The acquisition of germination and post-embryonic developmental ability during seed maturation is vital for seed vigor, an important trait for plant propagation and crop production. How seed vigor is ...established in seeds is still poorly understood. Here, we report the crucial function of Arabidopsis histone variant H3.3 in endowing seeds with post-embryonic developmental potentials. H3.3 is not essential for seed formation, but loss of H3.3 results in severely impaired germination and post-embryonic development. H3.3 exhibits a seed-specific 5' gene end distribution and facilitates chromatin opening at regulatory regions in seeds. During germination, H3.3 is essential for proper gene transcriptional regulation. Moreover, H3.3 is constantly loaded at the 3' gene end, correlating with gene body DNA methylation and the restriction of chromatin accessibility and cryptic transcription at this region. Our results suggest a fundamental role of H3.3 in initiating chromatin accessibility at regulatory regions in seed and licensing the embryonic to post-embryonic transition.
The stability of eukaryotic genomes relies on the faithful transmission of DNA sequences and the maintenance of chromatin states through DNA replication. Plant TONSOKU (TSK) and its animal ortholog ...TONSOKU-like (TONSL) act as readers for newly synthesized histones and preserve DNA integrity via facilitating DNA repair at post-replicative chromatin. However, whether TSK/TONSL regulate the maintenance of chromatin states remains elusive. Here, we show that TSK is dispensable for global histone and nucleosome accumulation but necessary for maintaining repressive chromatin modifications, including H3K9me2, H2A.W, H3K27me3, and DNA methylation. TSK physically interacts with H3K9 methyltransferases and Polycomb proteins. Moreover, TSK mutation strongly enhances defects in Polycomb pathway mutants. TSK is intended to only associate with nascent chromatin until it starts to mature. We propose that TSK ensures the preservation of chromatin states by supporting the recruitment of chromatin modifiers to post-replicative chromatin in a critical short window of time following DNA replication.
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•TSK is dispensable for global histone and nucleosome accumulation•TSK contributes to the maintenance of repressive chromatin modifications•TSK associates with the H3K9 methyltransferases SUVH5 and SUVH6•TSK physically and genetically interacts with PcG proteins
Plant TONSOKU (TSK) and its animal ortholog TONSOKU-like (TONSL) have been found to aid in DNA damage repair during DNA replication. Here, Wang et al. show that TSK also participates in the maintenance of chromatin modifications, suggesting multiple functions of TSK/TONSL in safeguarding both DNA integrity and chromatin states.
Rationale: Splenic infarction usually occurs in patients with underlying illnesses such as thromboembolic disorders and infiltrative hematologic diseases. Herein, we report a rare case of splenic ...infarction in a previously healthy boy diagnosed with infectious mononucleosis (IM). Splenic infarction is a rare complication of IM and its incidence is unknown. This case report summarizes the clinical characteristics, treatment options, and anticipated time for recovery from splenic infarction in IM. Patient concern: A16-year-old boy presented to our clinic with complaints of fever, sore throat, and general sweakness for 7 days. The patient was diagnosed with IM due to an Epstein–Barr virus infection. Two days later, the patient developed severe abdominal pain in the left upper quadrant and returned to our ER for further evaluation. Diagnosis: IM complicated with splenic infarction. Interventions: Contrast-enhanced CT confirmed the diagnosis of splenic infarction. This patient was admitted for supportive treatment and close medical monitoring. Surgical Outcomes: The patient recovered well with conservative treatment. Lessons: IM is most often seen in adolescents and young adults. Splenic infarction is a rare complication of IM, particularly in patients who do not usually have any underlying predisposing medical conditions. Contrast-enhanced CT is the imaging modality of choice in suspected cases. Early recognition and treatment of splenic infarction in patients with IM can help prevent potentially life-threatening events. Patients should be advised to avoid sports that may precipitate splenic rupture. However it is still unknown when it is safe for patients to resume sports. In our case, 6 weeks after the splenic infarction, the patient generally felt well with complete resolution of objective symptoms and splenomegaly, and resumed sports without experiencing any adverse events.
Abstract
BACKGROUND
Guidelines regarding stereotactic radiosurgery (SRS) for brain metastases are missing recently published evidence.
OBJECTIVE
To conduct a systematic review and provide an ...objective summary of publications regarding SRS in managing patients with 1 to 4 brain metastases.
METHODS
Using Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, a systematic review was conducted using PubMed and Medline up to November 2016. A separate search was conducted for SRS for larger brain metastases.
RESULTS
Twenty-seven prospective studies, critical reviews, meta-analyses, and published consensus guidelines were reviewed. Four key points came from these studies. First, there is no detriment to survival by withholding whole brain radiation (WBRT) in the upfront management of brain metastases with SRS. Second, while SRS on its own provides a high rate of local control (LC), WBRT may provide further increase in LC. Next, WBRT does provide distant brain control with less need for salvage therapy. Finally, the addition of WBRT does affect neurocognitive function and quality of life more than SRS alone.
For larger brain metastases, surgical resection should be considered, especially when factoring lower LC with single-session radiosurgery. There is emerging data showing good LC and/or decreased toxicity with multisession radiosurgery.
CONCLUSION
A number of well-conducted prospective and meta-analyses studies demonstrate good LC, without compromising survival, using SRS alone for patients with a limited number of brain metastases. Some also demonstrated less impact on neurocognitive function with SRS alone. Practice guidelines were developed using these data with International Stereotactic Radiosurgery Society consensus.
Despite numerous reports indicating the significant impact of RNA modification on malignant glioblastoma (GBM) cell behaviors such as proliferation, invasion and therapy efficacy, its specific ...involvement in glioblastoma (GBM) angiogenesis is remains unclear and is currently under investigation. In this study, we aimed to investigate the relevance between RNA modification regulators and GBM angiogenesis. Our study employed bioinformatic analyses, including Gene Set Enrichment Analysis (GSEA), differential expression analysis, and Kaplan-Meier survival analysis, to identify regulators of angiogenesis-associated RNA modification (RM). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were applied to identify the enrichment of angiogenesis associated signatures in ALKBH5-high expression GBMs. We also utilized Western blot to verify the upregulation of ALKBH5 in clinical GBM samples. By a series of in vitro and in vivo assays, including plasmid transfection, wound healing, transwell invasion test, tube formation, RT-qPCR, ELISA assays and xenograft mice model, we validated the angiogenesis regulation ability of ALKBH5 in GBM. The N6-methyladenosine (m6A) modification "erase" ALKBH5 emerged as a candidate regulator associated with angiogenesis, demonstrating elevated expression and robust prognostic predictive ability in GBM patients. We also revealed enrichment of vasculature development biological process in GBMs with high ALKBH5 expression. Subsequently, we validated the elevated the expression of ALKBH5 in clinical GBM and paired adjacent tissues through western blot. Additionally, we knocked down the expression of ALKBH5 using sh-RNAs in U87 GBM cells to access the angiogenesis induction ability in U87 cells. In vitro experiments, Human Umbilical Vein Endothelial Cells (HUVECs) were used to perform wound healing, transwell migration and tube formation analysis, results indicated that ALKBH5 knock-down of U87 cells could decrease the pro-angiogenesis ability of U87 GBM cells. Further validation of our bioinformatic findings confirmed that ALKBH5 knockdown impaired VEGFA secretion in both in vitro and in vivo settings in U87 cells. These results comprehensively affirm the crucial role of ALKBH5 in regulating GBM-induced angiogenesis, both in vitro and in vivo. ALKBH5 not only emerges as a promising prognostic factor for GBM patients, but also plays a pivotal role in sustaining GBM progression by promoting angiogenesis.
Over the past three decades several randomized trials have enabled evidence-based practice for patients presenting with limited brain metastases. These trials have focused on the role of surgery or ...stereotactic radiosurgery (SRS) with or without whole brain radiation therapy (WBRT). As a result, it is clear that local control should be optimized with surgery or SRS in patients with optimal prognostic factors presenting with up to 4 brain metastases. The routine use of adjuvant WBRT remains debatable, as although greater distant brain control rates are observed, there is no impact on survival, and modern outcomes suggest adverse effects from WBRT on patient cognition and quality of life. With dramatic technologic advances in radiation oncology facilitating the adoption of SRS into mainstream practice, the optimal management of patients with multiple brain metastases is now being put forward. Practice is evolving to SRS alone in these patients despite a lack of level 1 evidence to support a clinical departure from WBRT. The purpose of this review is to summarize the current state of the evidence for patients presenting with limited and multiple metastases, and to present an in-depth analysis of the technology and dosimetric issues specific to the treatment of multiple metastases.
We reviewed the treatment for patients with spine metastases who initially received conventional external beam radiation (EBRT) and were reirradiated with 1-5 fractions of stereotactic body ...radiotherapy (SBRT) who did or did not subsequently develop radiation myelopathy (RM).
Spinal cord dose-volume histograms (DVHs) for 5 RM patients (5 spinal segments) and 14 no-RM patients (16 spine segments) were based on thecal sac contours at retreatment. Dose to a point within the thecal sac that receives the maximum dose (P(max)), and doses to 0.1-, 1.0-, and 2.0-cc volumes within the thecal sac were reviewed. The biologically effective doses (BED) using α/β = 2 Gy for late spinal cord toxicity were calculated and normalized to a 2-Gy equivalent dose (nBED = Gy(2/2)).
The initial conventional radiotherapy nBED ranged from ~30 to 50 Gy(2/2) (median ~40 Gy(2/2)). The SBRT reirradiation thecal sac mean P(max) nBED in the no-RM group was 20.0 Gy(2/2) (95% confidence interval CI, 10.8-29.2), which was significantly lower than the corresponding 67.4 Gy(2/2) (95% CI, 51.0-83.9) in the RM group. The mean total P(max) nBED in the no-RM group was 62.3 Gy(2/2) (95% CI, 50.3-74.3), which was significantly lower than the corresponding 105.8 Gy(2/2) (95% CI, 84.3-127.4) in the RM group. The fraction of the total P(max) nBED accounted for by the SBRT P(max) nBED for the RM patients ranged from 0.54 to 0.78 and that for the no-RM patients ranged from 0.04 to 0.53.
SBRT given at least 5 months after conventional palliative radiotherapy with a reirradiation thecal sac P(max) nBED of 20-25 Gy(2/2) appears to be safe provided the total P(max) nBED does not exceed approximately 70 Gy(2/2), and the SBRT thecal sac P(max) nBED comprises no more than approximately 50% of the total nBED.
In the field of self-regulated learning ability for college students, prior research usually neglected the role of parents when considering the physical distance between college and home. Indeed, an ...underlying describable driving force of learning remains embedded in the relationship between parents and students, even at the college stage. This study aimed to explore the relationships among perceived parental academic expectations, mastery goal orientation, self-reflection, and self-regulated learning ability of college students. Mediation and moderated mediation analyses were employed to analyze a sample of 691 college students. The results indicate that mastery goal orientation partially mediates the relationship between perceived parental academic expectations and self-regulated learning. In addition, self-reflection moderates the relationship between perceived parental academic expectations and self-regulated learning. The positive correlation between perceived parental academic expectation and self-regulated learning is stronger for students with low self-reflection than those with high self-reflection.
Anaphora is the main linguistic means to establish discourse coherence, and anaphora resolution is the psychological process to maintain this coherence. Chinese discourse is characterized with ...providing multiplicity of linguistic clues to readers by employing various referential apparatuses such as pronoun anaphora, zero anaphora, and so on. As a way of avoiding repeated reference to an object that is mentioned beforehand, zero anaphora is frequently employed in discourse. The production and resolution of zero anaphora largely concerns some constraints underlying psychological mechanisms. We particularly focus on zero anaphora resolution in the present study to try to discover some specific aspects of the underlying mechanism, hoping to find out some factors unique to the resolution process. We designed the first two experiments to probe into the psychological reality when participants were presented with sentences containing either pronoun anaphora or zero anaphora or both under discourse condition with topic continuity in Experiment 1a and topic discontinuity in Experiment 1b. We did not find any significant difference in the reaction time between zero anaphora resolution and pronoun anaphora resolution, indicating that zero anaphora possibly works within the processing mechanism on which pronoun anaphora resolution depends. However, we found significantly longer time in reading the first sentence in any of the discourse, showing that the first-mention effect exists in anaphora resolution. We further explored the time course of zero anaphora resolution by measuring the reaction time during the period when participants read sentences that varied according to the location where zero anaphora occurred under two conditions: topic continuity (Experiment 2a) vs. topic discontinuity (Experiment 2b). The strategies of searching for the referential information were found divergent: the exhaustive searching strategy was adopted when the topics within a discourse were kept continuous and the heuristic searching strategy was employed when the topics were discontinuous. The design of Experiment 5 took the factor of voice type and situation consistency into consideration, investigating in what way do those factors influence the resolution of zero anaphora. The voice type, according to the results, plays a significant role for its exclusively close relationship with the first-mention effect.
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