Distribution of O-Acetylated Sialic Acids among Target Host Tissues for Influenza Virus.

Sialic acids (Sias) are important glycans displayed on the cells and tissues of many different animals and are frequent targets for binding and modification by pathogens, including influenza viruses. Influenza virus hemagglutinins bind Sias during the infection of their normal hosts, while the encoded neuraminidases and/or esterases remove or modify the Sia to allow virion release or to prevent rebinding. Sias naturally occur in a variety of modified forms, and modified Sias can alter influenza virus host tropisms through their altered interactions with the viral glycoproteins. However, the distribution of modified Sia forms and their effects on pathogen-host interactions are still poorly understood. Here we used probes developed from viral Sia-binding proteins to detect O-acetylated (4-O-acetyl, 9-O-acetyl, and 7,9-O-acetyl) Sias displayed on the tissues of some natural or experimental hosts for influenza viruses. These modified Sias showed highly variable displays between the hosts and tissues examined. The 9-O-acetyl (and 7,9-) modified Sia forms were found on cells and tissues of many hosts, including mice, humans, ferrets, guinea pigs, pigs, horses, dogs, as well as in those of ducks and embryonated chicken egg tissues and membranes, although in variable amounts. The 4-O-acetyl Sias were found in the respiratory tissues of fewer animals, being primarily displayed in the horse and guinea pig, but were not detected in humans or pigs. The results suggest that these Sia variants may influence virus tropisms by altering and selecting their cell interactions. IMPORTANCE Sialic acids (Sias) are key glycans that control or modulate many normal cell and tissue functions while also interacting with a variety of pathogens, including many different viruses. Sias are naturally displayed in a variety of different forms, with modifications at several positions that can alter their functional interactions with pathogens. In addition, Sias are often modified or removed by enzymes such as host or pathogen esterases or sialidases (neuraminidases), and Sia modifications can alter those enzymatic activities to impact pathogen infections. Sia chemical diversity in different hosts and tissues likely alters the pathogen-host interactions and influences the outcome of infection. Here we explored the display of 4-O-acetyl, 9-O-acetyl, and 7,9-O-acetyl modified Sia forms in some target tissues for influenza virus infection in mice, humans, birds, guinea pigs, ferrets, swine, horses, and dogs, which encompass many natural and laboratory hosts of those viruses

Ectoparasites of hedgehogs: From flea mite phoresy to their role as vectors of pathogens

Hedgehogs are synanthropic mammals, reservoirs of several vector-borne pathogens and hosts of ectoparasites. Arthropod-borne pathogens (i.e., Rickettsia spp., Borrelia spp., and Anaplasmataceae) were molecularly investigated in ectoparasites collected on hedgehogs (n = 213) from Iran (161 Hemiechinus auritus, 5 Erinaceus concolor) and Italy (47 Erinaceus europaeus). In Iran, most animals examined (n = 153; 92.2%) were infested by ticks (Rhipicephalus turanicus, Hyalomma dromedarii), and 7 (4.2%) by fleas (Archeopsylla erinacei, Ctenocephalides felis). Of the hedgehogs infested by arthropods in Italy (i.e., 44.7%), 18 (38.3%) were infested by fleas (Ar. erinacei), 7 (14.9%) by ticks (Haemaphysalis erinacei, Rh. turanicus, Rhipicephalus sanguineus sensu lato), and 6 (12.8%) by mites (Caparinia tripilis, Acarus nidicolous, Ornithonyssus spp.). Phoretic behavior of C. tripilis on Ar. erinacei was detected in two flea specimens from Italy. At the molecular analysis Rickettsia spp. was detected in 93.3% of the fleas of Italy. In Iran, Rickettsia spp. was detected in 8.0% out of 212 Rh. turanicus ticks, and in 85.7% of the Ar. erinacei fleas examined. The 16S rRNA gene for Ehrlichia/Anaplasma spp. was amplified in 4.2% of the 212 Rh. turanicus ticks. All sequences of Rickettsia spp. from fleas presented 100% nucleotide identity with Rickettsia asembonensis, whereas Rickettsia spp. from Rh. turanicus presented 99.84%–100% nucleotide identity with Rickettsia slovaca, except for one sequence, identical to Rickettsia massiliae. The sequences of the 16S rRNA gene revealed 99.57%–100% nucleotide identity with Anaplasma spp., except for one, identical to Ehrlichia spp. A new phoretic association between C. tripilis mites and Ar. erinacei fleas has been herein reported, which could be an important route for the spreading of this mite through hedgehog populations. Additionally, spotted fever group rickettsiae were herein detected in ticks and fleas, and Anaplasma/Ehrlichia spp. in ticks, suggesting that hedgehogs play a role as reservoirs for these vector-borne pathogens

Determination and Diversity of Bovine Coccidia in Zabol, East of Iran

The present study was designed to investigate the prevalence of Eimeria spp. in Zabol, east of Iran. The samples were examined microscopically for the presence of oocysts from February 2015 to December 2016. Out of 196 cattle, 124 (63.26%) were identified to be positive for Eimeria species. Eight species of Eimeria were found as follows: E. bovis (42.54%), E. zuernii (38.67%), E. subspherica (5.52%), E. brasiliensis (4.97%), E. ellipsoidalis (4.41%), E. cylindrical (1.65%), E. pellita (1.65%), and E. wyomingensis (0.55%). Multiple infections with two or three species were identified in 56 (45.16%) and 2 (1.61%) cases, respectively. The infection rate was observed to be higher in calves (75%) as compared to adult cattle (59.02%). The prevalence of Eimeria was greater in female cattle (67.94%). The highest prevalence and mean number of oocysts were observed in winter (69%) and autumn (209.09), respectively. All the faecal samples had an oocysts per gram of feces (OPG) less than 1000. The prevalence of infection and mean OPG were directly correlated with rainfall and relative humidity and inversely correlated with temperature. Considering the high prevalence of bovine coccidiosis in Zabol, increasing awareness of farmers and veterinarians regarding the economic importance of bovine coccidiosis should be regarded as an important factor in preventing and controlling the infection. Keywords: Prevalence, Cattle, Eimeria spp., Risk factors, Ira

Polyclonal human antibodies against glycans bearing red meat-derived non-human sialic acid N-glycolylneuraminic acid are stable, reproducible, complex and vary between individuals: Total antibody levels are associated with colorectal cancer risk.

BACKGROUND: N-glycolylneuraminic acid (Neu5Gc) is a non-human red-meat-derived sialic acid immunogenic to humans. Neu5Gc can be metabolically incorporated into glycan chains on human endothelial and epithelial surfaces. This represents the first example of a "xeno-autoantigen", against which circulating human "xeno-autoantibodies" can react. The resulting inflammation ("xenosialitis") has been demonstrated in human-like Neu5Gc-deficient mice and contributed to carcinoma progression via antibody-mediated inflammation. Anti-Neu5Gc antibodies have potential as biomarkers for diseases associated with red meat consumption such as carcinomas, atherosclerosis, and type 2 diabetes. METHODS: ELISA assays measured antibodies against Neu5Gc or Neu5Gc-glycans in plasma or serum samples from the Nurses' Health Studies, the Health Professionals Follow-up Study, and the European Prospective Investigation into Cancer and Nutrition, including inter-assay reproducibility, stability with delayed sample processing, and within-person reproducibility over 1-3 years in archived samples. We also assessed associations between antibody levels and coronary artery disease risk (CAD) or red meat intake. A glycan microarray was used to detected antibodies against multiple Neu5Gc-glycan epitopes. A nested case-control study design assessed the association between total anti-Neu5Gc antibodies detected in the glycan array assay and the risk of colorectal cancer (CRC). RESULTS: ELISA assays showed a wide range of anti-Neu5Gc responses and good inter-assay reproducibility, stability with delayed sample processing, and within-person reproducibility over time, but these antibody levels did not correlate with CAD risk or red meat intake. Antibodies against Neu5Gc alone or against individual Neu5Gc-bearing epitopes were also not associated with colorectal cancer (CRC) risk. However, a sialoglycan microarray study demonstrated positive association with CRC risk when the total antibody responses against all Neu5Gc-glycans were combined. Individuals in the top quartile of total anti-Neu5Gc IgG antibody concentrations had nearly three times the risk compared to those in the bottom quartile (Multivariate Odds Ratio comparing top to bottom quartile: 2.98, 95% CI: 0.80, 11.1; P for trend = 0.02). CONCLUSIONS: Further work harnessing the utility of these anti-Neu5Gc antibodies as biomarkers in red meat-associated diseases must consider diversity in individual antibody profiles against different Neu5Gc-bearing glycans. Traditional ELISA assays for antibodies directed against Neu5Gc alone, or against specific Neu5Gc-glycans may not be adequate to define risk associations. Our finding of a positive association of total anti-Neu5Gc antibodies with CRC risk also warrants confirmation in larger prospective studies

A Comprehensive Investigation on Common Polymorphisms in the MDR1/ABCB1 Transporter Gene and Susceptibility to Colorectal Cancer

ATP Binding Cassette B1 (ABCB1) is a transporter with a broad substrate specificity involved in the elimination of several carcinogens from the gut. Several polymorphic variants within the ABCB1 gene have been reported as modulators of ABCB1-mediated transport. We investigated the impact of ABCB1 genetic variants on colorectal cancer (CRC) risk. A hybrid tagging/functional approach was performed to select 28 single nucleotide polymorphisms (SNPs) that were genotyped in 1,321 Czech subjects, 699 CRC cases and 622 controls. In addition, six potentially functional SNPs were genotyped in 3,662 German subjects, 1,809 cases and 1,853 controls from the DACHS study. We found that three functional SNPs (rs1202168, rs1045642 and rs868755) were associated with CRC risk in the German population. Carriers of the rs1202168_T and rs868755_T alleles had an increased risk for CRC (Ptrend = 0.016 and 0.029, respectively), while individuals bearing the rs1045642_C allele showed a decreased risk of CRC (Ptrend = 0.022). We sought to replicate the most significant results in an independent case-control study of 3,803 subjects, 2,169 cases and 1,634 controls carried out in the North of Germany. None of the SNPs tested were significantly associated with CRC risk in the replication study. In conclusion, in this study of about 8,800 individuals we show that ABCB1 gene polymorphisms play at best a minor role in the susceptibility to CRC

Comparison of Characteristic Property among Tehran Offensive and Non-Offensive Drivers Using Cloninger, s Treatment and Character Inventory

 Backgrounds and Aims: Characteristic property among Tehran offensive and non- offensive drivers using Cloninger, s treatment and Character Inventory questionnaire was studied. Materials and Methods: A cross- sectional study was carried out after coordinating with traffic police. 300 drivers: 150 offensive ( drivers with more than ten penalty points and 150 non- offensive drivers with less than ten penalty points in one year prior were selected randomly. Data was collected using Cloninger, s treatment and Character Inventory standard questionnaire by trained experts in three different routes of Tehran. Results: The average age was 20-34 years (82% male, 18% female). Based on Cloninger,s treatment and Character Inventory standard questionnaire, a significant differences was observed in novelty seeking, harm avoidance, reward dependence, self-directive ness, co- operation (p<0.001) and persistence (p<0.013) among offensive and non-offensive drivers. By one score increasing of novelty seeking the chance of to be offencer will be increased 4.5 times (OR= 4.520, p<0.007), in harm avoidance will be half (OR= 0.504, p<0.045) and in reward dependence will be one fourth (OR= 0.278, p<0.033). Conclusion: Novelty seeking sub scale of Cloningers treatment and Character Inventory questionnaire was higher and harm avoidance and reward dependence was lower among offensive drivers. REFERENCES World report on road traffic injury prevention 2004. World Health Organization (WHO) and the World Bank report; 2010; Available from: http://www.who.int/world-health-day/2004/en.Haghshenas H, Hassani M, Jamshidi M, Azizi HR. Relationship between characteristic property and driving behaviour in Shiraz city. Hakim. 2008;11:47-54Rothengather T. Psychological aspects of road user behaviours, an international review. Applied psychology. 1997; 46(3): 223-34.Lingard H, Rowlinson S. Lingard H, Rowlinson S. The Wilful Traffic Offender Profile and its implications for education and training. PhD Research Summary, School of Psychology, University of  Exeter, 2000. USA and Canada: Taylor& Francis group; 2005.Burns P C, Wilde G J S. Risk taking in male taxi drivers: relationship among personality, observational data and driver records. Personality and Individual Differences. 1995; 18(2):267-78.Parker D, Reason J T, Manstead A S R, Stradling S. Driving errors, driving violations and accident involvement. Ergonomics. 1995; 38(5): 1038-48. Sommer  M, Herle  M, Hausler  J, Risser  R, Schutzhofer  B, Chaloupka  C. Cognitive and personality determinants of fitness to drive. Transportation of Research Board (TRB) 2008; 11(5):362-75.Sujata M, Patil J T S, Trivellore E R, Raymond C B. The Role of Personality Characteristics in Young Adult Driving.Traffic Inj Prev. 2006; 7(4): 328–34. Jonah BA, Thiessen R, Au-Yeung E. Sensation seeking, risky driving and behavioral adaptation. Accident Analysis & Prevention. 2001; 33(5): 679–84.Ulleberg P, Rundmo T. Personality, attitudes and risk perception as predictors of risky driving behaviour among young drivers. Saf. Sci. 2003; 41(5):427–43.Vassallo S, Smart D, Sanson A, Harrison W, Harris A, Cockfield S and et al. Risky driving among young Australian drivers: trends, precursors and correlates. Accid Anal Prev. 2007; 39(3): 444–58.Sigve O, Torbjørn R. The effects of personality and gender on risky driving behaviour and accident involvement. Saf. Sci. 2006; 44(7): 621-8. Machin M, Anthony S, Kim S. Relationships between young drivers' personality characteristics, risk perceptions, and driving behaviour. Accid Anal Prev. 2008; 40(2): 541-7.Dahlen E R, Martin R C, Ragan K, Kuhlman M M. Driving anger, sensation seeking, impulsiveness, and boredom proneness in the prediction of unsafe driving. Accid Anal Prev. 2005; 37(2): 341-8.Galanter M. Personality and alcoholism: Issues, methods, and etiological processes, Characteristics of children of alcoholics: Putative risk factors. New York: Kluwer Academic/ Plenum; 2005

Synthesis of a Bifunctional Peptide Inhibitor–IgG1 Fc Fusion That Suppresses Experimental Autoimmune Encephalomyelitis

Multiple sclerosis (MS) is a neurodegenerative disease that is estimated to affect over 2.3 million people worldwide. The exact cause for this disease is unknown but involves immune system attack and destruction of the myelin protein surrounding the neurons in the central nervous system. One promising class of compounds that selectively prevent the activation of immune cells involved in the pathway leading to myelin destruction are bifunctional peptide inhibitors (BPIs). Treatment with BPIs reduces neurodegenerative symptoms in experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. In this work, as an effort to further improve the bioactivity of BPIs, BPI peptides were conjugated to the N- and C-termini of the fragment crystallizable (Fc) region of the human IgG1 antibody. Initially, the two peptides were conjugated to IgG1 Fc using recombinant DNA technology. However, expression in yeast resulted in low yields and one of the peptides being heavily proteolyzed. To circumvent this problem, the poorly expressed peptide was instead produced by solid phase peptide synthesis and conjugated enzymatically using a sortase-mediated ligation. The sortase-mediated method showed near-complete conjugation yield as observed by SDS-PAGE and mass spectrometry in small-scale reactions. This method was scaled up to obtain sufficient quantities for testing the BPI-Fc fusion in mice induced with EAE. Compared to the PBS-treated control, mice treated with the BPI-Fc fusion showed significantly reduced disease symptoms, did not experience weight loss, and showed reduced de-myelination. These results demonstrate that the BPI peptides were highly active at suppressing EAE when conjugated to the large Fc scaffold in this manner

Linguatulosis in small ruminants in southeastern Iran: Epidemiological, histopathological and phylogenetic findings and its public health importance

Linguatulosis, as a zoonotic disease, can infect most ruminants and cause accidental infections in humans. The objective of this study was to explore the epidemiological, histopathological and phylogenetic profiles of Linguatula serrata infection in sheep and goats and its public health importance during 2015�2018. Mesenteric lymph nodes (MLNs) and liver tissue of goats and sheep were selected randomly in Kerman slaughterhouse. Nymphal samples were used for DNA extraction, amplification and subsequently phylogenetic analysis using 18s rRNA and cytochrome C oxidase subunit 1 (cox1). Overall, of 828 examined livestock, 179 (42.4) goats and 71 (17.5) sheep were found to be infected with the nymphal stage of L. serrata. A significant difference was observed between linguatulosis and age. In the histopathological assessment, longitudinal and transverse sections of L. serrata nymphs were observed within the cyst-like spaces surrounded by a wall of fine fibrosis and compact lymphocytes. Moreover, comparing with the L. serrata reference sequences, we found only a single nucleotide change in our goat haplotype in 18s genetic region; while much nucleotide variations were observed in cox1 gene sequences. The results of the present study showed a high infection rate among goats and sheep in southeastern Iran. A better understanding of the disease could be achieved when the parasite species, their molecular characterization and the extent of infection in the area are determined. It is fundamental to select a comprehensive control program in order to take proper preventive and therapeutic measures against the infection. © 2020 Elsevier Lt