More Like this

1. Machine-learning-powered extraction of molecular diffusivity from single-molecule images for super-resolution mapping

   https://doi.org/10.1038/s42003-023-04729-x  

   Park, Ha H.; Wang, Bowen; Moon, Suhong; Jepson, Tyler; Xu, Ke (March 2023, Communications Biology)

   Abstract While critical to biological processes, molecular diffusion is difficult to quantify, and spatial mapping of local diffusivity is even more challenging. Here we report a machine-learning-enabled approach, pixels-to-diffusivity (Pix2D), to directly extract the diffusion coefficientDfrom single-molecule images, and consequently enable super-resolvedDspatial mapping. Working with single-molecule images recorded at a fixed framerate under typical single-molecule localization microscopy (SMLM) conditions, Pix2D exploits the often undesired yet evident motion blur,i.e., the convolution of single-molecule motion trajectory during the frame recording time with the diffraction-limited point spread function (PSF) of the microscope. Whereas the stochastic nature of diffusion imprints diverse diffusion trajectories to different molecules diffusing at the same givenD, we construct a convolutional neural network (CNN) model that takes a stack of single-molecule images as the input and evaluates aD-value as the output. We thus validate robustDevaluation and spatial mapping with simulated data, and with experimental data successfully characterizeDdifferences for supported lipid bilayers of different compositions and resolve gel and fluidic phases at the nanoscale. 

   more » « less
2. The genome of cowpea ( Vigna unguiculata [L.] Walp.)

   https://doi.org/10.1111/tpj.14349  

   Lonardi, Stefano; Muñoz‐Amatriaín, María; Liang, Qihua; Shu, Shengqiang; Wanamaker, Steve I.; Lo, Sassoum; Tanskanen, Jaakko; Schulman, Alan H.; Zhu, Tingting; Luo, Ming‐Cheng; et al (May 2019, The Plant Journal)

   Summary Cowpea (Vigna unguiculata[L.] Walp.) is a major crop for worldwide food and nutritional security, especially in sub‐Saharan Africa, that is resilient to hot and drought‐prone environments. An assembly of the single‐haplotype inbred genome of cowpea IT97K‐499‐35 was developed by exploiting the synergies between single‐molecule real‐time sequencing, optical and genetic mapping, and an assembly reconciliation algorithm. A total of 519 Mb is included in the assembled sequences. Nearly half of the assembled sequence is composed of repetitive elements, which are enriched within recombination‐poor pericentromeric regions. A comparative analysis of these elements suggests that genome size differences betweenVignaspecies are mainly attributable to changes in the amount ofGypsyretrotransposons. Conversely, genes are more abundant in more distal, high‐recombination regions of the chromosomes; there appears to be more duplication of genes within the NBS‐LRR and the SAUR‐like auxin superfamilies compared with other warm‐season legumes that have been sequenced. A surprising outcome is the identification of an inversion of 4.2 Mb among landraces and cultivars, which includes a gene that has been associated in other plants with interactions with the parasitic weedStriga gesnerioides. The genome sequence facilitated the identification of a putative syntelog for multiple organ gigantism in legumes. A revised numbering system has been adopted for cowpea chromosomes based on synteny with common bean (Phaseolus vulgaris). An estimate of nuclear genome size of 640.6 Mbp based on cytometry is presented. 

   more » « less
3. A 1:1 flavone cocrystal with cyclic trimeric perfluoro- o -phenylenemercury

   https://doi.org/10.1107/S2056989024005346  

   Novikov, Egor M; Castañeda, Raúl; Fonari, Marina S; Timofeeva, Tatiana V (July 2024, Acta Crystallographica Section E Crystallographic Communications)

   The title compound, systematic name tris(μ₂-perfluoro-o-phenylene)(μ₂-3-phenyl-4H-chromen-4-one)-triangulo-trimercury, [Hg₃(C₆F₄)₃(C₁₅H₁₀O₂)], crystallizes in the monoclinicP2₁/nspace group with one flavone (FLA) and one cyclic trimeric perfluoro-o-phenylenemercury (TPPM) molecule per asymmetric unit. The FLA molecule is located on one face of the TPPM acceptor and is linked in an asymmetric coordination of its carbonyl oxygen atom with two Hg centers of the TPPM macrocycle. The angular-shaped complexes pack in zigzag chains where they stackviatwo alternating TPPM–TPPM and FLA–FLA stacking patterns. The distance between the mean planes of the neighboring TPPM macrocycles in the stack is 3.445 (2) Å, and that between the benzo-γ-pyrone moieties of FLA is 3.328 (2) Å. The neighboring stacks are interdigitated through the shortened F...F, CH...F and CH...π contacts, forming a dense crystal structure. 

   more » « less
4. SPIND : a reference-based auto-indexing algorithm for sparse serial crystallography data

   https://doi.org/10.1107/s2052252518014951  

   Li, Chufeng; Li, Xuanxuan; Kirian, Richard; Spence, John_C H; Liu, Haiguang; Zatsepin, Nadia A (January 2019, IUCrJ)

   SPIND(sparse-pattern indexing) is an auto-indexing algorithm for sparse snapshot diffraction patterns (`stills') that requires the positions of only five Bragg peaks in a single pattern, when provided with unit-cell parameters. The capability ofSPINDis demonstrated for the orientation determination of sparse diffraction patterns using simulated data from microcrystals of a small inorganic molecule containing three iodines, 5-amino-2,4,6-triiodoisophthalic acid monohydrate (I3C) [Beck & Sheldrick (2008),Acta Cryst.E64, o1286], which is challenging for commonly used indexing algorithms.SPIND, integrated withCrystFEL[Whiteet al.(2012),J. Appl. Cryst.45, 335–341], is then shown to improve the indexing rate and quality of merged serial femtosecond crystallography data from two membrane proteins, the human δ-opioid receptor in complex with a bi-functional peptide ligand DIPP-NH₂and the NTQ chloride-pumping rhodopsin (CIR). The study demonstrates the suitability ofSPINDfor indexing sparse inorganic crystal data with smaller unit cells, and for improving the quality of serial femtosecond protein crystallography data, significantly reducing the amount of sample and beam time required by making better use of limited data sets.SPINDis written in Python and is publicly available under the GNU General Public License from https://github.com/LiuLab-CSRC/SPIND. 

   more » « less
5. Rational Design and Identification of Harmine‐Inspired, N ‐Heterocyclic DYRK1A Inhibitors Employing a Functional Genomic In Vivo Drosophila Model System**

   https://doi.org/10.1002/cmdc.202100512  

   Huizar, Francisco_J; Hill, Harrison_M; Bacher, Emily_P; Eckert, Kaitlyn_E; Gulotty, Eva_M; Rodriguez, Kevin_X; Tucker, Zachary_D; Banerjee, Monimoy; Liu, Haining; Wiest, Olaf; et al (January 2022, ChemMedChem)

   Abstract Deregulation of dual‐specificity tyrosine phosphorylation‐regulated kinase 1A (DYRK1A) plays a significant role in developmental brain defects, early‐onset neurodegeneration, neuronal cell loss, dementia, and several types of cancer. Herein, we report the discovery of three new classes ofN‐heterocyclic DYRK1A inhibitors based on the potent, yet toxic kinase inhibitors, harmine and harmol. An initial in vitro evaluation of the small molecule library assembled revealed that the core heterocyclic motifs benzofuranones, oxindoles, and pyrrolones, showed statistically significant DYRK1A inhibition. Further, the utilization of a low cost, high‐throughput functional genomic in vivo model system to identify small molecule inhibitors that normalizeDYRK1Aoverexpression phenotypes is described. This in vivo assay substantiated the in vitro results, and the resulting correspondence validates generated classes as architectural motifs that serve as potential DYRK1A inhibitors. Further expansion and analysis of these core compound structures will allow discovery of safe, more effective chemical inhibitors of DYRK1A to ameliorate phenotypes caused by DYRK1A overexpression. 

   more » « less