Historical Changes and Current Distribution of Caribou, Rangifer tarandus, in Quebec

We examined published historical information, reports on aerial surveys conducted since 1953, and harvest data collected since 1971 to describe changes in the distribution and abundance of Caribou (Rangifer tarandus) in Québec. The southern limit of the Caribou distribution diminished considerably in the late 19th century, and the decline in numbers probably continued until the 1960s and 1970s east of the 62nd meridian. South of the 49th parallel, only four small populations still persist. Despite the fact that all Caribou of the province were assigned to the same sub-species (R. t. caribou), three ecotypes with specific habitats and behaviour are found. The Barren-Ground ecotype, the only migratory form, is found north of the 52nd parallel. This ecotype currently occupies ≈ 255 000 km2 in fall and winter, mainly in the ecological subzones of the forest tundra and the taiga. The Barren-Ground Caribou was characterized by a very low abundance from the end of the 19th century until the mid-1950s, but increased markedly thereafter reaching over a million individuals at the beginning of the 1990s. Populations of the Mountain ecotype have been identified in the southeastern and, possibly, in the northeastern parts of the province. The latter Mountain population is virtually unknown. The southeastern population is sedentary and uses mainly the boreal forest. This population has decreased over the last century and currently numbers only ≈ 140 individuals. Finally, the Forest-Dwelling ecotype is found discontinuously, mainly between the 49th and 55th parallels. Its current distribution covers ≈ 235 000 km2, mainly east of the 72nd meridian. This sedentary ecotype is found almost exclusively in the boreal forest, principally in areas with long forest fire cycles. Its abundance has also decreased over the years. Large Forest-Dwelling populations still persisted during the 1950s and 1960s, but they apparently disappeared. The current abundance is not known precisely, but based on density estimates and considering the current distribution, it probably does not exceed 3000 individuals. Current data are insufficient to identify precisely the causes of the population decline, although hunting seems to be an important proximal cause.Nous avons utilisé les données historiques publiées, les rapports d’inventaires aériens réalisés depuis 1953 et les statistiques de récolte sportive colligées depuis 1971 pour décrire les changements dans la répartition et l’abondance du Caribou (Rangifer tarandus) au Québec. La limite méridionale de l’aire de répartition a beaucoup diminué à la fin du 19e siècle et la régression s’est probablement poursuivie durant les années 1960 et 1970 à l’est du 62e méridien. Au sud du 49e parallèle, on ne retrouve plus que quatre petites populations. Bien que tous les caribous du Québec soient considérés appartenir à la même sous-espèce (R. t. caribou), on distingue trois écotypes fréquentant des milieux différents et arborant des comportements spécifiques. Au nord du 52e parallèle, on retrouve l’écotype Toundrique, lequel est migrateur. Ces Caribous se répartissent sur ≈ 255 000 km2 durant l’automne et l’hiver, principalement dans les sous-zones écologiques de la toundra forestière et de la taïga. Cet écotype était peu abondant entre la fin du 19e siècle et le milieu des années 1950, mais il s’est accru considérablement pour atteindre plus d’un million d’individus au début des années 1990. Une population de l’écotype Montagnard est présente au sud-est de la province et une autre existe possiblement au nord-est. Cette dernière n’est pas bien connue. Celle du sud-est utilise principalement la forêt boréale. Cette population sédentaire a diminué considérablement depuis une centaine d’années et elle ne compte plus qu’environ 140 individus. Finalement, l’écotype Forestier est présent de façon discontinue, principalement entre les 49e et 55e parallèles. Ces Caribous sont également sédentaires. On les retrouve presque exclusivement en forêt boréale, principalement là où le cycle des feux de forêt est long. Leur répartition actuelle couvre ≈ 234 000 km2, principalement à l’est du 72e méridien. D’importantes populations forestières existaient encore durant les années 1950 et 1960, mais elles semblent avoir disparu. L’abondance actuelle n’est pas connue mais elle pourrait difficilement dépasser 3000 individus si l’on se base sur les estimations de la densité et de l’aire de répartition. Les données disponibles sont insuffisantes pour identifier les causes exactes des diminutions d’effectifs bien que la chasse semble une cause proximale importante

Calcineurin inhibitor effects on kidney electrolyte handling and blood pressure:tacrolimus versus voclosporin

Background Calcineurin inhibitors (CNIs) affect kidney electrolyte handling and blood pressure (BP) through an effect on the distal tubule. The second-generation CNI voclosporin causes hypomagnesaemia and hypercalciuria less often than tacrolimus. This suggests different effects on the distal tubule, but this has not yet been investigated experimentally. Methods Rats were treated with voclosporin, tacrolimus or vehicle for 28 days. Dosing was based on a pilot experiment to achieve clinically therapeutic concentrations. Drug effects were assessed by electrolyte handling at day 18 and 28, thiazide testing at day 20, telemetric BP recordings and analysis of messenger RNA (mRNA) and protein levels of distal tubular transporters at day 28. Results Compared with vehicle, tacrolimus but not voclosporin significantly increased the fractional excretions of calcium (>4-fold), magnesium and chloride (both 1.5-fold) and caused hypomagnesaemia. Tacrolimus but not voclosporin significantly reduced distal tubular transporters at the mRNA and/or protein level, including the sodium-chloride cotransporter, transient receptor melastatin 6, transient receptor potential vanilloid 5, cyclin M2, sodium-calcium exchanger and calbindin-D28K. Tacrolimus but not voclosporin reduced the mRNA level and urinary excretion of epidermal growth factor. The saluretic response to hydrochlorothiazide at day 20 was similar in the voclosporin and vehicle groups, whereas it was lower in the tacrolimus group. The phosphorylated form of the sodium-chloride cotransporter was significantly higher at day 28 in rats treated with voclosporin than in those treated with tacrolimus. Tacrolimus transiently increased BP, whereas voclosporin caused a gradual but persistent increase in BP that was further characterized by high renin, normal aldosterone and low endothelin-1. Conclusions In contrast to tacrolimus, voclosporin does not cause hypercalciuria and hypomagnesaemia, but similarly causes hypertension. Our data reveal differences between the distal tubular effects of tacrolimus and voclosporin and provide a pathophysiological basis for the clinically observed differences between the two CNIs.Graphical Abstrac

Antiviral TRIMs: friend or foe in autoimmune and autoinflammatory disease?

The concept that viral sensing systems, via their ability to drive pro-inflammatory cytokine and interferon production, contribute to the development of autoimmune and autoinflammatory disease is supported by a wide range of clinical and experimental observations. Recently, the tripartite motif-containing proteins (TRIMs) have emerged as having key roles in antiviral immunity — either as viral restriction factors or as regulators of pathways downstream of viral RNA and DNA sensors, and the inflammasome. Given their involvement in these pathways, we propose that TRIM proteins contribute to the development and pathology of autoimmune and autoinflammatory conditions, thus making them potential novel targets for therapeutic manipulation

Cationic Host Defence Peptides:Potential as Antiviral Therapeutics

There is a pressing need to develop new antiviral treatments; of the 60 drugs currently available, half are aimed at HIV-1 and the remainder target only a further six viruses. This demand has led to the emergence of possible peptide therapies, with 15 currently in clinical trials. Advancements in understanding the antiviral potential of naturally occurring host defence peptides highlights the potential of a whole new class of molecules to be considered as antiviral therapeutics. Cationic host defence peptides, such as defensins and cathelicidins, are important components of innate immunity with antimicrobial and immunomodulatory capabilities. In recent years they have also been shown to be natural, broad-spectrum antivirals against both enveloped and non-enveloped viruses, including HIV-1, influenza virus, respiratory syncytial virus and herpes simplex virus. Here we review the antiviral properties of several families of these host peptides and their potential to inform the design of novel therapeutics

The role of defensins and C-X-C chemokines in mammalian innate immunity

In humans, defensins constitute the largest group of host defence peptides that are evolutionarily conserved components of innate immunity. Defensins share many structural and functional characteristics with C-X-C chemokines, including a C-X-C amino acid motif, net positive charge, disulphide bonding, three-dimensional shape and chemokine activity. Deficiencies in α-defensins and C-X-C chemokines have been correlated with susceptibility to infection and chronic inflammatory diseases. However the genetics and diversity of defensins and mechanisms underlying these disorders were not well understood. This thesis comprises three separate but overlapping approaches to address these issues. The genomic content of murine α-defensins within the reference C57BL/6J strain was characterized. Novel α-defensin (11) and defensin-related cryptdin (3) genes were found, as were gene duplications and differences in genomic content between strains of mice. A next-generation sequencing method was developed for the quantitative analysis of α-defensin and defensin-related cryptdin gene expression. The α-defensin DEFA1 induced interleukin (IL) 8 and IL10 release from human PBMCs. The mechanism(s) of action of defensins, which appears to involve induction of chemokines and anti-inflammatory cytokines, needs further elucidation in vivo. Consequently, novel murine models of inflammation and immunosuppression were developed. The IL8 and Il10 genes were separately cloned, behind an intestine-specific promoter, into eukaryotic expression vectors, which were used to transfect murine embryonic stem cells. Correct targeting was confirmed for both constructs and germline transmission achieved for the IL8 mice. Conditional homozygous mice were generated, which, upon breeding with Cre-expressing mice, will express IL8, a C-X-C chemokine, in an intestinal-specific manner. This will enable analyses of effects of chemokine overexpression on intestinal infection, and on peptide efficacy in the resolution of infection. In other studies to address innate immune mechanisms, the transcriptional profiles of patients susceptible to Salmonella and mycobacterial infections due to immunodeficiencies in IL12- and interferon-γ-mediated immunity were generated. These data indicated that the chemokines CXCL9 and CXCL10 might mediate immunity to Mycobacteria whereas additional defects in TLR4 responses appeared to underlie susceptibility to Salmonella. The data presented here strengthen our understanding of the murine defensin repertoire and provide tools that enable sophisticated systems level studies of in vivo function.Science, Faculty ofMicrobiology and Immunology, Department ofGraduat

Neutrophil-derived defensins as modulators of innate immune function

Cationic host defence peptides are an evolutionarily conserved component of the immune system and have been found across a wide variety of species. In lower organisms they comprise a major component of the defensive repertoire, whereas in higher species they are a part of the complex immune system dedicated to protecting against infection. Human neutrophils contain large amounts of the cationic α-defensin peptides, HNP-1−3, as well as HNP-4, which is present in lower amounts, while two Paneth cell α-defensins, HD-5 and HD-6, are also found in the gut. It is now becoming clear that α-defensins have multiple functions in the immune system; however, it is also apparent that although there is redundancy in their function, they also each have unique roles within the ever-increasing complexity of the immune system

Lessons from the inflammasome: a molecular sentry linking Candida and Crohn's disease

Candida albicans is a diploid fungus that colonizes the gastrointestinal tract asymptomatically in a large proportion of the human population, but can cause life-threatening conditions in immunocompromised patients. Recent immunological investigations have revealed the Nod-like receptor pyrin domain-containing protein 3 (NLRP3) to be a cytosolic surveillance mechanism against germinating Candida. These observations point to the idea of a molecular link between Candida and a spectrum of auto-inflammatory diseases. When excessive activation of NLRP3 occurs, it can confer resistance against disseminating Candida infection but might also cause NLRP3-associated periodic syndromes. Alternatively, we propose a pathophysiological model whereby a defective NLRP3-coupled inflammasome can result in enhanced mucosal colonization of granuloma-provoking microorganisms, including C. albicans, precipitating the formation of Crohn's disease-associated inflammatory lesions

Cathelicidins and functional analogues as antisepsis molecules

The emergence of antibiotic-resistant bacteria together with the limited success of sepsis therapeutics has lead to an urgent need for the development of alternative strategies for the treatment of systemic inflammatory response syndrome and related disorders. Immunomodulatory compounds that do not target the pathogen directly (therefore limiting the development of pathogen resistance), and target multiple inflammatory mediators, are attractive candidates as novel therapeutics. Cationic host defence peptides such as cathelicidins have been demonstrated to be selectively immunomodulatory in that they can confer anti-infective immunity and modulate the inflammatory cascade through multiple points of intervention. The human cathelicidin LL-37, for example, has modest direct antimicrobial activity under physiological conditions, but has been demonstrated to have potent antiendotoxin activity in animal models, as well as the ability to resolve certain bacterial infections. A novel synthetic immunomodulatory peptide, IDR-1, built on this same theme has no direct antimicrobial activity, but is effective in restricting many types of infection, while limiting pro-inflammatory responses. The ability of these peptides to selectively suppress harmful pro-inflammatory responses, while maintaining beneficial infection-fighting components of host innate defences makes them a good model for antisepsis therapies that merit further investigation

Role of genetics in infection-associated arthritis

Genetic discoveries in arthritis and their associated biological pathways spanning the innate and adaptive immune system demonstrate the strong association between susceptibility to arthritis and control of exogenous organisms. The canonical theory of the aetiology of immune-mediated arthritis and other immune-mediated diseases is that the introduction of exogenous antigenic stimuli to a genetically susceptible host sets up the environment for an abnormal immune response manifesting as disease. A disruption in host-microbe homeostasis driven by disease-associated genetic variants could ultimately provide the source of exogenous antigen triggering disease development. We discuss genetic variants impacting the innate and adaptive arms of the immune system and their relationship to microbial control and arthritic disease. We go on to consider the evidence for a relationship between HLA-B27, infection and arthritis, and then emerging evidence for an interaction between microbiota and rheumatoid arthritis