scholarly journals Three-dimensional CRISPR screening reveals epigenetic interaction with anti-angiogenic therapy

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Michael Y. He ◽  
Michael M. Halford ◽  
Ruofei Liu ◽  
James P. Roy ◽  
Zoe L. Grant ◽  
...  
Keyword(s):  
Epigenetic Regulation ◽  
Molecular Basis ◽  
Three Dimensional ◽  
Eye Diseases ◽  
Chromosomal Structure ◽  
Angiogenic Therapy ◽  
Functional Inhibition ◽  
Pathway Analyses ◽  
Structure And Activity ◽  
Insight Into

AbstractAngiogenesis underlies development, physiology and pathogenesis of cancer, eye and cardiovascular diseases. Inhibiting aberrant angiogenesis using anti-angiogenic therapy (AAT) has been successful in the clinical treatment of cancer and eye diseases. However, resistance to AAT inevitably occurs and its molecular basis remains poorly understood. Here, we uncover molecular modifiers of the blood endothelial cell (EC) response to a widely used AAT bevacizumab by performing a pooled genetic screen using three-dimensional microcarrier-based cell culture and CRISPR–Cas9. Functional inhibition of the epigenetic reader BET family of proteins BRD2/3/4 shows unexpected mitigating effects on EC survival and/or proliferation upon VEGFA blockade. Moreover, transcriptomic and pathway analyses reveal an interaction between epigenetic regulation and anti-angiogenesis, which may affect chromosomal structure and activity in ECs via the cell cycle regulator CDC25B phosphatase. Collectively, our findings provide insight into epigenetic regulation of the EC response to VEGFA blockade and may facilitate development of quality biomarkers and strategies for overcoming resistance to AAT.

Structure and function of neural networks in the retina

1988 ◽  
Vol 46 ◽  
pp. 26-27
Author(s):  
Peter Sterling
Keyword(s):  
Ganglion Cells ◽  
Three Dimensional ◽  
Structure And Function ◽  
Synaptic Connections ◽  
Visual Axis ◽  
One Dimensional ◽  
Cat Retina ◽  
Ultrathin Sections ◽  
And Function ◽  
Insight Into

The synaptic connections in cat retina that link photoreceptors to ganglion cells have been analyzed quantitatively. Our approach has been to prepare serial, ultrathin sections and photograph en montage at low magnification (˜2000X) in the electron microscope. Six series, 100-300 sections long, have been prepared over the last decade. They derive from different cats but always from the same region of retina, about one degree from the center of the visual axis. The material has been analyzed by reconstructing adjacent neurons in each array and then identifying systematically the synaptic connections between arrays. Most reconstructions were done manually by tracing the outlines of processes in successive sections onto acetate sheets aligned on a cartoonist's jig. The tracings were then digitized, stacked by computer, and printed with the hidden lines removed. The results have provided rather than the usual one-dimensional account of pathways, a three-dimensional account of circuits. From this has emerged insight into the functional architecture.

scholarly journals Completely non-fused electron acceptor with 3D-interpenetrated crystalline structure enables efficient and stable organic solar cell

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Lijiao Ma ◽  
Shaoqing Zhang ◽  
Jincheng Zhu ◽  
Jingwen Wang ◽  
Junzhen Ren ◽  
...  
Keyword(s):  
Organic Solar Cell ◽  
Low Cost ◽  
Three Dimensional ◽  
Molecular Geometry ◽  
Interpenetrating Network ◽  
Fused Ring ◽  
Molecule Design ◽  
End Capping ◽  
Conversion Efficiencies ◽  
Insight Into

AbstractNon-fullerene acceptors (NFAs) based on non-fused conjugated structures have more potential to realize low-cost organic photovoltaic (OPV) cells. However, their power conversion efficiencies (PCEs) are much lower than those of the fused-ring NFAs. Herein, a new bithiophene-based non-fused core (TT-Pi) featuring good planarity as well as large steric hindrance was designed, based on which a completely non-fused NFA, A4T-16, was developed. The single-crystal result of A4T-16 reveals that a three-dimensional interpenetrating network can be formed due to the compact π–π stacking between the adjacent end-capping groups. A high PCE of 15.2% is achieved based on PBDB-TF:A4T-16, which is the highest value for the cells based on the non-fused NFAs. Notably, the device retains ~84% of its initial PCE after 1300 h under the simulated AM 1.5 G illumination (100 mW cm−2). Overall, this work provides insight into molecule design of the non-fused NFAs from the aspect of molecular geometry control.

Insight Into The Molecular Basis Of The Anti‑Hyperglycemic Activity Of Ra‑3 In Type 2 Diabetic Rats And Its Cardioprotective Potential In Cultured Cardiomyoblasts

Metabolism ◽  
2021 ◽  
Vol 116 ◽  
pp. 154646
Author(s):  
R.A. Mosa ◽  
S.E. Mabhida ◽  
N.F. Sangweni ◽  
P.V. Dludla ◽  
A.R. Opoku ◽  
...  
Keyword(s):  
Molecular Basis ◽  
Diabetic Rats ◽  
Type 2 Diabetic ◽  
Insight Into

scholarly journals The distribution of myosin II in Dictyostelium discoideum slug cells.

1991 ◽  
Vol 115 (5) ◽  
pp. 1267-1274 ◽  
Author(s):  
S Eliott ◽  
P H Vardy ◽  
K L Williams
Keyword(s):  
Cell Motility ◽  
Dictyostelium Discoideum ◽  
Immunofluorescence Microscopy ◽  
Molecular Genetic ◽  
Myosin Ii ◽  
Three Dimensional ◽  
Homogeneous Distribution ◽  
Multicellular Development ◽  
Insight Into

While the role of myosin II in muscle contraction has been well characterized, less is known about the role of myosin II in non-muscle cells. Recent molecular genetic experiments on Dictyostelium discoideum show that myosin II is necessary for cytokinesis and multicellular development. Here we use immunofluorescence microscopy with monoclonal and polyclonal antimyosin antibodies to visualize myosin II in cells of the multicellular D. discoideum slug. A subpopulation of peripheral and anterior cells label brightly with antimyosin II antibodies, and many of these cells display a polarized intracellular distribution of myosin II. Other cells in the slug label less brightly and their cytoplasm displays a more homogeneous distribution of myosin II. These results provide insight into cell motility within a three-dimensional tissue and they are discussed in relation to the possible roles of myosin II in multicellular development.

Analysis of SiC CVD Growth in a Horizontal Hot-Wall Reactor by Experiment and 3D Modelling

2007 ◽  
Vol 556-557 ◽  
pp. 61-64
Author(s):  
Y. Shishkin ◽  
Rachael L. Myers-Ward ◽  
Stephen E. Saddow ◽  
Alexander Galyukov ◽  
A.N. Vorob'ev ◽  
...  
Keyword(s):  
Growth Rate ◽  
Growth Process ◽  
Three Dimensional ◽  
Chemical Species ◽  
3D Modelling ◽  
Complete Model ◽  
Cvd Growth ◽  
Dimensional Simulation ◽  
Insight Into ◽  
Hot Zone

A fully-comprehensive three-dimensional simulation of a CVD epitaxial growth process has been undertaken and is reported here. Based on a previously developed simulation platform, which connects fluid dynamics and thermal temperature profiling with chemical species kinetics, a complete model of the reaction process in a low pressure hot-wall CVD reactor has been developed. Close agreement between the growth rate observed experimentally and simulated theoretically has been achieved. Such an approach should provide the researcher with sufficient insight into the expected growth rate in the reactor as well as any variations in growth across the hot zone.

scholarly journals Structural insight into the molecular mechanism of p53-mediated mitochondrial apoptosis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Hudie Wei ◽  
Lingzhi Qu ◽  
Shuyan Dai ◽  
Yun Li ◽  
Haolan Wang ◽  
...  
Keyword(s):  
Molecular Basis ◽  
Mitochondrial Membrane ◽  
Ternary Complex ◽  
Mitochondrial Apoptosis ◽  
Tumor Suppressor P53 ◽  
Dimer Interface ◽  
Bona Fide ◽  
Structural Insight ◽  
Mitochondrial Membrane Permeabilization ◽  
Insight Into

AbstractThe tumor suppressor p53 is mutated in approximately half of all human cancers. p53 can induce apoptosis through mitochondrial membrane permeabilization by interacting with and antagonizing the anti-apoptotic proteins BCL-xL and BCL-2. However, the mechanisms by which p53 induces mitochondrial apoptosis remain elusive. Here, we report a 2.5 Å crystal structure of human p53/BCL-xL complex. In this structure, two p53 molecules interact as a homodimer, and bind one BCL-xL molecule to form a ternary complex with a 2:1 stoichiometry. Mutations at the p53 dimer interface or p53/BCL-xL interface disrupt p53/BCL-xL interaction and p53-mediated apoptosis. Overall, our current findings of the bona fide structure of p53/BCL-xL complex reveal the molecular basis of the interaction between p53 and BCL-xL, and provide insight into p53-mediated mitochondrial apoptosis.

The Three-Dimensional Surface Topographic Characterisation of Diamond Grinding Wheels

2010 ◽  
Vol 126-128 ◽  
pp. 690-695
Author(s):  
David Lee Butler
Keyword(s):  
Measurement Techniques ◽  
Three Dimensional ◽  
Surface Measurement ◽  
Grinding Wheel ◽  
Profile Measurement ◽  
Detailed Knowledge ◽  
Grinding Wheels ◽  
Diamond Grinding ◽  
Insight Into ◽  
Dimensional Surface

Surface measurement using three-dimensional stylus instruments is a relatively new technique that offers numerous advantages over more traditional profilometry methods. The information generated is, unlike profile measurement, less subjective and more statistical providing additional insight into the surface structure. One application of surface measurement that has encountered problems when using the profilometry method is that of grinding wheel characterisation. The wheel surface texture (topography) and the conditions under which it is generated have a profound effect upon the grinding performance as characterised by the grinding forces, power consumption, temperature, and surface integrity of components. A detailed knowledge of the nature of the topography of the grinding wheel would provide further insight into surface interactions between the wheel and workpiece as well as enabling improved control of the grinding process in general. In this paper four diamond grinding wheels of 91 and 181 micron grit size were subjected to differing dressing conditions to produce varying final wheel topographies. Three-dimensional surface measurement techniques were employed to quantitatively characterise the topographic change and provide an aerial estimation of the number of cutting grains. The results demonstrate that the techniques can distinguish between a worn and dressed wheel. In addition, the parametric values generated from the various surfaces can aid the user in determining when re-dressing is required.

Insight into Bile Duct Reaction to Obstruction from a Three-dimensional Perspective Using ex Vivo Phase-Contrast CT

Radiology ◽  
2021 ◽  
pp. 203967
Author(s):  
Wen-Juan Lv ◽  
Xin-Yan Zhao ◽  
Dou-Dou Hu ◽  
Xiao-Hong Xin ◽  
Li-Li Qin ◽  
...  
Keyword(s):  
Bile Duct ◽  
Phase Contrast ◽  
Ex Vivo ◽  
Three Dimensional ◽  
Contrast Ct ◽  
Insight Into

Three-Dimensional Aerodynamic Characteristics of Oscillating Supersonic and Transonic Annular Cascades

1982 ◽  
Author(s):  
M. Namba ◽  
A. Ishikawa
Keyword(s):  
Three Dimensional ◽  
Aerodynamic Characteristics ◽  
Aerodynamic Forces ◽  
Numerical Work ◽  
Dimensional Effects ◽  
Mathematical Expressions ◽  
Strip Theory ◽  
Clear Insight ◽  
Theory Approximation ◽  
Insight Into

A lifting surface theory is developed for unsteady three-dimensional flow in rotating subsonic, transonic and supersonic annular cascades with fluctuating blade loadings. Application of a finite radial eigenfunction series approximation not only affords a clear insight into the three-dimensional structures of acoustic fields but also provides mathematical expressions advantageous to numerical work. The theory is applied to oscillating blades. Numerical examples are presented to demonstrate three-dimensional effects on aerodynamic characteristics. Three-dimensional effects in supersonic cascades are generally small and strip theory predicts local aerodynamic forces as well as total aerodynamic forces with good accuracy. In transonic flow, however, the strip theory approximation breaks down near the sonic span station and three-dimensional effects are of primary importance.

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