title: Immunogenicity of a recombinant coronavirus spike glycoprotein expressed in transgenic plants

text: Recently, it has been demonstrated that plants offer the possibility of producing low cost subunit vaccines that can be either parenterally or orally administered. Here we review data we obtained on the immunological response elicited by two recombinant versions of the glycoprotein S from the swine transmissible gastroenteritis coronavirus (TGEV) expressed in transgenic plants. Arabidopsis or potato plants were genetically transformed with cDNAs constructs encoding the N-terminal domain (aa residues 1–750) or the full-length glycoprotein S of TGEV, responsible for the neutralizing antibody induction against the virus, under the control of the cauliflower mosaic virus 35S (CaMV 35S) promoter. Genomic DNA and mRNA analysis of leave extracts from transformed plants demonstrated the incorporation of the foreign cDNA into the plant genomes as well as their transcription. Expression of recombinant polypeptides was observed in most transgenic plants by ELISA using specific antibodies. Mice immunized either parenterally with leave extracts from transgenic arabidopsis plants or, more interestingly, fed with potato tubers, developed antibodies that specifically reacted with TGEV in ELISA, immunoprecipitated the glycoprotein S and in some cases neutralized the virus infectivity. From the above results, we conclude that transgenic plants expressing glycoprotein S polypeptides may be potentially used as a source of recombinant antigen for vaccine production.


Liste risikobewerteter Spender- und Empfängerorganismen für gentechnische Arbeiten Bekanntmachung nach § 5 Absatz 6 Gentechnik-Sicherheitsverordnung in der Fassung der Bekanntmachung vom 14.3.1995 (BGBl. I S. 297): Bekanntmachung nach § 5 Absatz 6 Gentechnik-Sicherheitsverordnung in der Fassung der Bekanntmachung vom 14.3.1995 (BGBl. I S. 297)


Virology: Coronaviruses


Insect biochemistry


Gene Control: Histones—Animal and Vegetable


The virus of acute diarrhoea


Biochemistry of viruses


title: Cavitation as a Mechanism for the Synthesis of Natural Diamonds

text: LET us grant, in accordance with Galimov's proposals(1), that cavitation can occur when flowing magma in a pipe encounters a constriction, and that in the ensuing collapse of a bubble very substantial transient dynamic pressures, of magnitude sufficient to be of thermodynamic importance for diamond synthesis, can be produced. In granting this, we overlook some quantitative details in his calculation, such as the apparent implication that the bubbles would contain gas at 10 or 20 kbar, and yet that their compression (by a factor of 64,000 in volume) can be calculated by ideal gas theory. He ignores the fundamental difference in rate control between martensitic conversion of crystals from one modification to another, which makes a product of the same chemical composition as the starting material, and other processes of crystal growth requiring a composition change. In the former class, to which production of diamond by the action of shock waves on graphite belongs, the limit on growth velocity is essentially the shock wave velocity. Thus, so far as that is concerned, quite a large diamond might be made within a few microseconds. Further characteristics of martensitic processes are, however, that the product takes the form of thin lenses, whereby the constraint by the matrix on shape change in the converting region is minimised and, second, that as a rule there is a multiplicity of orientations of the martensitic product in the parent crystal, so that a microcrystalline product results.


Molecular genetics


Ecology of photosynthesis


Complementary genetics


Progress in coronaviruses


title: CYTOMEGALOVIREMIA IN HEALTHY ASYMPTOMATIC PREGNANT ADOLESCENTS

text: Based upon clinical observations it has been deduced that human cytomegalovirus (HCMV) may be transmitted with blood. It has been estimated that approximately 5% of healthy individuals are asymptomatic carriers of HCMV in blood. Although isolation of this virus from blood is relatively easily accomplished in immunosuppressed individuals or from those with symptomatic HCMV-associated clinical conditions, efforts to recover virus from the blood of asymptomatic healthy carriers have been largely and repeatedly unsuccessful. Only one report has documented viremia in healthy individuals (in 1969 Diosi and associates reported recovery of HCMV from blood in 2 of 35 blood bank donors).¶In the course of studies of healthy pregnant adolescents in North Carolina and in Maryland, HCMV was recovered from the blood in 5 of 96 and 2 of 41 subjects respectively, or 5% in each population. There was no demonstrable association with prenatal transmission of HCMV, with subject well-being or outcome of pregnancy.¶The risk of HCMV reactivation in young pregnant women may relate to gestational and endocrine factors. It is also possible that reactivation of HCMV occurs most frequently soon after primary infection and that the risk of reactivation is inversely related to the elapsed time since virus acquisition. These observations may assist in defining risk factors for transfusion-related transmission as well as for reactivation and prenatal acquistion of HCMV.


title: 1081 BACTERIOPHAGE ARE PRESENT IN THE SPUTUM OF PATIENTS WITH BRONCHOPULMONARY Ps. AERUGINOSA INFECTIONS

text: Although it is generally appreciated that Ps. aeruginosa specific-phage can be isolated from natural sources in which Ps. aeruginosa can be found, such as seawater and sewage, the presence of phage at the sites of Pseudomonas infection in man is not widely recognized. Using routine bacteriological procedures we show that species-specific phage can be consistently recovered from the sputum of patients with chronic Ps. aeruginosa bronchopulmonary infections, including 6 patients with cystic fibrosis and one non CF individual. Ps. aeruginosa specific-phage were present in sputum at concentrations ranging between 10(3) to 10(7) viable particles/ml with as many as 4 different phage strains recovered from a single individual. Of the 16 phage isolates, at least 12 different phage strains could be identified based on bacterial host sensitivity and electron microscopic morphology. It would appear that Ps. aeruginosa and its phage commonly coexist at the site of human bronchopulmonary infections, and most probably at all sites of Ps. aeruginosa infection, and should be considered as possible factors influencing the pathogenicity of Ps. aeruginosa.


Prospective Evaluation of Community-Acquired and Nosocomial Viral Respiratory Tract Infections in a Neonatal and Pediatric Intensive Care Unit


Selected Abstracts from the 100th J Project Meeting, Antalya, Turkey, March 12-14, 2014


title: 1083 DIFFUSION OF MOXALACTAM INTO CSF OF CHILDREN WITH BACTERIAL MENINGITIS

text: Moxalactam (MOX), a new oxa-β-lactam antibiotic,is active against an expanded spectrum of gram negative organisms including Haemophilus influenzae. It has also been reported to diffuse into cerebrospinal fluid. We administered IV MOX to children (6 wks-4½ yrs) receiving conventional antimicrobial therapy for bacterial meningitis. Plasma and CSF specimens were collected 2 to 3 hours after a dose and assayed for MOX concentration by HPLC (capable of detecting 1 μg/ml of MOX). Eight patients received single doses of 15 or 25 mg/kg. In 11 determinations the plasma levels ranged between 4.7 and 29.4 μg/ml but MOX was detected in the CSF in only one instance. Eight patients received 50 mg/kg of MOX every 8 hours for 3 doses, and in 5 patients the drug diffused into CSF. MOX was detectable in 3/5 of CSF specimens early in the course of illness (2nd or 3rd day) and averaged 20% (range 2.5 to 30%) of plasma concentration. It was detectable in 5/11 of CSF specimens obtained later in the illness (13th to 22nd day) and averaged 15.7% (6 to 36%) of plasma concentration. There was no correlation between the diffusion of MOX into CSF and the CSF white cell count, however MOX diffused to a greater extent in patients with higher CSF protein content. In summary, MOX diffuses into CSF but such diffusion is unpredictable. Caution must be exercised in using MOX alone in the treatment of meningitis.


News items


title: 1082 EFFECTS OF PERSISTENT MIDDLE EAR EFFUSION (PMEE) ON DEVELOPMENT OF SPEECH AND LANGUAGE (S&L)

text: To determine effects of PMEE occurring during the first 3 yrs. of life, we administered tests of S&L to 218 3 y.o., white, English-speaking children with normal developmental histories. All had been followed prospectively since birth; we stratified according to duration of PMEE, sex, type of health-care, and socio-economic status (SES). Below are selected results for children with PMEE (130+ days) and those without PMEE (<30 days) in a suburban, private practice (I) and an urban clinic (II). These data suggest that PMEE early in life is associated with significant impairment of S&L; children from higher SES appear at greater risk. This study does not show if such effects are permanent or transient.


title: 1084 UNUSUAL LABORATORY FINDINGS IN ECHOVIRUS-11 MENINGITIS

text: Echovirus 11(E-11) was isolated from the cerebrospinal fluid (CSF) of 22 children in a 1980 summer outbreak of meningitis. Seventeen(77%) were <6 mos old(range 2 wk-9 yr). 54% had CSF cell counts >300/mm(3) and 14% had >500/mm(3)(range 0-2250). 59% had ≥50% polymorphonuclears(P) and 24% had >90% P. None had CSF glucose <40mg/dl; 41% had CSF protein ≥45mg/dl and 6% had >75mg/dl. Three patients(pts) had entirely normal CSF. In 86% peripheral WBC was 5000-15000/mm(3); only 3 had >75% P but 20% had absolute band count >500/mm(3) Four pts(<3 mos old) had repeat CSF exams. All had >50 cells/mm(3) and the two youngest(age 2 wk) still had >50% P after 1 and 3 days. CSF findings were compared with data from pts with bacterial meningitis(B). Cell count >500/mm(3), glucose ≤45mg/dl, and protein >75mg/dl were statistically associated with B. However, 14% of E-11 pts had at least one of these findings and 20% of B pts had none of these findings. CSF P >75% was as frequent in E-11 pts as in B pts. Peripheral WBC <5000 or >15000/mm(3) and absolute band count >500/mm(3) were statistically associated with B but 38% of E-ll pts had one of these abnormalities. Certain CSF findings in our pts have not been reported for E-11 and are uncharacteristic of viral meningitis: 1) leukocyte response more characteristic of bacterial meningitis: CSF P >90%, persistence of CSF P beyond 24 hrs, peripheral band count >500, and 2) entirely normal CSF.


Inhibition of RSV, Coronavirus (CV), and Rhinovirus (RV)-Induced Interleukin-8 (IL-8) Elaboration and Virus Replication by Diphenylene Iodonium Chloride (DPI)


title: INAPPARENT INTRAUTERINE HSV INFECTION DETECTED BY IMMUNOHISTOCHEMISTRY

text: We have used glucose oxidate-avidin-biotin (GAB) immunohistochemistry to detect herpes simplex virus (HSV) 1 & 2 virion antigen in fixed tissue. Cases were selected by placental or cord pathology &/or clinical findings in the fetus/neonate. Virus was detected in placenta, umbilical cord &/or fetal/infant organs from 17 pregnancies (1 set twins; 15 newborns & 3 stillborns). Antigen was found in single mesenchymal & epithelial cells without characteristic viral cytopathology. Viral cultures were positive in one case (skin vesicles). Five mothers had clinical or laboratory evidence of HSV 1/2 infections before or during pregnancy, but none had evidence of active infection at delivery. Thirteen pregnancies ended prematurely & 5 infants/fetuses were small for gestational age. Ten newborns were severely ill. Four infants died before 7-1/2 months of age. Of 11 survivors, 2 have severe CNS abnormalities, 1 persistent pulmonary disease & 2 remain hospitalized. Diagnoses associated with GAB positive herpes virus in specific organs include NEC, hepatitis with cholestatic jaundice, interstitial pneumonitis, aseptic meningitis, progressive cystic brain degeneration, & cardiac arrhythmias. We conclude that intrauterine HSV infection is more common than believed & that intrauterine HSV infection may persist in the fetus & neonate chronically without cytopathology or detectable virus & may be associated with prematurity, intrauterine & neonatal death, organ damage, & progressive neonatal disease.


title: 1085 DIAGNOSIS AND TREATMENT OF PURULENT NASOPHARYNGITIS – A DOUBLE-BLIND, TWO-DRUG EVALUATION

text: 132 children with purulent nasopharyngitis and no other indication for specific treatment had gram stain and bacterial culture of nasopharyngeal discharge and were randomized to 4 treatment groups with antibiotic (A=cephalexin) or decongestant/anti-histamine (D=pseudoephedrine/triprolidine) or their corresponding placebo equivalents (A+D+, A+D−, A−D+, A−D−). Follow-up parent, physician, and bacteriologic evaluations were performed after 5 days of therapy without knowledge of active drug status. Groups were comparable for age, sex, race, number of patients withdrawn from study, days ill, fever >38.0 C, appearance of discharge, nasal crusting, and number of days until follow-up. 21% of patients grew H. influenzae type b and only 8% S. pyogenes on initial culture. Nasal crusting was significantly (p<0.01) associated with the growth of S. pneumoniae or H. influenzae type b, suggesting a possible pathologic relationship. There were, however, no significant differences between active drug and placebo treatment groups for change in nasal discharge, complications, apparent drug benefit, or change in nasal flora with active antibiotic treatment. Significantly (p<0.05) more side effects were attributed to the D+ treatment groups. Routine culture and/or treatment of purulent nasopharyngitis cannot be recommended unless properly controlled studies demonstrate a significant drug benefit.


title: THE USE OF HOMOLOGOUS AND HETEROLOGOUS ROTAVIRUS ANTIBODIES FOR THE PREVENTION OF ROTAVIRUS GASTROENTERITIS

text: Rotavirus is an important cause of serious gastroenteritis in children. One possible strategy for the prevention of rotavirus gastroenteritis is the oral administration of rotavirus specific immunoglobulin. We utilized a mouse model of rotavirus infection to examine the efficacy of rotavirus antibody for the prevention of symptomatic rotavirus diarrhea. This model consists of the feeding of seronegative infant mice a predetermined amount of murine rotavirus and antibody and then assaying the animals for intestinal antigen excretion, liquid colonic contents, and immune response. We found that mouse serum containing homologous antibodies to murine rotavirus completely protected animals from symptomatic infection and viral shedding while non-immune serum provided no protection. Neither immune nor non-immune mouse milk offered any protection from infection. In the case of heterologous sources of sera obtained from animals experimentally infected with human or bovine rotaviruses, and antibodies derived from the yolks of eggs obtained from chickens immunized with rotaviruses full protection was provided from symptomatic disease. Non-immune sera and immune human milk did not protect the animal from infection. The majority of the animals treated with effective specific immunoglobulin preparations developed a rotavirus systemic antibody response. These studies indicate that homologous and heterologous sources of rotavirus antibodies can provide protection from rotavirus diarrhea and may allow for active immunity to occur.


Obituary Dr. Morten Eskildsen


title: DGENERATIVE CHANGES IN NEUTROPHILS-AN INDICATOR OF BACTERIAL INFECTION

text: In 157 neonates in whom a sepsis work-up was performed, 195 peripheral blood smears were reviewed. Neutrophil degenerative changes (vacuolization and toxic granulation) were seen frequently in culture proven bacterial sepsis. Seventeen of 21 peripheral blood smears from neonates subsequently proven to have bacterial infection had vacuolization in neutrophils for a sensitivity of 81%, specificity of 93% and positive predictive accuracy of 59%. Comparison of relative values for predicting neonatal bacterial infection utililizing five items from a single blood sample are shown in the table: Vacuolization and toxic granulation of neutrophils are often found in the peripheral blood smear of neonates with bacterial infection and appear to be more reliable indicators of septicemia than traditional tests.


Viral Upper Respiratory Infection in School Children: Effects on Middle Ear Pressures


Hartmut Krauss, Albert Weber, Max Appel, Burkhard Enders, Henry D. Isenberg, Hans Gerd Schiefer, Werner Slenczka, Alexander von Graevenitz, and Horst Zahner. Zoonoses: infectious diseases transmissible from animals to humans, 3rd edition


title: 1086 CORONAVIRUS-LIKE PARTICLES AND NEONATAL GASTROINTES-TINAL DISEASE

text: Coronavirus-like particles (CVLP) are associated with gastrointestinal (GI) symptoms (sx) in mammals, including man. We report an intensive care nursery (NICU) outbreak of GI sx associated with CVLP, identified by electron microscopy, in the stools of affected infants. Immune aggregation of stool CVLP occurred with sera of CVLP positive (+) infants only. Prevalence of stool CVLP, ascertained by 8 NICU-wide surveys over 40 weeks, fell from 67% to less than 10%, paralleling prevalence changes in the community. Most infants surveyed were premature. Overall, 36% (32/88) of all infants were CVLP +. Prenatal or intrapartum acquisition was suggested by the finding that 34% (11/32) of the CVLP + infants were examined within 72 hours of birth. CVLP + infants were more likely to have GI sx within 7 da of survey (p<.005), including water loss stools (p<.005), and the following sx persisting for more than 2 days: gastric retention (p<.001), bilious gastric aspirates (p<.02), abdominal distention (p<.01) and gross or occult blood in the stool (p<.005). CVLP + infants were also more likely to have multiple sx and to have feeds discontinued for more than 3 days due to GI sx. We conclude that stool Coronavirus-like particles are associated with clinically significant GI disease in the newborn.


title: DETECTION OF MEASLES IgM

text: Fewer physicians have experience in diagnosis of measles as the number of cases continues to decline. For this reason an Enzyme Linked Immunosorbent Assay (ELISA) was developed to detect measles virus specific IgM antibody (MIgMA). Anti-human μ chain is affixed to a solid phase to which a 1:100 dilution of serum is added. Only 0.005 ml of patient's serum is needed. Treatment of 3 MIgMA positive sera with dithiothreitol but not Staph protein A removed MIgMA. The values for 24 cord sera (0.030 ± 0.007), 60 adult sera (0.034 ± 0.011), and 47 sera from children prior to measles immunization (0.030 ± 0.015) were used to establish a seronegative range. Sera yielding reactions greater than 3 SD of the mean for the latter group were considered to be positive for the presence of MIgMA. MIgMA was not detected in sera with high titers of rheumatoid factor. Five unpaired and the first of 14 of 17 paired sera obtained from patients with measles were positive for MIgMA. The 3 convalescent samples from patients having MIgMA negative initial sera, also were positive. MIgMA was detected as early as 1 day and as late as 41 days following onset of illness. No MIgMA could be detected in 47 vaccinees tested 2-1/2 months or more after measles vaccination. Neither recent immunization nor the presence of rheumatoid factor produce reactions which are likely to obfuscate the interpretation of this very sensitive test which, in most cases, can confirm the clinical diagnosis of measles on a single serum specimen obtained soon after onset of rash.


title: IMMUNOLOGIC STUDIES OF ENTERIC CORONAVIRUS-LIKE PARTICLES(CVLP)

text: CVLP have been implicated in gastrointestinal illness sporadically among children and in an intensive care nursery outbreak at our hospital. Fecal examination by electron microscopy(EM) is the only means of diagnosis. We developed an enzyme-linked immunosorbent assay(ELISA) using ammonium sulfate precipitated CVLP from feces. The purified CVLP was immunogenic in rabbits. Sera containing antibodies against bovine enteric, canine, OC43, and 229E coronaviruses(CV) did not block binding of rabbit anti-CVLP to microtiter wells coated with purified CVLP. Immune EM using these antisera and nonaggregated CVLP also suggested that CVLP are antigenically distinct from other CV. False positives occurred when stools negative for CVLP by EM were tested. This nonspecific reaction was not blocked by sonicates of E.coli, Strep. fecalis, B.fragilis, or C.difficile, or by C.difficile antitoxin. Absorption of rabbit anti-CVLP serum with suckling mouse intestine did not improve specificity. More sophisticated purification of fecal CVLP is needed to improve ELISA sensitivity and specificity, and to characterize the antigen.


Announcement


title: The classification and nomenclature of viruses: Summary of results of meetings of the International Committee on Toxonomy of Viruses in Madrid, September 1975

text: The results of the meetings of the International Committee on Taxonomy of Viruses, held in Madrid, September 1975, are briefly reported: rules of viral nomenclature, composition of the new Executive Committee, and a list of the names so far officially agreed.


The 21st meeting of the Executive Committee of the International Committee on Taxonomy of Virsues (ICTV): The ICTVdB project and other initiatives


VIIth International Symposium on Coronaviruses and Arteriviruses Parador de Segovia, Segovia, Spain May 10 to 15th, 1997


Obituary Léon Hirth (1916–1991)


Changes to virus taxonomy 2004


Vaccine design: Innovative Approaches and Novel Strategies Edited by Rino Rappuoli and Fabio Bagnoli (2011): Caister Academic Press, Norfolk, UK, 380 pages. ISBN :978-1-904455-74-5, Hardcover. $319 from Amazon.com


Recently published papers in the field of molecular evolution


Resistance to fatal central nervous system disease by mouse hepatitis virus, strain JHM: I. Genetic analysis


Involvement of cysteine in Semliki Forest virus (SFV) induced fusion ofAedes albopictus cells


In vitro protein synthesis by cells infected with different types of bovine herpesvirus 1


Gene expression


Detection of viruses by electron microscopy in fecal samples from patients with gastroenteritis in the canton of Vaud


Recently published papers in the field of molecular evolution: General aspects


Bovine herpesvirus 1 and caprine herpesvirus 1: Viral polypeptides exhibiting shared and unique antigenic determinants


News from the Internet


Contents of Volume 31, 2005


Oral Presentations


Viral agents in marmoset colitis: Dr. Robert Russell, University of Washington, Seattle, and Dr. David Brian, University of Tennessee, Knoxville


Book Review: AN INTRODUCTION TO THE U.S. HEALTH CARE SYSTEM. Fifth Edition. By Steven Jonas, New York: Springer Publishing Company, 2003, 233 pp., $36.95 (softcover)


title: Examining the Links between Biodiversity and Human Health: An Interdisciplinary Research Initiative at the U.S. Environmental Protection Agency

text: Under the U.S. Environmental Protection Agency’s mission to protect human health and the environment, the agency seeks to conduct research on the structure and function of ecosystems and to improve our understanding of the processes that contribute to the sustained health of the nation’s ecosystems and the well-being of human populations. Changes in biodiversity can profoundly impact the ability of ecosystems to provide clean water, energy, food, recreation, and other services that contribute to human well-being. In addition, changes in biodiversity can affect the transmission of infectious disease to humans, particularly vectorborne diseases such as malaria and Lyme disease. The Environmental Protection Agency’s new initiative supports interdisciplinary research to characterize the mechanisms that link biodiversity and human health and to use this knowledge to develop integrative tools and approaches for quantifying and predicting these relationships. Research on these links can have an important impact on our view of biodiversity and how we manage resources to protect human and ecosystem health.


Emerging Infectious Diseases and the Socio-ecological Dimension


1(st) International One Health Congress Abstracts: Plenary Abstracts


Wildlife Trade: Threat to Global Health


A Fall From Grace To… Virulence?


title: All Hands on Deck: Transdisciplinary Approaches to Emerging Infectious Disease

text: The increasing burden of emerging infectious diseases worldwide confronts us with numerous challenges, including the imperative to design research and responses that are commensurate to understanding the complex social and ecological contexts in which infectious diseases occur. A diverse group of scientists met in Hawaii in March 2005 to discuss the linked social and ecological contexts in which infectious diseases emerge. A subset of the meeting was a group that focused on “transdisciplinary approaches” to integrating knowledge across and beyond academic disciplines in order to improve prevention and control of emerging infections. This article is based on the discussions of that group. Here, we outline the epidemiological legacy that has dominated infectious disease research and control up until now, and introduce the role of new, transdisciplinary and systems-based approaches to emerging infectious diseases. We describe four cases of transboundary health issues and use them to discuss the potential benefits, as well as the inherent difficulties, in understanding the social–ecological contexts in which infectious diseases occur and of using transdisciplinary approaches to deal with them.


JIC Award 2008


title: Wildlife Trade and the Emergence of Infectious Diseases

text: Most recent emerging infectious diseases have been zoonotic in origin. It is our contention that one of the factors responsible for such emergence is the trade in wildlife and bushmeat in particular. This article considers the effect of increasing diversity in the species hunted on the probability of global epidemics such as SARS. In particular, we develop a mathematical model of the probability of such an outbreak in terms of the number of species hunted, the number of susceptibles, and the rate of contact. Hence, we postulate that local biodiversity loss and increasing rates of animal trafficking, and trade and transportation of animals to large cities—where there is a greater potential for person-to-person transmission—may increase the probability of such outbreaks dramatically.


Restriction site maps of a new type of bovine herpesvirus 1


title: Marketing in Heterozygous Advantage

text: As the rapidly advancing possibilities of biotechnology have outstripped the adaptive capacity of current legal and ethical institutions, a vigorous debate has arisen that considers the boundaries of appropriate use of this technology, particularly when applied to humans. This article examines ethical concerns surrounding the development of markets in a particular form of human genetic engineering in which heterozygotes are fitter than both homozygotes, a condition known as heterozygous advantage. To begin, we present a generalized model of the condition, illuminated by the application to sickle-cell anemia. Next, we propose a typology of related markets, some of which are currently functioning with available products and services, and others that are widely viewed as imminent. We suggest the manner in which perverse incentives may arise for firms that market genetic intervention in circumstances where heterozygous advantage is possible. Finally, we propose that this misalignment of incentives with social welfare has arisen from both ill-conceived market intervention where markets are capable of achieving efficient outcomes and the lack of market intervention where markets have failed. We offer specific legal and regulatory approaches for reform.


title: Label-free microcantilever-based immunosensors for highly sensitive determination of avian influenza virus H9

text: We report on label-free immunosensors for the highly sensitive detection of avian influenza virus. The method makes use of the microcantilevers of an atomic force microscope onto which monoclonal antibodies against avian influenza virus were covalently immobilized. The factors influencing the performance of the resulting immunosensors were optimized by measuring the deflections of the cantilever via optical reflection, and this resulted in low detection limits and a wide analytical range. The differential deflection signals revealed specific antigen binding and their intensity is proportional to the logarithm of the concentrations of the virus in solution. Under optimal conditions, the immunosensors exhibit a linear response in the 7.6 ng mL(−1) to 76 μg mL(−1) concentration range of avian influenza virus, and the detection limit is 1.9 ng mL(−1). [Figure: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00604-013-1129-x) contains supplementary material, which is available to authorized users.


Book Review


Evaluating viral agents in marmoset colitis


title: Anthropogenic Environmental Change, Mosquito-borne Diseases and Human Health in New Zealand

text: Anthropogenic environmental change is acknowledged as a primary factor in the emergence of diseases. New Zealand’s history since human occupation has been characterized by extensive anthropogenic disturbance and the establishment of numerous exotic species. As a result, highly modified habitats have been created, which, in conjunction with introduced organisms, provide suitable conditions for the establishment of exotic systems likely to lead to outbreaks of mosquito-borne disease. The interactions among some disturbance factors in the New Zealand environment are discussed, and the potential public health implications.


title: An improved method for detection of Edwardsiella tarda by loop-mediated isothermal amplification by targeting the EsrB gene

text: Edwardsiella tarda is a major pathogen in aquatic environments that can cause heavy economic losses. An improved method for quick and accurate detection of E. tarda by loop-mediated isothermal amplification (LAMP) with two additional loop primers was developed by targeting the EsrB gene (EsrB — LAMP). In this method, the Mg(2+) concentration, reaction temperature, and reaction time were optimized to 8 mmol/L, 61°C, and 40 min, respectively. The detection limit with the EsrB gene was as low as 10 copies, which is 100 times more sensitive than that of conventional polymerase chain reaction (PCR). The EsrB-LAMP assay was shown more sensitive and rapid than previously reported LAMP assays targeting the hemolysin gene ( hemolysin -LAMP) for detection of E. tarda. The EsrB -LAMP was also highly specific to E. tarda and had no cross-reaction with 13 other strains of bacteria. The assay can be carried out in a simple heating device and the EsrB-LAMP products can be visually detected by adding fluorescent dye to the reaction mixture. Taken together, the improved EsrB-LAMP diagnostic protocol has the potential for detection of E. tarda from indoor and outdoor samples.


Regulation of the promoters in SV40 chromosomes and construction of a substituted SV40 containing aDrosophila hsp70 promoter


Incubus


title: N′-[4-[(Substituted imino)methyl]benzylidene]-substituted benzohydrazides: synthesis, antimicrobial, antiviral, and anticancer evaluation, and QSAR studies

text: ABSTRACT: A variety of N′-[4-[(substituted imino)methyl]benzylidene]-substituted benzohydrazides have been synthesized and evaluated for antimicrobial and anticancer potential. Results from testing of antimicrobial activity indicated the most potent antimicrobial agents had pMIC (am) = 1.51. The synthesized compounds were bacteriostatic and fungistatic in action. Results from evaluation of antiviral activity indicated that none of the synthesized hydrazide derivatives inhibited viral replication at sub-toxic concentrations. Results from anti-HIV screening against HIV-2 strain ROD indicated that one compound was more potent (IC (50) ≥ 1 μg/cm(3)) than the standard drug nevirapine (IC (50) ≥ 4 μg/cm(3)) and another was equipotent (IC (50) ≥ 4 μg/cm(3)). The most effective anticancer agent against both HCT116 and MCF7 cancer cell lines had IC (50) = 19 and 18 μg/cm(3), respectively. QSAR analysis indicated the importance of Wiener index (W) and energy of the lowest unoccupied molecular orbital (LUMO) in describing the antimicrobial activity of the synthesized compounds. GRAPHICAL ABSTRACT: [Image: see text]


Book reviews


title: Genetic structure of mountain lion (Puma concolor) populations in California

text: Analysis of 12 microsatellite loci from431 mountain lions (Puma concolor)revealed distinct genetic subdivision that wasassociated with geographic barriers andisolation by distance in California. Levels ofgenetic variation differed among geographicregions, and mountain lions that inhabitedcoastal areas exhibited less heterozygositythan those sampled inland. The San FranciscoBay and Sacramento-San Joaquin River Delta, theCentral Valley, and the Los Angeles Basinappeared to be substantial barriers to geneflow, and allele frequencies of populationsseparated by those features differedsubstantially. A partial barrier to gene flowappeared to exist along the crest of the SierraNevada. Estimated gene flow was high amongmountain lions inhabiting the Modoc Plateau,the western Sierra Nevada, and northern sectionof the eastern Sierra Nevada. SouthernCalifornia mountain lion populations mayfunction as a metapopulation; however, humandevelopments threaten to eliminate habitat andmovement corridors. While north-south geneflow along the western Sierra Nevada wasestimated to be very high, projected loss andfragmentation of foothill habitat may reducegene flow and subdivide populations. Preservation of existing movement corridorsamong regions could prevent population declinesand loss of genetic variation. This studyshows that mountain lion management andconservation efforts should be individualizedaccording to region and incorporatelandscape-level considerations to protecthabitat connectivity.


Phospholipids, cerebroside, and cerebroside sulfate levels in the CNS of mice withacute experimental viral demyelination


IUPAC-IUBMB Joint Commission on Biochemical Nomenclature (JCBN) and Nomenclature Committee of IUBMB (NC-IUBMB) Newsletter 1996


Gerald L. Mandell, John E. Bennett, Raphael Dolin (eds): Principles and Practice of Infectious Diseases, 6th edn: Elsevier, Philadelphia, 2005; two volumes + CD-ROM, hardbound, pp 3661 + XXXVIII; €314.90, US$329, GBP 201.13; ISBN 0-443-06643-4


title: Ecology of Increasing Diseases: Population Growth and Environmental Degradation

text: The World Health Organization (WHO) and other organizations report that the prevalence of human diseases during the past decade is rapidly increasing. Population growth and the pollution of water, air, and soil are contributing to the increasing number of human diseases worldwide. Currently an estimated 40% of world deaths are due to environmental degradation. The ecology of increasing diseases has complex factors of environmental degradation, population growth, and the current malnutrition of about 3.7 billion people in the world.


Book Review: DECEIT AND DENIAL. THE DEADLY POLITICS OF INDUSTRIAL POLLUTION. By Gerald Markowitz and David Rosner, Berkeley: University of California Press/The Millbank Memorial Fund, 2003, 408 pp., illustrated, $34.95 (hardcover)


title: Health of Antarctic birds: a review of their parasites, pathogens and diseases

text: Antarctic birds are not beyond the effects of parasites or pathogens. However, potential ecological consequences of wide-spread infections for bird populations in Antarctica have received little attention. In this paper, we review the information published about disease and parasites, and their effects on Antarctic birds. The information on host species, parasites and pathogens, and geographic regions is incomplete and data on ecological effects on the populations, including how birds respond to pathogens and parasites, are almost inexistent. We conclude that more research is needed to establish general patterns of spatial and temporal variation in pathogens and parasites, and to determine how such patterns could influence hosts. This information is crucial to limit the spread of outbreaks and may aid in the decision-making process should they occur.


title: Pandemic simulation of antivirals + school closures: buying time until strain-specific vaccine is available

text: A strain-specific vaccine is unlikely to be available in the early phases of a potential H5N1 avian influenza pandemic. It could be months and at the current production rate may not provide timely protection to the population. Intervention strategies that control the spread of infection will be necessary in this situation, such as the use of the US stockpile of antiviral medication coupled with a 6-month school closure. The agent-based simulation model, EpiSimS, was used to assess the impact of this intervention strategy followed by three different vaccine approaches: (1) 2-dose, 80% effective, (2) 1-dose, 30% effective, and (3) 1 dose, 80% effective. Simulations show that the combination of antivirals, school closures, and a strain-specific vaccine can reduce morbidity and mortality while in effect. A significant second infection wave can occur with current vaccine technology once school closures are relaxed, though an ideal vaccine is able to contain it. In our simulations, worker absenteeism increases in all cases mostly attributed to household adults staying home with children due to the school closures.


Abstracts of papers submitted to the American Motility Society


Human biochemistry and disease: by Gerald Litwack, Elsevier, Amsterdam-Boston-Heidelberg-London-New-York-Oxford-Paris, 2008, 1254 p., $199.95


title: Carbon nanotag based visual detection of influenza A virus by a lateral flow immunoassay

text: The authors report on a rapid and direct visual test for the detection of influenza A virus using a carbon nanotag based lateral flow assay. Carbon nanoparticles in the form of nanostrings are acting as reporters. As carbon nanotags accumulate in the test zone due to formation of an antibody-antigen-carbon nanotag antibody complex, and this allows for the direct visualization of the analytical signal. Under optimal conditions, influenza A virus can be determined in allantoic fluid inoculated with the virus with a limit of detection of 350 TCID(50).mL(−1) (i.e., the 50% tissue culture infectious dose). No interference is found for several other tested proteins, and for closely related viruses. Cell lysates containing different seasonal strains of influenza A viruses (including the H1N1 and H3N2 strains) collected from clinical samples were analyzed. It is demonstrated that the method can detect both influenza A viruses without interference by biological matrices. In our perception, this method has a wide potential in that it may be extended to a generally applicable platform for rapid diagnosis influenza A viruses. [Figure: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00604-017-2191-6) contains supplementary material, which is available to authorized users.


title: Micro-flow analysis by molecular tagging velocimetry and planar Raman-scattering

text: The two dimensional molecular tagging velocimetry (2D-MTV) has been used to measure velocity fields of the flow in a micro mixer. Instead of commonly used micro particles an optical tagging of the flow has been performed by using a caged dye. The pattern generation is done by imaging a mask for the first time. This allows to generate nearly any imaginable pattern. The flow induces a deformation of the optically written pattern that can be tracked by laser induced fluorescence. The series of raw images acquired in this way were analyzed quantitatively with a novel optical flow based technique. The reference measurements have been carried out allowing to draw conclusions about the accuracy of this procedure. A comparison to the standard technique of μPIV has also been conducted. Apart from measuring flow velocities in microfluidic mixing processes, the spatial distribution of concentration fields for different species has also been measured. To this end, a new technique has been developed that allows spatial measurements from Planar Spontaneous Raman Scattering (PSRS). The Raman stray light of the relevant species has been spectrally selected by a narrow bandpass filter and thus detected unaffectedly by the Raman stray light of other species. The successful operation of this measurement procedure in micro flows will be demonstrated exemplary for a mixing process of water and ethanol.


title: Simulating influenza pandemic dynamics with public risk communication and individual responsive behavior

text: Individual responsive behavior to an influenza pandemic has significant impacts on the spread dynamics of this epidemic. Current influenza modeling efforts considering responsive behavior either oversimplify the process and may underestimate pandemic impacts, or make other problematic assumptions and are therefore constrained in utility. This study develops an agent-based model for pandemic simulation, and incorporates individual responsive behavior in the model based on public risk communication literature. The resultant model captures the stochastic nature of epidemic spread process, and constructs a realistic picture of individual reaction process and responsive behavior to pandemic situations. The model is then applied to simulate the spread dynamics of 2009 H1N1 influenza in a medium-size community in Arizona. Simulation results illustrate and compare the spread timeline and scale of this pandemic influenza, without and with the presence of pubic risk communication and individual responsive behavior. Sensitivity analysis sheds some lights on the influence of different communication strategies on pandemic impacts. Those findings contribute to effective pandemic planning and containment, particularly at the beginning of an outbreak.


title: Detection of the antigen-antibody reaction by light scattering spectroscopy

text: The possibility of recording the results of serologic reactions not yielding visible phenomena by means of light scattering spectroscopy (LSS) was studied. Influenza virus andMycoplasma pneumoniae antigens and the corresponding antisera were used as the test objects. It was shown that, in principle, LSS can be used to detect the antigen-antibody complex in serologic reactions not yielding viible phenomena.


What’s New?


Issues in infectious diseases, Vol. 4. Emerging viral diseases of Southeast Asia. Lal Sunil K (ed): Karger, Basel, 2007, ISBN 3-8055-8175-0, € 123


title: Detection of viral aerosols by use of real-time quantitative PCR

text: PCR quantification is regarded as one of the most promising techniques for real-time identification of bio-aerosols. We have, therefore, validated a QPCR assay for quantification of a viral aerosol sample using the double-stranded DNA-binding dye SYBR green I, an economical alternative for quantification of target microorganisms. To achieve this objective we used mycobacteriophage D29 as model organism. Phage D29 aerosol was produced in an aerosol cabinet and then collected by use of an AGI liquid sampler. A standard curve was created by use of purified genomic DNA from the phage in liquid culture of known concentration measured by titration. To prevent false-positive results caused by formation of primer–dimers, an additional data-acquisition step was added to the three-step QPCR procedure; the new technique was called four-step QPCR. The standard curve was then used to quantify the total amount of phage D29 in liquid culture and aerosol samples. For liquid culture samples there was no significant difference (P > 0.05) between results from quantification of the virus using double-agar culture and QPCR. For aerosol samples, however, the result determined by the QPCR method was significantly (P < 0.05) higher than that from the double-agar culture method. The four-step SYBR green I QPCR method is a quick quantitative method for mycobacteriophage D29 aerosol. We believe that QPCR using SYBR green I dye will be an economical method for detection of airborne bio-aerosols.


title: Advances in molecular phytodiagnostics – new solutions for old problems

text: In the last decade, developments in molecular (nucleic acid-based) diagnostic methods have made significant improvements in the detection of plant pathogens. By using methods such as the polymerase chain reaction (PCR), the range of targets that can now be reliably diagnosed has grown to the extent that there are now extremely few, known pathogens that cannot be identified accurately by using laboratory-based diagnostics. However, while the detection of pathogens in individual, infected samples is becoming simpler, there are still many scenarios that present a major challenge to diagnosticians and plant pathologists. Amongst these are the detection of pathogens in soil or viruses in their vectors, high throughput testing and the development of generic methods, that allow samples to be simultaneously screened for large numbers of pathogens. Another major challenge is to develop robust technologies that avoid the reliance on well-equipped central laboratories and making reliable diagnostics available to pathologists in the field or in less-developed countries. In recent years, much of the research carried out on phytodiagnostics has focussed in these areas and as a result many novel, routine diagnostic tests are becoming available. This has been possible due to the introduction of new molecular technologies such real-time PCR and microarrays. These advances have been complemented by the development of new nucleic acid extraction methods, increased automation, reliable internal controls, assay multiplexing and generic amplification methods. With developments in new hardware, field-portable real-time PCR is now also a reality and offers the prospect of ultra-rapid, on-site molecular diagnostics for the first time. In this paper, the development and implementation of new diagnostic methods based upon novel molecular techniques is presented, with specific examples given to demonstrate how these new methods can be used to overcome some long-standing problems.


Ecological Studies of Diseases: Promise and Praxis


Morphological and biochemical changes in brain cells of mice infected with influenza virus


Oral session 17: Infection of the nervous system


19th European Congress of Pathology, Ljubljana, Slovenia, September 6-11, 2003


title: Simultaneous detection of multiple viruses in their co-infected cells using multicolour imaging with self-assembled quantum dot probes

text: The simultaneous detection and evaluation of the coinfection of a cell by multiple viruses or even multiple subtypes still is a difficult challenge. The authors introduce a method for simultaneous imaging, detection and quantitative evaluation of multiple viruses in single cells by using multicolor quantum dot (QD) probes and in a single staining cycle. The multicolor QD probes were fabricated via interaction between QDs conjugated to Staph. aureus protein A (SpA-QDs) and virus-specific antibodies. A cocktail of differently colored QD-SpA-MAbs probes were loaded into the same cells containing multiple viruses, and this enabled the different viruses to be fluorescently imaged and analyzed simultaneously. Specifically, influenza A viruses of type H1N1, H3N2, and H9N2, as well as human adenovirus species B type 3 (HAdV-B3) were imaged and detected in virus-infected cells or in their co-infected cells. In our perception, the method provides a flexible platform for simultaneous detection of multiple viruses in co-infected cells. Hence, it offers new opportunities for the molecular diagnosis of virus coinfection and for studies on virus-cell interactions. [Figure: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00604-017-2300-6) contains supplementary material, which is available to authorized users.


Key word index Volume 31, 2005


title: Emerging and Reemerging Infectious Diseases: Biocomplexity as an Interdisciplinary Paradigm

text: Understanding factors responsible for reemergence of diseases believed to have been controlled and outbreaks of previously unknown infectious diseases is one of the most difficult scientific problems facing society today. Significant knowledge gaps exist for even the most studied emerging infectious diseases. Coupled with failures in the response to the resurgence of infectious diseases, this lack of information is embedded in a simplistic view of pathogens and disconnected from a social and ecological context, and assumes a linear response of pathogens to environmental change. In fact, the natural reservoirs and transmission rates of most emerging infectious diseases primarily are affected by environmental factors, such as seasonality or meteorological events, typically producing nonlinear responses that are inherently unpredictable. A more realistic view of emerging infectious diseases requires a holistic perspective that incorporates social as well as physical, chemical, and biological dimensions of our planet’s systems. The notion of biocomplexity captures this depth and richness, and most importantly, the interactions of human and natural systems. This article provides a brief review and a synthesis of interdisciplinary approaches and insights employing the biocomplexity paradigm and offers a social–ecological approach for addressing and garnering an improved understanding of emerging infectious diseases. Drawing on findings from studies of cholera and other examples of emerging waterborne, zoonotic, and vectorborne diseases, a “blueprint” for the proposed interdisciplinary research framework is offered which integrates biological processes from the molecular level to that of communities and regional systems, incorporating public health infrastructure and climate aspects.


title: The Role of Ecotones in Emerging Infectious Diseases

text: Recognition of the significance of the boundary between ecological systems, often referred to as the ecotone, has a long history in the ecological sciences and in zoonotic disease research. More recent research in landscape ecology has produced an expanded view of ecotones and elaboration of their characteristics and functions in ecosystems. Parallel research on emerging infectious diseases (EIDs) and the causes of increased rates of pathogen transmission, spread, and adaptation suggests a correspondence between ecotonal processes and the ecological and evolutionary processes responsible for zoonotic and vector-borne emerging infections. A review of the literature suggests that ecotones play a role in a number of the most important EIDs. Yet these are the only diseases for which specific landscape ecological information exists in the literature or disease reports. However, the similar disease ecologies of these with about half of the approximately 130 zoonotic EIDs suggests ecotones, particularly their anthropogenic origination or modification, may be generally associated with ecotones and the global trend of increasing EIDs.


Cognitive-Behavioral Treatment of Health Anxiety Disorders


Keyword Index to Volume 22


title: Pneumonien bei immunsupprimierten Patienten

text: Pneumonia occurs frequently in immunocompromised patients and often shows a complicated course of disease when compared to immunocompetent persons. The type of pathogen involved is directly associated with the type of immunosuppression and includes a wide variety of pathogens. Congenital and primary immunodeficiencies often appear during childhood. Acquired immunodeficiencies are most commonly caused by immunosuppressive medication. The concept of immunosuppression can be extended to patients with COPD or elderly patients because the variety of pathogens and specific features regarding frequency and course of the disease are similar to immunosuppressed patients. Computed tomography can provide an indication of the pathogen and is superior to the chest x‑ray in this respect. Blood cultures, antigen and PCR tests are non-invasive diagnostic tools for pathogen diagnostics. Invasive tests include fiberoptic bronchoscopy and complete the diagnostic methods of identifying the causative pathogen.


Selected Abstracts of the Institut Pasteur Euroconference on Angiogenesis, Paris, France 8–9 March 2001


Book Review: AMERICA'S FORGOTTEN PANDEMIC. THE INFLUENZA OF 1918. Second Edition. By Alfred W. Crosby, Cambridge: Cambridge University Press, 2003, 337 pp., $60.00 (hardcover), $22.00 (softcover)


Avian Influenza (H5N1) and the Evolutionary and Social Ecology of Infectious Disease Emergence


title: Das neue Verständnis pulmonaler Infektionen

text: Epidemiological data on the distribution of mostly bacterial pathogens are still the basis for empirical treatment recommendations on respiratory infections. Because of the dynamic technological developments in molecular multiplexing and sequencing procedures, the spectrum of potential pathogens is increased and challenges the current dogma of virulence and pathogenicity of certain pathogens. Classical pathogens of the lungs are thereby not questioned but are increasingly placed in a context that reflects co-infections with viruses and changes of the local microbiome in more depth. Recent data indicate that integration of this novel information is required for a better understanding of the seasonal differences in the frequency of particular lung infections and to find new approaches to risk stratification of patients. This becomes most obvious in the subgroup of immunosuppressed patients who are at risk of severe courses of diseases with higher morbidity and mortality from infections with viruses and facultative pathogens, such as nontuberculous mycobacteria (NTM). Based on the fundamental knowledge on the spectrum of pathogens of community-acquired and nosocomial lung infections, novel approaches in pathogen diagnostics and lung microbiome analytics are discussed and the applicability with respect to the current clinical routine is questioned.


2(nd) World Congress on Women’s Mental Health March 17–20, 2004, Washington, DC


title: Vesicular membrane transfer between endoplasmic reticulum and golgi apparatus of a green alga,Micrasterias americana: A 16°C block and reconstitution in a cell-free system

text: Transfer of membranes between endoplasmic reticulum and Golgi apparatus of the unicellular green alga,Micrasterias americana, is facilitated by 50–70 nm vesicles that form from part-rough. part-smooth transitional regions of the endoplasmic reticulum. In growing cells, the vesicles are present at the normal growth temperature of 23°C. However, at 16°C, vesicle accumulations occur. Golgi apparatus of non-growing cells exhibited both larger numbers of vesicles and larger dictyosomes at all temperatures. In non-growing cells, vesicle numbers also were increased at 16°C. The 16°C block was reconstituted in a cell-free system using Golgi apparatus-and endoplasmic reticulum-enriched fractions prepared from suspension cultures. When incubated in the presence of ATP and cytosol, transitional endoplasmic reticulum fragments ofMicrasterias responded by formation of membrane blebs and vesicles resembling those seen in situ. When prepared from cells metabolically labeled with [(3)H]leucine, the isolated transition elements supported the transfer of radioactivity of Golgi apparatus preparations immobilized on nitrocellulose strips. The transfer was time-and temperaturedependent and stimulated by ATP. The ATP-dependent component of transfer expressed at 23°C was reduced or absent at temperatures of 16°C or below. This suggested that membrane transfer mediated by transition vesicles was the same rate-limiting step in endoplasmic reticulum to Golgi apparatus membrane trafficking both in situ and in the cell-free system. Growth, as evidenced by a progressively alteredMicrasterias morphology, was slowed at low temperatures but showed no abrupt temperature transition as seen with the vesicular traffic between the endoplasmic reticulum and the Golgi appatus.


Effect of insulin on Na, K-ATP-ase activity in rat brain microsomes


title: Feuchter Husten und protrahierte bakterielle Bronchitis bei Kindern und Jugendlichen

text: Persistent cough is one of the most common reasons patients present to outpatient practices. Especially in children, chronic cough (>4 weeks) is a significant burden on the child and family. While in the past, the lower airways were considered sterile, the concept of a physiologic microbiome of the lower respiratory tract has increasingly emerged. Of the differential diagnoses of chronic cough, protracted bacterial bronchitis (PBB) is more common in otherwise (pulmonary) healthy children under 6 years of age. Tracheomalacia may primarily exist or be the result of mechanically straining coughing, whereas apart from a reduced alveolar phagocytosis, there is usually no systemic or local immune weakness. Instead, an activated innate immunity with increased gene expression of the interleukin-1β signaling pathway can be immunologically detected. Here too, it is difficult to differentiate between cause and effect of chronic inflammatory events. Today, PBB and non-CF bronchiectasis, i.e., bronchiectasis not caused by cystic fibrosis (CF), are two sides of a disease spectrum of suppurative lung diseases, thus, making consequent therapy and long-term pediatric pneumological support of children with chronic productive cough necessary.


Three-step research strategies for ARDS: new target molecules—ACE2, HMGB1, and HSP47


Book Review: THE HUMAN IMMUNODEFICIENCY VIRUS. BIOLOGY, IMMMUNOLOGY, AND THERAPY. Edited by Emilio A. Emini, Princeton: Princeton University Press, 2003, 532 pp., $80.00 (hardcover)


title: Low temperature compartment formation in feline immunodeficiency virus-infected and uninfected feline kidney cells

text: This study was to determine if feline immunodeficiency virus (FIV)-infected and uninfected Crandall feline kidney (CRFK) cells exhibited a low temperature (16°C) block in membrane trafficking between transitional endoplasmic reticulum and Golgi apparatus represented by intermediate compartment formation. Cells were cultured at different temperatures and membrane changes involving the Golgi apparatus and Golgi apparatus-associated membrane structures were monitored by electron microscopy and quantitated. With 30 min of incubation, membranes of the Golgi apparatus stack increased in amount at temperatures of 16°C and below compared to temperatures above 18°C. The increase was greatest along the major polarity axis as evidenced by an increased stack height. Neither the number of cisternae per stack nor the average stack diameter (width) was affected by temperature. The response was maximal between 15 and 30 min of low temperature treatment of the cells. Results with cells infected and uninfected with feline immunodeficiency virus were similar. The increase in stack height was due primarily to an increase of membranes at the cis face (cis Golgi apparatus network). At 18°C, membranes of the trans Golgi apparatus network accumulated suggesting that import from the cis Golgi network could proceed at this temperature, whereas exit from the trans Golgi network was still at least partially blocked. Also increased at 16°C and below were numbers of transition vesicles in the space between the Golgi apparatus and the transitional endoplasmic reticulum associated with the cis Golgi apparatus face. The results suggested interruption of the orderly flux of membranes into the Golgi apparatus at 16°C and below. Moreover, the block appeared to be reversible. Upon transfer from 16°C to 37°C, there was a time-dependent decrease in the accumulations of cis compartment membrane accompanied by a corresponding equivalent increase in the membranes of the trans Golgi apparatus compartment.


title: Acute abdominal emergencies associated with cytomegalovirus infection in the young infant

text: Gastrointestinal signs and symptoms have rarely been reported in association with cytomegalovirus (CMV) infection in young infants. However, in 1981 clear pathologic evidence was presented implicating this virus as a cause of hypoganglionosis and bowel dysmotility. We report our experience with four infants with CMV infection in whom gastrointestinal dysfunction was the reason for emergency abdominal operation. Since the association was made retrospectively, we were unable to demonstrate hypoganglionosis, but our experience underscores the need to include CMV intestinal infection in the differential diagnosis of the acute surgical abdomen in young infants.


2. Metalloproteins


title: Structural Analogs of Umifenovir. 1. Synthesis and Biological Activity of Ethyl 5-Hydroxy-1-Methyl-2-(Trans-2-Phenylcyclopropyl)-1H-Indole-3-Carboxylate

text: Ethyl 5-hydroxy-1-methyl-2-(trans-2-phenylcyclopropyl)-1H-indole-3-carboxylate is the first prototype of conformationally restricted analogs of umifenovir. It has been prepared using a one-pot method and has undergone an antiviral study.


Virus hepatitis a in lower old-world monkeys (possible model for vaccine testing)


Contents to Volume 27(2005)


title: Ecology of Infectious Disease: Forging an Alliance

text: The Ecology of Infectious Diseases (EID) program is a joint National Science Foundation–National Institutes of Health initiative to produce predictive understanding of disease dynamics, with a focus on diseases with an environmental component. The interdisciplinary research projects funded by this program take advantage of the wide range of theoretical and methodological advances developed over the past 30 years. The challenge for disease ecology is to unravel these systems, discover how complex they truly are, and to determine if they can be predicted and controlled using targeted environmental, public health, or medical interventions. Between 1999 and 2005, a total of 42 research awards were made under the EID program. EID projects have had affects on policy in two areas: adoption of novel interventions on a local scale and use of models by government agencies for the purpose of allocating public health resources. The past 6 years have been an exciting time for the field of disease ecology; we expect the coming years to be even more exciting and productive.


How to Frame Mobility?


title: Predicting social response to infectious disease outbreaks from internet-based news streams

text: Infectious disease outbreaks often have consequences beyond human health, including concern among the population, economic instability, and sometimes violence. A warning system capable of anticipating social disruptions resulting from disease outbreaks is urgently needed to help decision makers prepare appropriately. We designed a system that operates in near real-time to identify and predict social response. Over 150,000 Internet-based news articles related to outbreaks of 16 diseases in 72 countries and territories were provided by HealthMap. These articles were automatically tagged with indicators of the disease activity and population reaction. An anomaly detection algorithm was implemented on the population reaction indicators to identify periods of unusually severe social response. Then a model was developed to predict the probability of these periods of unusually severe social response occurring in the coming week, 2 and 3 weeks. This model exhibited remarkably strong performance for diseases with substantial media coverage. For country-disease pairs with a median of 20 or more articles per year, the onset of social response in the next week was correctly predicted over 60% of the time, and 87% of weeks were correctly predicted. Performance was weaker for diseases with little media coverage, and, for these diseases, the main utility of our system is in identifying social response when it occurs, rather than predicting when it will happen in the future. Overall, the developed near real-time prediction approach is a promising step toward developing predictive models to inform responders of the likely social consequences of disease spread. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10479-017-2480-9) contains supplementary material, which is available to authorized users.


Biomedical vignette


title: Syndromic Surveillance and Patients as Victims and Vectors

text: Syndromic surveillance uses new ways of gathering data to identify possible disease outbreaks. Because syndromic surveillance can be implemented to detect patterns before diseases are even identified, it poses novel problems for informed consent, patient privacy and confidentiality, and risks of stigmatization. This paper analyzes these ethical issues from the viewpoint of the patient as victim and vector. It concludes by pointing out that the new International Health Regulations fail to take full account of the ethical challenges raised by syndromic surveillance.


Web alert


title: Surface display of recombinant protein on the cell surface of Bacillus subtilis by the CotB anchor protein

text: We developed a novel surface display system based on the CotB anchoring motif in order to express foreign protein on the surface of vegetative Bacillus subtilis cells. CotB is a protein in the B. subtilis spore coat. In this system, three repeats of the immunodominant ovalbumin T-cell epitope (OVA(323–339)) were linked with the cholera toxin B subunit (CTB) to construct a fusion protein, CTB-OVA epi, which was then fused to the C-terminal of the CotB protein so that CTB-OVA epi was expressed in vegetatively-growing B. subtilis. The expression and localization of the CTB-OVA epi protein was confirmed by western blotting, immunofluorescence microscopy, and flow cytometry. The results indicated that a CotB-based surface display system was successfully used to express the CTB-OVA epi protein on the surface of vegetative B. subtilis cells.


title: Cloning and expression of the membrane protein gene of TGEV HB06 strain

text: The membrane protein gene(M) of transmissible gastroenteritis virus (TGEV) strain HB06, isolated from the feces of piglets infected with TGEVon a pig farm in Hebei province, was amplified by reverse transcriptase-polymerase chain reaction (RT-PCR). The amplified PCR products of TGEV HB06 were cloned, sequenced, and compared with other TGEV strains genes selected from the GenBank. Then, the recombinant fragment in pMD18-T was subcloned into corresponding sites of prokaryotic expression vector pGEX-6P-1 after digestion with EcoRI and XhoI to construct a recombinant fusion expression vector pGEX-6P-M. Then, the verified recombinant plasmid was transformed into Escherichia coli Rossetta (DE3), and the expression of M fusion protein was induced by using isopropylthio-beta-D-galactoside (IPTG) as inducer. The results showed that the gene fragment of M at a length of 789 bp was amplified and cloned into the vector pMD18-T successfully, and sequence comparison with that reported in GenBank revealed that the M gene complete sequence shares more than 94% homology in nucleotide. The result of SDS-PAGE showed that the recombinant membrane protein had a molecular mass of approximately 56 kDa, which was the same as the expected results. It was proven by Western blotting that the recombinant membrane protein had strong positive reactions with TGEV-specific antibody. Therefore, the expressed fusion protein has a good antigenicity. This work established a good foundation for further studies on the production of anti-TGEV vaccines.


Annual Meeting Abstracts


title: Data Decision and Transmission Based on Mobile Data Health Records on Sensor Devices in Wireless Networks

text: The contradiction between a large population and limited and unevenly distributed medical resources is a serious problem in many developing countries. This problem not only affects human health but also leads to the occurrence of serious infection if treatment is delayed. With the development of wireless communication network technology, patients can acquire real-time medical information through wireless network equipment. Patients can have the opportunity to obtain timely medical treatment, which may alleviate the shortage of medical resources in developing countries. This study establishes a new method that can decide and transmit effective data based on sensor device mobile health in wireless networks. History data, collection data, and doctor-analyzed data could be computed and transmitted to patients using sensor devices. According to probability analysis, patients and doctors may confirm the possibility of certain diseases.


Chandra Wickramasinghe, A Journey with Fred Hoyle: The Search for Cosmic Life. Edited by Kamala Wickramasinghe: World Scientific Publishing, Singapore, 2005, US$ 33.00, ISBN-10 981-238-912-1


title: Clinical characteristics of 42 SARS patients and their treatment of integrative Chinese and western medicine

text: Objective: To understand the clinical manifestation of severe acute respiratory syndrome (SARS) and explore its effective treatment with integrative Chinese and western medicine (ICWM).Methods: The data of patients, whose diagnosis of SARS had been confirmed were summarized and analyzed, and clinical observation was conducted when the patients were treated with ICWM.Results: In the early stage of the 42 patients, the symptoms revealed were fever in 100% of SARS patients, headache in 92. 9%, aversion to cold in 76. 2%, chest stuffiness in 76. 2%, cough in 73. 8% and myalgia in 88. 1%; pulmonary lesion involves ≥3 lobes in 42. 9%, 2 lobes in 47. 6% and 1 lobe in 9. 5%; 61. 9% of them showed liver function abnormality (increase of ALT or AST), 47. 6% showed elevated myocardial enzyme (CK or CK-MB), 0. 48% showed an inclination of renal function (higher of BUN or Cr); in their T lymphocyte subsets, 91. 2% (31/34 patients) had lowered CD(3) and 76. 5% (26/34 patients) lowered CD(4)/CD(8) ratio. In the mid-late stage, the symptoms were lassitude and weakness in 85. 7%, scare in 81. 0%, short of breath or chest stuffiness in 71. 4%, loss of appetite in 64. 3%; light dark tongue proper in 52.4%, yellow and white tongue coating in 45. 2%, and yellow thick coating on the middle-root part of the tongue in 21. 4%. Most of them were asymptomatic when discharged from hospital, with 92. 8% of their pulmonary lesion, according to chest film, completely absorbed and liver function, myocardial enzyme and renal function all normalized. However, of the 30 patients who had CD(3) reexamination, 70% of the CD(3) showed lower than normal range and 36. 7% showed their CD(4)/CD(8) inclined to lower margin, follow-up should be done for these patients. Of the 42 patients, who received western medicine (WM) alone in the early stage and ICWM in the mid-late stage, 10 were severe cases and 3 critical cases, but none of them died. The mean defervescent time was 3. 52±0. 85 days, the time for complete absorption of pulmonary lesion judged by chest X-ray film was 26. 82±5. 98 days, and the mean hospitalization time was 33. 60±4. 37 days.Conclusion: The manifestation of SARS is multifarious, showing that there were damage in multiple organs. The T lymphocyte count percentage and its subsets, CD(3) and CD(4) /CD(8) ratio, are valuable for early diagnosis and follow-up in the rehabilitation stage. Majority of the patients could be clinically cured. Combined treatment of WM and TCM according to syndrome differentiation and psychiatric intervention are beneficial to remit partial symptoms and promote rehabilitation.


The vignette for V13N3 issue


title: Optimization of transfection methods for Huh-7 and Vero cells: A comparative study

text: Availability of an efficient transfection protocol is the first determinant in success of gene transferring studies in mammalian cells which is accomplished experimentally for every single cell type. Herein, we provide data of a comparative study on optimization of transfection condition by electroporation and chemical methods for Huh-7 and Vero cells. Different cell confluencies, DNA/reagent ratios and total transfection volumes were optimized for two chemical reagents including jetPEI™ and Lipofectamine™ 2000. Besides, the effects of electric field strength and pulse length were investigated to improve electroporation efficiency. Transfection of cells by pEGFP-N1 vector and tracking the expression of GFP by FACS and Fluorescence Microscopy analysis were the employed methods to evaluate transfection efficiencies. Optimized electroporation protocols yielded 63.73 ± 2.36 and 73.9 ± 1.6% of transfection in Huh-7 and Vero cells respectively, while maximum achieved level of transfection by jetPEI™ was 14.2 ± 0.69 and 28 ± 1.11% Huh-7 and Vero cells, respectively. Post transfectional chilling of the cells did not improve electrotransfection efficiency of Huh-7 cells. Compared to chemical based reagents, electroporation showed superior levels of transfection in both cell lines. The presented protocols should satisfy most of the experimental applications requiring high transfection efficiencies of these two cell lines.


Literature alert


title: Prophylactic and therapeutic effects of egg yolk immunoglobulin against porcine transmissible gastroenteritis virus in piglets

text: Porcine transmissible gastroenteritis virus (TGEV) is the causative agent of acute diarrhea of newborn piglets that provokes high mortality rates in affected farms. In this study, specific immunoglobulin from egg yolk against TGEV was produced by immunization of White leghorn hens. Enzyme-linked immunosorbent assay (ELISA) and virus neutralization (VN) test revealed that the specific antibody titer started to increase on the tenth day post-immunization, reached its peak on the eighth week, and remained at a high level until the last week that we tested. The prophylactic and therapeutic effects of egg yolk immunoglobulin (IgY) was investigated in piglets. IgY was found effective to increase piglets survival rate significantly after challenge exposures in prophylactic efficacy analysis. The therapeutic effects test revealed that the mortality was dramatically reduced by orally administered IgY. All these results in our study indicated that IgY specific to TGEV could be an alternative prophylactic method like colostral antibodies against TGEV in piglets.


title: Detection and analysis system for hybridization images of lab-in-a-tube microarray

text: A lab-in-a-tube microarray system is developed for sample inspection and signal detection by fabricating a flat transparent window cap of the Eppendorf tube. The oligonucleotide microarray is immobilized on the inner surface of the cap. A small vessel is placed in an Eppendorf tube for storing hybridization solutions. With the microarray system, the full biochemical processes, including gene fragment amplification, fluorescence labeling, hybridization, and fluorescence detection, have been performed in the sealed tube without opening the cap. The images are obtained from a fluorescence microscope and captured by a CCD, and the data are transported to a computer through the universal serial bus (USB). After noise reduction, signal intensity is determined from hybridization image and the presence of gene fragments is identified. The final data output includes sample information, process steps, and hybridization results. A lab-in-a-tube microarray system for detecting ten respiratory viruses at a single detection is designed. High detection throughput and accuracy have been demonstrated with the system.


The vignette for V15 N3 issue


title: Virus rejection with two model human enteric viruses in membrane bioreactor system

text: A membrane bioreactor (MBR) with gravity drain was tested for virus rejection with two coliphages, T4 and f2, which were used as surrogates for human enteric viruses. Virus rejection was investigated by PVDF and PP membrane modules, with the pore sizes of 0.22 and 0.1 μm, respectively. In tap water system, 2.1 lg rejection of coliphage T4 could be achieved by PVDF membrane compared with complete rejection by PP membrane, while for coliphage f2 with smaller diameter, 0.3–0.5 lg rejection of the influent virus was removed by the two membranes. In domestic wastewater system, cake layer and gel layer on the membrane surface changed the cut-off size of the membrane so that there was no significant difference between PP and PVDF for each coliphage. The removal ratios of coliphage T4 and f2 in the MBR were more than 5.5 and 3.0 lg, respectively. Compared with 5.5 lg removal for virus T4 in the MBR system, only 2.1 lg (96.8%–99.9%) removal rate was observed in the conventional activated sludge system with the influent virus concentration fluctuating from 1830 to 57000 PFU/mL. Only 0.8%–22% virus removal was the effect of adsorption to activated sludge, which showed a decreasing tendency with the retention time, while 75%–98% was the effect of virus inactivation by microbial activity. It indicated that the major mechanism of virus removal was not the transfer of viruses from the water phase to the sludge phase but inactivation in the biological treatment process.


Learn to fight from the war


Biomedical Vignette


title: Reducing Energy Consumption and Overhead Based on Mobile Health in Big Data Opportunistic Networks

text: A great number of people and non-equalizing medical resources, in developing countries, have become a serious contradiction. Not only does it affects the person’s life, but also causes serious epidemic contagious, because patients can not get help with hospital on time. With the development of wireless communication network, patient may get medical information by wireless network device. It can alleviate contradictions between patients and medical resources. But in developing countries, population quantity is a big data. How to solve data packets in wireless communication network is a big problem when researchers face huge population. In order to solve some problems in big data communication, this paper founds availability data transmission routing algorithm. This algorithm can reduce energy consumption and overhead, then improve deliver ratio in big data communication. Compare with Spray and Wait algorithm, Binary spray and wait algorithm in opportunistic networks, this algorithm acquires good results by reduce energy consumption, overhead and deliver ratio.


title: Experimental study on effect of Compound Biejia Ruangan prescription on high-resolution computerized tomographic images in bleomycin induced pulmonary fibrosis rats

text: Objective: To study the therapeutic effect of Compound Biejia Ruangan prescription (CBRP) on rat model with pulmonary fibrosis induced by bleomycin.Methods: Fifty-four male Sprague-Dawley rats were randomly divided into 6 groups (9 rats in each group). From the first day to the 28th day of the experiment, except to those in the sham-model control group that were treated with normal saline, the same amount of bleomycin injection as the normal saline given to the control group was given through endotracheal instillation to all the rats in all the other groups. From the 29th day of the modeling, CBRP solution of different dosages was respectively injected into the rats in the high, moderate and low CBRP dose group, while equal volume of normal saline was given to those in the sham-model control group and the model control group, and an equal volume of prednisone solution was given to rats in the prednisone group. On the 80th day, the high-resolution computerized tomographic (HRCT) images were observed on an equal footing, and HRCT-pathology was correlatively studied.Results: Different HRCT pathological changes were shown in the rats with pulmonary fibrosis, such as lung consolidation, thickening of interlobular septum and interlobular mesenchyma as well as lobular deformation, nodule shadow, abnormal brochiovascular tract, thickened pleura with irregular junction and polished glass-like dense shadows. Honeycomb lung was observed in some cases. Pathological sections showed fibrotic proliferation of lung tissues and noticeable pulmonary interstitial fibrosis. CBRP could improve HRCT images of rats with pulmonary fibrosis, and lower fibrotic proliferation of the lung tissue.Conclusion: CBRP plays its therapeutic role possibly through its effect on the structure of the lung in rats with pulmonary fibrosis.


title: Dynamics of HIV/AIDS in Turkey from 1985 to 2016

text: In this paper, we formulated a mathematical model that studies the dynamics of HIV/AIDS in Turkey from 1985 to 2016. We find two equilibrium points, disease free equilibrium and endemic equilibrium. Global stability analysis of the equilibria was conducted using Lyapunov function which depends on the basic reproduction ratio R (0). If R (0) < 1, the disease free equilibrium point is globally asymptotically stable, and if R (0) ≥ 1 the endemic equilibrium point is globally asymptotically stable. We computed and predicted the basic reproduction ratios across all the years. It was found out that there were flaws in the exact values of R (0) which is related to the poor registration system of HIV/AIDS in Turkey. Hence, there is need for the government to improve the system in order to cover the actual cases of the disease. The increase of the basic reproduction ratio over the years also shows the need for the relevant authorities to adopt appropriate control measures in combating the disease.


title: Therapeutic effect of integrative traditional Chinese and western medicine on 51 SARS patients and its influence on their T lymphocyte subsets

text: Objective: To observe the clinical effect of integrative Chinese and western medicine (IC-WM) in treatment of patients with severe acute respiratory syndrome (SARS) and its influence on their T-lymphocyte subsets.Methods: Fifty-one patients with SARS of severe type were observed with synchronous non-randomized controlled method. They were divided into the ICWM group (29 patients) and the western medicine (WM) group (22 patients). Western medical treatment was applied to both groups, but to the ICWM group, Chinese medicine was given additionally. The therapeutic course was 2–3 weeks for both groups. Clinical effect and changes of T-lymphocyte subsets (CD4(+)) after treatment were observed.Results: In the ICWM group, 26 patients (89. 66%) were cured and 3 (10. 34%) died, while in the WM group, 12 (54. 55%) cured and 10 (45. 45%) died, thus comparison of the cure rate between the two groups showing significant difference (P <0.01). The score of clinical symptoms in the ICWM group was decreased from 7.14±5.20 scores before treatment to 1.82±3.75 scores after treatment, while in the WM group, it lowered from 7. 36±3.84 scores before treatment to517±417 scores after treatment, significant difference shown in the comparison of the values between the two groups after treatment (P < 0.01). Immunological function test showed that CD4(+) T-lymphocyte in the ICWM group rose from 361 ± 278 cells/mm(3) before treatment to 630 ± 454 cells/mm(3) after treatment, showing significant difference (P < 001); but in the WM group, it merely rose from 288±186 cells/mm(3) to 376±285 cells/mm(3) in the corresponding period (P > 0.05).Conclusion: ICWM could improve the clinical symptoms of SARS patients markedly, enhance their T-lymphocyte immune function, and reduce their mortality.


title: Biomedical and Environmental Ethics Alliance: Common Causes and Grounds

text: In the late 1960s Van Rensselaer Potter, a biochemist and cancer researcher, thought that our survival was threatened by the domination of military policy makers and producers of material goods ignorant of biology. He called for a new field of Bioethics—“a science of survival.” Bioethics did develop, but with a narrower focus on medical ethics. Recently there have been attempts to broaden that focus to bring biomedical ethics together with environmental ethics. Though the two have many differences—in habits of thought, scope of concern, and value commitments—in this paper we argue that they often share common cause and we identify common ground through an examination of two case studies, one addressing drug development, the other food production.


title: Effective use of a Limited Antiviral Stockpile for Pandemic Influenza

text: Just allocation of resources for control of infectious diseases can be profoundly influenced by the dynamics of those diseases. In this paper we discuss the use of antiviral drugs for treatment of pandemic influenza. While the primary effect of such drugs is to alleviate and shorten the duration of symptoms for treated individuals, they can have a secondary effect of reducing transmission in the community. However, existing stockpiles may be insufficient for all clinical cases. Here we use simple mathematical models to present scenarios where the optimum policies to minimise morbidity and mortality, with a limited drug stockpile, are not always the most intuitively obvious and may conflict with theories of justice. We discuss ethical implications of these findings.


title: Control of acute virus diseases of calves in the Federal Republic of Germany

text: The most important acute viral diseases of calves in the Federal Republic of Germany (FRG) are: 1. Enzootic bronchopneumonia. 2. Bovine viral diarrhoea — mucosal disease (BVD-MD). 3. Infectious bovine rhinotracheitis — infectious pustular vulvovaginitis (IBR-IPV). 4. Rota- and Coronavirus infections. The incidence, diagnosis and control of these infections in the FRG are discussed. Stomatitis papulosa and malignant catarrhal fever are also briefly mentioned.


title: Organization and regulation of nucleocytoplasmic transport

text: Separation of DNA replication and transcription, which occur in the nucleus, from protein synthesis, which occurs in the cytoplasm, allows a more precise regulation of these processes. Selective exchange of macromolecules between the two compartments is mediated by proteins of the nuclear pore complex (NPC). Receptor proteins of the karyopherin family interact with NPC components and transfer their cargos between the nucleus and cytoplasm. Nucleocytoplasmic transport pathways are regulated at multiple levels by modulating the expression or function of individual cargoes, transport receptors, or the transport channel. The regulatory levels have increasingly broad effects on the transport pathways and affect a wide range of processes from gene expression to development and differentiation.


title: Emerging research fronts in science and technology: patterns of new knowledge development

text: Research fronts represent the most dynamic areas of science and technology and the areas that attract the most scientific interest. We construct a methodology to identify these fronts, and we use quantitative and qualitative methodology to analyze and describe them. Our methodology is able to identify these fronts as they form—with potential use by firms, venture capitalists, researchers, and governments looking to identify emerging high-impact technologies. We also examine how science and technology absorbs the knowledge developed in these fronts and find that fronts which maximize impact have very different characteristics than fronts which maximize growth, with consequences for the way science develops over time.


title: Targeting and expression of antigenic proteins in transgenic plants for production of edible oral vaccines

text: Exploiting plants as biological bioreactors for production and delivery of edible oral subunit vaccines is a promising application of biotechnology. Efforts to enhance expression levels of transgenes coding for antigenic proteins by exploiting promoters, targeting sequences, and enhancer elements have produced rather low quantities of the antigen in plant tissues, but enough to induce immune responses in feeding studies. This review will cover components of various gene constructs used in developing plant-based vaccines against a myriad of viral and bacterial diseases. Specifically, it will focus on sequences that are involved in targeting the antigen to mucosal tissues of the intestinal tract, thus enhancing the immunogenicity of the plant-based vaccine as well as those components that result in higher accumulation of the protein within the plant.


title: Enterotoxins from gram-negative bacteria relevant for veterinary medicine

text: The chemistry, mechanism of action, assay methods, pharmacology, and prevention and treatment of diarrhoea due to toxins of gram-negative microbes are discussed. Other virulence factors are mentioned briefly. Special emphasis is placed on non-specific treatment by oral rehydration.


title: In situ airborne virus inactivation by microwave irradiation

text: Infectious diseases cause tremendous costs of both human and economy annually. Previously, we have studied the bacterial, fungal, and allergen aerosol inactivation by direct microwave irradiation. Here, we further investigated its effects on airborne viruses. MS2 coliphage used as a human model virus was aerosolized and exposed to the direct microwave irradiation for ~2 min at three different power levels (700, 385, and 119 W). In addition to the survival rate, the viral genes before and after the microwave treatments were also examined using PCR and gel electrophoresis. Direct exposure of airborne MS2 viruses to the microwave irradiation at 700 W for less than 2 min was shown to result in more than 90 % inactivation efficiency, about 65 % at medium power level (385 W), and 50 % at the lowest level (119 W). The aerosol inactivation rate followed a linear relationship with the microwave exposure time (R (2) = 0.9889). Scanning electron images revealed visible damages to the viral surface after the exposure. Damages were also observed to the viral RNA genes coding for coat proteins, among which the A protein gene was completely destroyed. This study demonstrated that even without the filtration the direct microwave irradiation could also achieve rapid inactivation of viral aerosols. The information obtained can provide useful guidance on the development of microwave-based viral threat mitigation solutions in a closed or semi-closed space.


title: Search for the new potential RNA thermometers in the genome of Salmonella enterica

text: Currently, a number of structurally and functionally different temperature-sensitive elements such as RNA thermometers which control a variety of biological processes in bacteria, including virulence, are known. Based on computer and thermodynamic analysis of completely sequenced genomes of 25 Salmonella enterica isolates, the algorithm and criteria for the search of potential RNA thermometers were developed. It will make it possible to carry out the search for potential riboswitches in the genome of other socially important pathogens. For S. enterica, apart from the known 4U RNA thermometer, four hairpin-loop structures were identified which may probably act as additional RNA thermometers. They satisfy the necessary and sufficient conditions for formation of RNA thermometers and are highly conservative uncanonical structures, since these highly conservative structures were found in the genome of all 25 isolates of S. enterica. The hairpins forming a cruciform structure in the supercoiled pUC8 DNA were visualized by atomic force microscopy.


title: Transgenic plants for animal health: plant-made vaccine antigens for animal infectious disease control

text: A variety of plant species have been genetically modified to accumulate vaccine antigens for human and animal health and the first vaccine candidates are approaching the market. The regulatory burden for animal vaccines is less than that for human use and this has attracted the attention of researchers and companies, and investment in plant-made vaccines for animal infectious disease control is increasing. The dosage cost of vaccines for animal infectious diseases must be kept to a minimum, especially for non-lethal diseases that diminish animal welfare and growth, so efficient and economic production, storage and delivery are critical for commercialization. It has become clear that transgenic plants are an economic and efficient alternative to fermentation for large-scale production of vaccine antigens. The oral delivery of plant-made vaccines is particularly attractive since the expensive purification step can be avoided further reducing the cost per dose. This review covers the current status of plant-produced vaccines for the prevention of disease in animals and focuses on barriers to the development of such products and methods to overcome them.


title: Clinical controlled study of integrative Chinese and western medicine in treating 49 cases of SARS

text: Objective: To evaluate the efficacy of integrative Chinese and western medicine (ICWM) in treating severe acute respiratory syndrome (SARS) patients.Methods: Through parallel control design, 49 SARS patients were observed. Used as control, there were in the western medicine (WM) group 29 patients, who were treated with Ribavirin, Levofloxacin, Thymopentin, Azithromycin, methylprednisolone, etc., on the basis of “Recommended Protocol for Infectious Atypical Pneumonia” (abbreviated as “Recommended Protocol”) issueed by Ministry of Health. As the treated group, there were in the ICWM 20 cases. The protocol for treatment of SARS in “Special Science and Technological Action to Prevent and Treat SARS” (abbreviated as “Special S-T Action”), issued by Ministry of Science and Technology, together with the same WM as those for the control group.Results: (1) Time from the disease onset to the symptom improvement were 5.10±2. 83 days and 7. 62±2. 27 days in ICWM and WM group respectively,P < 0.05; (2) As to corticosteroid (CS) amount and days before reducing dosage, 2 groups showed no significant difference,P > 0.05; (3) There was no significant difference in the time from disease onset to the body temperature normalization and the total amount of CS and the duration of using CS before reducing it to 80 mg between the ICWM group and the WM group; (4) The days and amounts for use CS after reducing between the ICWM group and the WM group were significantly different (P < 0. 05).Conclusion: There were obvious advantages in ICWM to treat SARS, compared with that of WM alone, especially in improving the clinical symptoms, promoting the recovery of immune function, promoting the absorption of pulmonary inflammation and reducing the dosage and duration of CS treatment.


Animal Symposia


title: Role of siRNAs and miRNAs in the processes of RNA-mediated gene silencing during viral infections

text: Phenomenon of RNA-induced gene silencing is a highly conservative mechanism among eukaryotic organisms. Several classes of small RNAs (siRNAs and miRNAs) 21–25 nt in length, which play a significant role in the processes of development of an organism, occurred important components of antiviral defence in animals and plants. This review shortly describes the main stages of gene silencing mechanism, features of antiviral RNA silencing in plants, invertebrates, mammals, ways of suppression of RNA-interference by viruses, as well as possible approaches of utilization of abovementioned phenomenon for struggling against viral infections.


title: Recognition for avian influenza virus proteins based on support vector machine and linear discriminant analysis

text: Total 200 properties related to structural characteristics were employed to represent structures of 400 HA coded proteins of influenza virus as training samples. Some recognition models for HA proteins of avian influenza virus (AIV) were developed using support vector machine (SVM) and linear discriminant analysis (LDA). The results obtained from LDA are as follows: the identification accuracy (R (ia)) for training samples is 99.8% and R (ia) by leave one out cross validation is 99.5%. Both R (ia) of 99.8% for training samples and R (ia) of 99.3% by leave one out cross validation are obtained using SVM model, respectively. External 200 HA proteins of influenza virus were used to validate the external predictive power of the resulting model. The external R (ia) for them is 95.5% by LDA and 96.5% by SVM, respectively, which shows that HA proteins of AIVs are preferably recognized by SVM and LDA, and the performances by SVM are superior to those by LDA.


title: Synthesis, Biological Evaluation and Ligand Based Pharmacophore Modeling of New Aromatic Thiosemicarbazones as Potential Anticancer Agents

text: Two series of new aromatic thiosemicarbazone derivatives were synthesized by condensation of N-(4-cyanophenyl)hydrazine carbothioamide (I) and N-(4-methylsulfanylphenyl)hydrazine carbothioamide (II) with appropriate aromatic aldehydes in order to investigate their antiviral and cytostatic potency. The chemical structures of all compounds were fully characterized by elemental analysis and spectroscopic techniques. The results of the bioassays indicated that compounds Id, Ie, If and IIf proved inhibitory against influenza virus A (EC(50) = 13 – 27 μg/mL for strain H1N1 and 9.3 – 18 μg/mL for strain H3N2). Compounds Ig and IIg were the most cytostatic compounds with inhibition of HeLa cell proliferation at an IC(50) = 0.3 μg/mL for Ig and 1.9 μg/mL for IIg. Especially, compound Ig showed the highest cytostatic activity with IC(50) of 0.30, 0.70 and 2.50 μg/mL against HeLa, CEM and L1210 cell lines, respectively. This inhibition range was within the same order of magnitude as that for cisplatin. Furthermore, molecular modeling was carried out to examine the cytostatic activity and determine the best pharmacophore model as a guide for the design and development of potential prodrugs in future studies.


Applying integrative Chinese and western medicine in fighting SARS


Erratum to: Candidate Genes Associated with Susceptibility for SARS-Coronavirus