Preparation and ferroelectric properties of (124)-oriented SrBi4Ti4O15 ferroelectric thin film on (110)-oriented LaNiO3 electrode

A (124)-oriented SrBi4Ti4O15 (SBTi) ferroelectric thin film with high volume fraction of {\alpha}SBTi(124)=97% was obtained using a metal organic decomposition process on SiO2/Si substrate coated by (110)-oriented LaNiO3 (LNO) thin film. The remanent polarization and coercive field for (124)-oriented SBTi film are 12.1 {\mu}C/cm2 and 74 kV/cm, respectively. No evident fatigue of (124)-oriented SBTi thin film can be observed after 1{\times}10e9 switching cycles. Besides, the (124)-oriented SBTi film can be uniformly polarized over large areas using a piezoelectric-mode atomic force microscope. Considering that the annealing temperature was 650{\deg}C and the thickness of each deposited layer was merely 30 nm, a long-range epitaxial relationship between SBTi(124) and LNO(110) facets was proposed. The epitaxial relationship was demonstrated based on the crystal structures of SBTi and LNO.Comment: 11 pages, 4 figures, published in Journal of Materials Science: Materials in Electronics (JMSE), 19 (2008), 1031-103

Structural and Energetic Mechanisms of Cooperative Autoinhibition and Activation of Vav1

SummaryVav proteins are guanine nucleotide exchange factors (GEFs) for Rho family GTPases. They control processes including T cell activation, phagocytosis, and migration of normal and transformed cells. We report the structure and biophysical and cellular analyses of the five-domain autoinhibitory element of Vav1. The catalytic Dbl homology (DH) domain of Vav1 is controlled by two energetically coupled processes. The DH active site is directly, but weakly, inhibited by a helix from the adjacent Acidic domain. This core interaction is strengthened 10-fold by contacts of the calponin homology (CH) domain with the Acidic, pleckstrin homology, and DH domains. This construction enables efficient, stepwise relief of autoinhibition: initial phosphorylation events disrupt the modulatory CH contacts, facilitating phosphorylation of the inhibitory helix and consequent GEF activation. Our findings illustrate how the opposing requirements of strong suppression of activity and rapid kinetics of activation can be achieved in multidomain systems

Loci-specific phase separation of FET fusion oncoproteins promotes gene transcription

Abnormally formed FUS/EWS/TAF15 (FET) fusion oncoproteins are essential oncogenic drivers in many human cancers. Interestingly, at the molecular level, they also form biomolecular condensates at specific loci. However, how these condensates lead to gene transcription and how features encoded in the DNA element regulate condensate formation remain unclear. Here, we develop an in vitro single-molecule assay to visualize phase separation on DNA. Using this technique, we observe that FET fusion proteins undergo phase separation at target binding loci and the phase separated condensates recruit RNA polymerase II and enhance gene transcription. Furthermore, we determine a threshold number of fusion-binding DNA elements that can enhance the formation of FET fusion protein condensates. These findings suggest that FET fusion oncoprotein promotes aberrant gene transcription through loci-specific phase separation, which may contribute to their oncogenic transformation ability in relevant cancers, such as sarcomas and leukemia

Radiobiosynthesis of paralytic shellfish toxins in the dinoflagellate alexandrium tamarense

Paralytic shellfish toxins (PSTs) are a family of neurotoxic alkaloids produced by certain dinoflagellates including strains of Alexandrium tamarense that are found in Hong Kong and South China coastal waters. The frequent occurrence of these toxins in commercial shellfish and other seafood is a serious food safety, economic and environmental problem worldwide. There is an urgent need for sufficient quantities of 14C-labeled PSTs for toxicological studies and other research and development uses. In the present study, we set out to 1) produce 14C-labeled PSTs using appropriate 14C-labled precursors in an optimized culture of a local strain of Alexandrium tamarense (ATCI01) that produced mostly C2 toxin (C2) and to 2) optimize the post-column reaction conditions for different PSTs to maximize the sensitivity of their detection using high performance liquid chromatography (HPLC). Screwed flasks were used as culture vessels to incorporate 14C from bicarbonate, acetate or arginine into C2. Nitrate, but not ammonium, was a good nitrogen source for the culture and was required for both growth and toxin productivity. Bicarbonate was essential for both algal growth and toxin biosynthesis. Acetate was toxic to the culture at relatively high concentrations. Arginine significantly enhanced both toxin yield and cellular toxin content, suggesting that it is a committed precursor in PST biosynthesis in dinoflagellates. The 14C-C2 produced was purified by column chromatography, which could be converted to obtain 14C-labeled C 1 , gonaytoxin (GTX) 2, and GTX3. Under the post column reaction conditions optimized for each of the different toxins, the specific activity of each was precisely determined by HPLC and scintillation counting. Several million dpm of14C-C2 toxin were produced and purified in the present study. These products are useful for metabolism studies and for calibrating the analytical PST standards available from commercial sources

Surface Deformation Associated with the 22 August 1902 Mw 7.7 Atushi Earthquake in the Southwestern Tian Shan, Revealed from Multiple Remote Sensing Data

The 22 August 1902 Mw 7.7 Atushi earthquake is the most disastrous seismic event in the southwestern Tian Shan. However, the spatial distribution of surface rupture zones as well as the geometric feature of surface deformation remain unclear, and the seismogenic fault is still controversial. Based on geologic and geomorphic interpretations of multiple remote sensing imaging data, high-resolution DEM data derived from UAV imaging complemented by field investigations, we mapped two sub-parallel NEE-trending surface rupture zones with a total length of 108 km. In addition, ~60 km and ~48 km surface rupture zones are distributed along the pre-existing Atushi fault (ATF) and the Keketamu fault (KTF), respectively. The surface deformations are mainly characterized as bedrock scarp, hanging wall collapse scarp, pressure ridge, and thrust-related fold scarps along the two south-dipping thrust faults, which are defined as the seismogenic structure of the 1902 Mw 7.7 Atushi earthquake. Thus, we proposed the cascading-rupture model to explain the multiple rupture zones generated by the 1902 Mw 7.7 Atushi earthquake. Moreover, the multiple advanced remote sensing mapping techniques can provide a promising approach to recover the geometric and geomorphic features of the surface deformation caused by large seismic events in the arid and semi-arid regions

Surface Deformation Associated with the 22 August 1902 Mw 7.7 Atushi Earthquake in the Southwestern Tian Shan, Revealed from Multiple Remote Sensing Data

The 22 August 1902 Mw 7.7 Atushi earthquake is the most disastrous seismic event in the southwestern Tian Shan. However, the spatial distribution of surface rupture zones as well as the geometric feature of surface deformation remain unclear, and the seismogenic fault is still controversial. Based on geologic and geomorphic interpretations of multiple remote sensing imaging data, high-resolution DEM data derived from UAV imaging complemented by field investigations, we mapped two sub-parallel NEE-trending surface rupture zones with a total length of 108 km. In addition, ~60 km and ~48 km surface rupture zones are distributed along the pre-existing Atushi fault (ATF) and the Keketamu fault (KTF), respectively. The surface deformations are mainly characterized as bedrock scarp, hanging wall collapse scarp, pressure ridge, and thrust-related fold scarps along the two south-dipping thrust faults, which are defined as the seismogenic structure of the 1902 Mw 7.7 Atushi earthquake. Thus, we proposed the cascading-rupture model to explain the multiple rupture zones generated by the 1902 Mw 7.7 Atushi earthquake. Moreover, the multiple advanced remote sensing mapping techniques can provide a promising approach to recover the geometric and geomorphic features of the surface deformation caused by large seismic events in the arid and semi-arid regions

Abnormal phase separation of biomacromolecules in human diseases

Membrane-less organelles (MLOs) formed through liquid-liquid phase separation (LLPS) are associated with numerous important biological functions, but the abnormal phase separation will also dysregulate the physiological processes. Emerging evidence points to the importance of LLPS in human health and diseases. Nevertheless, despite recent advancements, our knowledge of the molecular relationship between LLPS and diseases is frequently incomplete. In this review, we outline our current understanding about how aberrant LLPS affects developmental disorders, tandem repeat disorders, cancers and viral infection. We also examine disease mechanisms driven by aberrant condensates, and highlight potential treatment approaches. This study seeks to expand our understanding of LLPS by providing a valuable new paradigm for understanding phase separation and human disorders, as well as to further translate our current knowledge regarding LLPS into therapeutic discoveries

CEBIT screening for inhibitors of the interaction between SARS-CoV-2 spike and ACE2

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, causing COVID-19, is the most challenging pandemic of the modern era. It has resulted in over 5 million deaths worldwide. To quickly explore therapeutics for COVID-19, we utilized a previously-established system, namely CEBIT. We performed a high-throughput screening of FDA-approved drugs to inhibit the interaction between the receptor-binding domain (RBD) of SARS-CoV-2 spike protein and its obligate receptor ACE2. This interaction is essential for viral entry and therefore represents a promising therapeutic target. Based on the recruitment of interacting molecules into phase-separated condensates as a readout, we identified six positive candidates from a library of 2572 compounds, most of which have been reported to inhibit the entry of SARS-CoV-2 into host cells. Our surface plasmon resonance (SPR) and molecular docking analyses revealed the possible mechanisms via which these compounds interfere with the interaction between RBD and ACE2. Hence, our results indicate that CEBIT is highly versatile for identifying drugs against SARS-CoV-2 entry, and targeting CoV-2 entry by small molecule drugs is a viable therapeutic option to treat COVID-19 in addition to commonly used monoclonal antibodies