-2a proliferate with cell passage. An immunofluorescence assay revealed that CPV-2a particles were mainly located in the cell nuclei of MDCK cell. Then transcriptome microarray revealed that gene expression pattern of MDCK with CPV-2a persistent infection is distinct compared with normal cells. Gene ontology annotation and Kyoto Encyclopedia of Genes and Genome pathway analysis demonstrated that CPV-2a infection induces a series of membrane-associated genes expression, including many MHC protein or MHC-related complexes. These genes are closely related to signaling pathways of virus–host interaction, including antigen processing and presentation pathway, intestinal immune network, graft-versus-host disease, and RIG-I-like helicases signaling pathway. In contrast, the suppressed genes mediated by CPV-2a showed low enrichment in any category, and were only involved in pathways linking to synthesis and metabolism of amino acids, which was confirmed by qPCR analysis. Our studies indicated that CPV-2a is a natural immune activator and has the capacity to activate host immune responses, which could be used for the development of antiviral strategy and biomaterial for medicine.


title: Interspecies transmission and host restriction of avian H5N1 influenza virus

text: Long-term endemicity of avian H5N1 influenza virus in poultry and continuous sporadic human infections in several countries has raised the concern of another potential pandemic influenza. Suspicion of the avian origin of the previous pandemics results in the close investigation of the mechanism of interspecies transmission. Entry and fusion is the first step for the H5N1 influenza virus to get into the host cells affecting the host ranges. Therefore receptor usage study has been a major focus for the last few years. We now know the difference of the sialic acid structures and distributions in different species, even in the different parts of the same host. Many host factors interacting with the influenza virus component proteins have been identified and their role in the host range expansion and interspecies transmission is under detailed scrutiny. Here we review current progress in the receptor usage and host factors.


title: On the Role of Asymptomatic Infection in Transmission Dynamics of Infectious Diseases

text: We propose a compartmental disease transmission model with an asymptomatic (or subclinical) infective class to study the role of asymptomatic infection in the transmission dynamics of infectious diseases with asymptomatic infectives, e.g., influenza. Analytical results are obtained using the respective ratios of susceptible, exposed (incubating), and asymptomatic classes to the clinical symptomatic infective class. Conditions are given for bistability of equilibria to occur, where trajectories with distinct initial values could result in either a major outbreak where the disease spreads to the whole population or a lesser outbreak where some members of the population remain uninfected. This dynamic behavior did not arise in a SARS model without asymptomatic infective class studied by Hsu and Hsieh (SIAM J. Appl. Math. 66(2), 627–647, 2006). Hence, this illustrates that depending on the initial states, control of a disease outbreak with asymptomatic infections may involve more than simply reducing the reproduction number. Moreover, the presence of asymptomatic infections could result in either a positive or negative impact on the outbreak, depending on different sets of conditions on the parameters, as illustrated with numerical simulations. Biological interpretations of the analytical and numerical results are also given.


title: Sequence Analysis of the S3 Gene from a Turkey Reovirus

text: The deduced σ2 protein sequence from the S3 gene segment of a novel turkey reovirus, designated NC98, isolated from the bursa of birds exhibiting poult enteritis and mortality syndrome was determined. The isolate, serologically distinct from other avian reoviruses, was isolated in turkey embryo kidney cells and RNA was purified for cDNA synthesis. Oligonucleotide primers were designed based on conserved avian S3 nucleotide sequence data. The NC98 S3 open reading frame comprised 1101 base pairs and encoded 366 amino acids with a predicated molecular mass of 40.5 kDa. Although the S3 nucleotide sequence from several chicken isolates share at least 86% identity, they share only 64% with the NC98 turkey isolate. Interestingly, the S3 nucleotide sequence from a muscovy duck reovirus shares 55% identity with NC98 and 53% identity with chicken isolates. As observed in other avian reovirus σ2 protein sequences, a zinc-binding motif and double-stranded RNA binding domain were found within the predicted amino acid sequence of NC98. Phylogenetic analysis of the deduced σ2 sequence demonstrated that NC98 separated as a distinct virus relative to other avian strains. The results of this study indicate that NC98 is a novel turkey reovirus that shares limited genomic sequence identity to isolates of chicken and duck origin and should be considered a separate virus species within subgroup 2 of the Orthoreovirus genus.


title: Avian Influenza

text: The current epidemic of H5N1 highly pathogenic avian influenza in Southeast Asia raises serious concerns that genetic reassortment will result in the next influenza pandemic. There have been 164 confirmed cases of human infection with avian influenza since 1996. In 2004, there were 45 cases of human H5N1 in Vietnam and Thailand, with a mortality rate more than 70%. In addition to the potential public health hazard, the current zoonotic epidemic has caused severe economic losses. Efforts must be concentrated on early detection of bird outbreaks with aggressive culling, quarantining, and disinfection. To prepare for and prevent an increase in human cases, it is essential to improve detection methods and stockpile effective antivirals. Novel therapeutic modalities, including short-interfering RNAs and new vaccine strategies that use plasmid-based genetic systems, offer promise should a pandemic occur.


title: Prevalence of subclinical coccidiosis in river buffalo calves of southwest of Iran

text: Despite the importance of buffalo farming in Iran, little is known in this country about the abundance and distribution of Eimeria spp. in the animal species. The present study was designed to investigate the prevalence and species characterization of Eimeria oocysts in river buffalo calves of Khuzestan province, southwest of Iran. Of the total 108 fecal samples examined for Eimeria, 108 (100%) were found infected with 11 species of the parasite. Among the identified species of Eimeria, E. bovis was found to be the predominant etiological agent (76.85%), followed in order by E. canadensis (62.96%), E. zuernii (47.2%), E. ellipsoidalis (26.85%), E. subspherica (25.92%), E. brasiliensis (19.4%), E. auburnensis (18.51%), E. alabamensis (14.81%), E. pellita (11.1%), E. illinoisensis (5.5%) and E. bukidnonensis (2.7%). In most calves multiple infections with three species were present. While, 20.7% of calves showed heavy infection, 50.4 and 24.8% of calves showed weak and moderate infection, respectively. There was no significant difference in the OPG values between the calves of different localities. There was also no significant difference between the prevalence rate of infection in males and females. A total of 16.6% of all faecal samples were found to be diarrheic. A highly significant relationship could be identified between the occurrence of diarrhea and the level of E. bovis and E. zuernii oocysts excretion. Considering the pervasive occurrence and negative effects of the infection on the health condition and the growth performance of buffalo calves, infections should receive increased attention by both farmers and veterinarians.


title: ROS and diseases: role in metabolism and energy supply

text: Researches dedicated to reactive oxygen species (ROS) had been performed for decades, yet the outcomes remain controversial. With the relentless effort of studies, researchers have explored the role of ROS in biosystem and various diseases. ROS are beneficial for biosystem presenting as signalling molecules and enhancing immunologic defence. However, they also have harmful effects such as causing tissue and organ damages. The results are controversial in studies focusing on ROS and ROS-related diseases by regulating ROS with inhibitors or promotors. These competing results hindered the process for further investigation of the specific mechanisms lying behind. The opinions presented in this review interpret the researches of ROS from a different dimension that might explain the competing results of ROS introduced so far from a broader perspective. This review brings a different thinking to researchers, with the neglected features and potentials of ROS, to relate their works with ROS and to explore the mechanisms between their subject and ROS.


title: Viral component of the human genome

text: Relationships between viruses and their human host are traditionally described from the point of view taking into consideration hosts as victims of viral aggression, which results in infectious diseases. However, these relations are in fact two-sided and involve modifications of both the virus and host genomes. Mutations that accumulate in the populations of viruses and hosts may provide them advantages such as the ability to overcome defense barriers of host cells or to create more efficient barriers to deal with the attack of the viral agent. One of the most common ways of reinforcing anti-viral barriers is the horizontal transfer of viral genes into the host genome. Within the host genome, these genes may be modified and extensively expressed to compete with viral copies and inhibit the synthesis of their products or modulate their functions in other ways. This review summarizes the available data on the horizontal gene transfer between viral and human genomes and discusses related problems.


Stem cell research: from molecular physiology to therapeutic applications


title: Remote sensing and geographic information systems in the spatial temporal dynamics modeling of infectious diseases

text: Similar to species immigration or exotic species invasion, infectious disease transmission is strengthened due to the globalization of human activities. Using schistosomiasis as an example, we propose a conceptual model simulating the spatio-temporal dynamics of infectious diseases. We base the model on the knowledge of the interrelationship among the source, media, and the hosts of the disease. With the endemics data of schistosomiasis in Xichang, China, we demonstrate that the conceptual model is feasible; we introduce how remote sensing and geographic information systems techniques can be used in support of spatio-temporal modeling; we compare the different effects caused to the entire population when selecting different groups of people for schistosomiasis control. Our work illustrates the importance of such a modeling tool in supporting spatial decisions. Our modeling method can be directly applied to such infectious diseases as the plague, lyme disease, and hemorrhagic fever with renal syndrome. The application of remote sensing and geographic information systems can shed light on the modeling of other infectious disease and invasive species studies.


title: A stochastic recovery model of influenza pandemic effects on interdependent workforce systems

text: Outbreaks of infectious diseases, such as pandemics, can result in adverse consequences and major economic losses across various economic sectors. Based on findings from the 2009 A H1N1 pandemic in the National Capital Region (NCR), this paper presents a recovery analysis for workforce disruptions using economic input–output modeling. The model formulation takes into consideration the dynamic interdependencies across sectors in an economic system in addition to the inherent characteristics of the economic sectors. From a macroeconomic perspective, the risk of the influenza disaster can be modeled using two risk metrics. First, there is the level of inoperability, which represents the percentage difference between the ideal production level and the degraded production level. Second, the economic loss metric represents the financial value associated with the reduced output. The contribution of this work revolves around the modeling of uncertainties triggered by new perturbations to interdependent economic sectors within an influenza pandemic timeline. We model the level of inoperability of economic sectors throughout their recovery horizon from the initial outbreak of the disaster using a dynamic model. Moreover, we use the level of inoperability values to quantify the cumulative economic losses incurred by the sectors within the recovery horizon. Finally, we revisit the 2009 NCR pandemic scenario to demonstrate the use of uncertainty analysis in modeling the inoperability and economic loss behaviors due to time-varying perturbations and their associated ripple effects to interdependent economic sectors.


title: Translation in plants-rules and exceptions

text: Translation processes in plants are very similar to those in other eukaryotic organisms and can in general be explained with the scanning model. Particularly among plant viruses, unconventional mRNAs are frequent, which use modulated translation processes for their expression: leaky scanning, translational stop codon readthrough or frameshifting, and transactivation by virus-encoded proteins are used to translate polycistronic mRNAs; leader and trailer sequences confer (cap-independent) efficient ribosome binding, usually in an end-dependent mechanism, but true internal ribosome entry may occur as well; in a ribosome shunt, sequences within an RNA can be bypassed by scanning ribosomes. Translation in plant cells is regulated under conditions of stress and during development, but the underlying molecular mechanisms have not yet been determined. Only a small number of plant mRNAs, whose structure suggests that they might require some unusual translation mechanisms, have been described.


Handlungstheorie, Methoden, Arbeitssoziologie, Genera-tionssoziologie


title: Molecular Characterization of Three New Avian Infectious Bronchitis Virus (IBV) Strains Isolated in Quebec

text: Three unrecognized field isolates of Infectious Bronchitis Virus (IBV) were recovered from commercial broiler chickens vaccinated with live Mass viral strain (H120). These isolates were identified by immunofluorescence using monoclonal antibodies produced against reference serotypes: Mass, Conn, and Ark. RT-PCRs were performed on viral RNAs to amplify S1 gene using a specific set of primers S1OLIGO3′ and S1OLIGO5′. Restriction polymorphism (RFLP) of PCR products was determined by the use of HaeIII restriction enzyme. As expected, patterns of PCR products were different from common pattern of strains assigned to Mass serotype M41, Beaudette, H120, and Florida. Molecular analysis showed a nucleotide insertion in hypervariable region one (HVR-1) of S1 gene of only Quebec isolates (Qu16, Qu_mv and Q_37zm). However, New Brunswick IBV isolate (NB_cp) did not display these insertions. Major amino acid changes involved insertion of two stretches (aa(118–119): Arg–Ser and aa(141–145): Sys–Ser–Asn–Ala–Ser–Cys) located at N-terminal and C-terminal regions of HVR-2. It is speculated that cysteine residue located upstream and downstream of Cys–Ser–Asn–Ala–Ser–Cys segment might be involved in the formation of loop structure and disulfide bond that could trigger important epitope changes. Insertion of new NXT and NXS (X≠P) glycosylation motifs scattered along S1 region and insertion of cysteine residues in HVR are contributing to the antigenic shifting of Quebec isolates. Fragment insertions were thought to be induced by inter-serotype recombination between vaccine strain (H120) that belongs to Mass serotype and another strain belonging to Ark serotype. Phylogenetic tree based on amino acid sequences showed that Quebec isolates formed a new phylogenetic cluster.


Proceedings of the Summer Scientific Meeting of the Faculty of Public Health Medicine 2015


title: A two-step high-risk immunization based on high-risk immunization

text: In this paper, the two-step high-risk immunization was investigated based on high-risk immunization for the SIRS model in small-world networks and scale-free networks. First, the effects of various immunization schemes are studied and compared. When the number of immune is same, the research result shows that the immune effect of the two-step high-risk immunization strategy is not the best nor the worst. However, the practicability is better compare with others. Furthermore, by changing the proportional of immunization the optimal immune effect can be achieved in the two-step high-risk immunization. Computation results verify that the two-step high-risk immunization is effective, and it is economic and feasible in practice.


title: Substrate regulation of ascorbate transport activity in astrocytes

text: Astrocytes possess a concentrativel-ascorbate (vitamin C) uptake mechanism involving a Na(+)-dependentl-ascorbate transporter located in the plasma membrane. The present experiments examined the effects of deprivation and supplementation of extracellularl-ascorbate on the activity of this transport system. Initial rates ofl-ascorbate uptake were measured by incubating primary cultures of rat astrocytes withl-[(14)C]ascorbate for 1 min at 37°C. We observed that the apparent maximal rate of uptake (V (max)) increased rapidly (<1 h) when cultured cells were deprived ofl-ascorbate. In contrast, there was no change in the apparent affinity of the transport system forl-[(14)C]ascorbate. The increase inV (max) was reversed by addition ofl-ascorbate, but notD-isoascorbate, to the medium. The effects of external ascorbate on ascorbate transport activity were specific in that preincubation of cultures withl-ascorbate did not affect uptake of 2-deoxy-D-[(3)H(G)]glucose. We conclude that the astroglial ascorbate transport system is modulated by changes in substrate availability. Regulation of transport activity may play a role in intracellular ascorbate homeostasis by compensating for regional differences and temporal fluctuations in external ascorbate levels.


title: Synthesis of triterpenoid acylates: Effective reproduction inhibitors of influenza A (H1N1) and papilloma viruses

text: The synthesis of a new group of triterpenoid acylates has been conducted on the basis of oleanolic, glycyrrhetic, and ursolic acids and betulin. 28-ortho-Methoxycynnamoylbetulin has been demonstrated to possess high activity against the influenza type A (H1N1) virus with the selectivity index SI > 100 while studying the activity of the synthesized compounds in relation to the reproduction of viral pathogens of respiratory infections. The high activity of 3,28-dinicotinoylbetulin against the papilloma virus (strain HPV-11) was detected with the selectivity index SI 35.


title: A Reed-Frost model taking into account uncertainties in the diagnostic of the infection

text: In this paper, we model the epidemic course of a pathogen infection within a semi-closed group which generates clinical signals which do not necessarily permit its ready and certain identification. Typical examples of such a pathogen are influenza-type viruses. We allow for time-varying infectivity levels among individuals, and model the probability of infection per contact as a function of the clinical signals. In order to accomplish this, we introduce a modified chain-binomial Reed-Frost model. We obtain an expression for the basic reproduction ratio and determine conditions which guarantee that the epidemic does not survive in the long-term. These conditions being functions of the signal’s distribution, they can be used to design and evaluate interventions, such as treatment protocols.


title: Structure-activity relationships in a series of semisynthetic polycyclic glycopeptide antibiotics

text: The main achievements in the development of methods for the design of semisynthetic antibiotics of a new generation belonging to the group of polycyclic glycopeptides directed against infections caused by multidrug-resistant bacteria and dangerous human and animal viruses are reviewed. The review is focused on the results obtained at the Gauze Institute in the area of chemical modification of natural antibiotics (eremomycin, vancomycin, teicoplanin, etc.) directed toward modification of their antibacterial and/or antiviral activity. A special emphasis is placed on the study of the mechanisms of action of these antibiotics, which could be the basis of a rational approach to their chemical modification involving the transformation of the inner binding pocket and the peripheral regions of the molecules that participate in the formation of their complexes with targets. The recently discovered antiviral activity of modified glycopeptides antibiotics is also discussed. A possibility of obtaining new highly active anti-HIV-1 and anti-HIV-2 preparations on the basis of hydrophobic derivatives of the aglycones of glycopeptide antibiotics was demonstrated. New semisynthetic derivatives of antibiotics that exhibit a high antibacterial activity in vivo, have good pharmacological characteristics, and are promising for practical use are described.


title: ‘System Destroys Trust?’—Regulatory Institutions and Public Perceptions of Food Risks in Taiwan

text: This article aims to explore public perceptions of global food risk issues and public attitudes towards government capacity to respond to concerns with technological and health uncertainties in an era of rapid economic development in newly industrialized countries. From cross-national comparative research on global food risk issues in the EU, UK, Germany, and Taiwan, survey results revealed distinct structural problems existing in Taiwan. In particular, it revealed that a long-term culture of authoritarian technological decision-making and positivistic risk assessment has lead to social risk perceptions being institutionally amplified and public trust gradually being destroyed.


The common cold


Genome-Wide Association Studies Complemented with Mechanistic Biological Studies Identify Sortilin 1 as a Novel Regulator of Cholesterol Trafficking


title: West Nile virus impacts in American crow populations are associated with human land use and climate

text: West Nile virus (WNV) was first detected in the western hemisphere during the summer of 1999, reawakening US public awareness of the potential severity of vector-borne pathogens. Since its New World introduction, WNV has caused disease in human, avian, and mammalian communities across the continent. American crows (Corvus brachyrhynchos) are a highly susceptible WNV host and when modeled appropriately, changes in crow abundances can serve as a proxy for the spatio-temporal presence of WNV. We use the dramatic declines in abundance of this avian host to examine spatio-temporal heterogeneity in WNV intensity across the northeastern US, where WNV was first detected. Using data from the Breeding Bird Survey, we identify significant declines in crow abundance after WNV emergence that are associated with lower forest cover, more urban land use, and warmer winter temperatures. Importantly, we document continued declines as WNV was present in an area over consecutive years. Our findings support the urban-pathogen link that human WNV incidence studies have shown. For each 1% increase in urban land cover we expect an additional 5% decline in the log crow abundance beyond the decline attributed to WNV in undeveloped areas. We also demonstrate a significant relationship between above-average winter temperatures and WNV-related declines in crow abundance. The mechanisms behind these patterns remain uncertain and hypotheses requiring further research are suggested. In particular, a strong positive relationship between urban land cover and winter temperatures may confound mechanistic understanding, especially when a temperature-sensitive vector is involved.


Abstracts: LVII Annual Meeting of the Italian Society for Veterin Ary Sciences (SISVET), Ischia 2003


title: How did the introduction of managed care for the uninsured in Iowa affect the use of substance abuse services?

text: Concerns about access under managed care have been raised for vulnerable populations such as publicly funded patients with substance abuse problems. To estimate the effects of the Iowa Managed Substance Abuse Care Plan (IMSACP) on substance abuse service use by publicly funded patients, service use before and after IMSACP was compared; adjustments were made for changes in population sociodemographic and clinical characteristics. Between fiscal years 1994 and 1997, patient case mix was marked by a higher burden of illness and the use of inpatient, residential non-detox, outpatient counseling, and assessment services declined, while use of intensive outpatient and residential detox services increased. Findings were similar among women, children, and homeless persons. Thus, care moved away from high-cost inpatient settings to less costly venues. Without knowing the impact on treatment outcomes, these changes cannot be interpreted as improved provider efficiency versus simply cost containment and profit maximization.


title: Cytotoxicity of HIV-gp41 segments expressed inE. coli

text: The failed attempt to express HIV-gp41 inE. coli led to the investigation of HIV-gp41 segments, which is responsible for the toxicity toE. coli cells. A series of deletion mutants containing different regions ofgp41 gene were constructed and expressed inE. coli BL21(DE3) strain. After IPTG induction, the high mortality of host bacteria was observed in host bacteria carrying the deletion mutants ofgp41 gene except for those transformed with pET-HN2; coordinately, the mRNA transcripts of thegp41 was rapidly decreased; and the release of [(3)H]uridine increased upon induction. All these data suggested that GP41 protein has a cytotoxic effect onE. coli, and it is the cytotoxicity of thegp41 gene product that contributes to the high mortality when expressed inE. coli.


title: Zika, public health, and the distraction of abortion

text: This paper suggests that the focus on abortion legalization in the aftermath of the Zika outbreak is distracting for policy and lawmakers from what needs to be done to address the outbreak effectively. Meeting basic health needs (i.e. preventive measures), together with research and development conducive to a vaccine or treatment for the Zika virus should be priorities.


title: Cloning and Sequence Analysis of the Spike Gene of Porcine Epidemic Diarrhea Virus Chinju99

text: The spike (S) gene of the porcine epidemic diarrhea virus (PEDV) Chinju99 which was previously isolated in Chinju, Korea was cloned and sequenced to aid in the development of genetically engineered vaccines and diagnostic reagents against PEDV. The nucleotide sequence encoding the entire S gene open reading frame (ORF) of Chinju99 was 4152 bases long encoding 1383 amino acids. It consisted of 1001 adenine (24.1%), 849 cytosine (20.4%), 877 guanine (21.1%) and 1425 thymine (34.3%) residues. The Chinju99 S ORF nucleotide sequence was 94.5% homologous with that of the Br1/87 and CV777 strains, respectively. The Chinju99 S protein had 92.8% amino acid identity with that of Br1/87 and CV777, respectively. The amino acid sequence contained 27 potential sites for asparagine (N)-linked glycosylation and there was a stretch of highly hydrophobic residues at position 1325–1350.


title: Climate impact on spreading of airborne infectious diseases: Complex network based modeling of climate influences on influenza like illnesses

text: In this study we combined a wide range of data sets to simulate the outbreak of an airborne infectious disease that is directly transmitted from human to human. The basis is a complex network whose structures are inspired by global air traffic data (from openflights.org) containing information about airports, airport locations, direct flight connections and airplane types. Disease spreading inside every node is realized with a Susceptible-Exposed-Infected-Recovered (SEIR) compartmental model. Disease transmission rates in our model are depending on the climate environment and therefore vary in time and from node to node. To implement the correlation between water vapor pressure and influenza transmission rate [J. Shaman, M. Kohn, Proc. Natl. Acad. Sci. 106, 3243 (2009)], we use global available climate reanalysis data (WATCH-Forcing-Data-ERA-Interim, WFDEI). During our sensitivity analysis we found that disease spreading dynamics are strongly depending on network properties, the climatic environment of the epidemic outbreak location, and the season during the year in which the outbreak is happening.


title: Antiviral effect of emodin from Rheum palmatum against coxsakievirus B(5) and human respiratory syncytial virus in vitro

text: Viral infections are the major causes of morbidity and mortality in elderly people and young children throughout the world. The most common pathogens include coxsackie virus (CV) and respiratory syncytial virus (RSV). However, no antiviral agents with low toxicity and drug resistance are currently available in clinic therapy. The present study aimed to examine the antiviral activities of emodin (an ingredient of Rheum palmatum) against CVB5 and RSV infections, in an attempt to discover new antiviral agents for virus infection. The monomer emodin was extracted and isolated from Rheum palmatum. The antiviral activities of emodin on HEp-2 cells were evaluated, including virus replication inhibition, virucidal and anti-absorption effects, by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tet-razolium bromide (MTT) assay and plaque reduction assay (PRA). The kinetics of virus inhibition by emodin in a period of 14 h was further determined by plaque assay and quantitative real time PCR (qPCR). Cytokine (IFN-γ, TNF-α) mRNA expressions after emodin treatment (7.5, 15, 30 μmol/L) were also assessed by qPCR post-infection. The results showed that emodin had potent inhibitory activities against CVB5 and RSV, with the 50% effective concentration (EC(50)) ranging from 13.06 to 14.27 μmol/L and selectivity index (SI) being 5.38–6.41 μmol/L. However, emodin couldn’t directly inactivate the viruses or block their absorption to cells. It acted as a biological synthesis inhibitor against CVB(4) and RSV in a concentration- and time-dependent manner, especially during the first 0–4 h post-infection. Moreover, emodin could decrease the mRNA expression of IFN-α but enhance TNF-γ expression significantly compared to the viral controls in vitro. Our results provide a molecular basis for development of emodin as a novel and safe antiviral agent for human enterovirus and respiratory virus infection in the clinical therapy.


Microbes: the hidden giant behind the biogeochemical cycling of elements in the hydrosphere


title: Immune predictors of oral poliovirus vaccine immunogenicity among infants in South India

text: Identification of the causes of poor oral vaccine immunogenicity in low-income countries might lead to more effective vaccines. We measured mucosal and systemic immune parameters at the time of vaccination with oral poliovirus vaccine (OPV) in 292 Indian infants aged 6–11 months, including plasma cytokines, leukocyte counts, fecal biomarkers of environmental enteropathy and peripheral blood T-cell phenotype, focused on gut-homing regulatory CD4+ populations. We did not find a distinct immune phenotype associated with OPV immunogenicity, although viral pathogens were more prevalent in stool at the time of immunization among infants who failed to seroconvert (63.9% vs. 45.6%, p = 0.002). Using a machine-learning approach, we could predict seroconversion a priori using immune parameters and infection status with a median 58% accuracy (cross-validation IQR: 50–69%) compared with 50% expected by chance. Better identification of immune predictors of OPV immunogenicity is likely to require sampling of mucosal tissue and improved oral poliovirus infection models.


Programming errors from patient-controlled analgesia


title: Initial Psychological Responses to Swine Flu

text: BACKGROUND: The emergence of influenza A (“swine flu”) in early 2009 led to widespread public concern. However, little research has examined the factors that underlie initial worry about infection and subsequent behavioral responses to such worry. PURPOSE: This study seeks to model some key predictors of worry and behavioral responses in the early stages of the swine flu pandemic (WHO pandemic stage 5). METHOD: A cross-sectional internet questionnaire study (N = 186). RESULTS: Twenty-five percent of respondents rated themselves as worried about being a victim of swine flu, 40% that they were worried of a family member contracting the virus. Twenty percent had bought, or intended to buy, preparatory materials (e.g., face masks), 20% intended to delay or cancel air travel. In a structural equation model, conservation values and family or friends perception of risks predicted worry about infection, while worry correlated with the purchase of preparatory materials, a lesser willingness to travel by public transport, and difficulty in focusing on everyday activities. CONCLUSION: While previous research on pandemic risk perception has focused on cognitive risk judgments, our data suggests that initial “emotional” concerns about infection are also significant predictors of behavioral responses to pandemic threat. Such worry is likely to be influenced by a variety of individual factors, such as personal values, as well as normative pressures. Practitioners can use and expand on such models of pandemic response when tailoring health campaigns to meet newly emergent threats.


title: Precise large deletions by the PCR-based overlap extension method

text: The authors describe an efficient method for generating large deletions (>200 nts) of precise length using the PCR-based method of gene splicing by overlap extension (1). This method is technically simple and less time consuming than conventional loop-out mutagenesis techniques requiring preparation of a single-stranded DNA template.


title: Angiotensin II type-1 receptor A1166C polymorphism is associated with increased risk of ischemic stroke in hypertensive smokers

text: Recent observations revealed a novel role of angiotensin-converting enzyme 2 and the angiotensin II type-1 receptor (AT1R) in lung injury, thereby extending knowledge about the functions of the angiotensin system. Angiotensin II, whose target is the AT1R, is a potent vasoconstrictor. Accordingly, an imbalance leading to enhanced activity of the angiotensin II-AT1R axis is postulated to contribute to both circulatory disturbances and lung injury. In this context, a functional single-nucleotide polymorphism, AT1R A1166C, which leads to enhanced responsiveness of the AT1R, has been postulated as a candidate susceptibility factor for ischemic stroke. The aim of our study was to investigate its occurrence in ischemic stroke and to analyze its possible synergistic associations with clinical risk factors. Genetic and clinical data on 308 consecutive patients with acutely developing ischemic stroke were analyzed. A total of 272 stroke and neuroimaging alteration-free subjects served as a control group. Univariate and logistic regression statistical approaches were used. Alone, the AT1R 1166C allele did not pose a risk of stroke. In hypertensive smokers, however, it was associated with an increased risk of ischemic stroke (OR 22.3, 95% CI 5.8–110.2, p<0.001). Further subgroup analysis revealed the same association for both small-vessel (OR 24.3, 95% CI 6.1–121.1, p<0.001) and large-vessel (OR 21.3, 95% CI 4.6–81.1, p<0.001) infarction. On a pathophysiological basis, our results suggest the possibility that the AT1R A1166C polymorphism might give rise to ischemic stroke indirectly via an unfavorable effect on the cardiorespiratory function.


Non bacterial gastroenteritis


Combating emerging infectious diseases in India: Orchestrating a symphony


title: Infectieziektebestrijding: jonge beroepsgroep in een robuuste organisatie

text: Maatregelen om verspreiding van infectieziekten tegen te gaan worden door alle kuddedieren genomen (zoals afzondering), en zullen dus ook zeker door onze prehistorische voorouders zijn genomen. Infectieziektebestrijding is derhalve een van de oudste medische kundes, maar de bestrijders bij de GGD’en zijn als beroepsgroep nog maar kort geleden begonnen. Sinds de Wcpv (1990) dicteert dat iedere gemeente een GGD in stand moest houden en daarin onder meer deskundigheid ten behoeve van infectieziektebestrijding onder moet brengen zijn de ontwikkelingen snel gegaan. De disciplines, sociaal geneeskundigen en sociaal verpleegkundigen, hebben zich inhoudelijk snel in de breedte en in de diepte ontwikkeld. Deze ontwikkelingen gaan nog steeds door: inhoudelijke verdieping is noodzakelijk om steeds nieuwe problemen aan te kunnen en om aansluiting bij klinische en laboratoriumontwikkelingen te behouden, maar ook om te kunnen blijven voldoen aan de steeds hoger wordende maatschappelijke eisen ten aanzien van de bestrijding, én aan de eisen die we zelf stellen: op rationele wijze werken met evidence-based richtlijnen.


title: Knowledge and Attitudes in Regard to Pandemic Influenza A(H1N1) in a Multiethnic Community of Malaysia

text: BACKGROUND: Assessment of general public’s knowledge and attitudes toward the development and prevention of new disease outbreaks is imperative because they have profound effects on health behaviors and may contribute to the control of the epidemic. PURPOSE: To investigate the level of knowledge and attitudes towards the influenza A(H1N1) outbreak across various ethnic groups and socio-demographic backgrounds in Malaysia. METHOD: A cross-sectional, population-based, computer-assisted telephone interview exploring knowledge and attitudes regarding influenza A(H1N1) was conducted in Malaysia. Between July 11 and September 12, 2009, a total of 1,050 respondents were interviewed (response rate 69.3%). RESULTS: The mean total knowledge score for the overall sample was 7.30 (SD ± 1.961) out of a possible score of 13 (Chinese had the highest scores, followed by Indians, then Malays). Some erroneous beliefs about the modes of transmission were identified. The majority of the participants (73.8%) perceived the A(H1N1) infection as often deadly. Despite the overestimation of the severity of A(H1N1) infection, high confidence in preventing infection and low perceived susceptibility of infection were reported. Influenza A(H1N1)-related stigma was prevalent and exhibited differences across ethnic groups. CONCLUSIONS: Findings suggest that provision of education and clear information are essential to correct the misconceptions, and increase perceived susceptibility to infection so that the general public will take precautions against A(H1N1) infection.


title: The long non-coding RNA expression profile of Coxsackievirus A16 infected RD cells identified by RNA-seq

text: Coxsackievirus A16 (CVA16) is one of major pathogens of hand, foot and mouth disease (HFMD) in children. Long non-coding RNAs (IncRNAs) have been implicated in various biological processes, but they have not been associated with CVA16 infection. In this study, we comprehensively characterized the landscape of IncRNAs of normal and CVA16 infected rhabdomyosarcoma (RD) cells using RNA-Seq to investigate the functional relevance of IncRNAs. We showed that a total of 760 IncRNAs were upregulated and 1210 IncRNAs were downregulated. Out of these dysregulated IncRNAs, 43.64% were intergenic, 22.31% were sense, 15.89% were intronic, 8.67% were bidirectional, 5.59% were antisense, 3.85% were sRNA host IncRNAs and 0.05% were enhancer. Six dysregulated IncRNAs were validated by quantitative PCR assays and the secondary structures of these IncRNAs were projected. Moreover, we conducted a bioinformatics analysis of an IncRNAs (ENST00000602478) to elucidate the diversity of modification and functions of IncRNAs. In summary, the current study compared the dysregulated IncRNAs profile upon CVA16 challenge and illustrated the intricate relationship between coding and IncRNAs transcripts. These results may not only provide a complete picture of transcription in CVA16 infected cells but also provide novel molecular targets for treatments of HFMD. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at 10.1007/s12250-015-3693-1 and is accessible for authorized users.


title: Production of HIV-1 p24 protein in transgenic tobacco plants

text: The production of antigens for vaccines in plants has the potential as a safe and cost-effective alternative to traditional production systems. Toward the development of a plant-based expression system for the production of human immunodeficiency virus type I (HIV-1) p24 capsid protein, the p24 gene was introduced into the genome of tobacco plants using Agrobacterium tumefaciens-mediated gene transfer. Southern blot analyses confirmed the presence of the p24 coding sequence within the genome of transgenic lines. Western blot analysis of protein extracts from transgenic plants identified plant-expressed p24 protein that cross-reacted with a p24-specific monoclonal antibody, thus confirming the maintenance of antigenicity. Quantification of the p24 protein using enzyme-linked immunosorbent assay (ELISA) estimated yields of approx 3.5 mg per g of soluble leaf protein. Similar accumulation levels of p24 were also detected in T1 plants, confirming that the p24 gene is transmitted stably. Our results indicate that plant-based transgenic expression represents a viable means of producing p24 for the development of HIV vaccine and for use in HIV diagnostic procedures.


title: What the granins tell us about the formation of secretory granules in neuroendocrine cells

text: The biochemical properties of the granins, studied in vitro and in a perforated TGN system, support the concept that the Sciective aggregation of regulated secretory proteins, promoted by the specific lumenal milieu of the TGN, is a key step in their segregation from constitutive secretory proteins in this compartment. A recently identified membrane-associated form of the granins is likely to also be involved in this aggregation, as well as in the membrane envelopment of the aggregate during the formation of an immature secretory granule.


title: Prevention of serious respiratory syncytial virus-related illness. I: Disease pathogenesis and early attempts at prevention

text: Respiratory syncytial virus (RSV) was first described 160 years ago but was not officially recognized as a cause of serious illness in children until the late 1950s. It has been estimated that virtually all children have had at least one RSV infection by their second birthday. RSV is responsible for annual disease outbreaks, usually during a defined winter seasonal period that can vary by community and year. RSV is recognized as the leading cause of hospitalization among young children worldwide. Infants of young chronologic age and children with predisposing factors, such as premature birth, pulmonary disease, or congenital heart disease, are most susceptible to serious illness. Unlike other viruses, immunity to RSV infection is incomplete and short lived, and reinfection is common throughout life. Initial attempts to develop a vaccine in the 1960s met with unexpected and tragic results; many children vaccinated with a formalin-inactivated wild-type virus developed serious pulmonary disease upon subsequent natural infection. Numerous other vaccine technologies have since been studied, including vectored approaches, virus-like particles, DNA vaccines, and live attenuated virus vaccine. As of early 2010, only two companies or institutions had RSV vaccine candidates in early clinical trials, and no vaccine is likely to be licensed for marketing in the immediate future.


SOCIETY: Social Science and the Public Interest March/April 2008


title: Genotyping of fimbrial adhesins inEscherichia coli strains isolated from slovak piglets suffering from diarrhea

text: One-hundred sixtyEscherichia coli isolates obtained from piglets with diarrhea from different parts of Slovakia were examined for the presence of genes coding for F4, F5, F6 and F41 fimbrial adhesins, and hemolytic activity. According to polymerase chain reaction tests 74 (46 %)E. coli isolates were positive for primers that detected genes coding for fimbrial adhesins. Of these 74 isolates, 64 were positive for genes encoding for F4(+), four for F5(+), five for F6(+), and one for both F41(+) and F5(+) adhesins.


title: Global analysis of an epidemic model with vaccination

text: In this paper, an epidemic dynamical model with vaccination is proposed. Vaccination of both newborn and susceptible is included in the present model. The impact of the vaccination strategy with the vaccine efficacy is explored. In particular, the model exhibits backward bifurcations under the vaccination level, and bistability occurrence can be observed. Mathematically, a bifurcation analysis is performed, and the conditions ensuring that the system exhibits backward bifurcation are provided. The global dynamics of the equilibrium in the model are also investigated. Numerical simulations are also conducted to confirm and extend the analytic results.


Role of viral infections in asthma and allergy


title: Mechanism of Inhibition of Hsp90 Dimerization by Gyrase B Inhibitor Coumermycin A1 (C–A1) Revealed by Molecular Dynamics Simulations and Thermodynamic Calculations

text: Heat shock protein (Hsp) 90 an emerging and attracting target in the anti-HIV drug discovery process due to the key role it plays in the pathogenicity of HIV-1 virus. In this research study, long-range all-atom molecular dynamics simulations were engaged for the bound and the unbound proteins to enhance the understanding of the molecular mechanisms of the Hsp90 dimerization and inhibition. Results evidently showed that coumermycin A1 (C–A1), a recently discovered Hsp90 inhibitor, binds at the dimer’s active site of the Hsp90 protein and leads to a substantial parting between dimeric opposed residues, which include Arg591.B, Lys594.A, Ser663.A, Thr653.B, Ala665.A, Thr649.B, Leu646.B and Asn669.A. Significant differences in magnitudes were observed in radius of gyration, root-mean-square deviation and root-mean-square fluctuation, which confirms a reasonably more flexible state in the apo conformation associated with it dimerization. In contrast, the bound conformer of Hsp90 showed less flexibility. This visibly highpoints the inhibition process resulting from the binding of the ligand. These findings were further validated by principal component analysis. We believe that the detailed dynamic analyses of Hsp90 presented in this study, would give an imperative insight and better understanding to the function and mechanisms of inhibition. Furthermore, information obtained from the binding mode of the inhibitor would be of great assistance in the design of more potent inhibitors against the HIV target Hsp90. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12013-016-0743-8) contains supplementary material, which is available to authorized users.


The Novelty of Jihadist Terror


title: Exploiting virus-like particles as innovative vaccines against emerging viral infections

text: Emerging viruses pose a major threat to humans and livestock with global public health and economic burdens. Vaccination remains an effective tool to reduce this threat, and yet, the conventional cell culture often fails to produce sufficient vaccine dose. As an alternative to cell-culture based vaccine, virus-like particles (VLPs) are considered as a highpriority vaccine strategy against emerging viruses. VLPs represent highly ordered repetitive structures via macromolecular assemblies of viral proteins. The particulate nature allows efficient uptake into antigen presenting cells stimulating both innate and adaptive immune responses towards enhanced vaccine efficacy. Increasing research activity and translation opportunity necessitate the advances in the design of VLPs and new bioprocessing modalities for efficient and cost-effective production. Herein, we describe major achievements and challenges in this endeavor, with respect to designing strategies to harnessing the immunogenic potential, production platforms, downstream processes, and some exemplary cases in developing VLP-based vaccines.


title: Hospital ventilation simulation for the study of potential exposure to contaminants

text: Airflow and ventilation are particularly important in healthcare rooms for controlling thermo-hygrometric conditions, providing anaesthetic gas removal, diluting airborne bacterial contamination and minimizing bacteria transfer airborne. An actual hospitalization room was the investigate case study. Transient simulations with computational fluid dynamics (CFD), based on the finite element method (FEM) were performed to investigate the efficiency of the existing heating, ventilation and air-conditioning (HVAC) plant with a variable air volume (VAV) primary air system. Solid modelling of the room, taking into account thermo-physical properties of building materials, architectural features (e.g., window and wall orientation) and furnishing (e.g., beds, tables and lamps) arrangement of the room, inlet turbulence high induction air diffuser, the return air diffusers and two patients lying on two parallel beds was carried out. Multiphysics modelling was used: a thermo-fluidynamic model (convection-conduction and incompressible Navier-Stokes) was combined with a convection-diffusion model. Three 3D models were elaborated considering different conditions/events of the patients (i.e., the first was considered coughing and/or the second breathing). A particle tracing and diffusion model, connected to cough events, was developed to simulate the dispersal of bacteria-carrying droplets in the isolation room equipped with the existing ventilation system. An analysis of the region of droplet fallout and the dilution time of bacteria diffusion of coughed gas in the isolation room was performed. The analysis of transient simulation results concerning particle path and distance, and then particle tracing combined with their concentration, provided evidence of the formation of zones that should be checked by microclimatic and contaminant control. The present study highlights the fact that the CFD-FEM application is useful for understanding the efficiency, adequacy and reliability of the ventilation system, but also provides important suggestions for controlling air quality, patients’ comfort and energy consumption in a hospital.


title: Epidemiological comparisons of codon usage patterns among HIV-1 isolates from Asia, Europe, Africa and the Americas

text: To investigate the genomic properties of HIV-1, we collected 3,081 sequences from the HIV Sequence Database. The sequences were categorized according to sampling region, country, year, subtype, gene name, and sequence and were saved in a database constructed for this study. The relative synonymous codon usage (RSCU) values of matrix, capsid, and gp120 and gp41 genes were calculated using correspondence analysis. The synonymous codon usage patterns based on the geographical regions of African countries showed broad distributions; when all the other regions, including Asia, Europe, and the Americas, were taken into account, the Asian countries tended to be divided into two groups. The sequences were clustered into nine non-CRF subtypes. Among these, subtype C showed the most distinct codon usage pattern. To determine why the codon usage patterns in Asian countries were divided into two groups for four target genes, the sequences of the isolates from the Asian countries were analyzed. As a result, the synonymous codon usage patterns among Asian countries were divided into two groups, the southern Asian countries and the other Asian countries, with subtype 01_AE being the most dominant subtype in southern Asia. In summary, the synonymous codon usage patterns among the individual HIV-1 subtypes reflect genetic variations, and this bioinformatics technique may be useful in conjunction with phylogenetic methods for predicting the evolutionary patterns of pandemic viruses.


title: Respiratory Syncytial Virus—A Comprehensive Review

text: Respiratory syncytial virus (RSV) is amongst the most important pathogenic infections of childhood and is associated with significant morbidity and mortality. Although there have been extensive studies of epidemiology, clinical manifestations, diagnostic techniques, animal models and the immunobiology of infection, there is not yet a convincing and safe vaccine available. The major histopathologic characteristics of RSV infection are acute bronchiolitis, mucosal and submucosal edema, and luminal occlusion by cellular debris of sloughed epithelial cells mixed with macrophages, strands of fibrin, and some mucin. There is a single RSV serotype with two major antigenic subgroups, A and B. Strains of both subtypes often co-circulate, but usually one subtype predominates. In temperate climates, RSV infections reflect a distinct seasonality with onset in late fall or early winter. It is believed that most children will experience at least one RSV infection by the age of 2 years. There are several key animal models of RSV. These include a model in mice and, more importantly, a bovine model; the latter reflects distinct similarity to the human disease. Importantly, the prevalence of asthma is significantly higher amongst children who are hospitalized with RSV in infancy or early childhood. However, there have been only limited investigations of candidate genes that have the potential to explain this increase in susceptibility. An atopic predisposition appears to predispose to subsequent development of asthma and it is likely that subsequent development of asthma is secondary to the pathogenic inflammatory response involving cytokines, chemokines and their cognate receptors. Numerous approaches to the development of RSV vaccines are being evaluated, as are the use of newer antiviral agents to mitigate disease. There is also significant attention being placed on the potential impact of co-infection and defining the natural history of RSV. Clearly, more research is required to define the relationships between RSV bronchiolitis, other viral induced inflammatory responses, and asthma.


title: Role of air changes per hour (ACH) in possible transmission of airborne infections

text: The cost of nosocomial infections in the United States is estimated to be $4 billion to $5 billion annually. Applying a scientifically based analysis to disease transmission and performing a site specific risk analysis to determine the design of the ventilation system can provide real and long term cost savings. Using a scientific approach and convincing data, this paper hypothetically illustrates how a ventilation system design can be optimized to potentially reduce infection risk to occupants in an isolation room based on a thorough risk assessment without necessarily increasing ventilation airflow rate. A computational fluid dynamics (CFD) analysis was performed to examine the transport mechanism, particle path and a suggested control strategy for reducing airborne infectious disease agents. Most studies on the transmission of infectious disease particles have concentrated primarily on air changes per hour (ACH) and how ACH provides a dilution factor for possible infectious agents. Although increasing ventilation airflow rate does dilute concentrations better when the contaminant source is constant, it does not increase ventilation effectiveness. Furthermore, an extensive literature review indicates that not every exposure to an infectious agent will necessarily cause a recipient infection. The results of this study suggest a hypothesis that in an enclosed and mechanically ventilated room (e.g., an isolation room), the dominant factor that affects the transmission and control of contaminants is the path between the contaminant source and exhaust. Contaminants are better controlled when this path is uninterrupted by an air stream. This study illustrates that the ventilation system design, i.e., when it conforms with the hypothesized path principle, may be a more important factor than flow rate (i.e., ACH). A secondary factor includes the distance from the contaminant source. This study provides evidence and supports previous studies that moving away from the patient generally reduces the infection risk in a transient (coughing) situation, although the effect is more pronounced under higher flow rate. It is noted that future research is needed to determine the exact mode of transmission for most recently identified organisms.


title: T-cells in human encephalitis

text: Encephalitis literally means inflammation of the brain. In general, this inflammation can result from a viral or bacterial infection in the brain itself or alternatively from a secondary autoimmune reaction against an infection or a tumor in the rest of the body. Besides this, encephalitis is present in (believed autoimmune) diseases with unknown etiology, such as multiple sclerosis or Rasmussen encephalitis (RE). This article summarizes the existing data on the role of T-cells in the pathogenesis of three types of human encephalitis: RE, paraneoplastic encephalomyelitis, and virus encephalitis. In all of them, T-cells play a major role in disease pathogenesis, mainly mediated by major histocompatiblity complex class I-restricted CD8(+) T-lymphocytes.


title: Secretory granule formation: The morphologist’s view

text: A deeper understanding of the regulated exocytic pathway, and for that matter the constitutive exocytic pathway, will depend on our ability to characterize the proteins in the vesicle membranes. Characterizing the protein composition of secretory granule membrane has proven to be a formidable task, and as far as I know, the work done to date has not told us a great deal about the mechanisms involved in sorting the contents of regulated secretory granules, or bringing about constitutive or regulated fusion with the plasma membrane. Without knowing a great deal more about the membranes, there seems to be little prospect of real further progress in understanding the key properties of the regulated exocytic pathway.


Views from Understanding Evolution: Parasites and Pathogens Take the Leap


Tracer gas is a suitable surrogate of exhaled droplet nuclei for studying airborne transmission in the built environment


title: Epidemiology of asthma in India

text: Allergic respiratory disorders, in particular asthma are increasing in prevalence, which is a global phenomenon. Even though genetic predisposition is one of the factors in children for the increased prevalence –urbanisation, air pollution andenvironmental tobacco smoke contribute more significantly. Our hospital based study on 20,000 children under the age of 18 years from 1979,1984,1989,1994 and 1999 in the city of Bangalore showed a prevalence of 9%, 10.5%, 18.5%, 24.5% and 29.5% respectively. The increased prevalence correlated well with demographic changes of the city. Further to the hospital study, a school survey in 12 schools on 6550 children in the age group of 6 to 15 years was undertaken for prevalence of asthma and children were categorized into three groups depending upon the geographical situation of the school in relation to vehicular traffic and the socioeconomic group of children. Group I-Children from schools of heavy traffic area showed prevalence of 19.34%, Group Il-Children from heavy traffic region and low socioeconomic population had 31.14% and Group III-Children from low traffic area school had 11.15% respectively. (P: I & II; II & III < 0.001). A continuation of study in rural areas showed 5.7% in children of 6–15 years. The persistent asthma also showed an increase from 20% to 27.5% and persistent severe asthma 4% to 6.5% between 1994-99. Various epidemiological spectra of asthma in children are discussed here.


title: Mathematical Analysis of a Model for Assessing the Impact of Antiretroviral Therapy, Voluntary Testing and Condom Use in Curtailing the Spread of HIV

text: This paper presents a deterministic model for evaluating the impact of anti-retroviral drugs (ARVs), voluntary testing (using standard antibody-based and a DNA-based testing methods) and condom use on the transmission dynamics of HIV in a community. Rigorous qualitative analysis of the model show that it has a globally-stable disease-free equilibrium whenever a certain epidemiological threshold, known as the effective reproduction number [Formula: see text], is less than unity. The model has an endemic equilibrium whenever [Formula: see text]. The endemic equilibrium is shown to be locally-asymptotically stable for a special case. Numerical simulations of the model show that the use of the combined testing and treatment strategy is more effective than the use of the standard ELISA testing method with ARV treatment, even for the use of condoms as a singular strategy. Furthermore, the universal strategy (which involves the use of condoms, the two testing methods and ARV treatment) is always more effective than the combined use of the standard ELISA testing method and ARVs.


title: Dissociation of oxytocin effects on body weight in two variants of female Sprague-Dawley rats

text: As a counterpoint to studies that make a case for the use of oxytocin in short-term inhibition of food intake, the aim of the present study was to determine whether the peptide facilitates weight gain in female rats in a more long-term perspective. Two different variants of female Sprague-Dawley rats were used. The two variants differed in daily weight gain (0.38 g/day vs. 1.41 g/day during 28 days), and were designated slowly and rapidly growing rats (SGR and RGR) respectively. Oxytocin 1 mg/kg given s.c. to SGR for a five-day period increased weight gain significantly in comparison to a previous five-day period with NaCl-treatment (18.0 g/5 days versus 5.0 g/5 days; p<0.01). In a separate study, oxytocin 1 mg/kg given for four days increased weight gain significantly in SGR versus saline-treated controls (7.5 g/4 days versus 1.6 g/4 days; p<0.05). The weight-difference persisted six days later (p<0.001). The weight increase of oxytocin occurred only during estrus (p<0.05) and was not accompanied by any measurable increase in food intake. In RGR, oxytocin-treatment decreased food intake significantly (p<0.001) and tended to decrease weight gain, although not significantly. The SGR and RGR also had different endocrine profiles with, for example, twice as high oxytocin (p<0.01) and insulin levels (p<0.01) in RGR compared to the SGR. These data suggest that oxytocin influences weight gain and food intake differently in the two variants of Sprague-Dawley rats, perhaps depending on factors such as endocrine profile and oxytocin sensitivity.


title: Recent development of highly sensitive protease assay methods: Signal amplification through enzyme cascades

text: Proteases are involved in almost all biological processes, and therefore, aberrant activity of many of these enzymes is an important indicator of disease. Various methods have been developed to analyze protease activity, among which, protease assays based on resonance energy transfer are currently used most widely. However, quantitative methods with relatively higher sensitivity are needed, especially for disease diagnosis at early stages. One of the strategies to achieve higher sensitivity is to implement signal amplification of the protease activity. In this review, we briefly summarize the protease assay methods based on resonance energy transfer, and then elaborate the efforts to develop sensitive protease assays through signal amplification by using enzyme cascades.


title: An examination of the ability of titanium dioxide nanoparticles and its conjugates with oligonucleotides to penetrate into eucariotis cells

text: In this study we examine the possibility that TiO(2) nanoparticles and their conjugates can penetrate into cultivated cells without any special transfection procedures. Oligonucleotides and their derivates were conjugated with the TiO(2) nanoparticles, which were obtained as colloidal solutions at a concentration of TiO(2) 0.3M by TiCl(4) hydrolysis. The electronic microscopy of various cell cultures (KCT, Vero, and MDCK) treated with nanoparticle solutions (20 µg/µl) showed that nanoparticles could enter the cells and accumulate in the vacuoles and phagosomes and form inclusions in cytoplasm. Thus, we demonstrated the penetration of TiO(2) nanoparticles and their oligonucleotide conjugates into intracellular space without any auxiliary operations. Most other researches used electroporation techniques for similar purposes [1, 2, 5].


title: Rational approaches to immune regulation

text: Our studies are mainly focused on developing strategies of immune regulation. In the case of infectious and neoplastic disease, our approach is to upregulate cell-mediated immunity to viral of tumor antigens using an intracellular bacterium as a vector for targeting these antigens to the major histocompatibility complex (MHC) class I and class II pathways of antigen processing, in addition to exploiting the adjuvant properties of the vector to stimulate innate immunity. In the area of autoimmunity, we are attempting to downregulate the immune response by specific immune intervention directed against autoreactive T cells. In these studies we use murine models for multiple sclerosis. Our approach is to use both rationally designed T cell receptor (TCR) peptide analogs and recombinant viral vectors that express TCR components to regulate the disease.


title: Import of Rift Valley fever to China: a potential new threat?

text: [Image: see text]


title: Facile synthesis of novel benzotriazole derivatives and their antibacterial activities

text: A series of benzotriazole derivatives (compounds 1–27) were synthesized, and 24 (compounds 1–5, 9–27) of which were first reported. Their chemical structures were confirmed by means of (1)H NMR, IR and elemental analyses, coupled with one selected single crystal structure (compound 1). All the compounds were assayed for antibacterial activities against three Gram positive bacterial strains (Bacillus subtilis, Staphylococcus aureus and Streptococcus faecalis) and three Gram negative bacterial strains (Escherichia coli, Pseudomonas aeruginosa and Enterobacter cloacae) by MTT method. Among the compounds tested, most of them exhibited potent antibacterial activity against the six bacterial strains. Most importantly, compound 3-benzotriazol-1-yl-1-(4-bromo-phenyl)-2-[1,2,4]triazol-1-ylpropan-1-one (19) showed the most favourable antibacterial activity against B. subtilis, S. aureus, S. faecalis, P. aeruginosa, E. coli and E. cloacae with MIC of 1.56 µg/mL, 1.56 µg/mL, 1.56 µg/mL, 3.12 µg/mL, 6.25 µg/mL and 6.25 µg/mL, respectively.


title: Risicoperceptie van infecties van mensen door het vogelgriepvirus in Nederland: Sterk gevoel van risico, maar beperkt vertrouwen in beschermingsmaatregelen

text: Risk perception of avian influenza in the Netherlands: high level of risk perception, but limited trust in protective measures Aim: To describe risk perception of avian influenza in the Netherlands in March 2006. To gain insight in the level of knowledge, precautionary actions, response and self efficacy, and use of media related to avian influenza. Methods: Through an Internet panel 579 respondents filled in an online questionnaire. Results. Risk perception of avian influenza in the Netherlands is, especially in case of an outbreak, high, 3,51 (scale 1 – 5). 23,7% of respondents believe that protection against avian influenza is possible, while 28,2% feel that they are able to protect oneself. A higher level of response and self efficacy is related to a lower level of risk perception. Respondents with an higher risk perception have taken more precautionary actions. 38% of respondents had taken at least one precautionary action. All respondents had heard of avian influenza, but knowledge was limited, 2,33 (scale 1 – 4). Television was the most important source of information. Conclusions: Risk perception of avian influenza is relatively high in the Netherlands at a time when no infections were reported. The low levels of response and self efficacy warrant attention so that advice about preventive measures will be adhered to in case of an outbreak.


title: Necrotizing enterocolitis

text: Improvement in survival rates of low birth-weight infants particularly in the neonatal intensive care units of India appears to be accompanied by frequent recognition of Necrotizing enterocolitis (NEC) among early survivors. As the philosophy and practice of advanced care for tiny infants becomes more acceptable and affordable in the country, a steady increase in survival of such infants is predictable. However there is growing concern in India that NEC could become a significant contributor to morbidity and mortality in the future. NEC is currently regarded as the most common acquired gastrointestinal emergency in the newborn period, and the outcome of this disease is universally poor. Improved understanding of the pathophysiology and pathogenesis of this condition is required for formulating optimal principles of prevention and management.


title: RNA interference targeting nucleocapsid protein inhibits porcine reproductive and respiratory syndrome virus replication in Marc-145 cells

text: Porcine reproductive and respiratory syndrome (PRRS) is an important disease, which leads to severe economic losses in swine-producing areas of the world. However, current antiviral strategies cannot provide highly effective protection. In this study, three theoretically effective interference target sites (71–91, 144–164, 218–238) targeting the nucleocapsid (N) gene of PRRSV were designed and selected, and then three siRNA-expressing plasmids were constructed, respectively named p2.1-N71, p2.1-N144, and p2.1-N218. The recombinant siRNA-expressing plasmids were transfected into Marc-145 cells; then the cells were infected with PRRSV (JL07SW strain); finally, after incubation for 48 h, the antiviral activity of those siRNA-expressing plasmids in Marc-145 cells was assessed by cytopathic effects, virus titers, indirect immunofluorescence, and quantitative real-time PCR. Experimental results demonstrated that these three siRNA-expressing plasmids could effectively and significantly inhibit the replication of PRRSV by 93.2%, 83.6%, and 89.2% in Marc-145 cells, respectively. Among these three siRNA-expressing plasmids, p2.1-N71 was found to be most effective, while p2.1-N144 and p2.1-N218 displayed relatively weak inhibition of virus replication. The results indicated that siRNA-expressing plasmids targeting the N gene of PRRSV could significantly inhibit PRRSV replication in Marc-145 cells. Based on our experimental results and previous reports, the 71–91, 179–197, and 234–252 sites of the N gene are good choices to effectively inhibit the replication of PRRSV, and this RNA interference technique can be a potential anti-PRRSV strategy.


title: Comparison of JEV neutralization assay using pseudotyped JEV with the conventional plaque-reduction neutralization test

text: We previously reported the development of a neutralization assay system for evaluating Japanese Encephalitis Virus (JEV) neutralizing antibody (NAb) using pseudotyped-JEV (JEV-PV). JEV-PV-based neutralization assay offers several advantages compared with the current standard plaque-reduction neutralization test (PRNT), including simplicity, safety, and speed. To evaluate the suitability of the JEV-PV assay as new replacement neutralization assay, we compared its repeatability, reproducibility, specificity, and correlated its results with those obtained using the PRNT. These analyses showed a close correlation between the results obtained with the JEV-PV assay and the PRNT, using the 50% plaque reduction method as a standard for measuring NAb titers to JEV. The validation results met all analytical acceptance criteria. These results suggest that the JEV-PV assay could serve as a safe and simple method for measuring NAb titer against JEV and could be used as an alternative approach for assaying the potency of JEV neutralization.


title: Genetic analysis of foot-and-mouth disease virus serotype A of Indian origin and detection of positive selection and recombination in leader protease- and capsid-coding regions

text: The leader protease (L(pro)) and capsid-coding sequences (P1) constitute approximately 3 kb of the foot-and-mouth disease virus (FMDV). We studied the phylogenetic relationship of 46 FMDV serotype A isolates of Indian origin collected during the period 1968–2005 and also eight vaccine strains using the neighbour-joining tree and Bayesian tree methods. The viruses were categorized under three major groups — Asian, Euro-South American and European. The Indian isolates formed a distinct genetic group among the Asian isolates. The Indian isolates were further classified into different genetic subgroups (<5% divergence). Post-1995 isolates were divided into two subgroups while a few isolates which originated in the year 2005 from Andhra Pradesh formed a separate group. These isolates were closely related to the isolates of the 1970s. The FMDV isolates seem to undergo reverse mutation or convergent evolution wherein sequences identical to the ancestors are present in the isolates in circulation. The eight vaccine strains included in the study were not related to each other and belonged to different genetic groups. Recombination was detected in the L(pro) region in one isolate (A IND 20/82) and in the VP1 coding 1D region in another isolate (A RAJ 21/96). Positive selection was identified at aa positions 23 in the L(pro) (P<0.05; 0.046*) and at aa 171 in the capsid protein VP1 (P<0.01; 0.003**).


title: A murine colitis model developed using a combination of dextran sulfate sodium and Citrobacter rodentium

text: Adult mice were treated with dextran sulfate sodium (DSS) and infected with Citrobacter rodentium for developing a novel murine colitis model. C57BL/6N mice (7-week-old) were divided into four groups. Each group composed of control, dextran sodium sulfate-treated (DSS), C. rodentium-infected (CT), and DSS-treated and C. rodentium-infected (DSS-CT) mice. The DSS group was administered 1% DSS in drinking water for 7 days. The CT group was supplied with normal drinking water for 7 days and subsequently infected with C. rodentium via oral gavage. The DSS-CT group was supplied with 1% DSS in drinking water for 7 days and subsequently infected with C. rodentium via oral gavage. The mice were sacrificed 10 days after the induction of C. rodentium infection. The DSS-CT group displayed significantly shorter colon length, higher spleen to body weight ratio, and higher histopathological score compared to the other three groups. The mRNA expression levels of tumor necrosis factor (TNF)-α and interferon (INF)-γ were significantly upregulated; however, those of interleukin (IL)-6 and IL-10 were significantly downregulated in the DSS-CT group than in the control group. These results demonstrated that a combination of low DSS concentration (1%) and C. rodentium infection could effectively induce inflammatory bowel disease (IBD) in mice. This may potentially be used as a novel IBD model, in which colitis is induced in mice by the combination of a chemical and a pathogen. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at 10.1007/s12275-018-7504-x and is accessible for authorized users.


title: Methyltransferase of a cell culture-adapted hepatitis E inhibits the MDA5 receptor signaling pathway

text: Hepatitis E virus (HEV) is a causative agent of acute hepatitis and jaundice. The number of human infections is approximated to be over 20 million cases per year. The transmission is mainly via the fecal-oral route and contaminated water and food are considered to be a major source of infection. As a mouse model is not available, a recent development of a cell culture-adapted HEV strain (47832c) is considered as a very important tools for molecular analysis of HEV pathogenesis in cells. Previously, we demonstrated that HEV-encoded methyltransferase (MeT) encoded by the 47832c strain inhibits MDA5- and RIG-I-mediated activation of interferon β (IFN-β) promoter. Here, we report that MeT impairs the phosphorylation and activation of interferon regulatory factor 3 and the p65 subunit of NF-κB in a dose-dependent manner. In addition, the MeT encoded by the 47832c, but not that of HEV clinical or field isolates (SAR-55, Mex-14, KC-1, and ZJ-1), displays the inhibitory effect. A deeper understanding of MeTmediated suppression of IFN-β expression would provide basis of the cell culture adaptation of HEV.


title: Use of recombinant cytokines for optimized induction of antiviral immunity against SIV in the nonhuman primate model of human AIDS

text: Outbreaks of infectious diseases such as HIV and the much televised and attention-getting outbreaks of diseases such as Ebola, Hantaviruses, and the most recent outbreak of SARS have induced a significant new interest in the formulations and more importantly the science of vaccinology, which has previously to a large extent been conducted empirically. Our laboratory has focused on the use of recombinant nonhuman primate cytokines as adjunctive therapies for inducing antigen-specific immune responses in monkeys because most recombinant human cytokines appear to be immunogenic. This article provides a summary of our work with such cytokines, which includes attempts to define optimum dosing schedules that lead to optimal primary and lasting memory antigen-specific immune responses.


title: Theory of early warning signals of disease emergenceand leading indicators of elimination

text: Anticipating infectious disease emergence and documenting progress in disease elimination are important applications for the theory of critical transitions. A key problem is the development of theory relating the dynamical processes of transmission to observable phenomena. In this paper, we consider compartmental susceptible–infectious–susceptible (SIS) and susceptible–infectious–recovered (SIR) models that are slowly forced through a critical transition. We derive expressions for the behavior of several candidate indicators, including the autocorrelation coefficient, variance, coefficient of variation, and power spectra of SIS and SIR epidemics during the approach to emergence or elimination. We validated these expressions using individual-based simulations. We further showed that moving-window estimates of these quantities may be used for anticipating critical transitions in infectious disease systems. Although leading indicators of elimination were highly predictive, we found the approach to emergence to be much more difficult to detect. It is hoped that these results, which show the anticipation of critical transitions in infectious disease systems to be theoretically possible, may be used to guide the construction of online algorithms for processing surveillance data.


Book Reviews


title: Antiviral effects of Lactobacillus ruminis SPM0211 and Bifidobacterium longum SPM1205 and SPM1206 on rotavirus-infected Caco-2 cells and a neonatal mouse model

text: Rotavirus is worldwide cause of severe gastroenteritis including severe diarrhea and fatal dehydration in infants and young children. There is an available vaccination program for preventing rotavirus infection, but it has limits and restrictions. Probiotics therapy could be an alternative method of antiviral prevention and modulation against rotavirus infection. In this study, we screened the antiviral activity of probiotic bacteria such as 3 Lactobacillus spp. and 14 Bifidobacterium spp. isolated from young Korean. Three of the bacteria, Lactobacillus ruminis SPM0211, Bifidobacterium longum SPM1205, and SPM1206, inhibited human strain Wa rotavirus infection in Caco-2 cells. Furthermore, these bacterial strains inhibited rotavirus replication in a rotavirus-infected neonatal mouse model. To clarify the mechanism of inhibition, we investigated gene expression of Interferon (IFN)-signaling components and IFN-inducible antiviral effectors. All 3 probiotics increased IFN-α and IFN-β levels compared with the control. Gene expression of IFNsignaling components and IFN-inducible antiviral effectors also increased. Overall, these results indicate that L. ruminis SPM0211, B. longum SPM1205 and 1206 efficiently inhibit rotavirus replication in vitro and in vivo. Especially, the antiviral effect of Lactobacillus ruminis SPM0211 is worthy of notice. This is the first report of L. ruminis with antiviral activity. Anti-rotaviral effects of the 3 probiotics are likely due to their modulation of the immune response through promoting type I IFNs, which are key regulators in IFN signaling pathway.


title: Engineering blood cells and proteins as blood substitutes: A short review

text: In this brief review, basic principles and recent progresses on the development of therapeutic substitutes for major blood components are briefly discussed with primary focus on the red cell substitutes.


title: Construction and Characterization of Virus-Like Particles: A Review

text: Over the last three decades, virus-like particles (VLPs) have evolved to become a widely accepted technology, especially in the field of vaccinology. In fact, some VLP-based vaccines are currently used as commercial medical products, and other VLP-based products are at different stages of clinical study. Several remarkable advantages have been achieved in the development of VLPs as gene therapy tools and new nanomaterials. The analysis of published data reveals that at least 110 VLPs have been constructed from viruses belonging to 35 different families. This review therefore discusses the main principles in the cloning of viral structural genes, the relevant host systems and the purification procedures that have been developed. In addition, the methods that are used to characterize the structural integrity, stability, and components, including the encapsidated nucleic acids, of newly synthesized VLPs are analyzed. Moreover, some of the modifications that are required to construct VLP-based carriers of viral origin with defined properties are discussed, and examples are provided. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12033-012-9598-4) contains supplementary material, which is available to authorized users.


From Newsroom to Classroom


title: Mechanisms of synergy in polymicrobial infections

text: Communities of microbes can live almost anywhere and contain many different species. Interactions between members of these communities often determine the state of the habitat in which they live. When these habitats include sites on the human body, these interactions can affect health and disease. Polymicrobial synergy can occur during infection, in which the combined effect of two or more microbes on disease is worse than seen with any of the individuals alone. Powerful genomic methods are increasingly used to study microbial communities, including metagenomics to reveal the members and genetic content of a community and metatranscriptomics to describe the activities of community members. Recent efforts focused toward a mechanistic understanding of these interactions have led to a better appreciation of the precise bases of polymicrobial synergy in communities containing bacteria, eukaryotic microbes, and/or viruses. These studies have benefited from advances in the development of in vivo models of polymicrobial infection and modern techniques to profile the spatial and chemical bases of intermicrobial communication. This review describes the breadth of mechanisms microbes use to interact in ways that impact pathogenesis and techniques to study polymicrobial communities.


title: Validation of biopharmaceutical purification processes for virus clearance evaluation

text: Any biopharmaceutical product that has involved the use of animal-derived material during the manufacturing process has the potential to be contaminated with animal viruses. To ensure safety of these products, extensive testing is performed on the starting materials, such as the cell banks, and on the raw materials used in manufacture. Additional testing is also performed at various stages of production and, in some cases, on the final product as well. Because of inherent limitations in direct testing methods, the capacity of the downstream purification process to remove/inactivate potential viral contaminants is also studied to give an extra degree of assurance that the final product will be free of infectious viruses.


Prevention of atopy—current concepts and personal experience


title: Antibacterial activity of two phloroglucinols, flavaspidic acids AB and PB, from Dryopteris crassirhizoma

text: The antimicrobial effect of solvent extracts from the rhizome of a thick-stemmed wood fern (Dryopteris crassirhizoma) was evaluated and its phloroglucinol components, flavaspidic acids PB and AB. Flavaspidic acids PB and AB were isolated from the D. crassirhizoma rhizomes by methanol extraction, followed by silica gel and Sephadex LH-20 column chromatography. The chemical structures were characterized by spectral techniques, including ESI-MS, UV, (1)H- and (13)C-NMR spectrum analysis. When the antimicrobial activity of the extracts and compounds was tested by the paper disc method, the extracts and compounds were highly active against Gram-positive bacteria, such as methicillin-resistant Staphylococcus aureus KCTC 1928 (a MRSA bacterium), Streptococcus mutans and Bacillus subtilis. The extracts and compounds were not active against fungi and chlorella. Our study revealed that the antibacterial activity of samples from D. crassirhizoma was mainly related to the flavaspidic acids.


title: Discovery of T-cell Driven Subunit Vaccines from Zika Virus Genome: An Immunoinformatics Approach

text: The recent outbreaks of Zika virus and the absence of a specific therapy have necessitated to identify T-cell-stimulating antigenic peptides as potential subunit vaccine candidates. The translated ssRNA (+) genome of Zika virus was explored in EMBOSS antigenic and VaxiJen to predict 63 peptides as potential antigens. Three MHC-II binding peptide prediction tools, viz. NetMHCIIpan, PREDIVAC and immune epitope database (IEDB) were employed in consensus on 63 antigenic peptides to propose 14 T-helper cell epitopes. Similarly, analysis on 63 antigenic peptides through NetMHC, NetCTL and IEDB MHC-I binding peptide prediction tool led to identification of 14 CTL epitopes. Seven T-cell epitopes, C:44-66, M:135-149, NS2A:124-144, NS3:421-453, NS3:540-554, NS4B:90-134 and NS4B:171-188, are observed to share overlapping MHC-I and MHC-II binding motifs and hence, are being proposed to constitute minimum T-cell antigens to elicit protective T-cell immune response against Zika. Three of them, C:44-66, NS3:421-453 and NS3:540-554 are identified to be conserved across all the selected strains of Zika virus. Moreover, the 21 T-cell epitopes are non-self to humans and exhibited good coverage in variable populations of 14 geographical locations. Therefore, 21 T-cell epitopes are proposed as potential subunit vaccines against Zika virus. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12539-017-0238-3) contains supplementary material, which is available to authorized users.


title: Influenza

text: Influenza continues to baffle humans by its constantly changing nature. The twenty-first century has witnessed considerable advances in the understanding of the influenza viral pathogenesis, its synergy with bacterial infections and diagnostic methods. However, challenges continue: to find a less expensive and more reliable point-of-care test for use in developing countries, to produce more efficacious antiviral drugs, to explore ways to combat emerging antiviral resistance and to develop vaccines that can either be produced in a shorter production time or can overcome the need for annual matching with the circulating influenza strains. Most importantly for India, as a nation that suffered the highest mortality in the influenza pandemic 1918, there is an urgent need to gear up our existing preparedness for the next pandemic which is capable to hit at any moment in time.


title: Developing Novel Antimicrobial and Antiviral Textile Products

text: In conjunction with an increasing public awareness of infectious diseases, the textile industry and scientists are developing hygienic fabrics by the addition of various antimicrobial and antiviral compounds. In the current study, sodium pentaborate pentahydrate and triclosan are applied to cotton fabrics in order to gain antimicrobial and antiviral properties for the first time. The antimicrobial activity of textiles treated with 3 % sodium pentaborate pentahydrate, 0.03 % triclosan, and 7 % Glucapon has been investigated against a broad range of microorganisms including bacteria, yeast, and fungi. Moreover, modified cotton fabrics were tested against adenovirus type 5 and poliovirus type 1. According to the test results, the modified textile goods attained very good antimicrobial and antiviral properties. Thus, the results of the present study clearly suggest that sodium pentaborate pentahydrate and triclosan solution-treated textiles can be considered in the development of antimicrobial and antiviral textile finishes.


title: Securing the food supply chain: understanding complex interdependence through agent-based simulation

text: The food industry has many points of vulnerability in its supply chain. It currently lacks integrated crisis management and response programs to understand the importance of decision-making during and in the aftermath of a bioterrorist attack on the food supply. Computer simulations have been used successfully in other industries as training and analysis tools. This paper describes an agent-based simulation for food defense training and analysis. Production information, consumption patterns, morbidity/mortality rates, recall costs and additional information were collected and provided to a data-driven simulation to anticipate the impact of decision-making on economic and public health during a terrorist attack. A case study is given with a representative exercise involving forty industry representatives who participated in a food defense simulation. Their decisions (recall and microbiological and toxicological testing) were derived from testing results, press releases, epidemiological data, and discussions with other industry and regulatory teams. Decisions made during the simulation resulted in over 76,000 illnesses, 45 deaths, and $132 million in recall costs. The no intervention, baseline scenario estimated to result in 91,000 illnesses and 54 deaths, indicating the improved public health outcomes resulting from players’ decisions. Participants identified three key learning points: 1) communication between all groups is pertinent and challenging, 2) approaches to solve inherent food safety problems cannot be used to address food defense situations, and 3) human resource procedures regarding new hires and disgruntled employees should involve additional security measures. This computer simulation could be a valuable resource in food defense awareness and help educate companies and regulators about food defense risks and decision-making consequences.


title: Two pathways of costimulation through CD28

text: CD28 is recognized as the primary costimulatory molecule involved in the activation of naïve T cells. However, the biochemical signaling pathways that are activated by CD28 and how these pathways are integrated with TCR signaling are still not understood. We have recently shown that there are at least two independent activation pathways induced by CD28 costimulation. One is integrated with TCR signaling in the context of the immunological synapse and is mediated through transcriptional enhancement and the second is mediated through the induction of mRNA stability. Here, we review the immunological consequences and biochemical mechanisms associated with CD28 costimulation and discuss the major questions that need to be resolved to understand the molecular mechanisms that transduce CD28 costimulation.


Cranial MRI findings in acute disseminated encephalomyelitis


title: Identifying key genes associated with Hirschsprung’s disease based on bioinformatics analysis of RNA-sequencing data

text: BACKGROUND: Hirschsprung’s disease (HSCR) is a type of megacolon induced by deficiency or dysfunction of ganglion cells in the distal intestine and is associated with developmental disorders of the enteric nervous system. To explore the mechanisms of HSCR, we analyzed the RNA-sequencing data of the expansion and the narrow segments of colon tissues separated from children with HSCR. METHODS: RNA-sequencing of the expansion segments and the narrow segments of colon tissues isolated from children with HSCR was performed. After differentially expressed genes (DEGs) were identified using the edgeR package in R, functional and pathway enrichment analyses of DEGs were carried out using DAVID software. To further screen the key genes, protein-protein interaction (PPI) network and module analyses were conducted separately using Cytoscape software. RESULTS: A total of 117 DEGs were identified in the expansion segment samples, including 47 up-regulated and 70 down-regulated genes. Functional enrichment analysis suggested that FOS and DUSP1 were implicated in response to endogenous stimulus. In the PPI network analysis, FOS (degree=20), EGR1 (degree=16), ATF3 (degree=9), NOS1 (degree=8), CCL5 (degree=8), DUSP1 (degree=7), CXCL3 (degree=6), VIP (degree=6), FOSB (degree=5), and NOS2 (degree=4) had higher degrees, which could interact with other genes. In addition, two significant modules (module 1 and module 2) were identified from the PPI network. CONCLUSIONS: Several genes (including FOS, EGR1, ATF3, NOS1, CCL5, DUSP1, CXCL3, VIP, FOSB, and NOS2) might be involved in the development of HSCR through their effect on the nervous system.