The role of SCL in haematopoiesis and leukaemogenesis

The fundamental question of how restriction of differentiation potential and activation of lineage-specific gene expression in progenitor cells are regulated is at the heart of research into the molecular mechanisms of biology. The basic helix-loop-helix (bHLH) transcription factor SCL/TAL-1 serves as a paradigm for a transcription factor with pivotal roles in haematopoietic stem cell (HSC) specification, maturation of haematopoietic lineages as well as T-cell leukaemogenesis. Interestingly, it has been described as both a transcriptional activator and a repressor. However, the molecular mechanisms conferring these opposing functions are currently unknown. As a first step towards characterising the role of SCL in haematopoiesis and leukaemogenesis, we performed a gain-of-function study using a transgenic mouse model over-expressing SCL. Although no leukaemia was observed, constitutive expression of SCL or a mutant lacking the DNA binding domain in HSCs and early progenitors caused a severe defect in T- and B-lymphopoiesis. This was likely due to an interaction with the important lymphoid regulator and SCL heterodimerisation partner E2A. Then, we set up a proteomics strategy to identify protein partners of SCL in haematopoiesis. We isolated SCL-containing protein complexes in erythroid cells and megakaryocytes using a novel purification strategy based on in vivo biotinylation of SCL. Mass spectrometry analysis led to the identification of several previously unknown candidate partners including ETO-2, a member of the ETO family of co-repressor proteins and SSDP2, a partner of LDB-1. Using several different approaches, we validated the SCL/ETO-2 interaction in cell lines as well as primary erythrocytes and megakaryocytes. We then identified Gfi-1 b, a critical regulator of erythropoiesis with repressive function and the co-repressor mSin3A as additional partners of SCL and ETO-2 in erythroid cells, but not megakaryocytes. Further characterisation in transactivation experiments and during in vitro differentiation of primary fetal liver cells led us to hypothesise that, in early erythropoiesis, ETO-2 might confer a repressive function to SCL. In conclusion, this study gives a first insight into how the composition of the multimeric protein complexes including SCL might modulate haematopoietic differentiation and cell fate decision

Multivariate Prediction of Total Water Storage Changes Over West Africa from Multi-Satellite Data

West African countries have been exposed to changes in rainfall patterns over the last decades, including a significant negative trend. This causes adverse effects on water resources of the region, for instance, reduced freshwater availability. Assessing and predicting large-scale total water storage (TWS) variations are necessary for West Africa, due to its environmental, social, and economical impacts. Hydrological models, however, may perform poorly over West Africa due to data scarcity. This study describes a new statistical, data-driven approach for predicting West African TWS changes from (past) gravity data obtained from the gravity recovery and climate experiment (GRACE), and (concurrent) rainfall data from the tropical rainfall measuring mission (TRMM) and sea surface temperature (SST) data over the Atlantic, Pacific, and Indian Oceans. The proposed method, therefore, capitalizes on the availability of remotely sensed observations for predicting monthly TWS, a quantity which is hard to observe in the field but important for measuring regional energy balance, as well as for agricultural, and water resource management.Major teleconnections within these data sets were identified using independent component analysis and linked via low-degree autoregressive models to build a predictive framework. After a learning phase of 72 months, our approach predicted TWS from rainfall and SST data alone that fitted to the observed GRACE-TWS better than that from a global hydrological model. Our results indicated a fit of 79 % and 67 % for the first-year prediction of the two dominant annual and inter-annual modes of TWS variations. This fit reduces to 62 % and 57 % for the second year of projection. The proposed approach, therefore, represents strong potential to predict the TWS over West Africa up to 2 years. It also has the potential to bridge the present GRACE data gaps of 1 month about each 162days as well as a—hopefully—limited gap between GRACE and the GRACE follow-on mission over West Africa. The method presented could also be used to generate a near real-time GRACE forecast over the regions that exhibit strong teleconnections

Assessing the morphodynamic response of a New England beach-barrier system to an artificial reef

As a result of climate change and the ensuing accelerating sea level rise, the Ninigret Trustom Pond beach barrier system, located along the southern shore of Rhode Island, USA, has become increasingly vulnerable to tropical storms, hurricanes, and Nor\u27easters affecting the region. In this work, we explore the ability of a segmented artificial reef (AR) to protect the Ninigret Trustom Pond beach barrier system, by reducing the incident wave energy and ultimately the beach erosion. A set of nine AR concepts are selected, which are predicted to be accretive based on Ranasinghe et al.’s (2010) design criterion (RVB), extended by van der Baan (2013) to apply to segmented submerged breakwaters. The effectiveness of each concept is then assessed through numerical simulations, for both average wave climate conditions and storm events, with and without sea level rise, using the 2D morphodynamic model XBeach. The AR concepts are evaluated based on their ability to reduce coastal erosion during the storm events, including with a near future sea level rise of 0.31 m (scenario based on local prediction by 2050 relative to 2020 following the intermediate NOAA scenario), while ensuring a slightly accretive behavior in average wave conditions. The reduction of the coastal erosion during the storm events is quantified by comparing the subaerial eroded volume at the site, with or without sea level rise, when implementing each of the nine pre-selected AR concepts. While all concepts are found to protect the shoreline during storm events, including with the 0.31 m sea level rise scenario, four of the nine AR concepts, pre-selected to be accretive based on the RVB criterion, are found to be erosive in average conditions. Assuming a given submergence level, the distance to the shoreline and the AR lateral confinement ratio, LC, (gap width to length ratio of the segments) are the main controlling parameter

Handreichungen fuer die berufs- und arbeitspaedagogische Ausbilderqualifizierung Ergebnisse aus dem Modellversuch Sozialvertraegliche Technikgestaltung als Gegenstand der Ausbildung der Ausbilder ; 5 Themenbereiche

IAB-94-179-55 BB 182 (1) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

REINFORCING ECOSYSTEM ENGINEERS WITH ENHANCED VEGETATION AND AN ARTIFICIAL REEF ALONG THE US RHODE ISLAND COASTAL BARRIER SYSTEMS

Beach barrier systems (BBS) act as “ecosystem engi-neers” (EE), protecting the mainland and back bays from direct wave impact and reducing storm surge and flow passing through their inlets. BBS naturally adapt to slowly evolving wave climates by regressing or transgressing. However, observations show that BBS have been destabilized during past periods of fast changes in sea level or wave climate, potentially leading to drowning of the barrier. In this respect, current predictions of large changes in future Sea Level Rise (SLR) and wave climate, combined with anthropogenic effects, are concerning as these could challenge the natural adaptability of BBS. This raises the following questions: (1) can the future protective ability of local EE be predicted? (2) can the added benefits of implementing selected Nature Based Solutions (NbS) to enhance this natural protective ability be quantified, as well as their potentially negative feedback effects? In this study, these questions are considered for the south shore of Rhode Island (RI) through numerical modeling, in part based on earlier regional storm hazard assessment (Grilli et al., 2020). Specifically, here, as part of a NOAA project (“Effects of Sea-Level Rise 2021, Coastal Resilience” program), we assess the efficiency of NbS in changing climate conditions, while integrating local concerns, observed trends, and supporting local ecosystem and people’s way of life

REeal data AnaLysis GOCE Gravity field determination from GOCE

The Earth's gravity field is determined within the BMBF project REeal data AnaLysis GOCE (REALGOCE)