As the major component of cell membranes, phosphatidylcholine (PC) is synthesized de novo in the Kennedy pathway and then undergoes extensive deacylation-reacylation remodeling via Lands' cycle. The ...re-acylation is catalyzed by lysophosphatidylcholine acyltransferase (LPCAT) and among the four LPCAT members in human, the LPCAT3 preferentially introduces polyunsaturated acyl onto the sn-2 position of lysophosphatidylcholine, thereby modulating the membrane fluidity and membrane protein functions therein. Combining the x-ray crystallography and the cryo-electron microscopy, we determined the structures of LPCAT3 in apo-, acyl donor-bound, and acyl receptor-bound states. A reaction chamber was revealed in the LPCAT3 structure where the lysophosphatidylcholine and arachidonoyl-CoA were positioned in two tunnels connected near to the catalytic center. A side pocket was found expanding the tunnel for the arachidonoyl CoA and holding the main body of arachidonoyl. The structural and functional analysis provides the basis for the re-acylation of lysophosphatidylcholine and the substrate preference during the reactions.
GPR52 is a class-A orphan G-protein-coupled receptor that is highly expressed in the brain and represents a promising therapeutic target for the treatment of Huntington's disease and several ...psychiatric disorders
. Pathological malfunction of GPR52 signalling occurs primarily through the heterotrimeric G
protein
, but it is unclear how GPR52 and G
couple for signal transduction and whether a native ligand or other activating input is required. Here we present the high-resolution structures of human GPR52 in three states: a ligand-free state, a G
-coupled self-activation state and a potential allosteric ligand-bound state. Together, our structures reveal that extracellular loop 2 occupies the orthosteric binding pocket and operates as a built-in agonist, conferring an intrinsically high level of basal activity to GPR52
. A fully active state is achieved when G
is coupled to GPR52 in the absence of an external agonist. The receptor also features a side pocket for ligand binding. These insights into the structure and function of GPR52 could improve our understanding of other self-activated GPCRs, enable the identification of endogenous and tool ligands, and guide drug discovery efforts that target GPR52.
Intraflagellar transport (IFT) trains, the polymers composed of two multi-subunit complexes, IFT-A and IFT-B, carry out bidirectional intracellular transport in cilia, vital for cilia biogenesis and ...signaling. IFT-A plays crucial roles in the ciliary import of membrane proteins and the retrograde cargo trafficking. However, the molecular architecture of IFT-A and the assembly mechanism of the IFT-A into the IFT trains in vivo remains elusive. Here, we report the cryo-electron microscopic structures of the IFT-A complex from protozoa Tetrahymena thermophila. We find that IFT-A complexes present two distinct, elongated and folded states. Remarkably, comparison with the in situ cryo-electron tomography structure of the anterograde IFT train unveils a series of adjustments of the flexible arms in apo IFT-A when incorporated into the anterograde train. Our results provide an atomic-resolution model for the IFT-A complex and valuable insights into the assembly mechanism of anterograde IFT trains.
Microwave pyrolysis of sludge: a review Li, Shaobai; Li, Caixia; Shao, Zhiguo
Journal of environmental engineering and management,
04/2022, Letnik:
32, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Abstract
As an environmentally friendly energy recovery technology, microwave pyrolysis has huge development potential in sludge resource treatment. This paper comprehensively reviews the progress of ...microwave pyrolysis of sludge, focusing on the mechanisms and development status of microwave pyrolysis equipment. The effects of pyrolysis temperature, heating rate, microwave absorbers, sludge properties and catalysts on microwave pyrolysis efficiency and its products are also discussed. Finally, the differentiation compared with conventional pyrolysis is summarized. It is suggested that target products can be controlled directionally by changing the pyrolysis conditions and exploring the harmful products produced in the microwave pyrolysis process. Future research directions are proposed to help the subsequent extensive application of microwave pyrolysis technology in sludge treatment.
RNA polymerase III (Pol III) synthesizes structured, essential small RNAs, such as transfer RNA, 5S ribosomal RNA and U6 small nuclear RNA. Pol III, the largest nuclear RNA polymerase, is composed of ...a conserved core region and eight constitutive regulatory subunits, but how these factors jointly regulate Pol III transcription remains unclear. Here, we present cryo-EM structures of human Pol III in both apo and elongating states, which unveil both an orchestrated movement during the apo-to-elongating transition and an unexpected apo state in which the RPC7 subunit tail occupies the DNA-RNA-binding cleft of Pol III, suggesting that RPC7 plays important roles in both autoinhibition and transcription initiation. The structures also reveal a proofreading mechanism for the TFIIS-like subunit RPC10, which stably retains its catalytic position in the secondary channel, explaining the high fidelity of Pol III transcription. Our work provides an integrated picture of the mechanism of Pol III transcription regulation.
A numerical study was conducted on the interaction of bubbles with different diameters and arrangements in shear-thinning viscoelastic fluids using OpenFOAM. The Volume of Fluid (VOF) method combined ...with the surface tension model was used to track the gas–liquid interface, and the rheological properties of the fluid were characterized with the Giesekus model. The numerical results are corresponded with the previous references, verifying the correctness of the simulation method. The influences of the initial bubble diameter, horizontal spacing, and arrangement on the motion state of three parallel bubbles were studied in detail. The flow pattern of the bubble rising was analyzed and compared with the motion state of parallel unequal double bubbles. As the diameter of the bubbles increases, the interaction among three equal size bubbles is changed from coalescence to detachment. Changing the diameter of one of the bubbles will significantly affect the movement of the larger diameter bubble, which is due to the enhancement in kinetic energy. The final state of some arrangement ways is consistent with the phenomenon of unequal double bubbles. The shear thinning effect, the velocity difference between bubbles, and the flow field around bubbles are considered the main reasons that decide the interaction between bubbles.
Telomerase, a multi-subunit ribonucleoprotein complex, is a unique reverse transcriptase that catalyzes the processive addition of a repeat sequence to extend the telomere end using a short fragment ...of its own RNA component as the template. Despite recent structural characterizations of human and Tetrahymena telomerase, it is still a mystery how telomerase repeatedly uses its RNA template to synthesize telomeric DNA. Here, we report the cryo-EM structure of human telomerase holoenzyme bound with telomeric DNA at resolutions of 3.5 Å and 3.9 Å for the catalytic core and biogenesis module, respectively. The structure reveals that a leucine residue Leu980 in telomerase reverse transcriptase (TERT) catalytic subunit functions as a zipper head to limit the length of the short primer-template duplex in the active center. Moreover, our structural and computational analyses suggest that TERT and telomerase RNA (hTR) are organized to harbor a preformed active site that can accommodate short primer-template duplex substrates for catalysis. Furthermore, our findings unveil a double-fingers architecture in TERT that ensures nucleotide addition processivity of human telomerase. We propose that the zipper head Leu980 is a structural determinant for the sequence-based pausing signal of DNA synthesis that coincides with the RNA element-based physical template boundary. Functional analyses unveil that the non-glycine zipper head plays an essential role in both telomerase repeat addition processivity and telomere length homeostasis. In addition, we also demonstrate that this zipper head mechanism is conserved in all eukaryotic telomerases. Together, our study provides an integrated model for telomerase-mediated telomere synthesis.
The prospect of emulating the impressive computational capabilities of biological systems has led to considerable interest in the design of analog circuits that are potentially implementable in very ...large scale integration CMOS technology and are guided by biologically motivated models. For example, simple image processing tasks, such as the detection of edges in binary and grayscale images, have been performed by networks of FitzHugh-Nagumo-type neurons using the reaction-diffusion models. However, in these studies, the one-to-one mapping of image pixels to component neurons makes the size of the network a critical factor in any such implementation. In this paper, we develop a simplified version of the employed reaction-diffusion model in three steps. In the first step, we perform a detailed study to locate this threshold using continuous Lyapunov exponents from dynamical system theory. Furthermore, we render the diffusion in the system to be anisotropic, with the degree of anisotropy being set by the gradients of grayscale values in each image. The final step involves a simplification of the model that is achieved by eliminating the terms that couple the membrane potentials of adjacent neurons. We apply our technique to detect edges in data sets of artificially generated and real images, and we demonstrate that the performance is as good if not better than that of the previous methods without increasing the size of the network.
Glycoprotein (GP) Ib-IX-V is the second most abundant platelet receptor for thrombin and other ligands crucial for hemostasis and thrombosis. Its activity is involved in platelet adhesion to vascular ...injury sites and thrombin-induced platelet aggregation. GPIb-IX-V is a heteromeric complex composed of four subunits, GPIbα, GPIbβ, GPV and GPIX, in a stoichiometric ratio that has been wildly debated. Despite its important physiological roles, the overall structure and molecular arrangement of GPIb-IX-V are not yet fully understood. Here, we purify stable and functional human GPIb-IX-V complex from reconstituted EXPi293F cells in high homogeneity, and perform biochemical and structural characterization of this complex. Single-particle cryo-electron microscopy structure of GPIb-IX-V is determined at ∼11 Å resolution, which unveils the architecture of GPIb-IX-V and its subunit organization. Size-exclusion chromatography-multi-angle static light scattering analysis reveals that GPIb-IX-V contains GPIb-IX and GPV at a 1:1 stoichiometric ratio and surface plasmon resonance assays show that association of GPV leads to slow kinetics of thrombin binding to GPIb-IX-V. Taken together, our results provide the first three-dimensional architecture of the intact GPIb-IX-V complex, which extends our understanding of the structure and functional mechanism of this complex in hemostasis and thrombosis.
A novel strategy is reported to produce low surface energy poly(pentadecafluorooctyl-5-norbornene-2-carboxylate) brushes (PNCA-F15) on surfaces of variable metals and metallic oxides. PNCA-F15 ...brushes are grafted from biomimic catecholic initiator via surface-initiated ring-opening metathesis polymerization at ambient conditions. The biomimic catecholic initiator can assemble on a variety of substrates, such as Ti(TiO2), Al(Al2O3), steel, Au, Cu, Ag, and Zn, and on both nanoparticles and planar substrates, allowing successful grafting of low surface energy polymer brushes from these substrates. The polymer brush modified substances were characterized by thermogravimetric analysis, X-ray photoelectron spectroscopy, water contact angle measurements, and atomic force microscopy. The PNCA-F15 brushes grow progressly with time with highly uniform surface coverage. Very uniform polymer layer with the thickness 11 nm is obtained after 2 h polymerization at 0.25 M monomer concentration. Thermogravimetric analysis shows the grafting amount of PNCA-F15 is 39.3% (2 h). Upon grafting on rough surfaces, e.g., electrochemically anodized alumina and titania, superhydrophobicity and superoleophobicity in particular can be achieved; e.g., the PNCA-F15 grafted rough TiO2 nanotubes films exhibit static water contact angle of 170°.
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