Present state and future perspectives of using pluripotent stem cells in toxicology research

The use of novel drugs and chemicals requires reliable data on their potential toxic effects on humans. Current test systems are mainly based on animals or in vitro–cultured animal-derived cells and do not or not sufficiently mirror the situation in humans. Therefore, in vitro models based on human pluripotent stem cells (hPSCs) have become an attractive alternative. The article summarizes the characteristics of pluripotent stem cells, including embryonic carcinoma and embryonic germ cells, and discusses the potential of pluripotent stem cells for safety pharmacology and toxicology. Special attention is directed to the potential application of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) for the assessment of developmental toxicology as well as cardio- and hepatotoxicology. With respect to embryotoxicology, recent achievements of the embryonic stem cell test (EST) are described and current limitations as well as prospects of embryotoxicity studies using pluripotent stem cells are discussed. Furthermore, recent efforts to establish hPSC-based cell models for testing cardio- and hepatotoxicity are presented. In this context, methods for differentiation and selection of cardiac and hepatic cells from hPSCs are summarized, requirements and implications with respect to the use of these cells in safety pharmacology and toxicology are presented, and future challenges and perspectives of using hPSCs are discussed

Spontaneous succession of riparian fynbos: Is unassisted recovery a viable restoration strategy?

The invasion of alien trees is a major threat to the freshwater resources and biodiversity of South Africa. The Working for Water (WfW) Program was initiated in 1995 in order to control the growth and spread of woody alien species in riparian zones, but the extent to which the indigenous vegetation naturally recovers following alien clearance remains poorly understood. In this study spontaneous succession of riparian vegetation following wild fires and alien clearing was monitored over a number of years at two sites on the Cape Peninsula: a pine plantation in an upland plateau and an Acacia spp.-invaded valley floodplain. After clearing, the vegetation at the pine site was successfully recovering along a trajectory towards Afromontane forest and as a result it is suggested that no active restoration is required. By contrast, our results show that areas cleared of Acacia spp. may be less resilient, with extensive regeneration of woody aliens and only a negligible recovery of indigenous trees. We propose that the absence of riparian trees may have been responsible for precipitating the transition to a community dominated by weedy nitrophilous grasses, and find evidence that this may be perpetuated through the continued removal of Acacia spp. It is hypothesized that this grass-dominated state may be resilient to natural restoration and thus represents an additional constraint to the recovery of riparian communities. Under such circumstances, we argue that active restoration would be required in order to re-instate the riparian community. © 2008 SAAB

Using riparian plant species to locate the 1:2-year floodline on single channel rivers

Riparian zones can be characterised botanically into two main areas, a wet bank and a dry bank. these areas have been linked to the duration of inundation by river flow, the boundary between the two being the 1:2 year floodline. Therefore the wet bank is inundated regularly by small floods and the dry bank by larger, less frequent floods, and each may support one to a few distinct plant communities laterally up the bank. Understanding these plant distributions helps rehabilitation projects and Environmental flow (Eflows) studies as it can inform re-vegetation strategies in the former and help understanding of the links between plants and the river’s flow regime in the latter. Systematic sampling and data analysis methods were developed for single channel rivers with relatively undisturbed natural vegetation to identify and locate the different plant communities in the riparian zone. Generic rules using distance and height from the water’s edge, rather than the presence or absence of plant species, were calculated to locate the communities. While these statistics were derived from the riparian vegetation along perennial Western Cape rivers, South Africa, the methods could be applied to other perennial single channel river anywhere

The Elephant Marsh, Malawi – Part 2: two-dimensional hydrodynamic modelling in support of an eco-social assessment

The Elephant Marsh lies on the floodplain of the lower Shire River, in southern Malawi. It is both a cultivated, seasonal floodplain and a wetland, characterised by a complex mosaic of meandering channels, marshland and shallow lakes. In 2016, the Marsh was granted RAMSAR status based on a series of supporting studies, including the modelling of eco-social options for managing its ecological condition. This paper describes two-dimensional (2-D) hydrodynamic modelling using RMA2, in support of this eco-social assessment. the hydraulic model was parameterised using mostly existing data but augmented with bathymetric channel and lake surveys. Calibration and verification used water level data from the hydrometric network for the period 1999 to 2009. generally, observed water level time-series are well replicated in the model, but there are large discrepancies prior to this period. These are due to temporal changes in hydraulic controls, mainly sedimentation, but also breaching of an embankment at the downstream end of the Marsh. Selected hydraulic-habitat variables (based on daily hydrological time-series 1976 to 2009) provide the indictors of hydrological and hydraulic change used to inform a DRIFT eco-social assessment. The Marsh displays moderate flood attenuation characteristics, but the importance of this will likely increase under continued sedimentation and predicted climate futures, which include more severe storms. the 2-D modelling contributes to an improved understanding of the Marsh’s hydraulic behaviour, particularly regarding anthropogenic influences since the early 1900s

The Elephant Marsh, Malawi – Part 1: reconstruction of the historic hydromorphology

The Elephant Marsh lies on the floodplain of the lower Shire River, in southern Malawi. It is both a cultivated, seasonal floodplain and an area of permanent shallow lakes. The Marsh is highly biodiverse, has a productive fishery and supports the livelihoods of a large human population. Chronicles and hand-drawn sketches by 19th-century explorers and subsequent travellers describing the Marsh landscape were used to develop an account of the Marsh’s historic hydromorphology. these anecdotal accounts are supported by Shire River outflows from Lake Malawi, inferred from observed water levels in the lake from c. 1900. Records show that the Marsh has experienced regular periods of drying out, followed by periods of greater inundation than it currently experiences. Long-term hydrological trends have been accompanied by anthropogenic influences such as catchment degradation and embankment construction, which have altered sedimentation patterns in the Marsh. The Marsh exhibits traits of resilience to natural long-term climate change through its ability to return to a similar state during wet periods, even following prolonged dry periods. over relatively short time frames, however, the ecology of the Marsh, as described when it was declared a RAMSAR site in 2017, likely has low resistance to hydrological regimes that are sensitive to climate change. An appreciation of long-term climate and recent human-induced changes afforded a unique opportunity for contextualising its hydromorphological trends within the Anthropocene

BEYONDPLANCK

We constrained the level of polarized anomalous microwave emission (AME) on large angular scales using Planck Low-Frequency Instrument (LFI) and WMAP polarization data within a Bayesian cosmic microwave background (CMB) analysis framework. We modeled synchrotron emission with a power-law spectral energy distribution, as well as the sum of AME and thermal dust emission through linear regression with the Planck High-Frequency Instrument (HFI) 353 GHz data. This template-based dust emission model allowed us to constrain the level of polarized AME while making minimal assumptions on its frequency dependence. We neglected CMB fluctuations, but show through simulations that these fluctuations have a minor impact on the results. We find that the resulting AME polarization fraction confidence limit is sensitive to the polarized synchrotron spectral index prior. In addition, for prior means βsâ <â 3.1 we find an upper limit of pAMEmaxâ ²0.6% (95% confidence). In contrast, for means βsâ =â 3.0, we find a nominal detection of pAMEâ =â 2.5±1.0% (95% confidence). These data are thus not strong enough to simultaneously and robustly constrain both polarized synchrotron emission and AME, and our main result is therefore a constraint on the AME polarization fraction explicitly as a function of βs. Combining the current Planck and WMAP observations with measurements from high-sensitivity low-frequency experiments such as C-BASS and QUIJOTE will be critical to improve these limits further

BEYONDPLANCK

We present a Bayesian calibration algorithm for cosmic microwave background (CMB) observations as implemented within the global end-to-end BEYONDPLANCK framework and applied to the Planck Low Frequency Instrument (LFI) data. Following the most recent Planck analysis, we decomposed the full time-dependent gain into a sum of three nearly orthogonal components: one absolute calibration term, common to all detectors, one time-independent term that can vary between detectors, and one time-dependent component that was allowed to vary between one-hour pointing periods. Each term was then sampled conditionally on all other parameters in the global signal model through Gibbs sampling. The absolute calibration is sampled using only the orbital dipole as a reference source, while the two relative gain components were sampled using the full sky signal, including the orbital and Solar CMB dipoles, CMB fluctuations, and foreground contributions. We discuss various aspects of the data that influence gain estimation, including the dipole-polarization quadrupole degeneracy and processing masks. Comparing our solution to previous pipelines, we find good agreement in general, with relative deviations of 0.67% (0.84%) for 30 GHz, 0.12% (0.04%) for 44 GHz and 0.03% (0.64%) for 70 GHz, compared to Planck PR4 and Planck 2018, respectively. We note that the BEYONDPLANCK calibration was performed globally, which results in better inter-frequency consistency than previous estimates. Additionally, WMAP observations were used actively in the BEYONDPLANCK analysis, which both breaks internal degeneracies in the Planck data set and results in an overall better agreement with WMAP. Finally, we used a Wiener filtering approach to smoothing the gain estimates. We show that this method avoids artifacts in the correlated noise maps as a result of oversmoothing the gain solution, which is difficult to avoid with methods like boxcar smoothing, as Wiener filtering by construction maintains a balance between data fidelity and prior knowledge. Although our presentation and algorithm are currently oriented toward LFI processing, the general procedure is fully generalizable to other experiments, as long as the Solar dipole signal is available to be used for calibration