Search

To enable selection of novel chemicals for new processes, there is a recognized need for alternative toxicity screening assays to assess potential risks to man and the environment. For human health hazard assessment these screening assays need to be translational to humans, have high throughput capability, and from an animal welfare perspective be harmonized with the principles of the 3Rs (Reduction, Refinement, Replacement). In the area of toxicology a number of cell culture systems are available but while these have some predictive value, they are not ideally suited for the prediction of developmental and reproductive toxicology (DART). This is because they often lack biotransformation capacity, multicellular or multi- organ complexity, for example, the hypothalamus pituitary gonad (HPG) axis and the complete life cycle of whole organisms. To try to overcome some of these limitations in this study, we have used Caenorhabditis elegans (nematode) and Danio rerio embryos (zebrafish) as alternative assays for DART hazard assessment of some candidate chemicals being considered for a new commercial application. Nematodes exposed to Piperazine and one of the analogs tested showed a slight delay in development compared to untreated animals but only at high concentrations and with Piperazine as the most sensitive compound. Total brood size of the nematodes was also reduced primarily by Piperazine and one of the analogs. In zebrafish Piperazine and analogs showed developmental delays. Malformations and mortality in individual fish were also scored. Significant malformations were most sensitively identified with Piperazine, significant mortality was only observed in Piperazine and only at the higest dose. Thus, Piperazine seemed the most toxic compound for both nematodes and zebrafish. The results of the nematode and zebrafish studies were in alignment with data obtained from conventional mammalian toxicity studies indicating that these have potential as developmental toxicity screening systems. The results of these studies also provided reassurance that none of the Piperazines tested are likely to have any significant developmental and/or reproductive toxicity issues to humans when used in their commercial applications. [ABSTRACT FROM AUTHOR]

Summary: The maintenance of stem cells in defined locations is crucial for all multicellular organisms. Although intrinsic factors and signals for stem cell fate have been identified in several species, it has remained unclear how these connect to the ability to reenter the cell cycle that is one of the defining properties of stem cells. We show that local reduction of expression of the RETINOBLASTOMA-RELATED (RBR) gene in Arabidopsis roots increases the amount of stem cells without affecting cell cycle duration in mitotically active cells. Conversely, induced RBR overexpression dissipates stem cells prior to arresting other mitotic cells. Overexpression of D cyclins, KIP-related proteins, and E2F factors also affects root stem cell pool size, and genetic interactions suggest that these factors function in a canonical RBR pathway to regulate somatic stem cells. Expression analysis and genetic interactions position RBR-mediated regulation of the stem cell state downstream of the patterning gene SCARECROW. [Copyright &y& Elsevier]

How cells acquire specific fates in conjunction with cell division is a major developmental question. In a recent issue of Nature, Caro and colleagues describe the Arabidopsis protein GEM, which interacts both with DNA-replication and transcriptional regulators (). The results are surprisingly reminiscent of the dual functions reported for Geminin in animals. [Copyright &y& Elsevier]

Human milk oligosaccharides (HMOs) belong to a group of multifunctional glycans that are abundantly present in human breast milk. While health effects of neutral oligosaccharides have been investigated extensively, a lot remains unknown regarding health effects of acidic oligosaccharides, such as the two sialyllactoses (SLs), 3′sialyllactose (3′SL), and 6′sialyllactose (6′SL). We utilized Caenorhabditis elegans (C. elegans) to investigate the effects of SLs on exercise performance. Using swimming as an endurance‐type exercise, we found that SLs decrease exhaustion, signifying an increase in endurance that is strongest for 6′SL. Through an unbiased metabolomics approach, we identified changes in energy metabolism that correlated with endurance performance. Further investigation suggested that these metabolic changes were related to adaptations of muscle mitochondria that facilitated a shift from beta oxidation to glycogenolysis during exercise. We found that the effect of SLs on endurance performance required AMPK‐ (aak‐1/aak‐2) and adenosine receptor (ador‐1) signaling. We propose a model where SLs alter the metabolic status in the gut, causing a signal from the intestine to the nervous system toward muscle cells, where metabolic adaptation increases exercise performance. Together, our results underline the potential of SLs in exercise‐associated health and contribute to our understanding of the molecular processes involved in nutritionally‐induced health benefits. [ABSTRACT FROM AUTHOR]

Klickt's? Zellen bauen extern zugegebene photoaktivierbare und für Klick ‐ Reaktionen geeignete Fettsäuren in verschiedenste bifunktionalisierte Phospholipide ein. Diese können durch UV ‐ Bestrahlung mit ihren Protein ‐ Bindungspartnern kovalent vernetzt werden. Die anschließende Markierung der „klickbaren“ Gruppe mit einem Reportermolekül ermöglicht die Identifizierung oder Visualisierung von Protein ‐ Lipid ‐ Interaktionen (siehe Schema). [ABSTRACT FROM AUTHOR]

Bifunctional lipid technology: Cells convert externally added photoactivatable and “clickable” fatty acids into a variety of bifunctional phospholipids that can be covalently linked to their protein‐binding partners by irradiation with UV light. Derivatization of the clickable group with a reporter molecule makes it possible to identify and image the lipid‐bound proteins in situ (see scheme). [ABSTRACT FROM AUTHOR]

Local accumulation of the plant growth regulator auxin mediates pattern formation in Arabidopsis roots and influences outgrowth and development of lateral root- and shoot-derived primordia. However, it has remained unclear how auxin can simultaneously regulate patterning and organ outgrowth and how its distribution is stabilized in a primordium-specific manner. Here we show that five PIN genes collectively control auxin distribution to regulate cell division and cell expansion in the primary root. Furthermore, the joint action of these genes has an important role in pattern formation by focusing the auxin maximum and restricting the expression domain of PLETHORA (PLT) genes, major determinants for root stem cell specification. In turn, PLT genes are required for PIN gene transcription to stabilize the auxin maximum at the distal root tip. Our data reveal an interaction network of auxin transport facilitators and root fate determinants that control patterning and growth of the root primordium. [ABSTRACT FROM AUTHOR]