The complete chloroplast genome sequence of Ficus altissima (Moraceae)

Ficus altissima plays an important role on biodiversity in tropical forests. In this study, the complete chloroplast genome sequence and the genome features of F. altissima were analyzed using the Illumina NovaSeq platform. The whole chloroplast genome sequence of F. altissima is 160,251 including a large single-copy region (LSC, 88,468 bp), a small single-copy region (SSC, 20,009 bp), and a pair of repeat regions (IRs, 25,887 bp, each). Further gene annotation revealed the chloroplast genome contains 124 genes, including 79 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. A total of 82 simple sequence repeats (SSRs) were identified in the chloroplast genome. Phylogenetic development was analyzed based on F. altissima with other species of Moraceae. This information will be useful for study on the evolution and genetic diversity of F. altissima in the future

Characterization of the complete chloroplast genome of medical plant Curculigo orchioides Gaertn. (Amaryllidaceae)

Curculigo orchioides Gaertn. distributed in subtropical regions of Asia including southern China and India. The plant is used as a traditional medicine in China for the treatment of menorrhagia, osteoporosis, and other gynecological problems. The complete chloroplast genome was reported in this study using the Illumina NovaSeq platform. The whole genome of this species was 157,472 bp in length, with a total GC content of 37.44%. The large single copy (LSC) was 86,507 bp, the small single copy (SSC) was 16,867 bp, and both of the two inverted repeats (IRs) were 27,049 bp, respectively. A total of 132 unique genes were identified, among which are 86 protein-coding genes, 38 tRNA genes and 8 rRNA genes. The phylogenetic analysis revealed that C. orchioides was highly clustered with C. capitulata. Our study will provide useful fundamental data for further phylogenetic and evolutionary studies of C. orchioides

The complete chloroplast genome of a medicinal plant Viscum articulatum Burm.f. (Loranthaceae)

Viscum articulatum is usually used as famous ethno-medicinal plant and popular drink in many provinces of China. In this study, the characterization of the complete chloroplast genome of V. articulatum was analyzed using the Illumina NovaSeq platform. The whole chloroplast genome sequence of V. articulatum is 131,825 including a large single-copy region (LSC, 76,069 bp), a small single-copy region (SSC, 8990 bp), and a pair of repeated regions (IRs, 23,383 bp, each). Further gene annotation in our study revealed the chloroplast genome contains 114 genes, including 36 tRNA genes, 8 rRNA genes and 70 protein-coding genes. A total of 118 simple sequence repeats (SSRs) were identified in the chloroplast genome. Phylogenetic development was analyzed based on V. articulatum with other species of Loranthaceae, the phylogenetic tree in our study revealed that V. articulatum is a lineage independent of other species in genus Viscum

Atypical peripheral actin band formation via overactivation of RhoA and nonmuscle myosin II in mitofusin 2-deficient cells

Cell spreading and migration play central roles in many physiological and pathophysiological processes. We have previously shown that MFN2 regulates the migration of human neutrophil-like cells via suppressing Rac activation. Here, we show that in mouse embryonic fibroblasts, MFN2 suppresses RhoA activation and supports cell polarization. After initial spreading, the wild-type cells polarize and migrate, whereas the Mfn2-/- cells maintain a circular shape. Increased cytosolic Ca2+ resulting from the loss of Mfn2 is directly responsible for this phenotype, which can be rescued by expressing an artificial tether to bring mitochondria and endoplasmic reticulum to close vicinity. Elevated cytosolic Ca2+ activates Ca2+/calmodulin-dependent protein kinase II, RhoA, and myosin light-chain kinase, causing an overactivation of nonmuscle myosin II, leading to a formation of a prominent F-actin ring at the cell periphery and increased cell contractility. The peripheral actin band alters cell physics and is dependent on substrate rigidity. Our results provide a novel molecular basis to understand how MFN2 regulates distinct signaling pathways in different cells and tissue environments, which is instrumental in understanding and treating MFN2-related diseases

Hyperexcitability and Pharmacological Responsiveness of Cortical Neurons Derived from Human iPSCs Carrying Epilepsy-Associated Sodium Channel Nav1.2-L1342P Genetic Variant.

With the wide adoption of genomic sequencing in children having seizures, an increasing number of SCN2A genetic variants have been revealed as genetic causes of epilepsy. Voltage-gated sodium channel Nav1.2, encoded by gene SCN2A, is predominantly expressed in the pyramidal excitatory neurons and supports action potential (AP) firing. One recurrent SCN2A genetic variant is L1342P, which was identified in multiple patients with epileptic encephalopathy and intractable seizures. However, the mechanism underlying L1342P-mediated seizures and the pharmacogenetics of this variant in human neurons remain unknown. To understand the core phenotypes of the L1342P variant in human neurons, we took advantage of a reference human-induced pluripotent stem cell (hiPSC) line from a male donor, in which L1342P was introduced by CRISPR/Cas9-mediated genome editing. Using patch-clamping and microelectrode array (MEA) recordings, we revealed that cortical neurons derived from hiPSCs carrying heterozygous L1342P variant have significantly increased intrinsic excitability, higher sodium current density, and enhanced bursting and synchronous network firing, suggesting hyperexcitability phenotypes. Interestingly, L1342P neuronal culture displayed a degree of resistance to the anticonvulsant medication phenytoin, which recapitulated aspects of clinical observation of patients carrying the L1342P variant. In contrast, phrixotoxin-3 (PTx3), a Nav1.2 isoform-specific blocker, can potently alleviate spontaneous and chemically-induced hyperexcitability of neurons carrying the L1342P variant. Our results reveal a possible pathogenic underpinning of Nav1.2-L1342P mediated epileptic seizures and demonstrate the utility of genome-edited hiPSCs as an in vitro platform to advance personalized phenotyping and drug discovery.SIGNIFICANCE STATEMENT A mounting number of SCN2A genetic variants have been identified from patients with epilepsy, but how SCN2A variants affect the function of human neurons contributing to seizures is still elusive. This study investigated the functional consequences of a recurring SCN2A variant (L1342P) using human iPSC-derived neurons and revealed both intrinsic and network hyperexcitability of neurons carrying a mutant Nav1.2 channel. Importantly, this study recapitulated elements of clinical observations of drug-resistant features of the L1342P variant, and provided a platform for in vitro drug testing. Our study sheds light on cellular mechanism of seizures resulting from a recurring Nav1.2 variant, and helps to advance personalized drug discovery to treat patients carrying pathogenic SCN2A variant