Identification of Neural Crest and Glial Enhancers at the Mouse Sox10 Locus through Transgenesis in Zebrafish

Sox10 is a dynamically regulated transcription factor gene that is essential for the development of neural crest–derived and oligodendroglial populations. Developmental genes often require multiple regulatory sequences that integrate discrete and overlapping functions to coordinate their expression. To identify Sox10 cis-regulatory elements, we integrated multiple model systems, including cell-based screens and transposon-mediated transgensis in zebrafish, to scrutinize mammalian conserved, noncoding genomic segments at the mouse Sox10 locus. We demonstrate that eight of 11 Sox10 genomic elements direct reporter gene expression in transgenic zebrafish similar to patterns observed in transgenic mice, despite an absence of observable sequence conservation between mice and zebrafish. Multiple segments direct expression in overlapping populations of neural crest derivatives and glial cells, ranging from pan-Sox10 and pan-neural crest regulatory control to the modulation of expression in subpopulations of Sox10-expressing cells, including developing melanocytes and Schwann cells. Several sequences demonstrate overlapping spatial control, yet direct expression in incompletely overlapping developmental intervals. We were able to partially explain neural crest expression patterns by the presence of head to head SoxE family binding sites within two of the elements. Moreover, we were able to use this transcription factor binding site signature to identify the corresponding zebrafish enhancers in the absence of overall sequence homology. We demonstrate the utility of zebrafish transgenesis as a high-fidelity surrogate in the dissection of mammalian gene regulation, especially those with dynamically controlled developmental expression

Causes and consequences of tipping points in river delta social-ecological systems

The sustainability of social-ecological systems within river deltas globally is in question as rapid development and environmental change trigger "negative” or “positive” tipping points depending on actors’ perspectives, e.g., regime shift from abundant sediment deposition to sediment shortage, agricultural sustainability to agricultural collapse or shift from rural to urban land. Using a systematic review of the literature, we show how cascading effects across anthropogenic, ecological, and geophysical processes have triggered numerous tipping points in the governance, hydrological and land use management of the world’s river deltas. Crossing tipping points had both positive and negative effects that generally enhanced economic development to the detriment of the environment. Assessment of deltas that featured prominently in the review revealed how outcomes of tipping points can inform the long-term trajectory of deltas towards sustainability or collapse. Management of key drivers at the delta scale can trigger positive tipping points to place social-ecological systems on a pathway towards sustainable development

Targeting Potential Drivers of COVID-19: Neutrophil Extracellular Traps

Coronavirus disease 2019 (COVID-19) is a novel, viral-induced respiratory disease that in ∼10-15% of patients progresses to acute respiratory distress syndrome (ARDS) triggered by a cytokine storm. In this Perspective, autopsy results and literature are presented supporting the hypothesis that a little known yet powerful function of neutrophils-the ability to form neutrophil extracellular traps (NETs)-may contribute to organ damage and mortality in COVID-19. We show lung infiltration of neutrophils in an autopsy specimen from a patient who succumbed to COVID-19. We discuss prior reports linking aberrant NET formation to pulmonary diseases, thrombosis, mucous secretions in the airways, and cytokine production. If our hypothesis is correct, targeting NETs directly and/or indirectly with existing drugs may reduce the clinical severity of COVID-19

Assessing Vulnerability and Risk to Livelihoods in River Deltas Socio-ecological Systems: Alignment of the GDRI With Global Frameworks’ Indicators

Disasters have significant impacts on the progress towards achieving the Sustainable Development Goals (SDGs). However, the interlinkage between sustainable development and disaster risk reduction is not considered enough in risk assessment tools. A greater alignment with global frameworks would ease the monitoring while increasing the capacity to address data availability issues for indicator-based assessments. To bridge this gap, we use the Global Delta Risk Index (GDRI), which is composed of multiple components to assess risks to livelihoods: hazards, vulnerability, and exposure of social-ecological systems. The modular library of indicators of the GDRI has been further aligned with the Sustainable Development Goals (SDG) and the Sendai Framework for Disaster and Risk Reduction (SFDRR). To improve the accuracy of the risk assessment, the list of indicators has been weighted and scored through consultation with stakeholders. This research presents the initial results of a multi-hazard risk assessment that encompasses SDG and SFDRR indicators in three Asian river deltas: Ganges-Brahmaputra-Meghna, Mekong and Red River. This work aims at better informing risk management and supporting delta-level interventions to influence progress towards sustainability and resilience of river deltas

Aligning the Global Delta Risk Index with SDG and SFDRR global frameworks to assess risk to socio-ecological systems in river deltas

River deltas globally are highly exposed and vulnerable to natural hazards and are often over-exploited landforms. The Global Delta Risk Index (GDRI) was developed to assess multi-hazard risk in river deltas and support decision-making in risk reduction interventions in delta regions. Disasters have significant impacts on the progress towards the Sustainable Development Goals (SDGs). However, despite the strong interlinkage between disaster risk reduction and sustainable development, global frameworks are still developed in isolation and actions to address them are delegated to different institutions. Greater alignment between frameworks would both simplify monitoring progress towards disaster risk reduction and sustainable development and increase capacity to address data gaps in relation to indicator-based assessments for both processes. This research aims at aligning the GDRI indicators with the SDGs and the Sendai Framework for Disaster and Risk Reduction (SFDRR). While the GDRI has a modular indicator library, the most relevant indicators for this research were selected through a delta-specific impact chain designed in consultation with experts, communities and stakeholders in three delta regions: the Red River and Mekong deltas in Vietnam and the Ganges–Brahmaputra–Meghna (GBM) delta in Bangladesh and India. We analyse how effectively the 143 indicators for the GDRI match (or not) the SDG and SFDRR global frameworks. We demonstrate the interconnections of the different drivers of risk to better inform risk management and in turn support delta-level interventions towards improved sustainability and resilience of these Asian mega-deltas

Discovery of VHE gamma-rays from the high-frequency-peaked BL Lac object RGB J0152+017

Aims: The BL Lac object RGB J0152+017 (z=0.080) was predicted to be a very high-energy (VHE; > 100 GeV) gamma-ray source, due to its high X-ray and radio fluxes. Our aim is to understand the radiative processes by investigating the observed emission and its production mechanism using the High Energy Stereoscopic System (H.E.S.S.) experiment. Methods: We report recent observations of the BL Lac source RGB J0152+017 made in late October and November 2007 with the H.E.S.S. array consisting of four imaging atmospheric Cherenkov telescopes. Contemporaneous observations were made in X-rays by the Swift and RXTE satellites, in the optical band with the ATOM telescope, and in the radio band with the Nancay Radio Telescope. Results: A signal of 173 gamma-ray photons corresponding to a statistical significance of 6.6 sigma was found in the data. The energy spectrum of the source can be described by a powerlaw with a spectral index of 2.95+/-0.36stat+/-0.20syst. The integral flux above 300 GeV corresponds to ~2% of the flux of the Crab nebula. The source spectral energy distribution (SED) can be described using a two-component non-thermal synchrotron self-Compton (SSC) leptonic model, except in the optical band, which is dominated by a thermal host galaxy component. The parameters that are found are very close to those found in similar SSC studies in TeV blazars. Conclusions: RGB J0152+017 is discovered as a source of VHE gamma-rays by H.E.S.S. The location of its synchrotron peak, as derived from the SED in Swift data, allows clearly classification it as a high-frequency-peaked BL Lac (HBL).Comment: Accepted for publication in A&A Letters (5 pages, 4 figures

H.E.S.S. observations of gamma-ray bursts in 2003-2007

Very-high-energy (VHE; >~100 GeV) gamma-rays are expected from gamma-ray bursts (GRBs) in some scenarios. Exploring this photon energy regime is necessary for understanding the energetics and properties of GRBs. GRBs have been one of the prime targets for the H.E.S.S. experiment, which makes use of four Imaging Atmospheric Cherenkov Telescopes (IACTs) to detect VHE gamma-rays. Dedicated observations of 32 GRB positions were made in the years 2003-2007 and a search for VHE gamma-ray counterparts of these GRBs was made. Depending on the visibility and observing conditions, the observations mostly start minutes to hours after the burst and typically last two hours. Results from observations of 22 GRB positions are presented and evidence of a VHE signal was found neither in observations of any individual GRBs, nor from stacking data from subsets of GRBs with higher expected VHE flux according to a model-independent ranking scheme. Upper limits for the VHE gamma-ray flux from the GRB positions were derived. For those GRBs with measured redshifts, differential upper limits at the energy threshold after correcting for absorption due to extra-galactic background light are also presented.Comment: 9 pages, 4 tables, 3 figure

Biodistribution, clearance, and long‐term fate of clinically relevant nanomaterials

Realization of the immense potential of nanomaterials for biomedical applications will require a thorough understanding of how they interact with cells, tissues, and organs. There is evidence that, depending on their physicochemical properties and subsequent interactions, nanomaterials are indeed taken up by cells. However, the subsequent release and/or intracellular degradation of the materials, transfer to other cells, and/or translocation across tissue barriers are still poorly understood. The involvement of these cellular clearance mechanisms strongly influences the long-term fate of used nanomaterials, especially if one also considers repeated exposure. Several nanomaterials, such as liposomes and iron oxide, gold, or silica nanoparticles, are already approved by the American Food and Drug Administration for clinical trials; however, there is still a huge gap of knowledge concerning their fate in the body. Herein, clinically relevant nanomaterials, their possible modes of exposure, as well as the biological barriers they must overcome to be effective are reviewed. Furthermore, the biodistribution and kinetics of nanomaterials and their modes of clearance are discussed, knowledge of the long-term fates of a selection of nanomaterials is summarized, and the critical points that must be considered for future research are addressed

Discovery of very-high-energy gamma-ray emission from the vicinity of PSR J1913+1011 with H.E.S.S

The H.E.S.S. experiment, an array of four Imaging Atmospheric Cherenkov Telescopes with high sensitivity and large field-of-view, has been used to search for emitters of very-high-energy (VHE, >100 GeV) gamma-rays along the Galactic plane, covering the region 30 deg < l < 60 deg, 280 deg < l < 330 deg, and -3 deg < b < 3 deg. In this continuation of the H.E.S.S. Galactic Plane Scan, a new extended VHE gamma-ray source was discovered at alpha(2000)=19h12m49s, delta(2000)=+10d09'06'' (HESS J1912+101). Its integral flux between 1-10 TeV is ~10% of the Crab Nebula flux in the same energy range. The measured energy spectrum can be described by a power law with a photon index Gamma = 2.7+-0.2(stat)+-0.3(sys). HESS J1912+101 is plausibly associated with the high spin-down luminosity pulsar PSR J1913+1011. We also discuss associations with an as yet unconfirmed SNR candidate proposed from low frequency radio observation and/or with molecular clouds found in 13CO data.Comment: 6 pages, 2 figures; Accepted for publication in A&A on February 20, 200

Upper Limits from HESS AGN Observations in 2005-2007

AIMS: Very high energy (VHE; E>100 GeV) gamma-ray studies were performed for 18 active galactic nuclei (AGN) from a variety of AGN classes. METHODS: VHE observations of a sample of 14 AGN, considered candidate VHE emitters, were made with the High Energy Stereoscopic System (HESS) between January 2005 and July 2007. Large-zenith-angle observations of three northern AGN (Mkn 421, Mkn 501, 1ES 1218+304), known to emit VHE gamma rays, were also performed in order to sample their spectral energy distributions (SEDs) above 1 TeV. In addition, the VHE flux from 1ES 1101-232, previously detected by HESS in 2004-2005, was monitored during 2006 and 2007. RESULTS: As significant detections from the HESS observation program are reported elsewhere, the results reported here are primarily integral flux upper limits. The average exposure for each of the 14 VHE-candidate AGN is ~7 h live time, and the observations have an average energy threshold between 230 GeV and 590 GeV. Upper limits for these 14 AGN range from <0.9% to <4.9% of the Crab Nebula flux, and eight of these are the most constraining ever reported for the object. The brief (<2.2 h each) large-zenith-angle observations yield upper limits for Mkn 501 (<20% Crab above 2.5 TeV) and 1ES 1218+304 (<17% Crab above 1.0 TeV), and a marginal detection (3.5 sigma) of Mkn 421 (50% Crab above 2.1 TeV). 1ES 1101-232 was marginally detected (3.6 sigma, 1.7% Crab above 260 GeV) during the 2006 (13.7 h live time) observations, but not in the 2007 (4.6 h live time) data. The upper limit in 2007 (<1.9% Crab above 260 GeV) is below the average flux measured by HESS from 2004-2006.Comment: 8 Pages, 2 Figures; Accepted on Nov 6, 2007 for publication in Astronomy & Astrophysic