Diurnal RNAPII-tethered chromatin interactions are associated with rhythmic gene expression in rice

Background: The daily cycling of plant physiological processes is speculated to arise from the coordinated rhythms of gene expression. However, the dynamics of diurnal 3D genome architecture and their potential functions underlying the rhythmic gene expression remain unclear. Results: Here, we reveal the genome-wide rhythmic occupancy of RNA polymerase II (RNAPII), which precedes mRNA accumulation by approximately 2 h. Rhythmic RNAPII binding dynamically correlates with RNAPII-mediated chromatin architecture remodeling at the genomic level of chromatin interactions, spatial clusters, and chromatin connectivity maps, which are associated with the circadian rhythm of gene expression. Rhythmically expressed genes within the same peak phases of expression are preferentially tethered by RNAPII for coordinated transcription. RNAPII-associated chromatin spatial clusters (CSCs) show high plasticity during the circadian cycle, and rhythmically expressed genes in the morning phase and non-rhythmically expressed genes in the evening phase tend to be enriched in RNAPII-associated CSCs to orchestrate expression. Core circadian clock genes are associated with RNAPII-mediated highly connected chromatin connectivity networks in the morning in contrast to the scattered, sporadic spatial chromatin connectivity in the evening; this indicates that they are transcribed within physical proximity to each other during the AM circadian window and are located in discrete “transcriptional factory” foci in the evening, linking chromatin architecture to coordinated transcription outputs. Conclusion: Our findings uncover fundamental diurnal genome folding principles in plants and reveal a distinct higher-order chromosome organization that is crucial for coordinating diurnal dynamics of transcriptional regulation

Characterizing microRNA editing and mutation sites in Autism Spectrum Disorder

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder whose pathogenesis is still unclear. MicroRNAs (miRNAs) are a kind of endogenous small non-coding RNAs that play important roles in the post-transcriptional regulation of genes. Recent researches show that miRNAs are edited in multiple ways especially in central nervous systems. A-to-I editing of RNA catalyzed by Adenosine deaminases acting on RNA (ADARs) happens intensively in brain and is also noticed in other organs and tissues. Although miRNAs are widely edited in human brain, miRNA editing in ASD is still largely unexplored. In order to reveal the editing events of miRNAs in ASD, we analyzed 131 miRNA-seq samples from 8 different brain regions of ASD patients and normal controls. We identified 834 editing sites with significant editing levels, of which 70 sites showed significantly different editing levels in the superior frontal gyrus samples of ASD patients (ASD-SFG) when compared with those of control samples. The editing level of an A-to-I editing site in hsa-mir-376a-1 (hsa-mir-376a-1_9_A_g) in ASD-SFG is higher than that of normal controls, and the difference is exaggerated in individuals under 10 years. The increased expression of ADAR1 is consistent with the increased editing level of hsa-mir-376a-1_9_A_g in ASD-SFG samples compared to normal SFG samples. Furthermore, we verify that A-to-I edited hsa-mir-376a-5p directly represses GPR85 and NAPB, which may contribute to the abnormal neuronal development of ASD patients. These results provide new insights into the mechanism of ASD

Multiple organ infection and the pathogenesis of SARS

After >8,000 infections and >700 deaths worldwide, the pathogenesis of the new infectious disease, severe acute respiratory syndrome (SARS), remains poorly understood. We investigated 18 autopsies of patients who had suspected SARS; 8 cases were confirmed as SARS. We evaluated white blood cells from 22 confirmed SARS patients at various stages of the disease. T lymphocyte counts in 65 confirmed and 35 misdiagnosed SARS cases also were analyzed retrospectively. SARS viral particles and genomic sequence were detected in a large number of circulating lymphocytes, monocytes, and lymphoid tissues, as well as in the epithelial cells of the respiratory tract, the mucosa of the intestine, the epithelium of the renal distal tubules, the neurons of the brain, and macrophages in different organs. SARS virus seemed to be capable of infecting multiple cell types in several organs; immune cells and pulmonary epithelium were identified as the main sites of injury. A comprehensive theory of pathogenesis is proposed for SARS with immune and lung damage as key features

Triphenyltin Chloride Delays Leydig Cell Maturation During Puberty in Rats

Triphenyltin chloride (TPT) is present in a wide range of human foods. TPT could disrupt testis function as a potential endocrine disruptor of Leydig cells. However, the effect of TPT on pubertal Leydig cell development is still unclear. The objective of the current study was to explore whether exposure to TPT affected Leydig cell developmental process and to clarify the underlying mechanisms. Male Sprague-Dawley rats at 35 days of age were randomly divided into four groups and received normal corn oil (control), 0.5, 1, or 2 mg/kg/day TPT for 18 days. Immature Leydig cells isolated from 35-day-old rat testes were treated with TPT (10 and 100 nM) for 24 h in vitro. In vivo exposure to ≥0.5 mg/kg TPT lowered serum testosterone levels and lowered Star mRNA. TPT at 2 mg/kg also lowered Lhcgr, Cyp11a1, Hsd3b1, Hsd17b3 as well as pAKT1/AKT1, pAKT2/AKT2, and pERK1/2/ERK1/2 ratios. In vitro exposure to TPT (100 nM) increased ROS production and induced cell apoptosis rate in rat immature Leydig cells. In conclusion, TPT exposure disrupts Leydig cell development possibly via interfering with the phosphorylation of AKT1, AKT2, and ERK1/2 kinases

Fibroblast Growth Factor 1 Promotes Rat Stem Leydig Cell Development

Fibroblast growth factor 1 (FGF1) is reported to be expressed in the testis. How FGF1 affects stem Leydig cell development remains unclear. Here, we report the effects of FGF1 on rat stem Leydig cell development in an ethane dimethane sulfonate (EDS)-treated model. FGF1 (100 ng/testis) significantly increased serum testosterone level, increased PCNA-positive Leydig cell percentage and Leydig cell number, but down-regulated the expression of Lhcgr, Star, Cyp11a1, Hsd3b1, Cyp17a1, and Hsd11b1 in Leydig cells per se, after its daily intratesticular injection from post-EDS day 14 for 14 days. Primary culture of the seminiferous tubules showed that FGF1 stimulated EdU incorporation to stem Leydig cells but blocked the differentiation into the Leydig cell lineage, possibly via FGFR1-mediated mechanism. In conclusion, FGF1 promotes stem Leydig cell proliferation but blocks its differentiation

Effect of sutureless scleral fixed intraocular lens implantation on aphakic eyes: a system review and meta-analysis

Abstract Background Sutureless scleral fixed intraocular lens implantation (SF-IOL) has become one of the mainstream schemes in clinical treatment of aphakic eyes because of its advantages, such as avoiding dislocation of intraocular lens or subluxation caused by suture degradation or fracture and significant improvement of postoperative visual acuity. However, a consensus on the relative effectiveness and safety of this operation and other methods is still lacking. This study aimed to compare the efficacy and safety of sutureless SF-IOL with other methods. Aphakia means that the lens leaves the normal position and loses its original function, including absence or complete dislocation and subluxation of the lens which could cause anisometropic amblyopia, strabismus, and loss of binocular function in children and adolescents. For adults, the loss of the lens could lead to high hyperopia and affect vision. Above all this disease can seriously affect the quality of life of patients. Methods Literature about sutureless SF-IOL in PubMed, Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure, China Technical Journal VIP database, and Wanfang database published from 2000 to 2022 was reviewed. The weighted average difference was calculated by RevMan5.3 software for analysis. Two researchers independently selected the study and used the Cochrane collaboration tool to assess the risk of errors. Cochrane bias risk tool was used to evaluate the quality of evidence. This study is registered on PROSPERO (CRD42022363282). Results The postoperative IOL-related astigmatism of sutureless SF-IOL was lower than that of suture SF-IOL, and there was statistical difference when we compared the absolute postoperative spherical equivalent after sutureless SF-IOL and suture SF-IOL. Indicating that the degree of refractive error after sutureless SF-IOL was lower. Meanwhile, the operation time of sutureless SF-IOL was shorter than that of suture SF-IOL. The subgroup analysis showed that the absolute postoperative spherical equivalent and astigmatism values in Yamane technique were lower than those in suture SF-IOL. Conclusion Sutureless SF-IOL has the advantages of stable refraction, short operation time, and less postoperative complications. However, high-quality literature to compare these technologies is lacking. Some long-term follow-up longitudinal prospective studies are needed to confirm the findings

The complete chloroplast genome sequence of Sorbus amabilis (Rosaceae)

Sorbus amabilis Cheng ex Yü, a small excellent ornamental tree species, is only distributed in Eastern China. In this study, we assembled and annotated the complete chloroplast (cp) genome of the species using the next-generation sequencing for the first time. The cp genome was 160,006 bp in size, consisting of two copies of invert repeat (IR) regions of 26,405 bp, one large single-copy (LSC) region of 87,870bp, and one small single-copy (SSC) region of 19,326 bp. The overall GC content of the genome was 36.55%. The genome was predicted to contain 128 genes, including 88 protein-coding genes, 37 tRNA genes, and eight rRNA genes. Phylogenetic analysis of 25 chloroplast genomes in Rosaceae indicated that S. amabilis is most closely related to S. commixta. These findings may provide useful information to the phylogeny of the genus Sorbus

The complete chloroplast genome of Rhamnus globosa (Rhamnaceae)

Rhamnus globosa Bunge is a small shrub that can be used in the treatment of swollen poison, because of the antimicrobial activity. Here, we constructed the complete chloroplast genome of the R. globosa using Illumina sequencing technology. The circular cp genome was 160,642 bp in size, and comprises a large single-copy (LSC) region of 88,889 bp, a small single-copy (SSC) region of 18,897 bp, and a pair of inverted repeats (IR) of 26,428 bp. The GC content was 37.14% overall, with 35.01%, 31.42%, and 42.75% for the LSC, SSC, and IR regions, respectively. The plastome comprised 129 unique genes including 81 protein-coding genes, 30 tRNAs, and 4 rRNAs. The ML phylogenetic analysis based on 44 chloroplast genomes in Rosales showed a strong sister relationship with Berchemia species

The complete plastome of Primula wilsonii, a heterostylous ornamental species

Primula wilsonii Dunn is a perennial herb in section Proliferae Pax of Primula L. with small population sizes in the field. Here, we constructed the complete plastome of the P. wilsonii using Illumina sequencing technology. The circular plastome was 151,677 bp in size, and comprises a large single-copy (LSC) region of 83,510 bp, a small single-copy (SSC) region of 17,765 bp, and a pair of inverted repeats (IR) of 25,201 bp. The GC content was 36.99% overall, with 34.89%, 30.18%, and 42.87% for the LSC, SSC, and IR regions, respectively. The plastome comprised 130 unique genes including 84 protein-coding genes, 37 tRNAs, and 8 rRNAs. The ML phylogenetic analysis based on 17 plastomes in Primulaceae showed a strong sister relationship with P. anisodora in section Proliferae

GTP binding protein 2 maintains the quiescence, self-renewal, and chemoresistance of mouse colorectal cancer stem cells via promoting Wnt signaling activation

Colorectal cancer (CRC) is one of the most common cancers and the second most deadly cancer across the globe. Colorectal cancer stem cells (CCSCs) fuel CRC growth, metastasis, relapse, and chemoresistance. A complete understanding of the modulatory mechanisms of CCSC biology is essential for developing efficacious CRC treatment. In the current study, we characterized the expression and function of GTP binding protein 2 (GTPBP2) in a chemical-induced mouse CRC model. We found that GTPBP2 was expressed at a higher level in CD133+CD44+ CCSCs compared with other CRC cells. Using a lentivirus-based Cas9/sgRNA system, GTPBP2 expression was ablated in CRC cells in vitro. GTPBP2 deficiency caused the following effects on CCSCs: 1) Significantly accelerating proliferation and increasing the proportions of cells at G1, S, and G2/M phase; 2) Impairing resistance to 5-Fluorouracil; 3) Weakening self-renewal but not impacting cell migration. In addition, GTPBP2 deficiency remarkably decreased β-catenin expression while increasing β-catenin phosphorylation in CCSCs. These effects of GTPBP2 were present in CCSCs but not in other CRC cell populations. The Wnt agonist SKL2001 completely abolished these changes in GTPBP2-deficient CCSCs. When GTPBP2-deficient CCSCs were implanted in nude mice, they exhibited consistent changes compared with GTPBP2-expressing CCSCs. Collectively, this study indicates that GTPBP2 positively modulates Wnt signaling to reinforce the quiescence, self-renewal, and chemoresistance of mouse CCSCs. Therefore, we disclose a novel mechanism underlying CCSC biology and GTPBP2 could be a therapeutic target in future CRC treatment