ZNF750 is a lineage-specific tumour suppressor in squamous cell carcinoma.

ZNF750 controls epithelial homeostasis by regulating epidermal-differentiation genes, a role underscored by its pathogenic mutations in esophageal squamous cell cancers (SCCs). However, the precise role of ZNF750 in SCC cell biology remains unclear. In this study, we report that ZNF750 is exclusively deleted, mutated and underexpressed in human SCCs, and low ZNF750 expression is associated with poor survival. Restoration of wildtype, but not mutant ZNF750 protein uniquely inhibited the malignant phenotypes of SCC cells both in vitro and in vivo. Notably, ZNF750 promoted the expression of a long non-coding RNA (TINCR), which mediated both cancer-inhibition and differentiation-induction effects of ZNF750. In addition, ZNF750 potently suppressed cell migration by directly inhibiting the transactivation of LAMC2. Together, our findings characterize ZNF750 as a crucial SCC-specific suppressor and uncover its novel anticancer-associated functions

Globally altered epigenetic landscape and delayed osteogenic differentiation in H3.3-G34W-mutant giant cell tumor of bone

The neoplastic stromal cells of giant cell tumor of bone (GCTB) carry a mutation in H3F3A, leading to a mutant histone variant, H3.3-G34W, as a sole recurrent genetic alteration. We show that in patient-derived stromal cells H3.3-G34W is incorporated into the chromatin and associates with massive epigenetic alterations on the DNA methylation, chromatin accessibility and histone modification level, that can be partially recapitulated in an orthogonal cell line system by the introduction of H3.3-G34W. These epigenetic alterations affect mainly heterochromatic and bivalent regions and provide possible explanations for the genomic instability, as well as the osteolytic phenotype of GCTB. The mutation occurs in differentiating mesenchymal stem cells and associates with an impaired osteogenic differentiation. We propose that the observed epigenetic alterations reflect distinct differentiation stages of H3.3 WT and H3.3 MUT stromal cells and add to H3.3-G34W-associated changes

A Top-Down Methodology for Global Urban Air Mobility Demand Estimation

International audienceThe convergence of several key technologies during the past decade are enabling the ideation of new Urban Air Mobility (UAM) concepts of operations. UAM systems have the potential to bring significant improvements to the way people move and commute within cities and these include a reduction in commuting time, a reduction of roadway congestion, and a reduction of emissions. Understanding the potential demand for UAM services is crucial for the various stakeholders in order to ensure that the air traffic management systems, the regulations, and the supporting infrastructure are ready and do not slow down the introduction of these services. This paper presents a top-down methodology to estimate the demand for UAM transportation worldwide by estimating the travelers' willingness to pay for UAM services and by estimating the potential volume of UAM traffic. The exercise is implemented as a case study for a set of 31 cities distributed all across the world in 2035

A Methodology for Supersonic Commercial Market Estimation and Environmental Impact Evaluation (Part II)

Presented at AIAA Aviation Conference 2020With the increasing research efforts in civil supersonic transport (SST) during the past decade, companies like Boom and Aerion are making the comeback of civil supersonic flight more promising than ever. Both companies believe that substantial demand exists in civil supersonic aviation, and opportunities are present. However, many regulatory hurdles and operational constraints impose strict limitations on supersonic flight and should not be overlooked. In addition, these aircraft are likely to have higher fuel burn per passenger compared to that for similarly-sized subsonic aircraft, and their effect on fleet-level emissions is unknown. In Part I of this two-part study, the research team successfully demonstrated a methodology that employs a bottom-up approach for estimating the future demand for supersonic commercial operation and its associated fuel burn and CO2 emission, using only publicly available subsonic baseline-fleet data. This paper seeks to fill the gaps and assumptions identified in the Part I paper by using robust, non-public data, and provides updated results on market estimation and environmental impact (in terms of both CO2 and NOx) between 2035 and 2050.This project has received funding from the Clean Sky 2 (CS2) Joint Undertaking (JU) under grant agreement No.864521. The JU receives support from the European Union’s Horizon 2020 research and innovation programme and the Clean Sky 2 JU

Mutational and transcriptomic profiling of acute leukemia of ambiguous lineage reveals obscure but clinically important lineage bias

10.3324/haematol.2018.202911Haematologica1045e200-e20

Molecular mechanism and therapeutic implications of selinexor (KPT-330) in liposarcoma

10.18632/oncotarget.13485Oncotarget857521-753