Knowledge mapping of idiopathic scoliosis genes and research hotspots (2002-2022): a bibliometric analysis.

Background: The etiology of idiopathic scoliosis (IS) remains unclear. Gene-based studies on genetic etiology and molecular mechanisms have improved our understanding of IS and guided treatment and diagnosis. Therefore, it is imperative to explicate and demarcate the preponderant areas of inquiry, key scholars, and their aggregate scholarly output, in addition to the collaborative associations amongst publications or researchers. Methods: Documents were retrieved from the Web of Science Core Collection (WoSCC) with the following criteria: TS = ("idiopathic scoliosis" AND gene) refined by search operators (genomic OR "hereditary substance" OR "germ plasm" OR Cistrons OR genetics OR genetic OR genes OR Polygenic OR genotype OR genome OR allele OR polygenes OR Polygene) AND DOCUMENT TYPES (ARTICLE OR REVIEW), and the timespan of 2002-01-01 to 2022-11-26. The online bibliometric analysis platform (bibliometric), bibliographic item co-occurrence matrix builder (BICOMB), CiteSpace 6.1. R6 and VOS viewer were used to evaluate articles for publications, nations, institutions, journals, references, knowledge bases, keywords, and research hotspots. Results: A total of 479 documents were retrieved from WoSCC. Fourty-four countries published relevant articles. The country with the most significant number of articles was China, and the institution with the most significant number of articles was Nanjing University. Citation analysis formed eight meaningful clusters and 16 high-frequency keywords. (2) The citation knowledge map included single nucleotide polymorphisms, whole exome sequencing, axonal dynamin, drug development, mesenchymal stem cells, dietary intake, curve progression, zebrafish development model, extracellular matrix, and rare variants were the current research hotspots and frontiers. Conclusions: Recent research has focused on IS-related genes, whereas the extracellular matrix and unusual variants are research frontiers and hotspots. Functional analysis of susceptibility genes will prove to be valuable for identifying this disease.

Expanding the genotypic and phenotypic spectrum associated with TBL1XR1 de novo variants.

BACKGROUND: The TBL1XR1 gene encodes the protein transducin-beta-like 1 receptor1, widely distributed in the pituitary, hypothalamus, white and brown adipose tissue, muscle, and liver. Current evidence suggests that heterozygous TBL1XR1 pathogenic variants can lead to a wide spectrum of phenotypes. This study aims to reveal the clinical phenotype and genetic profiles of de novo TBL1XR1 variations and summarize the relevant clinical and genetic features. METHODS: We analyzed four new cases harboring de novo TBL1XR1 variants and reviewed all reported cases. RESULTS: All probands suffered from global developmental delay. Moreover, patient 1 exhibited susceptibility to startle, patient 2 had hypovitaminosis D, short stature and hyponatremia, and patients 3 and 4 both presented with ASD (Autism spectrum disorder) and short stature. They all had a de novo TBL1XR1 variant (NM_024665.7), c.1184A > G (p.Tyr395Cys), c.1108G > A (p.Asp370Asn), c.1047 + 1G > C, and c.1097C > T (p.Ser366Phe) respectively. In addition, pooled analysis of 51 cases showed that they had speech impairment (38/39), intellectual developmental disorder (28/28), global developmental delay (42/42), and hypotonia (24/27), and some of them had epilepsy (10/22), ASD (13/25), and developmental regression (4/13). CONCLUSIONS: We report four new patients with de novo TBL1XR1 variants and provide a comprehensive overview of 47 previously reported individuals with TBL1XR1 variants, enriching the genotypic and phenotypic spectrum of TBL1XR1-related disease. This report further validates the pathogenicity de novo TBL1XR1 variants.

MYB42 inhibits hypocotyl cell elongation by coordinating brassinosteroid homeostasis and signalling in Arabidopsis thaliana.

BACKGROUND AND AIMS: The precise control of brassinosteroid (BR) homeostasis and signalling is a prerequisite for hypocotyl cell elongation in plants. Arabidopsis MYB42 and its paralogue MYB85 were previously identified to be positive regulators of secondary cell wall formation during mature stages. Here, we aim to reveal the role of MYB42 and MYB85 in hypocotyl elongation during the seedling stage and clarify how MYB42 coordinates BR homeostasis and signalling to regulate this process. METHODS: Histochemical analysis of proMYB42-GUS transgenic plants was used for determination of the MYB42 expression pattern. The MYB42, 85 overexpression, double mutant and some crossing lines were generated for phenotypic observation and transcriptome analysis. Transcription activation assays, quantitative PCR (qPCR), chromatin immunoprecipitation (ChIP)-qPCR and electrophoretic mobility shift assays (EMSAs) were conducted to determine the relationship of MYB42 and BRASSINAZOLE-RESISTANT 1 (BZR1), a master switch activating BR signalling. KEY RESULTS: MYB42 and MYB85 redundantly and negatively regulate hypocotyl cell elongation. They function in hypocotyl elongation by mediating BR signalling. MYB42 transcription was suppressed by BR treatment or in bzr1-1D (a gain-of-function mutant of BZR1), and mutation of both MYB42 and MYB85 enhanced the dwarf phenotype of the BR receptor mutant bri1-5. BZR1 directly repressed MYB42 expression in response to BR. Consistently, hypocotyl length of bzr1-1D was increased by simultaneous mutation of MYB42 and MYB85, but was reduced by overexpression of MYB42. Expression of a number of BR-regulated BZR1 (non-)targets associated with hypocotyl elongation was suppressed by MYB42, 85. Furthermore, MYB42 enlarged its action in BR signalling through feedback repression of BR accumulation and activation of DOGT1/UGT73C5, a BR-inactivating enzyme. CONCLUSIONS: MYB42 inhibits hypocotyl elongation by coordinating BR homeostasis and signalling during primary growth. The present study shows an MYB42, 85-mediated multilevel system that contributes to fine regulation of BR-induced hypocotyl elongation.

A High-Throughput Screening System for Populus Wood-Associated Transcription Factors and Its Application to Lignin Regulation.

Wood formation of trees is a complex and costly developmental process, whose regulatory network is involved in the protein-protein and protein-DNA interactions. To detect such interactions in wood development, we developed a high-throughput screening system with 517 Gal4-AD-wood-associated transcription factors (TFs) library from Populus alba × P. glandulosa cv "84K." This system can be used for screening the upstream regulators and interacting proteins of targets by mating-based yeast-one hybrid (Y1H) and yeast-two-hybrid (Y2H) method, respectively. Multiple regulatory modules of lignin biosynthesis were identified based on this Populus system. Five TFs interacted with the 500-bp promoter fragment of PHENYLALANINE AMMONIA-LYASE 2 (PAL2), the first rate-limiting enzyme gene in the lignin biosynthesis pathway, and 10 TFs interacted with PaMYB4/LTF1, a key regulator of lignin biosynthesis. Some of these interactions were further validated by EMSA and BiFC assays. The TF-PaPAL2 promoter interaction and TF-PaMYB4 interaction revealed a complex mechanism governing the regulation of lignin synthesis in wood cells. Our high-throughput Y1H/Y2H screening system may be an efficient tool for studying regulatory network of wood formation in tree species.