Habitat selection by brown bears with varying levels of predation rates on ungulate neonates

In northern Eurasia, large carnivores overlap with semi-domestic reindeer (Rangifer tarandus) and moose (Alces alces). In Scandinavia, previous studies have quantified brown bear (Ursus arctos) spring predation on neonates of reindeer (mostly in May) and moose (mostly in June). We explored if habitat selection by brown bears changed following resource pulses and whether these changes are more pronounced on those individuals characterised by higher predatory behaviour. Fifteen brown bears in northern Sweden (2010–2012) were fitted with GPS proximity collars, and 2585 female reindeers were collared with UHF transmitters. Clusters of bear positions were visited to investigate moose and reindeer predation. Bear kill rates and home ranges were calculated to examine bear movements and predatory behaviour. Bear habitat selection was modelled using resource selection functions over four periods (pre-calving, reindeer calving, moose calving, and post-calving). Coefficients of selection for areas closer to different land cover classes across periods were compared, examining the interactions between different degrees of predatory behaviour (i.e., high and low). Bear habitat selection differed throughout the periods and between low and high predatory bears. Differences among individuals’ predatory behaviour are reflected in the selection of habitat types, providing empirical evidence that different levels of specialization in foraging behaviour helps to explain individual variation in bear habitat selection

Neuropsychological outcome after cardiac arrest: a prospective case control sub-study of the Targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest trial (TTM2)

Background: This study is designed to provide detailed knowledge on cognitive impairment after out-of-hospital cardiac arrest (OHCA) and its relation to associated factors, and to validate the neurocognitive screening of the Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest trial (TTM2-trial), assessing effectiveness of targeted temperature management after OHCA. Methods: This longitudinal multi-center clinical study is a sub-study of the TTM2-trial, in which a comprehensive neuropsychological examination is performed in addition to the main TTM2-trial neurocognitive screening. Approximately 7 and 24 months after OHCA, survivors at selected study sites are invited to a standardized assessment, including performance-based tests of cognition and questionnaires of emotional problems, fatigue, executive function and insomnia. At 1:1 ratio, a matched control group from a cohort of acute myocardial infarction (MI) patients is recruited to perform the same assessment. We aim to include 100 patients per group. Potential differences between the OHCA patients and the MI controls at 7 and 24 months will be analyzed with a linear regression, using composite z-scores per cognitive domain (verbal, visual/constructive, working memory, episodic memory, processing speed, executive functions) as primary outcome measures. Results from OHCA survivors on the main TTM2-trial neurocognitive screening battery will be compared with neuropsychological test results at 7 months, using sensitivity and specificity analyses. Discussion: In this study we collect detailed information on cognitive impairment after OHCA and compare this to a control group of patients with acute MI. The validation of the TTM2 neurocognitive screening battery could justify its inclusion in routine follow-up. Our results may have a potential to impact on the design of future follow-up strategies and interventions after OHCA

Demographic change in models of endogenous economic growth. A survey

The purpose of this article is to identify the role of population size, population growth and population ageing in models of endogenous economic growth. While in exogenous growth models demographic variables are linked to economic prosperity mainly via the population size, the structure of the workforce, and the capital intensity of workers, endogenous growth models and their successors also allow for interrelationships between demography and technological change. However, most of the existing literature considers only the interrelationships based on population size and its growth rate and does not explicitly account for population ageing. The aim of this paper is (a) to review the role of population size and population growth in the most commonly used economic growth models (with a focus on endogenous economic growth models), (b) discuss models that also allow for population ageing, and (c) sketch out the policy implications of the most commonly used endogenous growth models and compare them to each other

Quiescence and γH2AX in neuroblastoma are regulated by ouabain/Na,K-ATPase

Cellular quiescence is a state of reversible proliferation arrest that is induced by anti-mitogenic signals. The endogenous cardiac glycoside ouabain is a specific ligand of the ubiquitous sodium pump, Na,K-ATPase, also known to regulate cell growth through unknown signalling pathways. To investigate the role of ouabain/Na,K-ATPase in uncontrolled neuroblastoma growth we used xenografts, flow cytometry, immunostaining, comet assay, real-time PCR, and electrophysiology after various treatment strategies. The ouabain/Na,K-ATPase complex induced quiescence in malignant neuroblastoma. Tumour growth was reduced by >50% when neuroblastoma cells were xenografted into immune-deficient mice that were fed with ouabain. Ouabain-induced S-G2 phase arrest, activated the DNA-damage response (DDR) pathway marker γH2AX, increased the cell cycle regulator p21Waf1/Cip1 and upregulated the quiescence-specific transcription factor hairy and enhancer of split1 (HES1), causing neuroblastoma cells to ultimately enter G0. Cells re-entered the cell cycle and resumed proliferation, without showing DNA damage, when ouabain was removed. Conclusion: These findings demonstrate a novel action of ouabain/Na,K-ATPase as a regulator of quiescence in neuroblastoma, suggesting that ouabain can be used in chemotherapies to suppress tumour growth and/or arrest cells to increase the therapeutic index in combination therapies

The influence of Holocene forest dynamics on the chironomid fauna of a boreal lake (Flocktjärn, northeast Sweden)

There is a notable lack of palaeoecological records, particularly quantitative palaeoenvironmental reconstructions, for northeast Sweden. Here I use a lake sediment record from lake Flocktjärn to reconstruct Holocene terrestrial vegetation change and lake ecosystem dynamics, and to study the relationship between these components of the environment. After a period in which the vegetation around the lake is characterised by boreal forest, thermophilous arboreal taxa such as Ulmus establish in the Flocktjärn area from 6000 cal. a BP onward. Picea becomes abundant from 2930 cal. a BP onward, in line with results from other records from the region. The chironomid fauna of the lake shows high turnover before 7700 cal. a BP, after which an assemblage dominated by taxa indicative of shallow, warm and relatively nutrient rich conditions establishes. A transition to chironomid taxa that are indicative of slightly lower temperatures and lower nutrient levels occurs at 5260 cal. a BP. A chironomid-inferred mean July air temperature record shows unreliable inferences for the record pre-dating 7700 cal. a BP, a Holocene Thermal Maximum with temperatures around 14 °C between 7700-5260 cal. a BP, and temperatures around 12.5 °C between 5260 cal. a BP and the present. A numerical comparison between upland vegetation change and chironomid faunal dynamics for the first time shows that either vegetation change directly impacted on the chironomid fauna of the lake, or alternatively an external factor impacted on both the terrestrial and the aquatic ecosystem, resulting in concurrent changes in both parts of the ecosystem. This novel evidence of ecosystem connectivity is of vital importance to landscape management, as ongoing climate and land use change is likely to lead to increased pressure on lake ecosystems

Selection, characterization and in vivo evaluation of novel CD44v6-targeting antibodies for targeted molecular radiotherapy

Abstract Molecular radiotherapy combines the advantages of systemic administration of highly specific antibodies or peptides and the localized potency of ionizing radiation. A potential target for molecular radiotherapy is the cell surface antigen CD44v6, which is overexpressed in numerous cancers, with limited expression in normal tissues. The aim of the present study was to generate and characterize a panel of human anti-CD44v6 antibodies and identify a suitable candidate for future use in molecular radiotherapy of CD44v6-expressing cancers. Binders were first isolated from large synthetic phage display libraries containing human scFv and Fab antibody fragments. The antibodies were extensively analyzed through in vitro investigations of binding kinetics, affinity, off-target binding, and cell binding. Lead candidates were further subjected to in vivo biodistribution studies in mice bearing anaplastic thyroid cancer xenografts that express high levels of CD44v6. Additionally, antigen-dependent tumor uptake of the lead candidate was verified in additional xenograft models with varying levels of target expression. Interestingly, although only small differences were observed among the top antibody candidates in vitro, significant differences in tumor uptake and retention were uncovered in in vivo experiments. A high-affinity anti-CD44v6 lead drug candidate was identified, mAb UU-40, which exhibited favorable target binding properties and in vivo distribution. In conclusion, a panel of human anti-CD44v6 antibodies was successfully generated and characterized in this study. Through comprehensive evaluation, mAb UU-40 was identified as a promising lead candidate for future molecular radiotherapy of CD44v6-expressing cancers due to its high affinity, excellent target binding properties, and desirable in vivo distribution characteristics