Temporal changes in the Swiss flora: implications for flower-visiting insects

BACKGROUND: Local floristic diversity has massively decreased during the twentieth century in Central Europe even though in the 1990s diversity began increasing again in several regions. However, little is known whether this increase is equally distributed among plant groups with different reproductive traits. METHODS: Our study is based on data of the Swiss Biodiversity Monitoring Program. In this program, plant species occurrence is recorded since 2001 in 450 regularly distributed 1 km$^{2}$ study sites. For all 1774 plant species registered in the study, we researched data on flower/pseudanthium type and colour, reproductive system, and groups of flower visitors. We then tested whether temporal changes in species frequency were equally distributed among species with different trait states. RESULTS: Species richness and functional richness significantly increased in the study sites while functional evenness decreased. The frequency of wind-pollinated species increased more strongly than that of insect-pollinated species. Further, the frequency of species with simple, open insect-pollinated flowers and pseudanthia visited by generalist groups of insects increased slightly more strongly than the frequency of species with complex flowers visited by more specialized groups of flower visitors. Additionally, the frequency of self-compatible species increased significantly more than that of self-incompatible species. Thus, the overall increase in local plant species richness in Switzerland is mostly driven by wind- and generalist insect-pollinated, self-compatible species. In contrast, species with complex flowers, which are essential for specialized groups of flower visitors and species with self-incompatible reproductive systems profited less. CONCLUSIONS: Our study thus emphasizes the need to consider functional traits in the planning and monitoring of conservation activities, and calls for a special focus on plant species with specialized reproductive traits

Modelling the 3D-Genome: The development of network theory approaches to characterise and predict active enhancers

Ph. D. Thesis.Gene regulation is an important mechanism that ensures the correct functioning of a cell and is generally orchestrated by gene regulatory elements such as transcriptional enhancers. Identification of these genomic regions are important in understanding a wide range of phenomena such as evolution, homeostasis and disease. During gene regulation, signals pertaining to transcriptional activation are transferred across the chromatin regulatory network from enhancers to genes in the form of transcription factors and cofactors that in turn, recruit transcriptional machinery such as RNA Polymerase II to increase the rate of gene transcription. Conceptually, we describe this as a flow of information from enhancers to genes, mediated by the chromatin conformation. We exploit this relationship in order to decode the regulatory landscape of genes and identify active enhancers. This thesis outlines the difficulties associated with identifying pathogenic mutations in the non-coding genome due to a lack of robust enhancer annotations. We use network theory to annotate these regions and develop a new method, 3D-SearchE, that serves to predict the location of novel putative active enhancers. 3D-SearchE achieves this by reverse engineering the flow of information between enhancers and genes to calculate an imputed activity score (IAS) at intergenic loci. We show that intergenic loci with a high IAS are also present for other enhancer associated features including the histone marks H3K27ac, H3K4me1 and H3K4me2, P300, CAGE-seq, Starr-seq, eQTLs and RNA Polymerase II. 3D-SearchE successfully leverages and summarises the relationship between the 3D organisation of chromatin and global gene expression and represents a novel enhancer associated feature that can be used to predict active enhancers

The dangers of using diagnoses outside of established psychiatric nosology in the courtroom: Analysis and discussion of current Swiss legal precedent from a medical perspective.

Akin to many jurisdictions, Switzerland has a dual system of sanctions comprising sentences and measures. To order a therapeutic measure per Article 59 or 63 of the Swiss Criminal Code, the presence of a "severe mental disorder" must be determined. Before the new legal precedent, this required a medical diagnosis according to recognised classification systems like the ICD or DSM. The court then decided if a disorder was "severe" in the legal sense, thereby requiring such a therapeutic measure. However, in two 2019 rulings, the Swiss Federal Supreme Court concluded that a severe mental disorder could legally exist without a diagnosis according to the ICD or DSM, if it is based on offence- and risk-relevant personality-related factors amenable to risk-reducing therapy. We examine the details and context of the rulings, alongside their wider dangers. Specifically, we outline how undue influence could be exerted by non-ICD/DSM diagnostic systems, which were developed within individual theoretical schools of thought and lack empirical validation, like in these two court cases. Such non-manual diagnoses could make the presence of a severe mental disorder dependent upon whether an expert witness employs a particular diagnostic system, which would undermine principles of legality. Moreover, the Court's requirement that the disorder is based on personality-related risk factors amenable to risk-reducing therapy is problematic because research has highlighted the low effectiveness of treatment provided independently of a psychiatric disorder. Finally, broadening entry criteria may increase the number of offenders who require psychiatric treatment, thus endangering the quality of care for those with ICD/DSM-based diagnoses that are known to respond well to treatment (e.g. schizophrenia). In short, fulfilling the Court's request that any non-manual diagnoses are based on personality-related risk factors that are amenable to risk-reducing therapy is not possible for such non-manual diagnoses. Using unvalidated diagnoses could also render the system susceptible to ethical issues and hypothetical misuse, which may adversely affect society's most vulnerable people. To counter these dangers, we suggest that in order to be admissible in court, any diagnostic system must mandatorily fulfil sufficient scientific standards

Best practices in justifying calibrations for dating language families

The use of computational methods to assign absolute datings to language divergence is receiving renewed interest, as modern approaches based on Bayesian statistics offer alternatives to the discredited techniques of glottochronology. The datings provided by these new analyses depend crucially on the use of calibration, but the methodological issues surrounding calibration have received comparatively little attention. Especially, underappreciated is the extent to which traditional historical linguistic scholarship can contribute to the calibration process via loanword analysis. Aiming at a wide audience, we provide a detailed discussion of calibration theory and practice, evaluate previously used calibrations, recommend best practices for justifying calibrations, and provide a concrete example of these practices via a detailed derivation of calibrations for the Uralic language family. This article aims to inspire a higher quality of scholarship surrounding all statistical approaches to language dating, and especially closer engagement between practitioners of statistical methods and traditional historical linguists, with the former thinking more carefully about the arguments underlying their calibrations and the latter more clearly identifying results of their work which are relevant to calibration, or even suggesting calibrations directly.</p

Same Data, Different Conclusions: Radical Dispersion in Empirical Results When Independent Analysts Operationalize and Test the Same Hypothesis

In this crowdsourced initiative, independent analysts used the same dataset to test two hypotheses regarding the effects of scientists’ gender and professional status on verbosity during group meetings. Not only the analytic approach but also the operationalizations of key variables were left unconstrained and up to individual analysts. For instance, analysts could choose to operationalize status as job title, institutional ranking, citation counts, or some combination. To maximize transparency regarding the process by which analytic choices are made, the analysts used a platform we developed called DataExplained to justify both preferred and rejected analytic paths in real time. Analyses lacking sufficient detail, reproducible code, or with statistical errors were excluded, resulting in 29 analyses in the final sample. Researchers reported radically different analyses and dispersed empirical outcomes, in a number of cases obtaining significant effects in opposite directions for the same research question. A Boba multiverse analysis demonstrates that decisions about how to operationalize variables explain variability in outcomes above and beyond statistical choices (e.g., covariates). Subjective researcher decisions play a critical role in driving the reported empirical results, underscoring the need for open data, systematic robustness checks, and transparency regarding both analytic paths taken and not taken. Implications for organizations and leaders, whose decision making relies in part on scientific findings, consulting reports, and internal analyses by data scientists, are discussed

Coronavirus infection and PARP expression dysregulate the NAD metabolome: An actionable component of innate immunity

Poly(ADP-ribose) polymerase (PARP) superfamily members covalently link either a single ADP-ribose (ADPR) or a chain of ADPR units to proteins using NAD as the source of ADPR. Although the well-known poly(ADP-ribosylating) (PARylating) PARPs primarily function in the DNA damage response, many noncanonical mono(ADP-ribosylating) (MARylating) PARPs are associated with cellular antiviral responses. We recently demonstrated robust up-regulation of several PARPs following infection with murine hepatitis virus (MHV), a model coronavirus. Here we show that SARS-CoV-2 infection strikingly up-regulates MARylating PARPs and induces the expression of genes encoding enzymes for salvage NAD synthesis from nicotinamide (NAM) and nicotinamide riboside (NR), while down-regulating other NAD biosynthetic pathways. We show that overexpression of PARP10 is sufficient to depress cellular NAD and that the activities of the transcriptionally induced enzymes PARP7, PARP10, PARP12 and PARP14 are limited by cellular NAD and can be enhanced by pharmacological activation of NAD synthesis. We further demonstrate that infection with MHV induces a severe attack on host cell NAD+ and NADP+. Finally, we show that NAMPT activation, NAM, and NR dramatically decrease the replication of an MHV that is sensitive to PARP activity. These data suggest that the antiviral activities of noncanonical PARP isozyme activities are limited by the availability of NAD and that nutritional and pharmacological interventions to enhance NAD levels may boost innate immunity to coronaviruses

Kinetic and Desorption Study of Selected Bioactive Compounds on Mesoporous Starbons : A Comparison with Microporous-Activated Carbon

A series of experiments were conducted to determine the chemical and physical differences between varieties of Starbon and activated carbon (AC). The adsorption process for all materials followed pseudo second order kinetics. High levels of adsorption were obtained for all materials; AC showed low levels of desorption for all bioactives over multiple washings, whereas the Starbons showed elevated desorption over the course of multiple washings

Dynamics of circulating TNF during adalimumab treatment using a drug-tolerant TNF assay

Patients with rheumatoid arthritis (RA) can be successfully treated with tumor necrosis factor (TNF) inhibitors, including the monoclonal antibody adalimumab. Once in remission, a proportion of patients can successfully discontinue treatment, indicating that blocking TNF is no longer required for disease control. To explore the dynamics of circulating TNF during adalimumab treatment, we developed a competition enzyme-linked immunosorbent assay that can quantify TNF in the presence of large amounts of TNF inhibitor, i.e., a “drug-tolerant” assay. In 193 consecutive adalimumab-treated patients with RA, we demonstrated that circulating TNF increased in average of &gt;50-fold upon treatment and reached a stable concentration in time for most patients. A similar increase in TNF was found in 30 healthy volunteers after one dose of adalimumab. This implies that TNF in circulation during anti-TNF treatment is not primarily associated with disease activity. During treatment, TNF was in complex with adalimumab and could be recovered as inactive 3:1 adalimumab-TNF complexes. No quantitative association was found between TNF and adalimumab concentrations. Low TNF concentrations at week 4 were associated with a higher frequency of antidrug antibodies (ADAs) at subsequent time points, less frequent methotrexate use at baseline, and less frequent remission after 52 weeks. Also in healthy volunteers, early low TNF concentrations are associated with ADAs. In conclusion, longitudinal TNF concentrations are mostly stable during adalimumab treatment and may therefore not predict successful treatment discontinuation. However, early low TNF is strongly associated with ADA formation and may be used as timely predictor of nonresponse toward adalimumab treatment.</p