Data-driven modeling predicts gene regulatory network dynamics during the differentiation of multipotential hematopoietic progenitors

Cellular differentiation during hematopoiesis is guided by gene regulatory networks (GRNs) comprising transcription factors (TFs) and the effectors of cytokine signaling. Based largely on analyses conducted at steady state, these GRNs are thought to be organized as a hierarchy of bistable switches, with antagonism between Gata1 and PU.1 driving red- and white-blood cell differentiation. Here, we utilize transient gene expression patterns to infer the genetic architecture—the type and strength of regulatory interconnections—and dynamics of a twelve-gene GRN including key TFs and cytokine receptors. We trained gene circuits, dynamical models that learn genetic architecture, on high temporal-resolution gene-expression data from the differentiation of an inducible cell line into erythrocytes and neutrophils. The model is able to predict the consequences of gene knockout, knockdown, and overexpression experiments and the inferred interconnections are largely consistent with prior empirical evidence. The inferred genetic architecture is densely interconnected rather than hierarchical, featuring extensive cross-antagonism between genes from alternative lineages and positive feedback from cytokine receptors. The analysis of the dynamics of gene regulation in the model reveals that PU.1 is one of the last genes to be upregulated in neutrophil conditions and that the upregulation of PU.1 and other neutrophil genes is driven by Cebpa and Gfi1 instead. This model inference is confirmed in an independent single-cell RNA-Seq dataset from mouse bone marrow in which Cebpa and Gfi1 expression precedes the neutrophil-specific upregulation of PU.1 during differentiation. These results demonstrate that full PU.1 upregulation during neutrophil development involves regulatory influences extrinsic to the Gata1-PU.1 bistable switch. Furthermore, although there is extensive cross-antagonism between erythroid and neutrophil genes, it does not have a hierarchical structure. More generally, we show that the combination of high-resolution time series data and data-driven dynamical modeling can uncover the dynamics and causality of developmental events that might otherwise be obscured.

Water quality response to hydropeaking regulation of the Three Gorges Dam and Gezhouba Dam, China

Hydropeaking as the most prominent feature of flow alterations resulting from hydropower plants has received attention worldwide. Ramifications of hydropower on the downstream river systems mainly focus on hydrological regimes or long-term water quality changes. Exceptional knowledge is expected on the sub-daily changes of water qualities in the downstream river reach that is affected by the hydropeaking. In this study, we investigate the dynamics of hydropeaking and thermopeaking at the outlet of the Three Gorges Dam TGD using a high temporal resolution dataset, and inspect its association with water chemistry indices. Hourly measurements are analysed for the downstream station Yunchi , and compared with the upstream station Nanjinguan. The results show that along with water temperature, water quality indices such as dissolved oxygen, total Phosphorus, total nitrogen, PH, and electricity conductivity all show evident ‘peaking’ phenomenon in a short time. These divergent variations, however, are not valid for non-hydropeaking affected indicators including turbidity, permanganate index, and ammonia nitrogen. These hydropeaking-induced perturbations are mitigated by the flood control operation from July to September. This study demonstrates that water quality indices are sensitive to hydropeaking and thermopeaking with respect to the magnitude of change and the seasonal component during a year. The results provide additional evidence for the environmental impacts of hydropower regulation on the receiving river reach, and bridge the gap between hydropeaking studies and thermopeaking, and study water qualities variations that were seldom connected from the same temporal perspective in river research.

Development of 222Rn Emanation Sources with Integrated Quasi 2π Active Monitoring

In this work, a novel approach for the standardization of low-level 222Rn emanation is presented. The technique is based on the integration of a 222Rn source, directly, with an α-particle detector, which allows the residual 222Rn to be continuously monitored. Preparation of the device entails thermal physical vapor deposition of 226RaCl2 directly onto the surface of a commercially available ion implanted Si-diode detector, resulting in a thin-layer geometry. This enables continuous collection of well resolved α-particle spectra of the nuclei, decaying within the deposited layer, with a detection efficiency of approximately 0.5 in a quasi 2π geometry. The continuously sampled α-particle spectra are used to derive the emanation by statistical inversion. It is possible to achieve this with high temporal resolution due to the small background and the high counting efficiency of the presented technique. The emanation derived in this way exhibits a dependence on the relative humidity of up to 15% in the range from 20% rH to 90% rH. Traceability to the SI is provided by employing defined solid-angle α-particle spectrometry to characterize the counting efficiency of the modified detectors. The presented technique is demonstrated to apply to a range covering the release of at least 1 to 210 222Rn atoms per second, and it results in SI-traceable emanation values with a combined standard uncertainty not exceeding 2%. This provides a pathway for the realization of reference atmospheres covering typical environmental 222Rn levels and thus drastically improves the realization and the dissemination of the derived unit of the activity concentration concerning 222Rn in air.

Investigation on effect of transmit condition on ultrasonic measurement of 2D motion velocity

A phase-sensitive 2D motion estimator is useful for measurement of minute tissue motion. However, the effect of conditions for emission of ultrasonic waves on the accuracy of such an estimator has not been investigated thoroughly. In the present study, the accuracy of the phase-sensitive 2D motion estimator was evaluated under a variety of transmission conditions. Although plane wave imaging with a single emission per frame achieved an extremely high temporal resolution of 10417 Hz, the accuracy in estimation of lateral velocities was worse than compound-based method or focused-beam method. By contrast, the accuracy in estimation of axial velocities hardly depended on the transmission conditions. Also, the phase-sensitive 2D motion estimator was combined with the block matching method to estimate displacements larger than the ultrasonic wavelength. Furthermore, the results show that the correlation coefficient in block matching has potential to be used for evaluation of the reliability of the estimated velocity.

EUREC⁴A's <i>Maria S. Merian</i> ship-based cloud and micro rain radar observations of clouds and precipitation

As part of the EUREC4A field campaign, the research vessel Maria S. Merian probed an oceanic region between 6 to 13.8∘ N and 51 to 60∘ W for approximately 32 d. Trade wind cumulus clouds were sampled in the trade wind alley region east of Barbados as well as in the transition region between the trades and the intertropical convergence zone, where the ship crossed some mesoscale oceanic eddies. We collected continuous observations of cloud and precipitation profiles at unprecedented vertical resolution (7–10 m in the first 3000 m) and high temporal resolution (1–3 s) using a W-band radar and micro rain radar (MRR), installed on an active stabilization platform to reduce the impact of ship motions on the observations. The paper describes the ship motion correction algorithm applied to the Doppler observations to extract corrected hydrometeor vertical velocities and the algorithm created to filter interference patterns in the MRR observations. Radar reflectivity, mean Doppler velocity, spectral width and skewness for W-band and reflectivity, mean Doppler velocity, and rain rate for MRR are shown for a case study to demonstrate the potential of the high resolution adopted. As non-standard analysis, we also retrieved and provided liquid water path (LWP) from the 89 GHz passive channel available on the W-band radar system. All datasets and hourly and daily quicklooks are publically available, and DOIs can be found in the data availability section of this publication. Data can be accessed and basic variables can be plotted online via the intake catalog of the online book “How to EUREC4A”.

Retinal axial motion analysis and implications for real-time correction in human retinal imaging

High-resolution ophthalmic imaging devices including spectral-domain and full-field optical coherence tomography (SDOCT and FFOCT) are adversely affected by the presence of continuous involuntary retinal axial motion. Here, we thoroughly quantify and characterize retinal axial motion with both high temporal resolution (200,000 A-scans/s) and high axial resolution (4.5 um), recorded over a typical data acquisition duration of 3 s with an SDOCT device over 14 subjects. We demonstrate that although breath-holding can help decrease large-and-slow drifts, it increases small-and-fast fluctuations, which is not ideal when motion compensation is desired. Finally, by simulating the action of an axial motion stabilization control loop, we show that a loop rate of 1.2 kHz is ideal to achieve 100% robust clinical in-vivo retinal imaging.

Matching high resolution satellite data and flux tower footprints improves their agreement in photosynthesis estimates

Mapping canopy photosynthesis in both high spatial and temporal resolution is essential for carbon cycle monitoring in heterogeneous areas. However, well established satellites in sun-synchronous orbits such as Sentinel-2, Landsat and MODIS can only provide either high spatial or high temporal resolution but not both. Recently established CubeSat satellite constellations have created an opportunity to overcome this resolution trade-off. In particular, Planet Fusion allows full utilization of the CubeSat data resolution and coverage while maintaining high radiometric quality. In this study, we used the Planet Fusion surface reflectance product to calculate daily, 3-m resolution, gap-free maps of the near-infrared radiation reflected from vegetation (NIRvP). We then evaluated the performance of these NIRvP maps for estimating canopy photosynthesis by comparing with data from a flux tower network in Sacramento-San Joaquin Delta, California, USA. Overall, NIRvP maps captured temporal variations in canopy photosynthesis of individual sites, despite changes in water extent in the wetlands and frequent mowing in the crop fields. When combining data from all sites, however, we found that robust agreement between NIRvP maps and canopy photosynthesis could only be achieved when matching NIRvP maps to the flux tower footprints. In this case of matched footprints, NIRvP maps showed considerably better performance than in situ NIRvP in estimating canopy photosynthesis both for daily sum and data around the time of satellite overpass (R 2 = 0.78 vs. 0.60, for maps vs. in situ for the satellite overpass time case). This difference in performance was mostly due to the higher degree of consistency in slopes of NIRvP -canopy photosynthesis relationships across the study sites for flux tower footprint-matched maps. Our results show the importance of matching satellite observations to the flux tower footprint and demonstrate the potential of CubeSat constellation imagery to monitor canopy photosynthesis remotely at high spatio-temporal resolution.

The 2018 European heatwave led to stem dehydration but not to consistent growth reductions in forests

Heatwaves exert disproportionately strong and sometimes irreversible impacts on forest ecosystems. These impacts remain poorly understood at the tree and species level and across large spatial scales. Here, we investigate the effects of the record-breaking 2018 European heatwave on tree growth and tree water status using a collection of high-temporal resolution dendrometer data from 21 species across 53 sites. Relative to the two preceding years, annual stem growth was not consistently reduced by the 2018 heatwave but stems experienced twice the temporary shrinkage due to depletion of water reserves. Conifer species were less capable of rehydrating overnight than broadleaves across gradients of soil and atmospheric drought, suggesting less resilience toward transient stress. In particular, Norway spruce and Scots pine experienced extensive stem dehydration. Our high-resolution dendrometer network was suitable to disentangle the effects of a severe heatwave on tree growth and desiccation at large-spatial scales in situ, and provided insights on which species may be more vulnerable to climate extremes.

BrainQuake: An Open-Source Python Toolbox for the Stereoelectroencephalography Spatiotemporal Analysis

Intracranial stereoelectroencephalography (SEEG) is broadly used in the presurgical evaluation of intractable epilepsy, due to its high temporal resolution in neural activity recording and high spatial resolution within suspected epileptogenic zones. Neurosurgeons or technicians face the challenge of conducting a workflow of post-processing operations with the multimodal data (e.g., MRI, CT, and EEG) after the implantation surgery, such as brain surface reconstruction, electrode contact localization, and SEEG data analysis. Several software or toolboxes have been developed to take one or more steps in the workflow but without an end-to-end solution. In this study, we introduced BrainQuake, an open-source Python software for the SEEG spatiotemporal analysis, integrating modules and pipelines in surface reconstruction, electrode localization, seizure onset zone (SOZ) prediction based on ictal and interictal SEEG analysis, and final visualizations, each of which is highly automated with a user-friendly graphical user interface (GUI). BrainQuake also supports remote communications with a public server, which is facilitated with automated and standardized preprocessing pipelines, high-performance computing power, and data curation management to provide a time-saving and compatible platform for neurosurgeons and researchers.

A kinase translocation reporter reveals real-time dynamics of ERK activity in Drosophila

Extracellular Signal-Regulated Kinase (ERK) lies downstream of a core signalling cascade that controls all aspects of development and adult homeostasis. Recent developments have led to new tools to image and manipulate the pathway. However, visualising ERK activity in vivo with high temporal resolution remains a challenge in Drosophila. We adapted a kinase translocation reporter (KTR) for use in Drosophila, which shuttles out of the nucleus when phosphorylated by ERK. We show that ERK-KTR faithfully reports endogenous ERK signalling activity in developing and adult tissues, and that it responds to genetic perturbations upstream of ERK. Using ERK-KTR in time-lapse imaging, we made two novel observations: firstly, sustained hyperactivation of ERK by expression of dominant-active Epidermal Growth Factor Receptor raised the overall level but did not alter the kinetics of ERK activity; secondly, heterogeneity in ERK activity in retinal basal glia correlated with the direction of migration of individual cells. Our results show that KTR technology can be applied in Drosophila to monitor ERK activity in real-time and suggest that this modular tool can be further adapted to study other kinases.