Integrated toxicity evaluation of a pulp deposit using organisms of different trophic levels

Purpose: In order to assess possible adverse effects originating from pulp deposits in a Swiss lake, a sediment quality triad approach was applied with chemical, ecotoxicological and ecological assessment methods. Materials and methods: To obtain an integrative picture of the potential ecotoxicological effects on organisms of different trophic levels, four test procedures were applied. The acute effects of pulp deposit pore water on a decomposer, the amphipod Gammarus fossarum, were monitored. Chronic toxicity of the pore water was evaluated on primary producers via a growth inhibition test with unicellular green algae (Pseudokirchneriella subcapitata) and on secondary consumers in a reproduction test with the water flea Ceriodaphnia dubia. To evaluate the effects of the pulp deposit on sediment inhabitants, a whole-life-cycle test with the non-biting midge Chironomus riparius was undertaken. Chemical assessment included dissolved organic carbon, extractable organic halogenic compounds, polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs) and heavy metals. The composition of the macrozoobenthos community was analysed in order to assess the ecological effects. Results and discussion: G. fossarum displayed increased locomotor activity at 12.5% but not at 25% sample concentration during a short-time exposure of 20h. Chronic effects compromised the reproduction and growth of C. dubia (lowest observed effect concentration, 12.5% sample concentration) with zero population growth in 100% pulp deposit pore water. In 100% pulp deposit, C. riparius exhibited increased mortality at 10 and 17days after oviposition. Pulp deposits of 50% and 100% concentration caused a significantly lower emergence compared with the reference treatments (lake sediment and quartz sand). Additionally, the locomotor activity of chironomids decreased significantly in 25-100% pulp deposit. No chronic effects of pulp deposit pore water on algae photosynthesis and growth could be detected. The bioassay results were in accordance with an elevated content of PAHs, PCBs and metals in the pulp deposit. Significantly more organisms known to be tolerant to organic pollution were present within the macrozoobenthos community. Conclusions: In general, for sediment inhabitants such as chironomids, the pulp deposit has to be classified toxic. In the present test setup, the toxicity of the pulp deposit was reflected better by the chronic test systems applied than by the acute ones. The applied testing framework could be a suitable tool to assess the risk of contaminated sites, and this information will help decide whether risk mitigation measures should be taken. In addition, with a similar approach, the success of any mitigation measures taken can be assesse

Recommendations, guidelines, and best practice for the use of human induced pluripotent stem cells for neuropharmacological studies of neuropsychiatric disorders

The number of individuals suffering from neuropsychiatric disorders (NPDs) has increased worldwide, with 3 million disability-adjusted life-years calculated in 2019. Though research using various approaches including genetics, imaging, clinical and animal models has advanced our knowledge regarding NPDs, we still lack basic knowledge regarding the underlying pathophysiological mechanisms. Moreover, there is an urgent need for highly effective therapeutics for NPDs. Human induced pluripotent stem cells (hiPSCs) generated from somatic cells enabled scientists to create brain cells in a patient-specific manner. However, there are challenges to the use of hiPSCs that need to be addressed. In the current paper, consideration of best practices for neuropharmacological and neuropsychiatric research using hiPSCs will be discussed. Specifically, we provide recommendations for best practice in patient recruitment, including collecting demographic, clinical, medical (before and after treatment and response), diagnostic (including scales) and genetic data from the donors. We highlight considerations regarding donor genetics and sex, in addition to discussing biological and technical replicates. Furthermore, we present our views on selecting control groups/lines, experimental designs, and considerations for conducting neuropharmacological studies using hiPSC-based models in the context of NPDs. In doing so, we explore key issues in the field concerning reproducibility, statistical analysis, and how to translate in vitro studies into clinically relevant observations. The aim of this article is to provide a key resource for hiPSC researchers to perform robust and reproducible neuropharmacological studies, with the ultimate aim of improving identification and clinical translation of novel therapeutic drugs for NPDs

Twenty-three unsolved problems in hydrology (UPH) – a community perspective

This paper is the outcome of a community initiative to identify major unsolved scientific problems in hydrology motivated by a need for stronger harmonisation of research efforts. The procedure involved a public consultation through on-line media, followed by two workshops through which a large number of potential science questions were collated, prioritised, and synthesised. In spite of the diversity of the participants (230 scientists in total), the process revealed much about community priorities and the state of our science: a preference for continuity in research questions rather than radical departures or redirections from past and current work. Questions remain focussed on process-based understanding of hydrological variability and causality at all space and time scales. Increased attention to environmental change drives a new emphasis on understanding how change propagates across interfaces within the hydrological system and across disciplinary boundaries. In particular, the expansion of the human footprint raises a new set of questions related to human interactions with nature and water cycle feedbacks in the context of complex water management problems. We hope that this reflection and synthesis of the 23 unsolved problems in hydrology will help guide research efforts for some years to come

Recommendations, guidelines, and best practice for the use of human induced pluripotent stem cells for neuropharmacological studies of neuropsychiatric disorders

The number of individuals suffering from neuropsychiatric disorders (NPDs) has increased worldwide, with 3 million disability-adjusted life-years calculated in 2019. Though research using various approaches including genetics, imaging, clinical and animal models has advanced our knowledge regarding NPDs, we still lack basic knowledge regarding the underlying pathophysiological mechanisms. Moreover, there is an urgent need for highly effective therapeutics for NPDs i. Human induced pluripotent stem cells (hiPSCs) generated from somatic cells enabled scientists to create brain cells in a patient-specific manner. However, there are challenges to the use of hiPSCs that need to be addressed. In the current paper, consideration of best practices for neuropharmacological and neuropsychiatric research using hiPSCs will be discussed. Specifically, we provide recommendations for best practice in patient recruitment, including collecting demographic, clinical, medical (before and after treatment and response), diagnostic (incl. scales) and genetic data from the donors. We highlight considerations regarding donor genetics and sex, in addition to discussing biological and technical replicates. Furthermore, we present our views on selecting control groups/lines, experimental designs, and considerations for conducting neuropharmacological studies using hiPSC-based models in the context of NPDs. In doing so, we explore key issues in the field concerning reproducibility, statistical analysis, and how to translate in vitro studies into clinically relevant observations. The aim of this article is to provide a key resource for hiPSC researchers to perform robust and reproducible neuropharmacological studies, with the ultimate aim of improving identification and clinical translation of novel therapeutic drugs for NPDs

4 Fachleute – 4 Strategien: Gonarthrose bei der Katze

Der Fall: Bei einer Katze wurde bei einer Lahmheitsuntersuchung (rechts stärker als links) eine Gonarthrose diagnostiziert. Was nun? Wie gehen Sie vor? Welche Möglichkeiten gibt es in Ihrem Fachgebiet

A Single MAPKKK Regulates the Hog1 MAPK Pathway in the Pathogenic Fungus Candida albicans

The Hog1 mitogen-activated protein kinase (MAPK) plays a central role in stress responses in the human pathogen Candida albicans. Here, we have investigated the MAPK kinase kinase (MAPKKK)-dependent regulation of the pathway. In contrast to the Hog1 pathway in Saccharomyces cerevisiae, which is regulated by three MAPKKKs (Ssk2, Ssk22, and Ste11), our results demonstrate that Hog1 in C. albicans is regulated by a single MAPKKK Ssk2. Deletion of SSK2 results in comparable stress and morphological phenotypes exhibited by hog1Δ cells, and Ssk2 is required for the stress-induced phosphorylation and nuclear accumulation of Hog1, and for Hog1-dependent gene expression. Furthermore, phenotypes associated with deletion of SSK2 can be circumvented by expression of a phosphomimetic mutant of the MAPKK Pbs2, indicating that Ssk2 regulates Hog1 via activation of Pbs2. In S. cerevisiae, the Hog1 pathway is also regulated by the MAPKKK Ste11. However, we can find no connection between Ste11 and the regulation of Hog1 in C. albicans. Furthermore, expression of a chimeric Pbs2 protein containing the Ste11-dependent regulatory region of S. cerevisiae Pbs2, fails to stimulate Ste11-dependent stress signaling in C. albicans. Collectively, our data show that Ssk2 is the sole MAPKKK to relay stress signals to Hog1 in C. albicans and that the MAPK signaling network in C. albicans has diverged significantly from the corresponding network in S. cerevisiae