Characterization of the C17.2 Cell Line as Test System for Endocrine Disruption-Induced Developmental Neurotoxicity

Hormone signaling plays an essential role during fetal life and is vital for brain development. Endocrine-disrupting chemicals can interfere with the hormonal milieu during this critical time-period, disrupting key neurodevelopmental processes. Hence, there is a need for the development of assays that evaluate developmental neurotoxicity (DNT) induced by an endocrine mode of action. Herein, we evaluated the neural progenitor C17.2 cell line as an in vitro test system to aid in the detection of endocrine disruption-induced DNT. For this, C17.2 cells were exposed during 10 days of differentiation to agonists and antagonists of the thyroid hormone (THR), glucocorticoid (GR), retinoic acid (RAR), retinoic x (RXR), oxysterol (LXR), estrogen (ER), androgen (AR), and peroxisome proliferator activated delta (PPARβ/δ) receptors, as well as to the agonist of the vitamin D (VDR) receptor. Upon exposure and differentiation, neuronal morphology (neurite outgrowth and branching) and the percentage of neurons in culture were assessed by immunofluorescence. For this, the cells were stained for βIII-tubulin (neuronal marker). C17.2 cells decreased neurite outgrowth and branching in response to RAR, RXR and PPARβ/δ agonists. Exposure to the GR agonist increased the number of cells differentiating into neurons, while exposure to the RXR agonist had the opposite effect. With this approach, we demonstrate that C17.2 cells are responsive to GR, RAR, RXR, and PPARβ/δ agonists and hence could be useful to develop a test system for hazard assessment of endocrine disruption-induced DNT.</p

Belimumab concentrations and immunogenicity in relation to drug effectiveness and safety in SLE within a Swedish real-world setting

OBJECTIVE: Studies supporting therapeutic drug monitoring to biopharmaceuticals in systemic lupus erythematosus (SLE) are scarce. We aimed to assess anti-drug antibody (ADA) occurrence in belimumab-treated SLE patients and associations between belimumab concentrations and clinical response, serological outcomes, and adverse events.METHODS: We included 100 patients treated with intravenous belimumab. Clinical data and biological samples were collected at baseline and months 3, 6, 12, and 24. Belimumab levels were determined by quantitative sandwich ELISA, and ADA by an acid-dissociation radioimmunoassay. Clinical activity was evaluated with the SLE disease activity index 2000 (SLEDAI-2K), revised SLE activity measure (SLAM-R), and physician's global assessment (PhGA). Serological markers included C3, C4, and anti-dsDNA. We performed cross-sectional Spearman's rank correlation analyses, and longitudinal analyses using generalised estimating equations.RESULTS: Belimumab concentrations varied widely (median: 25.8; IQR: 20.9-43.5 μg/ml) but were stable over time at the group level. Pre-existing ADA were detected in 2 patients, but no patient developed ADA during follow-up. Belimumab levels moderately correlated with SLEDAI-2K (ρ: -0.37; p= 0.003) and PhGA (ρ: -0.41; p= 0.005) at month 6, while longitudinal analysis revealed a very weak association with SLEDAI-2K (β: -0.10; SE: 0.05; p= 0.031) and a weak association with SLAM-R (β: -0.32; SE: 0.13; p= 0.014). Despite moderate correlations between belimumab levels and serological markers at month 6, there were no associations in longitudinal analysis. There was no relationship between belimumab levels and adverse events.CONCLUSION: Belimumab yielded no immunogenicity. Belimumab levels were modestly associated with clinical activity but not with serological activity or adverse events.</p

The Effects of Fenobucarb on the Physiology, Behavior, and Growth of Silver Barb (Barbonymus gonionotus)

This study assessed the effects of fenobucarb (F) (1%, 10%, and 20% of the LC50-96h value) on the brain cholinesterase (AChE) activity, food intake (FI), feed conversion rate (FCR), and growth of silver barb (Barbonymus gonionotus, Bleeker, 1849). It also assessed the AChE inhibition levels that cause the abnormal swimming, behavior, and mortality of silver barb and how the feeding regime affects the recovery rate of the AChE activity. The results showed that the brain AChE inhibition increased with the F concentrations. It peaked after nine hours, at 73.6% and 79.7% for the two highest concentrations, and then the AChE activity started to recover. After 96 h, the inhibition level was still 11.8% in the fish exposed to the two lowest concentrations and 30.5% in the fish exposed to the highest concentrations. Even when placed in clean water, the inhibition level in the fish that were exposed to the highest concentrations and only fed every third day was 32% after 14 days. Although there were no differences in the feed intake at any time, the fish exposed to F had a higher FCR and a lower specific growth rate and weight compared to the control fish at the later stages of the experiment. Thus, although the use of F in rice farming in the Mekong Delta may not lead to direct fish kills, it impacts the growth and health of the fish, which could have negative implications for wild fish populations and the long-term production of healthy fish in the Mekong Delta.</p

Opening Up the Black Box of Knowledge Production in International Development : An Intervention from a Practice-Theoretical Perspective

The increased emphasis on results and evidence in international development has made practices such as planning, monitoring, reporting, and evaluation more important. These practices depend on knowledge production, involving the systematic collection and analysis of data and information. As such, development practice follows a general trend in international politics where problems of global concern are increasingly subject to various forms of knowledge production by expert institutions. However, development research rarely treats knowledge production as a study object in itself. Consequently, this research note proposes a research agenda to open up the black box of knowledge production in international development. This research agenda mobilizes a burgeoning practice-theoretical literature, which international relations scholars have increasingly turned to in order to examine the practices of knowledge production that render problems and objects of global concern knowable and governable. I argue that practice-theoretical scholarship offers a conceptual vocabulary that allows for a systematic and critical examination of knowledge production in international development. Particularly, I contend that practice theory offers the analytical tools to: (1) identify the sites where knowledge production unfolds in international development, (2) analyze the mundane and routine practices of producing and communicating knowledge, and (3) investigate the political nature of knowledge production. This research agenda not only opens up the possibility to examine knowledge production in itself but also enables the deconstruction of its power-laden and colonial underpinnings.</p

Om behovet av samsyn och riktlinjer [Elektronisk resurs] : Fokusgruppsamtal om sexualitet och sexualundervisning i förskolan

On the Need for Consensus and Guidelines: Focus Group Discussions on Sexuality and Sexuality Education in Preschool.The article is based on a discourse analysis of focus group discussions with preschool practitioners in Sweden. It explores the professional considerations made in relation to children, sexuality, and Sexuality Education. Three subject positions emerge: the consensus-seeking teacher, characterized by uncertainty and a need for guidelines; the curriculum-oriented teacher, who uses the curriculum to support children’s rights; and the (reluctant) reporting teacher, who struggles between mandatory reporting and personal judgment. The study highlights the curriculum as a tool for professional competence, but that societal norms about children’s sexuality profoundly shape preschool practitioners’ professional considerations. This emphasizes the need for education and dialogue about children’s sexuality in preschool teacher education.</p

Open boundary conditions for nonlinear initial boundary value problems [Elektronisk resurs]

We present a straightforward energy stable weak implementation procedure of open boundary conditions for nonlinear initial boundary value problems. It is mathematically identical, reduces the number of parameters and simplifies previous work and its practical implementation.</p

Simulating nonadiabatic dynamics in benzophenone : Tracing internal conversion through photoelectron spectra <em aria-label="Open Access"></em>

Benzophenone serves as a prototype chromophore for studying the photochemistry of aromatic ketones, with applications ranging from biochemistry to organic light-emitting diodes. In particular, its intersystem crossing from the first singlet excited state to triplet states has been extensively studied, but experimental or theoretical studies on the preceding internal conversion within the singlet manifold are very rare. This relaxation mechanism is particularly important because direct population transfer of the first singlet excited state from the ground state is inefficient due to its low oscillator strength. In this work, our aim is to fill this gap by employing mixed quantum-classical and full quantum dynamics simulations and time-resolved photoelectron spectroscopy for gas-phase benzophenone and meta-methyl benzophenone. Our results show that nonadiabatic relaxation via conical intersections leads to an increase in the population of the first singlet excited state, which appears linear within the simulation time of 500 fs. This population transfer due to conical intersections can be directly detected by a bifurcation of the photoelectron signal. In addition, we discuss to clarify the role of the third singlet excited state degenerate to the second excited state—a topic that remains largely unexplored in the existing literature on benzophenone.</p

Integrative bioinformatics approaches reveal key hub genes in cyanobacteria : insights from <em>Synechocystis</em> sp. PCC 6803 and <em>Geminocystis</em> sp. NIES-3708 under abiotic stress conditions

Background  Cyanobacteria, particularly Synechocystis sp. PCC 6803, serve as model organisms for studying acclimation strategies that enable adaptation to various environmental stresses. Understanding the molecular mechanisms underlying these adaptations provides insight into how cells adjust gene expression in response to challenging conditions.Objective  To analyze the transcriptome data of Synechocystis sp. PCC 6803 under light, salinity, and iron stress conditions and to identify hub genes potentially involved in stress response, specifically comparing the findings with Geminocystis sp. NIES-3708.Methods  A comprehensive bioinformatics approach was applied, integrating meta-analysis, weighted gene co-expression network analysis (WGCNA), and a Random Forest (RF) machine learning algorithm. These approaches underscore the robustness of our findings, allowing for a more nuanced understanding of gene interactions and their functional relevance in stress responses. This methodology was used to identify key hub genes in Synechocystis sp. PCC 6803 that may have conserved roles in Geminocystis sp. NIES-3708. A total of four potential hub genes, including slr1392, slr1484, sll1549, and sll1863, were identified. Among these, only sll1549 had a homolog (GM3708_2556) with 71% sequence similarity and 70% query coverage in Geminocystis sp. NIES-3708. The expression of GM3708_2556 was further evaluated under nitrate, salt, and combined salinity-nitrate stress conditions using RT-qPCR.Results  Transcript levels of GM3708_2556 increased significantly under salt stress (3.35-fold, p-value &lt; 0.05) and combined salinity-nitrate stress (2.24-fold, p-value &lt; 0.05) compared to control conditions, while no significant change was observed under nitrate stress alone. These results suggest that GM3708_2556 may play a crucial role in the organism’s response to salt stress, with potential interactions in nitrate metabolism.Conclusion  This study highlights the gene GM3708_2556 as a significant factor in salt stress response, with implications for conserved functional roles across cyanobacterial species. Furthermore, the findings have potential relevance to biotechnology, particularly in engineering stress-resistant cyanobacterial strains for applications in sustainable agriculture and bioenergy production.</p