Differential wolf-pack-size persistence and the role of risk when hunting dangerous prey

Risk to predators hunting dangerous prey is an emerging area of research and could account for possible persistent differences in gray wolf (Canis lupus) pack sizes. We documented significant differences in long-term wolf-pack-size averages and variation in the Superior National Forest (SNF), Denali National Park and Preserve, Yellowstone National Park, and Yukon, Canada (p \u3c 0.01). The SNF differences could be related to the wolves’ risk when hunting primary prey, for those packs (N = 3) hunting moose (Alces americanus) were significantly larger than those (N = 10) hunting white-tailed deer (Odocoileus virginianus) (F1,8 = 16.50, p = 0.004). Our data support the hypothesis that differential pack-size persistence may be perpetuated by differences in primary prey riskiness to wolves, and we highlight two important extensions of this idea: (1) the potential for wolves to provision and defend injured packmates from other wolves and (2) the importance of less-risky, buffer prey to pack-size persistence and year-to-year variation

Determinants of Gray Wolf (Canis lupus) Sightings in Denali National Park

Wildlife viewing within protected areas is an increasingly popular recreational activity. Management agencies are often tasked with providing these opportunities, yet quantitative analyses of factors influencing wildlife sightings are lacking. We analyzed locations of GPS-collared wolves and wolf sightings from 2945 trips in Denali National Park and Preserve, Alaska, USA, to provide a mechanistic understanding of how viewing opportunities are influenced by attributes of wolves and physical, biological, and harvest characteristics. We found that the presence of masking vegetation, den site proximity to the road, pack size, and presence of a wolf harvest closure adjacent to the park affected wolf sightings, and the influence of den proximity on sightings depended on harvest management. Wolf sightings increased with den site proximity to the road in years with a harvest closure adjacent to the park but not in the absence of the closure. The effect of the harvest closure on sightings was similar in magnitude to an increase in pack size by two wolves or a more than a two-fold decrease in masking vegetation. These findings were consistent across a 10-fold change in spatial resolution. Quantitative analysis of the factors influencing wildlife sightings provides valuable insight for agencies tasked with managing viewing opportunities. L’observation de la faune dans les aires protégées est un loisir qui prend de plus en plus d’ampleur. Souvent, les organismes de gestion ont le mandat d’offrir de telles activités et pourtant, il n’y a toujours pas d’analyses quantitatives des facteurs qui exercent une influence sur les observations fauniques. Nous avons analysé les emplacements de loups munis de colliers GPS et les observations de loups découlant de 2 945 déplacements au parc national et à la réserve de Denali, en Alaska, aux États-Unis afin d’obtenir une compréhension mécaniste de la manière dont les activités d’observation sont influencées par les attributs des loups ainsi que par les caractéristiques physiques, biologiques et de récolte. Nous avons remarqué que la présence de végétation masquante, la proximité des tanières de la route, la taille des meutes et la présence d’une interdiction de récolte de loups dans le secteur adjacent au parc ont eu un effet sur les observations de loups, et que l’influence de la proximité des tanières par rapport aux observations dépendait de la gestion des récoltes. Les observations de loups augmentaient en fonction de la proximité des tanières par rapport à la route au cours des années pendant lesquelles il y avait interdiction de récolte de loups dans le secteur adjacent au parc, mais ce n’était pas le cas en l’absence d’interdiction. L’ampleur de l’effet de l’interdiction de récolte sur les observations était semblable à une augmentation de la taille de la meute correspondant à deux loups ou plus, ou à la diminution de plus du double de la végétation masquante. Ces constatations se recoupaient dans un changement correspondant au décuple dans la résolution spatiale. L’analyse quantitative des facteurs influençant les observations fauniques offre une importante perspective aux organismes dont le mandat consiste à gérer les activités d’observation.&nbsp

Longest terrestrial migrations and movements around the world

Long-distance terrestrial migrations are imperiled globally. We determined both round-trip migration distances (straight-line measurements between migratory end points) and total annual movement (sum of the distances between successive relocations over a year) for a suite of large mammals that had potential for long-distance movements to test which species displayed the longest of both. We found that caribou likely do exhibit the longest terrestrial migrations on the planet, but, over the course of a year, gray wolves move the most. Our results were consistent with the trophic-level based hypothesis that predators would move more than their prey. Herbivores in low productivity environments moved more than herbivores in more productive habitats. We also found that larger members of the same guild moved less than smaller members, supporting the 'gastro-centric' hypothesis. A better understanding of migration and movements of large mammals should aid in their conservation by helping delineate conservation area boundaries and determine priority corridors for protection to preserve connectivity. The magnitude of the migrations and movements we documented should also provide guidance on the scale of conservation efforts required and assist conservation planning across agency and even national boundaries

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

Abstract: Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors

Differential wolf-pack-size persistence and the role of risk when hunting dangerous prey

Risk to predators hunting dangerous prey is an emerging area of research and could account for possible persistent differences in gray wolf (Canis lupus) pack sizes. We documented significant differences in long-term wolf-pack-size averages and variation in the Superior National Forest (SNF), Denali National Park and Preserve, Yellowstone National Park, and Yukon, Canada (p \u3c 0.01). The SNF differences could be related to the wolves’ risk when hunting primary prey, for those packs (N = 3) hunting moose (Alces americanus) were significantly larger than those (N = 10) hunting white-tailed deer (Odocoileus virginianus) (F1,8 = 16.50, p = 0.004). Our data support the hypothesis that differential pack-size persistence may be perpetuated by differences in primary prey riskiness to wolves, and we highlight two important extensions of this idea: (1) the potential for wolves to provision and defend injured packmates from other wolves and (2) the importance of less-risky, buffer prey to pack-size persistence and year-to-year variation

Longest terrestrial migrations and movements around the world

Long-distance terrestrial migrations are imperiled globally. We determined both round-trip migration distances (straight-line measurements between migratory end points) and total annual movement (sum of the distances between successive relocations over a year) for a suite of large mammals that had potential for long-distance movements to test which species displayed the longest of both. We found that caribou likely do exhibit the longest terrestrial migrations on the planet, but, over the course of a year, gray wolves move the most. Our results were consistent with the trophic-level based hypothesis that predators would move more than their prey. Herbivores in low productivity environments moved more than herbivores in more productive habitats. We also found that larger members of the same guild moved less than smaller members, supporting the ‘gastro-centric’ hypothesis. A better understanding of migration and movements of large mammals should aid in their conservation by helping delineate conservation area boundaries and determine priority corridors for protection to preserve connectivity. The magnitude of the migrations and movements we documented should also provide guidance on the scale of conservation efforts required and assist conservation planning across agency and even national boundaries.publishedVersio

Implications of Harvest on the Boundaries of Protected Areas for Large Carnivore Viewing Opportunities

<div><p>The desire to see free ranging large carnivores in their natural habitat is a driver of tourism in protected areas around the globe. However, large carnivores are wide-ranging and subject to human-caused mortality outside protected area boundaries. The impact of harvest (trapping or hunting) on wildlife viewing opportunities has been the subject of intense debate and speculation, but quantitative analyses have been lacking. We examined the effect of legal harvest of wolves (<i>Canis lupus</i>) along the boundaries of two North American National Parks, Denali (DNPP) and Yellowstone (YNP), on wolf viewing opportunities within the parks during peak tourist season. We used data on wolf sightings, pack sizes, den site locations, and harvest adjacent to DNPP from 1997–2013 and YNP from 2008–2013 to evaluate the relationship between harvest and wolf viewing opportunities. Although sightings were largely driven by wolf population size and proximity of den sites to roads, sightings in both parks were significantly reduced by harvest. Sightings in YNP increased by 45% following years with no harvest of a wolf from a pack, and sightings in DNPP were more than twice as likely during a period with a harvest buffer zone than in years without the buffer. These findings show that harvest of wolves adjacent to protected areas can reduce sightings within those areas despite minimal impacts on the size of protected wolf populations. Consumptive use of carnivores adjacent to protected areas may therefore reduce their potential for non-consumptive use, and these tradeoffs should be considered when developing regional wildlife management policies.</p></div