Beneficial effects of curtailing immune susceptibility in an Alzheimer's disease model

Background Currently, there are no effective therapeutic options for Alzheimer's disease, the most common, multifactorial form of dementia, characterized by anomalous amyloid accumulation in the brain. Growing evidence points to neuroinflammation as a major promoter of AD. We have previously shown that the proinflammatory cytokine TNFSF10 fuels AD neuroinflammation, and that its immunoneutralization results in improved cognition in the 3xTg-AD mouse. Methods Here, we hypothesize that inflammatory hallmarks of AD might parallel with central and peripheral immune response dysfunction. To verify such hypothesis, we used a triple transgenic mouse model of AD. 3xTg-AD mice were treated for 12 months with an anti-TNFSF10 antibody, and thereafter immune/inflammatory markers including COX2, iNOS, IL-1 beta and TNF-alpha, CD3, GITR, and FoxP3 (markers of regulatory T cells) were measured in the spleen as well as in the hippocampus. Results Spleens displayed accumulation of amyloid-beta(1-42) (A beta(1-42)), as well as high expression of Treg cell markers FoxP3 and GITR, in parallel with the increased levels of inflammatory markers COX2, iNOS, IL-1 beta and TNF-alpha, and blunted IL-10 expression. Moreover, CD3 expression was increased in the hippocampus, consistently with FoxP3 and GITR. After chronic treatment of 3xTg-AD mice with an anti-TNFSF10 antibody, splenic FoxP3, GITR, and the above-mentioned inflammatory markers expression was restored to basal levels, while expression of IL-10 was increased. A similar picture was observed in the hippocampus. Such improvement of peripheral and CNS inflammatory/immune response was associated with decreased microglial activity in terms of TNF alpha production, as well as decreased expression of both amyloid and phosphorylated tau protein in the hippocampus of treated 3xTg-AD mice. Interestingly, we also reported an increased expression of both CD3 and FoxP3, in sections from human AD brain. Conclusions We suggest that neuroinflammation in the brain of 3xTg-AD mice triggered by TNFSF10 might result in a more general overshooting of the immune response. Treatment with an anti-TNFSF10 antibody blunted inflammatory processes both in the spleen and hippocampus. These data confirm the detrimental role of TNFSF10 in neurodegeneration, and corroborate the hypothesis of the anti-TNFSF10 strategy as a potential treatment to improve outcomes in AD

Diverse tick-borne microorganisms identified in free-living ungulates in Slovakia

Background: Free-living ungulates are hosts of ixodid ticks and reservoirs of tick-borne microorganisms in central Europe and many regions around the world. Tissue samples and engorged ticks were obtained from roe deer, red deer, fallow deer, mouflon, and wild boar hunted in deciduous forests of south-western Slovakia. DNA isolated from these samples was screened for the presence of tick-borne microorganisms by PCR-based methods. Results: Ticks were found to infest all examined ungulate species. The principal infesting tick was Ixodes ricinus, identified on 90.4% of wildlife, and included all developmental stages. Larvae and nymphs of Haemaphysalis concinna were feeding on 9.6% of wildlife. Two specimens of Dermacentor reticulatus were also identified. Ungulates were positive for A. phagocytophilum and Theileria spp. Anaplasma phagocytophilum was found to infect 96.1% of cervids, 88.9% of mouflon, and 28.2% of wild boar, whereas Theileria spp. was detected only in cervids (94.6%). Importantly, a high rate of cervids (89%) showed mixed infections with both these microorganisms. In addition to A. phagocytophilum and Theileria spp., Rickettsia helvetica, R. monacensis, unidentified Rickettsia sp., Coxiella burnetii, "Candidatus Neoehrlichia mikurensis", Borrelia burgdorferi (s.l.) and Babesia venatorum were identified in engorged I. ricinus. Furthermore, A. phagocytophilum, Babesia spp. and Theileria spp. were detected in engorged H. concinna. Analysis of 16S rRNA and groEL gene sequences revealed the presence of five and two A. phagocytophilum variants, respectively, among which sequences identified in wild boar showed identity to the sequence of the causative agent of human granulocytic anaplasmosis (HGA). Phylogenetic analysis of Theileria 18S rRNA gene sequences amplified from cervids and engorged I. ricinus ticks segregated jointly with sequences of T. capreoli isolates into a moderately supported monophyletic clade. Conclusions: The findings indicate that free-living ungulates are reservoirs for A. phagocytophilum and Theileria spp. and engorged ixodid ticks attached to ungulates are good sentinels for the presence of agents of public and veterinary concern. Further analyses of the A. phagocytophilum genetic variants and Theileria species and their associations with vector ticks and free-living ungulates are required.Fil: Kazimírová, Mária. Slovak Academy of Sciences. Institute of Zoology; EslovaquiaFil: Hamšíková, Zuzana. Slovak Academy of Sciences. Institute of Zoology; EslovaquiaFil: Spitalská, Eva. Slovak Academy of Sciences. Institute of Virology. Biomedical Research Center,; EslovaquiaFil: Minichová, Lenka. Slovak Academy of Sciences. Institute of Virology. Biomedical Research Center,; EslovaquiaFil: Mahríková, Lenka. Slovak Academy of Sciences. Institute of Zoology; EslovaquiaFil: Caban, Radoslav. Široká ; EslovaquiaFil: Sprong, Hein. National Institute for Public Health and Environment.Laboratory for Zoonoses and Environmental Microbiology; Países BajosFil: Fonville, Manoj. National Institute for Public Health and Environment.Laboratory for Zoonoses and Environmental Microbiology; Países BajosFil: Schnittger, Leonhard. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Patobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Kocianová, Elena. Slovak Academy of Sciences. Institute of Virology. Biomedical Research Center,; Eslovaqui

Cross border transhumance involvement in ticks and tick-borne pathogens dissemination and first evidence of Anaplasma centrale in Burkina Faso

In West Africa, cross-border transhumance, also called seasonal migration, is known to be a very important animal production strategy, as it involves about 70 to 90% of cattle. In spite of the cattle movements, some strategic areas of transhumance remain poorly explored regarding ticks and their associated pathogens investigations. The purpose of this study is to evaluate the involvement of transhumance in the spread of cattle ticks and associated pathogens in Burkina Faso (BF) and Benin (BN), in a context of speedy invasion of West African livestock by Rhipicephalus microplus. A longitudinal survey was performed on 210 cattle from BF, monitored for ticks and tick-borne pathogens (TBP) during one seasonal transhumance. The first sampling coded “T0BF” took place in eastern BF, at the transhumance departure. A second sampling “T1BN” was carried out in northern BN, the transhumance arrival zone. A third sampling “T2BF” was done at the return of cattle in eastern BF. Ticks were morphologically identified and TBP detected with reverse line blot hybridization (RLB) assay. A total of 1027 ticks (7 species), 1006 ticks (11 species) and 1211 ticks (9 species) were respectively found at T0BF, T1BN and T2BF. Some species were collected at the three times of sampling without any significant difference in their relative abundances. However, other tick species appeared only at T1BN and/or T2BF. The TBP species found at the three points surveyed were Theileria annulata, Theileria mutans, Theileria velifera, Babesia bigemina and Anaplasma marginale. The most prevalent was T. mutans with 166/210 (79%), 159/210 (75.7%) and 78/210 (37%) cattle positive respectively at T0BF, T1BN and T2BF. Anaplasma centrale was evidenced with 0.5% and 0.9% respectively at T0BF and T2BF. To our knowledge, this represents its first report in the study area. Overall, the TBP prevalences were significantly lower at T2BF, highlighting the effect of tick populations changes induced by transhumance combined with the seasonal variation influence. © 202

Genome wide association mapping for arabinoxylan content in a collection of tetraploid wheats

BACKGROUND: Arabinoxylans (AXs) are major components of plant cell walls in bread wheat and are important in bread-making and starch extraction. Furthermore, arabinoxylans are components of soluble dietary fibre that has potential health-promoting effects in human nutrition. Despite their high value for human health, few studies have been carried out on the genetics of AX content in durum wheat. RESULTS: The genetic variability of AX content was investigated in a set of 104 tetraploid wheat genotypes and regions attributable to AX content were identified through a genome wide association study (GWAS). The amount of arabinoxylan, expressed as percentage (w/w) of the dry weight of the kernel, ranged from 1.8% to 5.5% with a mean value of 4.0%. The GWAS revealed a total of 37 significant marker-trait associations (MTA), identifying 19 quantitative trait loci (QTL) associated with AX content. The highest number of MTAs was identified on chromosome 5A (seven), where three QTL regions were associated with AX content, while the lowest number of MTAs was detected on chromosomes 2B and 4B, where only one MTA identified a single locus. Conservation of synteny between SNP marker sequences and the annotated genes and proteins in Brachypodium distachyon, Oryza sativa and Sorghum bicolor allowed the identification of nine QTL coincident with candidate genes. These included a glycosyl hydrolase GH35, which encodes Gal7 and a glucosyltransferase GT31 on chromosome 1A; a cluster of GT1 genes on chromosome 2B that includes TaUGT1 and cisZog1; a glycosyl hydrolase that encodes a CelC gene on chromosome 3A; Ugt12887 and TaUGT1genes on chromosome 5A; a (1,3)-β-D-glucan synthase (Gsl12 gene) and a glucosyl hydrolase (Cel8 gene) on chromosome 7A. CONCLUSIONS: This study identifies significant MTAs for the AX content in the grain of tetraploid wheat genotypes. We propose that these may be used for molecular breeding of durum wheat varieties with higher soluble fibre content.Ilaria Marcotuli, Kelly Houston, Robbie Waugh, Geoffrey B. Fincher, Rachel A. Burton, Antonio Blanco, Agata Gadalet

Muscle activation during gait in children with Duchenne muscular dystrophy

The aim of this prospective study was to investigate changes in muscle activity during gait in children with Duchenne muscular Dystrophy (DMD). Dynamic surface electromyography recordings (EMGs) of 16 children with DMD and pathological gait were compared with those of 15 control children. The activity of the rectus femoris (RF), vastus lateralis (VL), medial hamstrings (HS), tibialis anterior (TA) and gastrocnemius soleus (GAS) muscles was recorded and analysed quantitatively and qualitatively. The overall muscle activity in the children with DMD was significantly different from that of the control group. Percentage activation amplitudes of RF, HS and TA were greater throughout the gait cycle in the children with DMD and the timing of GAS activity differed from the control children. Significantly greater muscle coactivation was found in the children with DMD. There were no significant differences between sides. Since the motor command is normal in DMD, the hyper-activity and co-contractions likely compensate for gait instability and muscle weakness, however may have negative consequences on the muscles and may increase the energy cost of gait. Simple rehabilitative strategies such as targeted physical therapies may improve stability and thus the pattern of muscle activity

Fifth European Dirofilaria and Angiostrongylus Days (FiEDAD) 2016

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