Assessing classical swine fever disease control measures using an individual-based model

Lange, M., Kramer-Schadt, S., Thulke, H.-H

Evolving toward a human-cell based and multiscale approach to drug discovery for CNS disorders

A disruptive approach to therapeutic discovery and development is required in order to significantly improve the success rate of drug discovery for central nervous system (CNS) disorders. In this review, we first assess the key factors contributing to the frequent clinical failures for novel drugs. Second, we discuss cancer translational research paradigms that addressed key issues in drug discovery and development and have resulted in delivering drugs with significantly improved outcomes for patients. Finally, we discuss two emerging technologies that could improve the success rate of CNS therapies: human induced pluripotent stem cell (hiPSC)-based studies and multiscale biology models. Coincident with advances in cellular technologies that enable the generation of hiPSCs directly from patient blood or skin cells, together with methods to differentiate these hiPSC lines into specific neural cell types relevant to neurological disease, it is also now possible to combine data from large-scale forward genetics and post-mortem global epigenetic and expression studies in order to generate novel predictive models. The application of systems biology approaches to account for the multiscale nature of different data types, from genetic to molecular and cellular to clinical, can lead to new insights into human diseases that are emergent properties of biological networks, not the result of changes to single genes. Such studies have demonstrated the heterogeneity in etiological pathways and the need for studies on model systems that are patient-derived and thereby recapitulate neurological disease pathways with higher fidelity. In the context of two common and presumably representative neurological diseases, the neurodegenerative disease Alzheimer’s Disease (AD), and the psychiatric disorder schizophrenia (SZ), we propose the need for, and exemplify the impact of, a multiscale biology approach that can integrate panomic, clinical, imaging, and literature data in order to c

The good, the bad, and the unseen: wild mammal encounters influence wildlife preferences of residents across socio-demographic gradients

As natural habitats decline and wildlife adapts to increasing anthropogenic disturbance, it is crucial to understand human-wildlife relationships in residential areas. However, relevant studies are limited and mostly focused on single cities. To address this knowledge gap, we investigated people’s preferences for seeing wild mammals in residential areas by conducting and analyzing an online survey distributed across Germany (n = 2997 participants). Our results revealed that preferred species (squirrels, hedgehogs, hares, roe deer) were frequently encountered, whereas unpreferred species were those encountered frequently (rats, martens), as well as those encountered rarely (wild boar, coypus, raccoons). We also found a moderately positive correlation between the number of encounters with mammals and them being preferred by humans. Finally, some socio-demographic variables, particularly gender, garden access, and urbanity, are significantly related to human preferences. Based on our results, we propose tailoring wildlife management in residential areas to promote the positive attributes of preferred wildlife as biodiversity ambassadors, while also addressing ways to mitigate encounters and negative perceptions associated with unpreferred species

Orientational transition in a nematic liquid crystal at a patterned surface

T. J. Atherton and J. Roy Sambles, Physical Review E, Vol. 74, article 022701 (2006) "Copyright © 2006 by the American Physical Society."We consider a semi-infinite nematic in contact with a periodic patterned surface with alternate planar and homeotropic stripes. Extending the work of Barbero et al., we find the free energy (assuming K1=K3) for the situations where the easy direction on the planar stripe is either perpendicular or parallel to the length of the stripes. We find the bulk free energy difference between the structures to be proportional to √ K2/K1 and so we consider the possibility of a spontaneous transition between the two states if the azimuthal anchoring energy is sufficiently weak and K1≠K2. We compute the critical azimuthal anchoring energy for such a transition in terms of the relative width of the stripes and the period of the pattern and find it to be ~10−6 J m−2, comparable to experimental values

Habitat selection models for European wildcat conservation

Populations of the European wildcat (Felis silvestris) are only slowly recovering in Central Europe after a severe decline in the last centuries and require specific conservation plans in many areas. However, detailed information on wildcat occurrence and habitat require- ments is still scarce and controversial. We present a fine-scale habitat selection model for wildcats based on detailed species and land use information and evaluate its accu- racy to predict habitat distribution in new areas. We analysed habitat use within home ranges using single locations of 12 radio-tracked individuals from south western Germany. Several competing models were fitted and compared using generalised linear mixed models (GLMM) and information-theoretic approaches. Radio-tracking data of 9 and 10 wildcats from two distant areas were used to evaluate the models. The selected model predicted habitat associated to close distance to forest, watercourses and mead- ows and a critical distance to villages, single houses and roads. To predict area suitable for home ranges we superimposed rules derived from home range attributes at a higher level of selection. Predictions from the combination of the fine-scale habitat model and home range rules matched well with more than 2000 wildcat observations of south- western Germany. We discuss the application of the model in wildcat conservation for finding potential reintroduction sites, identifying small isolated populations and aiding in the evaluation of the needs of mitigation and compensation within the scope of the European Habitats Directive.Peer Reviewe

Comprehensive User Engagement Sites (CUES) in Philadelphia: A Constructive Proposal

This paper is a study about Philadelphia’s comprehensive user engagement sites (CUESs) as the authors address and examine issues related to the upcoming implementation of a CUES while seeking solutions for its disputed questions and plans. Beginning with the federal drug schedules, the authors visit some of the medical and public health issues vis-à-vis safe injection facilities (SIFs). Insite, a successful Canadian SIF, has been thoroughly researched as it represents a paradigm for which a Philadelphia CUES can expand upon. Also, the existing criticisms against SIFs are revisited while critically unpackaged and responded to in favor of the establishment. In the main section, the authors propose the layout and services of the upcoming CUES, much of which would be in congruent to Vancouver’s Insite. On the other hand, the CUES would be distinct from Insite, as the authors emphasize, in that it will offer an information center run by individuals in recovery and place additional emphasis on early education for young healthcare professionals by providing them a platform to work at the site. The paper will also briefly investigate the implementation of a CUES site under an ethical scope of the Harm Reduction Theory. Lastly, the authors recommend some strategic plans that the Philadelphia City government may consider employing at this crucial stage

Detection of regulator genes and eQTLs in gene networks

Genetic differences between individuals associated to quantitative phenotypic traits, including disease states, are usually found in non-coding genomic regions. These genetic variants are often also associated to differences in expression levels of nearby genes (they are "expression quantitative trait loci" or eQTLs for short) and presumably play a gene regulatory role, affecting the status of molecular networks of interacting genes, proteins and metabolites. Computational systems biology approaches to reconstruct causal gene networks from large-scale omics data have therefore become essential to understand the structure of networks controlled by eQTLs together with other regulatory genes, and to generate detailed hypotheses about the molecular mechanisms that lead from genotype to phenotype. Here we review the main analytical methods and softwares to identify eQTLs and their associated genes, to reconstruct co-expression networks and modules, to reconstruct causal Bayesian gene and module networks, and to validate predicted networks in silico.Comment: minor revision with typos corrected; review article; 24 pages, 2 figure

The frequent five: Insights from interviews with urban wildlife professionals in Germany

1. Wildlife in cities divides people, with some animals bringing positive benefits and others causing conflict, for example due to property damage. 2. Urban wildlife professionals from municipal administration, nature conservation, and hunting associations have a crucial role in shaping human-wildlife relationships in cities and fostering conflict-free coexistence. While many studies on urban wildlife have focused on the views of citizens, few have investigated the perspectives of experts to date. To address this knowledge gap, we interviewed 36 urban wildlife professionals giving guidance in the context of urban wildlife management, either in one of the four largest German cities by population (Berlin, Hamburg, Munich and Cologne) or at the national level. 3. Red foxes, wild boars, raccoons, stone martens and Eurasian beavers were the five mammal species most frequently highlighted in interviews to cause human-wildlife conflicts. The interviewees saw wild boars and raccoons as the most controversial urban wild mammals but emphasized the need to create refuges for beavers and better inform the public about foxes. 4. Management in terms of public outreach, urban planning and population control, as well as establishing official contact points and stricter fines of activities violating regulations were highlighted as important elements of a toolkit to manage urban wildlife conflicts

Psychological and behavioural impact of returning personal results from whole-genome sequencing: the HealthSeq project

Providing ostensibly healthy individuals with personal results from whole-genome sequencing could lead to improved health and well-being via enhanced disease risk prediction, prevention, and diagnosis, but also poses practical and ethical challenges. Understanding how individuals react psychologically and behaviourally will be key in assessing the potential utility of personal whole-genome sequencing. We conducted an exploratory longitudinal cohort study in which quantitative surveys and in-depth qualitative interviews were conducted before and after personal results were returned to individuals who underwent whole-genome sequencing. The participants were offered a range of interpreted results, including Alzheimer’s disease, type 2 diabetes, pharmacogenomics, rare disease-associated variants, and ancestry. They were also offered their raw data. Of the 35 participants at baseline, 29 (82.9%) completed the 6-month follow-up. In the quantitative surveys, test-related distress was low, although it was higher at 1-week than 6-month follow-up (Z=2.68, P=0.007). In the 6-month qualitative interviews, most participants felt happy or relieved about their results. A few were concerned, particularly about rare disease-associated variants and Alzheimer’s disease results. Two of the 29 participants had sought clinical follow-up as a direct or indirect consequence of rare disease-associated variants results. Several had mentioned their results to their doctors. Some participants felt having their raw data might be medically useful to them in the future. The majority reported positive reactions to having their genomes sequenced, but there were notable exceptions to this. The impact and value of returning personal results from whole-genome sequencing when implemented on a larger scale remains to be seen

Genetical genomics: spotlight on QTL hotspots

No abstract available