Modeling biochemical transformation processes and information processing with Narrator

BACKGROUND: Software tools that model and simulate the dynamics of biological processes and systems are becoming increasingly important. Some of these tools offer sophisticated graphical user interfaces (GUIs), which greatly enhance their acceptance by users. Such GUIs are based on symbolic or graphical notations used to describe, interact and communicate the developed models. Typically, these graphical notations are geared towards conventional biochemical pathway diagrams. They permit the user to represent the transport and transformation of chemical species and to define inhibitory and stimulatory dependencies. A critical weakness of existing tools is their lack of supporting an integrative representation of transport, transformation as well as biological information processing. RESULTS: Narrator is a software tool facilitating the development and simulation of biological systems as Co-dependence models. The Co-dependence Methodology complements the representation of species transport and transformation together with an explicit mechanism to express biological information processing. Thus, Co-dependence models explicitly capture, for instance, signal processing structures and the influence of exogenous factors or events affecting certain parts of a biological system or process. This combined set of features provides the system biologist with a powerful tool to describe and explore the dynamics of life phenomena. Narrator's GUI is based on an expressive graphical notation which forms an integral part of the Co-dependence Methodology. Behind the user-friendly GUI, Narrator hides a flexible feature which makes it relatively easy to map models defined via the graphical notation to mathematical formalisms and languages such as ordinary differential equations, the Systems Biology Markup Language or Gillespie's direct method. This powerful feature facilitates reuse, interoperability and conceptual model development. CONCLUSION: Narrator is a flexible and intuitive systems biology tool. It is specifically intended for users aiming to construct and simulate dynamic models of biology without recourse to extensive mathematical detail. Its design facilitates mappings to different formal languages and frameworks. The combined set of features makes Narrator unique among tools of its kind. Narrator is implemented as Java software program and available as open-source from

Could resource rents finance universal access to infrastructure? A first exploration of needs and rents

It is often argued that, ethically, resource rents should accrue to all citizens. Yet, in reality, the rents from exploiting national resources are often concentrated in the hands of a few. If resource rents were to be taxed, on the other hand, substantial amounts of public money could be raised and used to cover the population's infrastructure needs, such as access to electricity, water, sanitation, communication technology and roads, which all play important roles in a nation's economic development process. Here, the authors examine to what extent existing resource rents could be used to provide universal access to these infrastructures

Taking Differences in Institutional Quality into Account in Global Forest Modelling

Forest cover and land-use change models are commonly used for climate scenarios and provide policy advice. The IIASA Global Forest Model (G4M) compares the net present value of agriculture and forestry, and makes a land-use change decision, based on this comparison. Moving beyond this purely economic rationale, we aimed at understanding in how far integrating differences in environmental institutional quality, could allow improving the representation of forest cover change processes of the model. Through an econometric regression analysis, we identified the most significant out of a larger set of variables on environmental institutional quality and created a composite index. We then implemented the composite index into the model. Its components are: the internalization of environmental norms, the strength of institutions, the ability of the institutions to guarantee macroeconomic stability, the quality of the administration and the efficiency of the bureaucracy. Through the inclusion of the composite index, the model’s residual could be significantly reduced. The results suggest that future research should consider taking differences in environmental institutional quality into account to improve modeling of deforestation processes. Moreover, the implementation of the index into the model allows for the first time to create scenarios for institutional quality and its impact on forest cover

Differential microRNA expression analyses across two brain regions in Alzheimer’s disease

Dysregulation of microRNAs (miRNAs) is involved in the pathogenesis of neurodegenerative diseases, including Alzheimer’s disease (AD). Hitherto, sample sizes from differential miRNA expression studies in AD are exceedingly small aggravating any biological inference. To overcome this limitation, we investigated six candidate miRNAs in a large collection of brain samples. Brain tissue was derived from superior temporal gyrus (STG) and entorhinal cortex (EC) from 99 AD patients and 91 controls. MiRNA expression was examined by qPCR (STG) or small RNA sequencing (EC). Brain region-dependent differential miRNA expression was investigated in a transgenic AD mouse model using qPCR and FISH. Total RNA sequencing was used to assess differential expression of miRNA target genes. MiR-129-5p, miR-132-5p, and miR-138-5p were significantly downregulated in AD vs. controls both in STG and EC, while miR-125b-5p and miR-501-3p showed no evidence for differential expression in this dataset. In addition, miR-195-5p was significantly upregulated in EC but not STG in AD patients. The brain region-specific pattern of miR-195-5p expression was corroborated in vivo in transgenic AD mice. Total RNA sequencing identified several novel and functionally interesting target genes of these miRNAs involved in synaptic transmission (GABRB1), the immune-system response (HCFC2) or AD-associated differential methylation (SLC16A3). Using two different methods (qPCR and small RNA-seq) in two separate brain regions in 190 individuals we more than doubled the available sample size for most miRNAs tested. Differential gene expression analyses confirm the likely involvement of miR-129-5p, miR-132-5p, miR-138-5p, and miR-195-5p in AD pathogenesis and highlight several novel potentially relevant target mRNAs

Dem Stickstoff auf der Spur: N2O Prozesse und Nmin Dynamik nach Grünlanderneuerung

Eine weit verbreitete Maßnahme des Grünlandmanagements, die zur Beseitigung von Narbenschäden und zur Steigerung der Futterqualität in unproduktiven Grünländern angewendet wird, ist die Grünlanderneuerung. Die mechanische Bearbeitung von Grünlandböden und die dadurch gesteigerte Mineralisation durch den Abbau organischer Bodensubstanz und der alten Grasnarbe kann zu hohen N-Verlusten in Form des klimarelevanten Treibhausgases Lachgas (N2O) und/oder Nitratauswaschung (NO3-) führen. Bisher gibt es jedoch über die Dauer des beschriebenen Effektes, sowie den Einfluss unterschiedlicher Grünlanderneuerungstechniken nur wenige Informationen. Insbesondere für die nationale Treibhausgasbilanzierung ist es jedoch von Bedeutung, die Prozesse der N2O Umsetzung und ihre Quellen zu kennen und zu erfassen, da sich nur so Maßnahmen zur Emissionsminderung ableiten lassen. Zu diesem Zweck wurde ein Parzellenversuch (2013-2015) auf zwei Standorten (Plaggenesch, Anmoorgley) in der Nähe von Oldenburg (Niedersachsen) mit unterschiedlichen Erneuerungsvarianten etabliert. Als Referenzvarianten dienten: Grünlandumwandlung in Ackerland (Mais) und langjähriges Dauergrünland. Die N2O Flüsse und die Dynamik des mineralischen N (Nmin) wurden über einen Zeitraum von zwei Jahren untersucht. Zusätzlich wurden Nmin Profile (0-90 cm) genutzt, um den N-Verlust über Winter zu quantifizieren und das Risiko einer möglichen NO3- Auswaschung abzuschätzen. Obwohl die N2O Flüsse für einen kurzen Zeitraum (2 Monate) nach der Bearbeitung erhöht waren, konnte kein Jahreseffekt festgestellt werden. Im ersten Winter nach dem Aufbrechen der alten Grasnarbe trat jedoch für den Plaggenesch ein erhöhtes Risiko für NO3- Auswaschung auf. Die Untersuchung der N2O-Produktionswege und der N2O-Reduktion zu N2 (dem Endprodukt der Denitrifikation) erfolgte unter Nutzung stabiler Isotope. Hierzu wurde die 15N-Gasflussmethode im Sommer 2014 angewendet (1). Zusätzlich wurden natürlich vorhandene stabile Isotopensignaturen im bodenbürtigen N2O (δ15NbulkN2O, δ18ON2O und δ15NSPN2O = intramolekulare Verteilung von 15N im N2O Molekül) genutzt, um Quellen der N2O-Bildung im ersten Jahr nach Grünlanderneuerung (2013-2014) zu ermitteln. Auf dem Anmoorgley wurden große N-Verluste durch den Prozess der Denitrifikation bestimmt, wobei N2 die Emissionen dominerte. Für den Plaggenesch konnten generell geringere gasförmige Verluste festgestellt werden

Corrigendum to: Who feels affected by “out of control” sexual behavior? Prevalence and correlates of indicators for ICD-11 Compulsive Sexual Behavior Disorder in the German Health and Sexuality Survey (GeSiD)

As a result of a mistake made during the production phase, the above paper was published with the in-text citations appearing in an incorrect order, first as an Online First article on 20 September 2022, and later in the 3rd issue of Volume 11 (2022) on 26 September 2022. DOI: 10.1556/2006.2022.0006

Epigenome-wide association study in peripheral tissues highlights DNA methylation profiles associated with episodic memory performance in humans

The decline in episodic memory (EM) performance is a hallmark of cognitive aging and an early clinical sign in Alzheimer’s disease (AD). In this study, we conducted an epigenome-wide association study (EWAS) using DNA methylation (DNAm) profiles from buccal and blood samples for cross-sectional (n = 1019) and longitudinal changes in EM performance (n = 626; average follow-up time 5.4 years) collected under the auspices of the Lifebrain consortium project. The mean age of participants with cross-sectional data was 69 ± 11 years (30–90 years), with 50% being females. We identified 21 loci showing suggestive evidence of association (p < 1 × 10−5) with either or both EM phenotypes. Among these were SNCA, SEPW1 (both cross-sectional EM), ITPK1 (longitudinal EM), and APBA2 (both EM traits), which have been linked to AD or Parkinson’s disease (PD) in previous work. While the EM phenotypes were nominally significantly (p < 0.05) associated with poly-epigenetic scores (PESs) using EWASs on general cognitive function, none remained significant after correction for multiple testing. Likewise, estimating the degree of “epigenetic age acceleration” did not reveal significant associations with either of the two tested EM phenotypes. In summary, our study highlights several interesting candidate loci in which differential DNAm patterns in peripheral tissue are associated with EM performance in humans

Research priorities for negative emissions

Carbon dioxide removal from the atmosphere (CDR)—also known as ‘negative emissions’—features prominently in most 2 °Cscenarios and has been under increased scrutiny by scientists, citizens, and policymakers. Critics argue that ‘negative emission technologies’ (NETs) are insufficiently mature to rely on them for climate stabilization. Some even argue that 2 °Cis no longer feasible or might have unacceptable social and environmental costs. Nonetheless, the Paris Agreement endorsed an aspirational goal of limiting global warming to even lower levels, arguing that climate impacts— especially for vulnerable nations such as small island states—will be unacceptably severe in a 2 °C world. While there are few pathways to 2 °Cthat do not rely on negative emissions, 1.5 °Cscenarios are barely conceivable without them. Building on previous assessments of NETs, we identify some urgent research needs to provide a more complete picture for reaching ambitious climate targets, and the role that NETs can play in reaching them

Syntactic architecture and its consequences I: Syntax inside the grammar

This volume collects novel contributions to comparative generative linguistics that “rethink” existing approaches to an extensive range of phenomena, domains, and architectural questions in linguistic theory. At the heart of the contributions is the tension between descriptive and explanatory adequacy which has long animated generative linguistics and which continues to grow thanks to the increasing amount and diversity of data available to us. The chapters address research questions on the relation of syntax to other aspects of grammar and linguistics more generally, including studies on language acquisition, variation and change, and syntactic interfaces. Many of these contributions show the influence of research by Ian Roberts and collaborators and give the reader a sense of the lively nature of current discussion of topics in synchronic and diachronic comparative syntax ranging from the core verbal domain to higher, propositional domains. This book is complemented by volume II available at https://langsci-press.org/catalog/book/276 and volume III available at https://langsci-press.org/catalog/book/277