Association of Scalp High-Frequency Oscillation Detection and Characteristics With Disease Activity in Pediatric Epilepsy.

INTRODUCTION: High-frequency oscillation (HFO) in scalp electroencephalography is a promising new noninvasive prognostic epilepsy biomarker, but further data are needed to ascertain the utility of this parameter. The present work investigated the association between epileptic activity and scalp HFO in pediatric patients with various types of epilepsy, using multivariable regression models to correct for possible confounding factors. METHODS: The authors analyzed 97 subjects who were divided into groups with active epilepsy (within 1 year of seizure), seizure-free epilepsy (>1 year without seizure), and nonepilepsy. Regarding the frequency of seizure occurrence as an indicator of epileptic activity, we categorized subjects into four groups (Daily/Weekly, Monthly, Yearly, and Rarely). RESULTS: Multiple linear regression analysis showed that the scalp HFO detection rate was significantly higher in patients with active epilepsy than in those with nonepilepsy (ß [95% confidence interval] = 2.77 [1.79-4.29]; P < 0.001). The association between scalp HFO detection rate and frequency of seizure occurrence was highest in the Daily/Weekly group (ß [95% confidence interval] = 3.38 [1.57-7.27]; P = 0.002), followed by Monthly and Yearly groups (ß [95% confidence interval] = 2.42 [1.02-5.73]; P = 0.046 and 0.36 [0.16-0.83]; P = 0.017). In addition, HFO duration, number of peaks, and number of channels detected were significantly higher in patients with active epilepsy. CONCLUSIONS: Pediatric patients with active epilepsy and high frequency of seizure occurrence exhibited a higher scalp HFO detection rate. These results may help to establish HFO detectable by noninvasive scalp electroencephalography as a biomarker of active epilepsy in pediatric patients.

The 33rd International Conference on Arabidopsis Research (ICAR2023).

The 33rd International Conference on Arabidopsis Research (ICAR2023) was held at Makuhari Messe International Conference Hall in Chiba prefecture from June 5 to 9, 2023. This annual conference, which rotates among hosts in North America, Asia-Oceania, and Europe, covers the full range of plant biology research involving Arabidopsis and other plant species. The conference hosted more than 1200 participants, including approximately 800 international attendees from 42 countries (or regions), and featured about 900 oral and poster presentations. Reflecting the conference theme, "Arabidopsis for Sustainable Development Goals (SDGs)," there were numerous exemplary presentations regarding basic plant science using Arabidopsis and translational research conducted to achieve SDGs by exploiting the knowledge gained from Arabidopsis to improve crop production. The conference concluded on a high note, with more than 99% of survey respondents expressing their general satisfaction with ICAR2023. This report aims to summarize the organization, objectives, and outcomes of the conference.

Illuminating the path to shoot meristem regeneration: Molecular insights into reprogramming cells into stem cells.

Plant cells possess the ability to dedifferentiate and reprogram into stem cell-like populations, enabling the regeneration of new organs. However, the maintenance of stem cells relies on specialized microenvironments composed of distinct cell populations with specific functions. Consequently, the regeneration process necessitates the orchestrated regulation of multiple pathways across diverse cellular populations. One crucial pathway involves the transcription factor WUSCHEL HOMEOBOX 5 (WOX5), which plays a pivotal role in reprogramming cells into stem cells and promoting their conversion into shoot meristems through WUSCHEL (WUS). Additionally, cell and tissue mechanics, including cell wall modifications and mechanical stress, critically contribute to de novo shoot organogenesis by regulating polar auxin transport. Furthermore, light signaling emerges as a key regulator of plant regeneration, directly influencing expression of meristem genes and potentially influencing aforementioned pathways as well.

The Ratio of miR-122 to miR-20a (miR-122/miR-20a) Is a Useful Minimally Invasive Biomarker for Non-Alcoholic Fatty Liver Disease Detection.

Background: The increasing prevalence of non-alcoholic fatty liver disease (NAFLD) has become a global health problem. NAFLD has few initial symptoms and may be difficult to detect early, so there is need for a minimally invasive early detection marker. We hypothesized that miR-122 and miR-20a levels combined, as the miR-122/miR-20a ratio might detect NAFLD more sensitively. Methods: This study involved 167 participants with low alcohol intake. Those who had an increase in echogenicity of the liver parenchyma and hepato-renal contrast on ultrasonography were classified as the NAFLD group (n = 44), which was further classified into mild (n = 26) and severe (n = 18) groups based on echogenic intensity and hepatic vessel and diaphragm visualization. Participants without fatty liver were included in the normal group, except for those with an abnormal body mass index, glycated hemoglobin, and systolic blood pressure (n = 123) values. Serum miR-122 and miR-20a expression levels in participants were measured by real-time polymerase chain reaction, and the miR-122/miR-20a was calculated. Results: In the NAFLD group, miR-122 expression was significantly higher and the miR-20a was significantly lower than in the normal group, in agreement with previous studies. miR-122/miR-20a was also significantly higher in the NAFLD group. Receiver operating characteristic curve analysis was performed with miR-122/miR-20a as an NAFLD detection marker, and the area under the curve of miR-122/miR-20a was significantly larger than that of miR-122 or miR-20a alone. Conclusions: The miR-122/miR-20a ratio, combined with miR-122 and miR-20a levels, is a useful biomarker to detect NAFLD with high sensitivity.

Epigenomic reprogramming in plant regeneration: Locate before you modify.

Plants possess remarkable abilities for regeneration, and this developmental capability is strongly influenced by environmental conditions. Previous research has highlighted the positive effects of wound signaling and warm temperature on plant regeneration, and recent studies suggest that light and nutrient signals also influence the regenerative efficiencies. Several epigenetic factors, such as histone acetyl-transferases (HATs), POLYCOMB REPRESSIVE COMPLEX 2 (PRC2), and H2A variants, play crucial roles in regulating the expression of genes implicated in plant regeneration. However, how these epigenetic factors recognize specific genomic regions to regulate regeneration genes is still unclear. In this article, we describe the latest studies of epigenetic regulation and discuss the functional coordination between transcription factors and epigenetic modifiers in plant regeneration.

Factors associated with mental health among undergraduate nursing students early in the COVID-19 pandemic: an integrative review.

OBJECTIVES: We aimed to synthesize research findings identifying factors associated with mental health in undergraduate nursing students early in the COVID-19 pandemic. METHODS: Seven electronic databases were searched using key terms and subject headings. JBI Critical Appraisal Checklists were used to evaluate research report quality. RESULTS: Among 23 reports (19 quantitative and four qualitative) meeting inclusion criteria, negative emotional responses to COVID-19 (fear of infection, perceived risk, uncertainty about care/future), negative behavioral responses to COVID-19 (eating behaviors, problematic internet use, insomnia), and negative coping strategies were associated with more adverse mental health symptoms. Conversely, social support, professional identity, preventive behaviors, sufficient personal protective equipment (PPE), and positive coping strategies were related to fewer symptoms. CONCLUSIONS: During a pandemic, undergraduate nursing students require educational support to promote their ability to avoid severe mental health disorders. Also, educators should strengthen students' professional identity, provide infection prevention knowledge and skills, and supply sufficient PPE.

WUSCHEL-RELATED HOMEOBOX 13 suppresses de novo shoot regeneration via cell fate control of pluripotent callus.

Plants can regenerate their bodies via de novo establishment of shoot apical meristems (SAMs) from pluripotent callus. Only a small fraction of callus cells is eventually specified into SAMs but the molecular mechanisms underlying fate specification remain obscure. The expression of WUSCHEL (WUS) is an early hallmark of SAM fate acquisition. Here, we show that a WUS paralog, WUSCHEL-RELATED HOMEOBOX 13 (WOX13), negatively regulates SAM formation from callus in Arabidopsis thaliana. WOX13 promotes non-meristematic cell fate via transcriptional repression of WUS and other SAM regulators and activation of cell wall modifiers. Our Quartz-Seq2-based single cell transcriptome revealed that WOX13 plays key roles in determining cellular identity of callus cell population. We propose that reciprocal inhibition between WUS and WOX13 mediates critical cell fate determination in pluripotent cell population, which has a major impact on regeneration efficiency.

How do plants reprogramme the fate of differentiated cells?

Being able to change cell fate after differentiation highlights the remarkable developmental plasticity of plant cells. Recent studies show that phytohormones, such as auxin and cytokinin, promote cell cycle reactivation, a critical first step to reprogramme mitotically inactive, differentiated cells into organogenic stem cells. Accumulating evidence suggests that wounding provides an additional cue to convert the identity of differentiated cells by promoting the loss of existing cell fate and/or acquisition of new cell fate. Differentiated cells can also alter cell fate without undergoing cell division and in this case, wounding and phytohormones induce master regulators that can directly assign new cell fate.

Cytokinin signaling promotes root hair growth by directly regulating RSL4 expression.

Root hairs are single-celled tubular structures produced from the epidermis, which play an essential role in water and nutrient uptake from the soil. Therefore, root hair formation and elongation are controlled not only by developmental programs but also by environmental factors, enabling plants to survive under fluctuating conditions. Phytohormones are key signals that link environmental cues to developmental programs; indeed, root hair elongation is known to be controlled by auxin and ethylene. Another phytohormone, cytokinin, also affects root hair growth, while whether cytokinin is actively involved in root hair growth and, if so, how it regulates the signaling pathway governing root hair development have remained unknown. In this study, we show that the two-component system of cytokinin, which involves the B-type response regulators ARABIDOPSIS RESPONSE REGULATOR 1 (ARR1) and ARR12, promotes the elongation process of root hairs. They directly up-regulate ROOT HAIR DEFECTIVE 6-LIKE 4 (RSL4) encoding a basic helix-loop-helix (bHLH) transcription factor that plays a central role in root hair growth, whereas the ARR1/12-RSL4 pathway does not crosstalk with auxin or ethylene signaling. These results indicate that cytokinin signaling constitutes another input onto the regulatory module governed by RSL4, making it possible to fine-tune root hair growth in changing environments.

Arabidopsis histone H3 lysine 9 methyltransferases KYP/SUVH5/6 are involved in leaf development by interacting with AS1-AS2 to repress KNAT1 and KNAT2.

The Arabidopsis H3K9 methyltransferases KRYPTONITE/SUPPRESSOR OF VARIEGATION 3-9 HOMOLOG 4 (KYP/SUVH4), SUVH5 and SUVH6 are redundantly involved in silencing of transposable elements (TEs). Our recent study indicated that KYP/SUVH5/6 can directly interact with the histone deacetylase HDA6 to synergistically regulate TE expression. However, the function of KYP/SUVH5/6 in plant development is still unclear. The transcriptional factors ASYMMETRIC LEAVES1 (AS1) and AS2 form a transcription complex, which is involved in leaf development by repressing the homeobox genes KNOTTED-LIKE FROM ARABIDOPSIS THALIANA 1 (KNAT1) and KNAT2. In this study, we found that KYP and SUVH5/6 directly interact with AS1-AS2 to repress KNAT1 and KNAT2 by altering histone H3 acetylation and H3K9 dimethylation levels. In addition, KYP can directly target the promoters of KNAT1 and KNAT2, and the binding of KYP depends on AS1. Furthermore, the genome-wide occupancy profile of KYP indicated that KYP is enriched in the promoter regions of coding genes, and the binding of KYP is positively correlated with that of AS1 and HDA6. Together, these results indicate that Arabidopsis H3K9 methyltransferases KYP/SUVH5/6 are involved in leaf development by interacting with AS1-AS2 to alter histone H3 acetylation and H3K9 dimethylation from KNAT1 and KNAT2 loci.

Molecular Mechanisms of Plant Regeneration from Differentiated Cells: Approaches from Historical Tissue Culture Systems.

Plants can exert remarkable capacity for cell reprogramming even from differentiated cells. This ability allows plants to regenerate tissues/organs and even individuals in nature and in vitro. In recent decades, Arabidopsis research has uncovered molecular mechanisms of plant regeneration; however, our understanding of how plant cells retain both differentiated status and developmental plasticity is still obscure. In this review, we first provide a brief outlook of the representative modes of plant regeneration and key factors revealed by Arabidopsis research. We then re-examine historical tissue culture systems that enable us to investigate the molecular details of cell reprogramming in differentiated cells and discuss the different approaches, specifically highlighting our recent progress in shoot regeneration from the epidermal cell of Torenia fournieri.

Auxin-Induced WUSCHEL-RELATED HOMEOBOX13 Mediates Asymmetric Activity of Callus Formation upon Cutting.

Plants have the regenerative ability to reconnect cut organs, which is physiologically important to survive severe tissue damage. The ability to reconnect organs is utilized as grafting to combine two different individuals. Callus formation at the graft junction facilitates organ attachment and vascular reconnection. While it is well documented that local wounding signals provoke callus formation, how callus formation is differentially regulated at each cut end remains elusive. Here, we report that callus formation activity is asymmetrical between the top and bottom cut ends and is regulated by differential auxin accumulation. Gene expression analyses revealed that cellular auxin response is preferentially upregulated in the top part of the graft. Disruption of polar auxin transport inhibited callus formation from the top, while external application of auxin was sufficient to induce callus formation from the bottom, suggesting that asymmetric auxin accumulation is responsible for active callus formation from the top end. We further found that the expression of a key regulator of callus formation, WUSCHEL-RELATED HOMEOBOX 13 (WOX13), is induced by auxin. The ectopic callus formation from the bottom end, which is triggered by locally supplemented auxin, requires WOX13 function, demonstrating that WOX13 plays a pivotal role in auxin-dependent callus formation. The asymmetric WOX13 expression is observed both in grafted petioles and incised inflorescence stems, underscoring the generality of our findings. We propose that efficient organ reconnection is achieved by a combination of local wounding stimuli and disrupted long-distance signaling.

MYB3R-SCL28-SMR module with a role in cell size control negatively regulates G2 progression in Arabidopsis.

Cell size control is one of the prerequisites for plant growth and development. Recently, a GRAS family transcription factor, SCARECROW-LIKE28 (SCL28), was identified as a critical regulator for both mitotic and postmitotic cell-size control. Here, we show that SCL28 is specifically expressed in proliferating cells and exerts its function to delay G2 progression during mitotic cell cycle in Arabidopsis thaliana. Overexpression of SCL28 provokes a significant enlargement of cells in various organs and tissues, such as leaves, flowers and seeds, to different extents depending on the type of cells. The increased cell size is most likely due to a delayed G2 progression and accelerated onset of endoreplication, an atypical cell cycle repeating DNA replication without cytokinesis or mitosis. Unlike DWARF AND LOW-TILLERING, a rice ortholog of SCL28, SCL28 may not have a role in brassinosteroid (BR) signaling because sensitivity against brassinazole, a BR biosynthesis inhibitor, was not dramatically altered in scl28 mutant and SCL28-overexpressing plants. Collectively, our findings strengthen a recently proposed model of cell size control by SCL28 and suggest the presence of diversified evolutionary mechanisms for the regulation and action of SCL28.

[Bleeding due to acquired factor V inhibitor successfully treated with platelet transfusion during treatment for recurrent prostate squamous cell carcinoma].

A 78-year-old man with prostate squamous cell carcinoma recurrence in his pelvis was admitted to our hospital. Rectal obstruction led to creation of an artificial anus on the transverse colon. Then, docetaxel and radiation therapies were started. A week later, severe hematuria and melena occurred. Activated partial thromboplastin time (APTT) and prothrombin time (PT) were extremely prolonged. Cross-mixing test for APTT and PT revealed an inhibitor pattern, which was diagnosed as acquired factor V inhibitor. Fresh frozen plasma and vitamin K infusions were ineffective, but platelet transfusion successfully stopped the bleeding. Platelet factor V derived from megakaryocytes may affect local hemostasis. The patient received prednisolone (PSL), and the inhibitor disappeared on day 70 and was in remission. PSL could be stopped on day 100. Later, we demonstrated APTT and PT shortening of factor V deficient plasma by the supernatant of activated platelets with collagen.

Association between the Extent of Peripheral Blood DNA Methylation of HIF3A and Accumulation of Adiposity in community-dwelling Women: The Yakumo Study.

INTRODUCTION: DNA methylation in the CpG sites of intron 1 of HIF3A is associated with body mass index (BMI). This cross-sectional study investigated correlations between DNA methylation of HIF3A and BMI or adiposity parameters in the Japanese population. METHOD: DNA methylation of HIF3A was quantified via pyrosequencing. RESULT: DNA methylation of HIF3A differed only in women; DNA methylation level at cg27146050 was associated with visceral adipose tissue thickness and correlated with BMI and percent (%) body fat after excluding smokers. CONCLUSION: Peripheral blood DNA methylation at the CpG site (cg27146050) of HIF3A correlated with VAT thickness in Japanese women.

SUPPRESSOR OF PHYTOCHROME B-4 #3 reduces the expression of PIF-activated genes and increases expression of growth repressors to regulate hypocotyl elongation in short days.

SUPPRESSOR OF PHYTOCHROME B-4 #3 (SOB3) is a member of the AT-HOOK MOTIF CONTAINING NUCLEAR LOCALIZED (AHL) family of transcription factors that are involved in light-mediated growth in Arabidopsis thaliana, affecting processes such as hypocotyl elongation. The majority of the research on the AHLs has been conducted in continuous light. However, there are unique molecular events that promote growth in short days (SD) compared to constant light conditions. Therefore, we investigated how AHLs affect hypocotyl elongation in SD. Firstly, we observed that AHLs inhibit hypocotyl growth in SD, similar to their effect in constant light. Next, we identified AHL-regulated genes in SD-grown seedlings by performing RNA-seq in two sob3 mutants at different time points. Our transcriptomic data indicate that PHYTOCHROME INTERACTING FACTORS (PIFs) 4, 5, 7, and 8 along with PIF-target genes are repressed by SOB3 and/or other AHLs. We also identified PIF target genes that are repressed and have not been previously described as AHL-regulated, including PRE1, PIL1, HFR1, CDF5, and XTR7. Interestingly, our RNA-seq data also suggest that AHLs activate the expression of growth repressors to control hypocotyl elongation, such as HY5 and IAA17. Notably, many growth-regulating and other genes identified from the RNA-seq experiment were differentially regulated between these two sob3 mutants at the time points tested. Surprisingly, our ChIP-seq data suggest that SOB3 mostly binds to similar genes throughout the day. Collectively, these data suggest that AHLs affect gene expression in a time point-specific manner irrespective of changes in binding to DNA throughout SD.

Transcriptional activation of auxin biosynthesis drives developmental reprogramming of differentiated cells.

Plant cells exhibit remarkable plasticity of their differentiation states, enabling regeneration of whole plants from differentiated somatic cells. How they revert cell fate and express pluripotency, however, remains unclear. In this study, we demonstrate that transcriptional activation of auxin biosynthesis is crucial for reprogramming differentiated Arabidopsis (Arabidopsis thaliana) leaf cells. Our data show that interfering with the activity of histone acetyltransferases dramatically reduces callus formation from leaf mesophyll protoplasts. Histone acetylation permits transcriptional activation of PLETHORAs, leading to the induction of their downstream YUCCA1 gene encoding an enzyme for auxin biosynthesis. Auxin biosynthesis is in turn required to accomplish initial cell division through the activation of G2/M phase genes mediated by MYB DOMAIN PROTEIN 3-RELATED (MYB3Rs). We further show that the AUXIN RESPONSE FACTOR 7 (ARF7)/ARF19 and INDOLE-3-ACETIC ACID INDUCIBLE 3 (IAA3)/IAA18-mediated auxin signaling pathway is responsible for cell cycle reactivation by transcriptionally upregulating MYB3R4. These findings provide a mechanistic model of how differentiated plant cells revert their fate and reinitiate the cell cycle to become pluripotent.

Topoisomerase VI participates in an insulator-like function that prevents H3K9me2 spreading.

The organization of the genome into transcriptionally active and inactive chromatin domains requires well-delineated chromatin boundaries and insulator functions in order to maintain the identity of adjacent genomic loci with antagonistic chromatin marks and functionality. In plants that lack known chromatin insulators, the mechanisms that prevent heterochromatin spreading into euchromatin remain to be identified. Here, we show that DNA Topoisomerase VI participates in a chromatin boundary function that safeguards the expression of genes in euchromatin islands within silenced heterochromatin regions. While some transposable elements are reactivated in mutants of the Topoisomerase VI complex, genes insulated in euchromatin islands within heterochromatic regions of the Arabidopsis thaliana genome are specifically down-regulated. H3K9me2 levels consistently increase at euchromatin island loci and decrease at some transposable element loci. We further show that Topoisomerase VI physically interacts with S-adenosylmethionine synthase methionine adenosyl transferase 3 (MAT3), which is required for H3K9me2. A Topoisomerase VI defect affects MAT3 occupancy on heterochromatic elements and its exclusion from euchromatic islands, thereby providing a possible mechanistic explanation to the essential role of Topoisomerase VI in the delimitation of chromatin domains.

Trihelix transcription factors GTL1 and DF1 prevent aberrant root hair formation in an excess nutrient condition.

Root hair growth is tuned in response to the environment surrounding plants. While most previous studies focused on the enhancement of root hair growth during nutrient starvation, few studies investigated the root hair response in the presence of excess nutrients. We report that the post-embryonic growth of wild-type Arabidopsis plants is strongly suppressed with increasing nutrient availability, particularly in the case of root hair growth. We further used gene expression profiling to analyze how excess nutrient availability affects root hair growth, and found that RHD6 subfamily genes, which are positive regulators of root hair growth, are downregulated in this condition. However, defects in GTL1 and DF1, which are negative regulators of root hair growth, cause frail and swollen root hairs to form when excess nutrients are supplied. Additionally, we observed that the RHD6 subfamily genes are mis-expressed in gtl1-1 df1-1. Furthermore, overexpression of RSL4, an RHD6 subfamily gene, induces swollen root hairs in the face of a nutrient overload, while mutation of RSL4 in gtl1-1 df1-1 restore root hair swelling phenotype. In conclusion, our data suggest that GTL1 and DF1 prevent unnecessary root hair formation by repressing RSL4 under excess nutrient conditions.

4-Phenylbutyric acid promotes plant regeneration as an auxin by being converted to phenylacetic acid via an IBR3-independent pathway.

4-Phenylbutyric acid (4PBA) is utilized as a drug to treat urea cycle disorders and is also being studied as a potential anticancer drug that acts via its histone deacetylase (HDAC) inhibitor activity. During a search to find small molecules that affect plant regeneration in Arabidopsis, we found that 4PBA treatment promotes this process by mimicking the effect of exogenous auxin. Specifically, plant tissue culture experiments revealed that a medium containing 4PBA enhances callus formation and subsequent shoot regeneration. Analyses with auxin-responsive or cytokinin-responsive marker lines demonstrated that 4PBA specifically enhances AUXIN RESPONSE FACTOR (ARF)-dependent auxin responses. Our western blot analyses showed that 4PBA treatment does not enhance histone acetylation in Arabidopsis, in contrast to butyric acid and trichostatin A, other chemicals often used as HDAC inhibitors, suggesting this mechanism of action does not explain the observed effect of 4PBA on regeneration. Finally, mass spectroscopic analysis and genetic approaches uncovered that 4PBA in Arabidopsis plants is converted to phenylacetic acid (PAA), a known natural auxin, in a manner independent of peroxisomal IBR3-related ß-oxidation. This study demonstrates that 4PBA application promotes regeneration in explants via its auxin activity and has potential applications to not only plant tissue culture engineering but also research on the plant ß-oxidation pathway.