LSD1 controls metastasis of androgen-independent prostate cancer cells through PXN and LPAR6

Lysine-specific demethylase 1 (LSD1) was shown to control gene expression and cell proliferation of androgen-dependent prostate cancer (PCa) cells, whereas the role of LSD1 in androgen-independent metastatic prostate cancer remains elusive. Here, we show that depletion of LSD1 leads to increased migration and invasion of androgen-independent PCa cells. Transcriptome and cistrome analyses reveal that LSD1 regulates expression of lysophosphatidic acid receptor 6 (LPAR6) and cytoskeletal genes including the focal adhesion adaptor protein paxillin (PXN). Enhanced LPAR6 signalling upon LSD1 depletion promotes migration with concomitant phosphorylation of PXN. In mice LPAR6 overexpression enhances, whereas knockdown of LPAR6 abolishes metastasis of androgen-independent PCa cells. Taken together, we uncover a novel mechanism of how LSD1 controls metastasis and identify LPAR6 as a promising therapeutic target to treat metastatic prostate cancer

On mapping seafloor mineral deposits with central loop transient electromagnetics

Electromagnetic methods are commonly employed in exploration for land-based mineral deposits. A suite of airborne, land, and borehole electromagnetic techniques consisting of different coil and dipole configurations have been developed over the last few decades for this purpose. In contrast, although the commercial value of marine mineral deposits has been recognized for decades, the development of suitable marine electromagnetic methods for mineral exploration at sea is still in its infancy. One particularly interesting electromagnetic method, which could be used to image a mineral deposit on the ocean floor, is the central loop configuration. Central loop systems consist of concentric transmitting and receiving loops of wire. While these types of systems are frequently used in land-based or airborne surveys, to our knowledge neither system has been used for marine mineral exploration. The advantages of using central loop systems at sea are twofold: (1) simplified navigation, because the transmitter and receiver are concentric, and (2) simplified operation because only one compact unit must be deployed. We produced layered seafloor type curves for two particular types of central loop methods: the in-loop and coincident loop configurations. In particular, we consider models inspired by real marine mineral exploration scenarios consisting of overburdens 0 to 5 m thick overlying a conductive ore body 5 to 30 m thick. Modeling and resolution analyses showed that, using a 50 m(2) transmitting loop with 20 A of current, these two configurations are useful tools to determine the overburden depth to a conductive ore deposit and its thickness. In the most extreme case, absolute voltage errors on the order of 10 nV are required to resolve the base of a 30 m thick ore deposit. Whether such noise floors can be achieved in real marine environments remains to be seen

Marine dipole–dipole controlled source electromagnetic and coincident-loop transient electromagnetic experiments to detect seafloor massive sulphides: effects of three-dimensional bathymetry

Seafloor massive sulphides (SMSs) are regarded as a potential future resource to satisfy the growing global demand of metals including copper, zinc and gold. Aside from mining and retrieving profitable amounts of massive sulphides from the seafloor, the present challenge is to detect and delineate significant SMS accumulations, which are generally located near mid-ocean ridges and along submarine volcanic arc and backarc spreading centres. Currently, several geophysical technologies are being developed to detect and quantify SMS occurrences that often exhibit measurable contrasts in their physical parameters compared to the surrounding host rock. Here, we use a short, fixed-offset controlled source electromagnetic (CSEM) system and a coincident-loop transient electromagnetic (TEM) system, which in theory allow the detection of SMS in the shallow seafloor due to a significant electrical conductivity contrast to their surroundings. In 2016, CSEM and TEM experiments were carried out at several locations near the Trans-Atlantic Geotraverse hydrothermal field to investigate shallow occurrences of massive sulphides below the seafloor. Measurements were conducted in an area that contains distinct SMS sites located several kilometres off-axis from the Mid-Atlantic ridge, some of which are still connected to hydrothermal activity and others where hydrothermal activity has ceased. Based on the quality of the acquired data, both experiments were operationally successful. However, the data analysis indicates bias caused by three-dimensional (3D) effects of the rough bathymetry in the study area and, thus, data interpretation remains challenging. Therefore, we study the influence of 3D bathymetry for marine CSEM and TEM experiments, focusing on shallow 3D conductors located beneath mound-like structures. We analyse synthetic inversion models for attributes associated with 3D distortions of CSEM and TEM data that are not sufficiently accounted for in conventional 1D (TEM) and 2D (CSEM) interpretation schemes. Before an adequate quantification of SMS in the region is feasible, these 3D effects need to be studied to avoid over/underestimation of SMS using the acquired EM data. The sensitivity of CSEM and TEM to bathymetry is investigated by means of 3D forward modelling, followed by 1D (TEM) and 2D (CSEM) inversion of the synthetic data using realistic error conditions. Subsequently, inversion models of the synthetic 3D data are analysed and compared to models derived from the measured data to illustrate that 3D distortions are evident in the recorded data sets

Tectonic Controls on Gas Hydrate Distribution off SW Taiwan

The northern part of the South China Sea is characterized by widespread occurrence of bottom simulating reflectors (BSR) indicating the presence of marine gas hydrate. Because the area covers both a tectonically inactive passive margin and the termination of a subduction zone, the influence of tectonism on the dynamics of gas hydrate systems can be studied in this region. Geophysical data show that there are multiple thrust faults on the active margin while much fewer and smaller faults exist in the passive margin. This tectonic difference matches with a difference in the geophysical characteristics of the gas hydrate systems. High hydrate saturation derived from ocean bottom seismometer data and controlled source electromagnetic data and conspicuous high‐amplitude reflections in P‐Cable 3D seismic data above the BSR are found in the anticlinal ridges of the active margin. In contrast all geophysical evidence for the passive margin points to normal to low hydrate saturations. Geochemical analyses of gas samples collected at seep sites on the active margin show methane with heavy δ13C isotope composition, while gas collected at the passive margin shows light carbon isotope composition. Thus, we interpret the passive margin as a typical gas hydrate province fuelled by biogenic production of methane and the active margin gas hydrate system as a system that is fuelled not only by biogenic gas production but also by additional advection of thermogenic methane from the subduction system

Lysine-specific demethylase 1 regulates differentiation onset and migration of trophoblast stem cells

Propagation and differentiation of stem cell populations are tightly regulated to provide sufficient cell numbers for tissue formation while maintaining the stem cell pool. Embryonic parts of the mammalian placenta are generated from differentiating trophoblast stem cells (TSCs) invading the maternal decidua. Here we demonstrate that lysine-specific demethylase 1 (Lsd1) regulates differentiation onset of TSCs. Deletion of Lsd1 in mice results in the reduction of TSC number, diminished formation of trophectoderm tissues and early embryonic lethality. Lsd1-deficient TSCs display features of differentiation initiation, including alterations of cell morphology, and increased migration and invasion. We show that increased TSC motility is mediated by the premature expression of the transcription factor Ovol2 that is directly repressed by Lsd1 in undifferentiated cells. In summary, our data demonstrate that the epigenetic modifier Lsd1 functions as a gatekeeper for the differentiation onset of TSCs, whereby differentiation-associated cell migration is controlled by the transcription factor Ovol2

Tectonic Controls on Gas Hydrate Distribution off SW of Taiwan

The northern part of the South China Sea is characterized by wide-spread occurrence of bottom simulating reflectors (BSR), indicating the presence of marine gas hydrates. Because the area covers both the tectonically inactive passive margin and the northern termination of the Manila Trench subduction zone while sediment input is broadly similar, this area provides an excellent opportunity to study the influence of tectonic processes on the dynamics of gas hydrate systems. Long-offset multi-channel seismic data show that movement along thrust faults and blind thrust faults caused anticlinal ridges on the active margin, while faults are absent on the passive margin. This coincides with high-hydrate saturations derived from ocean bottom seismometer data and controlled source electromagnetic data, and conspicuous high-amplitude reflections in P-Cable 3D seismic data above the BSR in the anticlinal ridges of the active margin. On the contrary, all geophysical evidence for the passive margin points to normal- to low-hydrate saturations. Geochemical analysis of gas samples collected at seep sites on the active margin show methane with heavy δ13C isotope composition, while gas collected on the passive margin shows highly depleted (light) carbon isotope composition. Thus, we interpret the passive margin as a typical gas hydrate province fuelled by biogenic production of methane and the active margin gas hydrate system as a system that is fuelled not only by biogenic gas production but also by additional advection of thermogenic methane from the subduction system. The location of the highest gas hydrate saturations in the hanging wall next to the thrust faults suggests that the thrust faults represent pathways for the migration of methane. Our findings suggest that the most promising gas hydrate occurrences for exploitation of gas hydrate as an energy source may be found in the core of the active margin roll over anticlines immediately above the BSR and that high-amplitude reflections in the seismic reflection data may be a good proxy for these targets