Using an agent-based model to simulate the development of risk behaviors during adolescence

Adolescents tend to adopt behaviors that are similar to those of their friends, and also tend to become friends with peers that have similar interests and behaviors. This tendency towards homogeneity applies not only to conventional behaviors such as working for school and participating in sports activities, but also to risk behaviors such as drug use, oppositional behavior or unsafe sex. The current study aims at building an agent model to answer the following related questions: How do friendship groups evolve and what is the role of behavioral similarity in friendship formation? How does homogeneity among peers emerge, with regard to conventional as well as risk behaviors? On the basis of the theoretical and empirical literature on friendship selection and influences on risk behavior during adolescence we first developed a conceptual framework, which was then translated into a mathematical model of a dynamic system and implemented as an agent-based computer simulation consisting of simple behavioral rules and principles. Each agent in the model holds distinct property matrices including an individual behavioral profile with a list of risky (i.e., alcohol use, aggressiveness, soft drugs) and conventional behaviors (i.e., school attendance, sports, work). The computer model simulates the development, during one school year, of a social network (i.e. formation of friendships and cliques), the (dyadic) interactions between pupils and their behavioral profiles. During the course of simulation, the agents' behavioral profiles change on the basis of their interactions resulting in individual developmental curves of conventional and risk behaviors. These profiles are used to calculate the (behavioral) similarity and differences between the various agents. Generally, the model output is analyzed by means of visual inspection (i.e., plotting developmental curves of behavior and social networks), systematic comparison and by calculating additional measures (i.e., using specific social analysis software packages). Simulation results conclusively indicate model validity. The model simulates qualitative properties currently found in research on adolescent development, namely the role of homophily, the appearance of friendship clusters, and the increase in behavioral homogeneity among friends. The model not only converges with empirical findings, but furthermore helps to explain social psychological phenomena (e.g. the emergence of homophily among adolescents)

Finding relevant relations in relevant documents

This work studies the combination of a document retrieval and a relation extraction system for the purpose of identifying query-relevant relational facts. On the TREC Web collection, we assess extracted facts separately for correctness and relevance. Despite some TREC topics not being covered by the relation schema, we find that this approach reveals relevant facts, and in particular those not yet known in the knowledge base DBpedia. The study confirms that mention frequency, document relevance, and entity relevance are useful indicators for fact relevance. Still, the task remains an open research problem

S-acylation of the Wnt receptor Frizzled-5 by zDHHC5 controls its cellular localization and synaptogenic activity in the rodent hippocampus

Proper localization of receptors for synaptic organizing factors is crucial for synapse formation. Wnt proteins promote synapse assembly through Frizzled (Fz) receptors. In hippocampal neurons, the surface and synaptic localization of Fz5 is regulated by neuronal activity, but the mechanisms involved remain poorly understood. Here, we report that all Fz receptors can be post-translationally modified by S-acylation and that Fz5 is S-acylated on three C-terminal cysteines by zDHHC5. S-acylation is essential for Fz5 localization to the cell surface, axons, and presynaptic sites. Notably, S-acylation-deficient Fz5 is internalized faster, affecting its association with signalosome components at the cell surface. S-acylation-deficient Fz5 also fails to activate canonical and divergent canonical Wnt pathways. Fz5 S-acylation levels are regulated by the pattern of neuronal activity. In vivo studies demonstrate that S-acylation-deficient Fz5 expression fails to induce presynaptic assembly. Our studies show that S-acylation of Frizzled receptors is a mechanism controlling their localization and function

Mechanisms underlying cognitive deficits in a mouse model for Costello Syndrome are distinct from other RASopathy mouse models

RASopathies, characterized by germline mutations in genes encoding proteins of the RAS-ERK signaling pathway, show overlapping phenotypes, which manifest themselves with a varying severity of intellectual disability. However, it is unclear to what extent they share the same downstream pathophysiology that underlies the cognitive deficits. Costello syndrome (CS) is a rare RASopathy caused by activating mutations in the HRAS gene. Here we investigated the mechanisms underlying the cognitive deficits of HRas G12V/G12V mice. HRas G12V/G12V mice showed robust upregulation of ERK signaling, neuronal hypertrophy, increased brain volume, spatial learning deficits, and impaired mGluR-dependent long-term depression (LTD). In contrast, long-term potentiation (LTP), which is affected in other RASopathy mouse models was unaffected. Treatment with lovastatin, a HMG-CoA-Reductase inhibitor which has been shown to rescue the behavioral phenotypes of mouse models of NF1 and Noonan syndrome, was unable to restore ERK signaling and the cognitive deficits of HRas G12V/G12V mice. Administration of a potent mitogen-activated protein kinase (MEK) inhibitor rescued the ERK upregulation and the mGluR-LTD deficit of HRas G12V/G12V mice, but failed to rescue the cognitive deficits. Taken together, this study indicates that the fundamental molecular and cellular mechanisms underlying the cognitive aspects of different RASopathies are remarkably distinct, and may require disease specific treatments

The dorsoanterior brain of adult amphioxus shares similarities in expression profile and neuronal composition with the vertebrate telencephalon

Funder: FP7 People: Marie-Curie Actions; doi: http://dx.doi.org/10.13039/100011264; Grant(s): 229597Abstract: Background: The evolutionary origin of the telencephalon, the most anterior part of the vertebrate brain, remains obscure. Since no obvious counterpart to the telencephalon has yet been identified in invertebrate chordates, it is difficult to trace telencephalic origins. One way to identify homologous brain parts between distantly related animal groups is to focus on the combinatorial expression of conserved regionalisation genes that specify brain regions. Results: Here, we report the combined expression of conserved transcription factors known to specify the telencephalon in the vertebrates in the chordate amphioxus. Focusing on adult specimens, we detect specific co-expression of these factors in the dorsal part of the anterior brain vesicle, which we refer to as Pars anterodorsalis (PAD). As in vertebrates, expression of the transcription factors FoxG1, Emx and Lhx2/9 overlaps that of Pax4/6 dorsally and of Nkx2.1 ventrally, where we also detect expression of the Hedgehog ligand. This specific pattern of co-expression is not observed prior to metamorphosis. Similar to the vertebrate telencephalon, the amphioxus PAD is characterised by the presence of GABAergic neurons and dorsal accumulations of glutamatergic as well as dopaminergic neurons. We also observe sustained proliferation of neuronal progenitors at the ventricular zone of the amphioxus brain vesicle, as observed in the vertebrate brain. Conclusions: Our findings suggest that the PAD in the adult amphioxus brain vesicle and the vertebrate telencephalon evolved from the same brain precursor region in ancestral chordates, which would imply homology of these structures. Our comparative data also indicate that this ancestral brain already contained GABA-, glutamatergic and dopaminergic neurons, as is characteristic for the olfactory bulb of the vertebrate telencephalon. We further speculate that the telencephalon might have evolved in vertebrates via a heterochronic shift in developmental timing

GrassPlot - a database of multi-scale plant diversity in Palaearctic grasslands

GrassPlot is a collaborative vegetation-plot database organised by the Eurasian Dry Grassland Group (EDGG) and listed in the Global Index of Vegetation-Plot Databases (GIVD ID EU-00-003). GrassPlot collects plot records (releves) from grasslands and other open habitats of the Palaearctic biogeographic realm. It focuses on precisely delimited plots of eight standard grain sizes (0.0001; 0.001;... 1,000 m(2)) and on nested-plot series with at least four different grain sizes. The usage of GrassPlot is regulated through Bylaws that intend to balance the interests of data contributors and data users. The current version (v. 1.00) contains data for approximately 170,000 plots of different sizes and 2,800 nested-plot series. The key components are richness data and metadata. However, most included datasets also encompass compositional data. About 14,000 plots have near-complete records of terricolous bryophytes and lichens in addition to vascular plants. At present, GrassPlot contains data from 36 countries throughout the Palaearctic, spread across elevational gradients and major grassland types. GrassPlot with its multi-scale and multi-taxon focus complements the larger international vegetationplot databases, such as the European Vegetation Archive (EVA) and the global database " sPlot". Its main aim is to facilitate studies on the scale-and taxon-dependency of biodiversity patterns and drivers along macroecological gradients. GrassPlot is a dynamic database and will expand through new data collection coordinated by the elected Governing Board. We invite researchers with suitable data to join GrassPlot. Researchers with project ideas addressable with GrassPlot data are welcome to submit proposals to the Governing Board

Clinical and virological characteristics of hospitalised COVID-19 patients in a German tertiary care centre during the first wave of the SARS-CoV-2 pandemic: a prospective observational study

Purpose: Adequate patient allocation is pivotal for optimal resource management in strained healthcare systems, and requires detailed knowledge of clinical and virological disease trajectories. The purpose of this work was to identify risk factors associated with need for invasive mechanical ventilation (IMV), to analyse viral kinetics in patients with and without IMV and to provide a comprehensive description of clinical course. Methods: A cohort of 168 hospitalised adult COVID-19 patients enrolled in a prospective observational study at a large European tertiary care centre was analysed. Results: Forty-four per cent (71/161) of patients required invasive mechanical ventilation (IMV). Shorter duration of symptoms before admission (aOR 1.22 per day less, 95% CI 1.10-1.37, p < 0.01) and history of hypertension (aOR 5.55, 95% CI 2.00-16.82, p < 0.01) were associated with need for IMV. Patients on IMV had higher maximal concentrations, slower decline rates, and longer shedding of SARS-CoV-2 than non-IMV patients (33 days, IQR 26-46.75, vs 18 days, IQR 16-46.75, respectively, p < 0.01). Median duration of hospitalisation was 9 days (IQR 6-15.5) for non-IMV and 49.5 days (IQR 36.8-82.5) for IMV patients. Conclusions: Our results indicate a short duration of symptoms before admission as a risk factor for severe disease that merits further investigation and different viral load kinetics in severely affected patients. Median duration of hospitalisation of IMV patients was longer than described for acute respiratory distress syndrome unrelated to COVID-19

Exome sequencing of individuals with Huntington’s disease implicates FAN1 nuclease activity in slowing CAG expansion and disease onset

The age at onset of motor symptoms in Huntington’s disease (HD) is driven by HTT CAG repeat length but modified by other genes. In this study, we used exome sequencing of 683 patients with HD with extremes of onset or phenotype relative to CAG length to identify rare variants associated with clinical effect. We discovered damaging coding variants in candidate modifier genes identified in previous genome-wide association studies associated with altered HD onset or severity. Variants in FAN1 clustered in its DNA-binding and nuclease domains and were associated predominantly with earlier-onset HD. Nuclease activities of purified variants in vitro correlated with residual age at motor onset of HD. Mutating endogenous FAN1 to a nuclease-inactive form in an induced pluripotent stem cell model of HD led to rates of CAG expansion similar to those observed with complete FAN1 knockout. Together, these data implicate FAN1 nuclease activity in slowing somatic repeat expansion and hence onset of HD

Wie sagen wir es unseren Kunden: Einführung von Preisen für zuvor kostenlose wertschöpfende Dienstleistungen

Unternehmen versuchen die Attraktivität ihres Kernangebots durch wertschöpfenden Dienstleistungen zu steigern um sich vom Wettbewerb zu differenzieren. Diese werden oftmals kostenlos angeboten, wie zum Beispiel erweiterte Mobilitätsgarantien beim Kauf eines neuen Autos. Preise für ehemals kostenlose wertschöpfende Dienstleistungen einzuführen stellt aufgrund negativer Kundenreaktionen eine große Herausforderung für Manager dar. Unsere Studie zeigt, dass die Preiseinführung für eine zuvor kostenlose wertschöpfende Dienstleistung mit Hilfe von Motiven kommuniziert werden sollte, um negative Kundenreaktionen zu vermeiden bzw. zu reduzieren. Neben den preisbasierten Motiven (kosten-, nutzen-, wettbewerbsorientierte Motive) kann eine wertschöpfende Dienstleistung in ihrer Funktionalität (Motiv der Nichtvergleichbarkeit ) verändert werden. Die Studie zeigt, dass insbesondere kosten- und nutzenbasierte Motive einen positiven Effekt auf die wahrgenommene Preisfairness haben. Hingegen erweist sich die gleichzeitige Angabe eines preisbasierten Motivs und Änderung der wertschöpfenden Dienstleistung als nicht adäquat. Im Falle dass preisbasierte Motive nicht kommuniziert werden können, sollte die zuvor kostenlose wertschöpfende Dienstleistung so verändert werden, dass eine neue Funktionalität hinzugefügt wird