Host spatiotemporal overlap in a park with high endemicity of Echinococcus multilocularis

There has been a spate of recent cases of human alveolar echinococcosis (AE) in Alberta, Canada. Alveolar echinococcosis is caused by Echinococcus multilocularis, which is prevalent among coyote populations and present in domestic dogs in Alberta. Using qPCR, we estimated the seasonal fecal prevalence of E. multilocularis in coyotes and dogs in a multiuse recreation area close to Edmonton, Alberta, where we also setup remote cameras to model seasonal changes in the overlap in temporal activity and the spatial intensity of use among coyotes, humans, and dogs, as a proxy of potential transmission. We detected E. multilocularis in 18 of 137 wild canid feces and none in 44 dog feces. After correcting for the qPCR test’s sensitivity and specificity, we estimated at 15.7% (9.7-22.7%, 95% CrI) the true fecal prevalence for coyotes. Temporal overlap between coyotes and both humans and dogs increased in the fall and winter relative to the spring and summer. Coyote intensity of use showed seasonal variations and was higher on maintained trails and locations closer to visitor parking and at sites with high intensity of dog use. Our results reinforce the need of an integrated approach, typical of both One-Health and Eco-Health, to park management for minimizing the likelihood of transmission where human and dog activity results in significant overlap with the one of the natural definitive hosts of zoonotic parasites

Cytomegalovirus is associated with depression and anxiety in older adults

Infection with cytomegalovirus (CMV), a β-herpesvirus, is common within the population. Although asymptomatic, infection is associated with increased serum concentrations of cytokines such as TNFα and IL-6, which are also related to mood and wellbeing. The present study examined whether infection with CMV was associated with mood in a community-based sample of olderadults. Blood samples and scores on the General Health Questionnaire were available for 137 participants. Serum was analysed for the presence of CMV-specific IgG and the antibody titre was used as an indirect measure of viral load. The majority of the participants (66%) were CMV-seropositive and seropositive status was not associated with psychological morbidity. However, within the CMV-positive group, individuals with higher CMV-specific antibody titres were more likely to be depressed, anxious, and suffer more overall psychological morbidity. This association could be mediated by the impact of affect-moderating cytokines secreted through the CMV-specific immune response.\ud \u

Electrodeposited lead dioxide coatings

Lead dioxide coatings on inert substrates such as titanium and carbon now offer new opportunities for a material known for 150 years. It is now recognised that electrodeposition allows the preparation of stable coatings with different phase structures and a wide range of surface morphologies. In addition, substantial modification to the physical properties and catalytic activities of the coatings are possible through doping and the fabrication of nanostructured deposits or composites. In addition to applications as a cheap anode material in electrochemical technology, lead dioxide coatings provide unique possibilities for probing the dependence of catalytic activity on layer composition and structure (critical review, 256 references)

Genomics, environment and balancing selection in behaviorally bimodal populations : the caribou case

Selection forces that favor different phenotypes in different environments can change frequencies of genes between populations along environmental clines. Clines are also compatible with balancing forces, such as negative frequency‐dependent selection (NFDS), which maintains phenotypic polymorphisms within populations. For example, NFDS is hypothesized to maintain partial migration, a dimorphic behavioral trait prominent in species where only a fraction of the population seasonally migrates. Overall, NFDS is believed to be a common phenomenon in nature, yet, a scarcity of studies were published linking naturally occurring allelic variation with bimodal or multimodal phenotypes and balancing selection. We applied a Pool‐seq approach and detected selection on alleles associated with environmental variables along a North‐South gradient in western North American caribou, a species displaying partially migratory behavior. On 51 loci, we found a signature of balancing selection, which could be related to NFDS and ultimately the maintenance of the phenotypic polymorphisms known within these populations. Yet, remarkably, we detected directional selection on a locus when our sample was divided in two behaviorally distinctive groups regardless of geographic provenance (a subset of GPS‐collared migratory or sedentary individuals), indicating that, within populations, phenotypically homogeneous groups were genetically distinctive. Loci under selection were linked to functional genes involved in oxidative stress response, body development and taste perception. Overall, results indicated genetic differentiation along an environmental gradient of caribou populations, which we found characterized by genes potentially undergoing balancing selection. We suggest that the underlining balancing force, NFDS plays a strong role within populations harboring multiple haplotypes and phenotypes, as it is the norm in animals, plants and humans too

Cure of mammary carcinomas in Her-2 transgenic mice through sequential stimulation of innate (neoadjuvant interleukin-12) and adaptive (DNA vaccine electroporation) immunity.

Purpose: Whereas neoadjuvant therapy is emerging as a treatment option in early primary breast cancer, no data are available on the use of antiangiogenic and immunomodulatory agents in a neoadjuvant setting. In a model of Her-2 spontaneous mammary cancer, we investigated the efficacy of neoadjuvant interleukin 12 (IL-12) followed by ‘‘immune-surgery’’ of the residual tumor. Experimental Design: Female BALB/c mice transgenic for the rat Her-2 oncogene inexorably develop invasive carcinomas in all their mammary glands by the 23rd week of age. Mice with multifocal in situ carcinomas received four weekly i.p. injections of 100 ng IL-12 followed by a 3-week rest. This course was given four times. A few mice additionally received DNA plasmids encoding portions of the Her-2 receptor electroporated through transcutaneous electric pulses. Results: The protection elicited by IL-12 in combination with two DNA vaccine electroporations kept 63% of mice tumor-free. Complete protection of all 1-year-old mice was achieved when IL-12-treated mice received four vaccine electroporations. Pathologic findings, in vitro tests, and the results from immunization of both IFN-; andimmunoglobulin gene knockout transgenic mice and of adoptive transfer experiments all show that IL-12 augments the B- and T-cell response elicited by vaccination and slightly decreases the number of regulatory T cells. In addition, IL-12 strongly inhibits tumor angiogenesis. Conclusions: In Her-2 transgenic mice, IL-12 impairs tumor progression and triggers innate immunity so markedly that DNA vaccination becomes effective at late points in time when it is ineffective on its own

LAG-3 enables DNA vaccination to persistently prevent mammary carcinogenesis in HER-2/neu transgenic BALB/c mice

Within 33 weeks of life, all 10 mammary glands of virgin BALB/c mice transgenic for the transforming rat HER-2/neu oncogene under the mammary tumor virus promoter (BALB-neuT mice) progress from atypical hyperplasia to invasive palpable carcinoma. Repeated DNA vaccination with plasmids coding for the extracellular and transmembrane domain of the protein product of rat HER-2/neu (r-p185neu) delayed tumor onset and reduced tumor multiplicity, but this protection eventually declined, and few mice were tumor free at 1 year of age. Association of plasmid vaccination with administration of soluble mouse LAG-3 (lymphocyte activation gene-3/CD223) generated by fusing the extracellular domain of murine LAG-3 to a murine IgG2a Fc portion (mLAG-3Ig) elicited a stronger and sustained protection that kept 70% of 1-year-old mice tumor free. Moreover, this combined vaccination, which was performed when multiple in situ carcinomas were already evident, extended disease-free survival and reduced carcinoma multiplicity. Inhibition of carcinogenesis was associated with markedly reduced epithelial cell proliferation and r-p185neu expression, whereas the few remaining hyperplastic foci were heavily infiltrated by reactive leukocytes. A stronger and enduring r-p185neu-specific cytotoxicity, a sustained release of IFN-γ and interleukin 4, and a marked expansion of both CD8+/CD11b+/CD28+ effector and CD8+/CD11b+/CD28- memory effector T-cell populations were induced in immunized mice. This combined vaccination also elicited a quicker and higher antibody response to r-p185neu, as well as an early antibody isotype switch. These data suggest that the appropriate costimulation provided by mLAG-3Ig enables DNA vaccination to establish an effective protection, probably by enhancing cross-presentation of the DNA coded antigen

The biogeography of the caribou lungworm, Varestrongylus eleguneniensis (Nematoda: Protostrongylidae) across northern North America

Varestrongylus eleguneniensis (Nematoda; Protostrongylidae) is a recently described species of lungworm that infects caribou (Rangifer tarandus), muskoxen (Ovibos moschatus) and moose (Alces americanus) across northern North America. Herein we explore the geographic distribution of V. eleguneniensis through geographically extensive sampling and discuss the biogeography of this multi-host parasite. We analyzed fecal samples of three caribou subspecies (n = 1485), two muskox subspecies (n = 159), and two moose subspecies (n = 264) from across northern North America. Protostrongylid dorsal-spined larvae (DSL) were found in 23.8%, 73.6%, and 4.2% of these ungulates, respectively. A portion of recovered DSL were identified by genetic analyses of the ITS-2 region of the nuclear rDNA or the cytochrome oxidase c subunit I (COI) region of the mtDNA. We found V. eleguneniensis widely distributed among caribou and muskox populations across most of their geographic prange in North America but it was rare in moose. Parelaphostrongylus andersoni was present in caribou and moose and we provide new geographic records for this species. This study provides a substantial expansion of the knowledge defining the current distribution and biogeography of protostrongylid nematodes in northern ungulates. Insights about the host and geographic range of V. eleguneniensis can serve as a geographically extensive baseline for monitoring current distribution and in anticipating future biogeographic scenarios under a regime of accelerating climate and anthropogenic perturbation

Early onset and enhanced growth of autochthonous mammary carcinomas in C3-deficient Her2/neu transgenic mice

Aside from its classical role in fighting infections, complement is an important, although poorly understood, component of the tumor microenvironment. In particular, the tumor growth-regulatory activities of complement remain under debate. To assess the role of the complement system in the progression of autochthonous mammary carcinomas, we have crossed complement component 3 (C3)-deficient (C3(−/−)) BALB/c male mice with BALB/c females expressing the activated rat Her2/neu oncogene (neuT). Although neuT transgenic mice develop spontaneous mammary cancers with 100% penetrance, a significantly shorter tumor latency (i.e., earlier onset of the first palpable tumor), a higher frequency of multiple tumors (multiplicity), and a dramatic increase in the tumor growth rate were found in neuT-C3(−/−) animals. The accelerated tumor onset observed in neuT-C3(−/−) mice was paralleled by an earlier onset of spontaneous lung metastases and by an increase in Her2 expression levels, primarily on the surface of tumor cells. The percentage of immune cells infiltrating neuT carcinomas was similar in C3-deficient and C3-proficient mice, with the exception of a significant increase in the frequency of regulatory T cells in neuT-C3(−/−) tumors. Of particular interest, the enhanced immunosuppression imparted by C3 deficiency clearly influenced the immunogenic phenotype of autochthonous mammary tumors as neuT-C3(−/−) malignant cells transplanted into syngeneic immunocompetent hosts gave rise to lesions with a significantly delayed kinetics and reduced incidence as compared with cells obtained from neuT C3-proficient tumors. Finally, increased blood vessel permeability was evident in neuT-C3(−/−) tumors, although a similar number of tumor vessels was found in neuT and neuT-C3(−/−) lesions. Altogether, these data suggest that complement plays a crucial role in the immunosurveillance and, possibly, the immunoediting of Her2-driven autochthonous mammary tumors

Relevance of ARID1A Mutations in Endometrial Carcinomas

Since the Cancer Genome Atlas (TCGA) project identified four distinct groups based on molecular alterations, mutation analyses have been integrated into the characterization of endometrial carcinomas (ECs). ARID1A seems to be the subunit more involved in the loss of function of the SWI/SNF complex in ECs. The aim of this study is to define the relevance of ARID1A alterations in a cohort of EC, studying the possible associations between DNA mutation (genomic level), RNA expression (transcriptomic level), and protein expression (proteomic level). A total of 50 endometrial carcinomas were characterized for ARID1A mutations (using targeted DNA next-generation sequencing—NGS), ARID1A gene expression (using RNAseq and qRT-PCR), and ARID1A protein expression (using immunohistochemistry—IHC). Moreover, we have investigated if ARID1A mutations may alter the protein structure, using the Protein Data Bank sequence. We found a good correlation between ARID1A mutations and protein immunostaining, even if we did not find statistically significant differences in the ARID1A expression levels. In conclusion, our data demonstrated that the molecular characterization of ARID1A should be associated with IHC analysis, mainly in those cases harboring “novel” ARID1A mutations or in those alterations with “uncertain” pathogenic significance

Vanishing native American dog lineages

<p>Abstract</p> <p>Background</p> <p>Dogs were an important element in many native American cultures at the time Europeans arrived. Although previous ancient DNA studies revealed the existence of unique native American mitochondrial sequences, these have not been found in modern dogs, mainly purebred, studied so far.</p> <p>Results</p> <p>We identified many previously undescribed mitochondrial control region sequences in 400 dogs from rural and isolated areas as well as street dogs from across the Americas. However, sequences of native American origin proved to be exceedingly rare, and we estimate that the native population contributed only a minor fraction of the gene pool that constitutes the modern population.</p> <p>Conclusions</p> <p>The high number of previously unidentified haplotypes in our sample suggests that a lot of unsampled genetic variation exists in non-breed dogs. Our results also suggest that the arrival of European colonists to the Americas may have led to an extensive replacement of the native American dog population by the dogs of the invaders.</p