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Polycomb repressive complex 2 (PRC2) is an evolutionarily conserved epigenetic modifier responsible for tri-methylation of lysine 27 on histone H3 (H3K27me3). Previous studies have linked PRC2 to invariant natural killer T (iNKT) cell development, but its physiological and precise role remained unclear. To address this, we conditionally deleted Eed, a core subunit of PRC2, in mouse T cells. The results showed that Eed-deficient mice exhibited a severe reduction in iNKT cell numbers, particularly NKT1 and NKT17 cells, while conventional T cells and NKT2 cells remained intact. Deletion of Eed disrupted iNKT cell differentiation, leading to increased cell death, which was accompanied by a severe reduction in H3K27me3 levels and abnormal expression of Zbtb16, Cdkn2a, and Cdkn1a. Interestingly, Eed-deficient mice were highly susceptible to acetaminophen-induced liver injury and inflammation in an iNKT cell-dependent manner, highlighting the critical role of Eed-mediated H3K27me3 marks in liver-resident iNKT cells. These findings provide further insight into the epigenetic orchestration of iNKT cell-specific transcriptional programs. [ABSTRACT FROM AUTHOR]

Introduction. This review presents the current knowledge about the methods of lens surgery for the correction of refractive errors in patients with presbyopia and other refractive errors. And also about possible methods of minimization of ultrasound load during the surgery.Purpose. To present current relevant literature scientific knowledge on refractive lens surgery, possible ways of minimization of ultrasound load and new IOL models.Material and methods. To perform the review the literature references were searched through the abstract databases PubMed and Scopus for the period up to and including 2023 using the keywords “zero phaco”, “refractive lens exchange”, “presbyopia”, “femtosecond laser”, “U/S phaco”, “premium IOL”, “refractive error surgery”, “endothelial dystrophy”. A total of 76 articles related to the review topic were selected.Results. Multiple studies confirmed efficacy, safety and fast visual rehabilitation after lens surgery with maximal ultrasound load reduction, in particular in patients with metabolic disorders and predisposition to corneal dystrophies.Conclusion. The literature review suggests that with increasing patient expectations and the use of premium IOLs in the era of refractive lens surgery, predictability and accuracy have become essential. Thus, the technology of safe lens femtosurgery has greatly improved surgical techniques and has revolutionized ophthalmic surgery in recent decades.

Background: Our objective was to test the association between hematoma volume and long-term (> 72 h) edema extension distance (EED) evolution and the association between peak EED and early EED increase with functional outcome at 3 months in patients with intracerebral hemorrhage (ICH). Methods: This retrospective cohort study included patients with spontaneous supratentorial ICH between January 2006 and January 2014. EED, an edema measure defined as the distance between the hematoma border and the outer edema border, was calculated by using absolute hematoma and edema volumes. We used multivariable logistic regression accounting for age, ICH volume, and location and receiver operating characteristic analysis for assessing measures associated with functional outcome and EED evolution. Functional outcome after 3 months was assessed by using the modified Rankin Scale (0–3 = favorable, 4–6 = unfavorable). To identify properties associated with peak EED multivariable linear and logistic regression analyses were conducted. Results: A total of 292 patients were included. Median age was 70 years (interquartile range [IQR] 62–78), median ICH volume on admission 17.7 mL (IQR 7.9–40.2), median peak perihemorrhagic edema (PHE) volume was 37.5 mL (IQR 19.1–60.6), median peak EED was 0.67 cm (IQR 0.51–0.84) with an early EED increase up to 72 h (EED72–0) of 0.06 cm (− 0.02 to 0.15). Peak EED was found to be independent of ICH volume (R2 = 0.001, p = 0.6). In multivariable analyses, peak EED (odds ratio 0.224, 95% confidence interval [CI] [0.071–0.705]) and peak PHE volume (odds ratio 0.984 [95% CI 0.973–0.994]) were inversely associated with favorable functional outcome at 3 months. Receiver operating characteristic analysis identified a peak PHE volume of 26.8 mL (area under the curve 0.695 [95% CI 0.632–0.759]; p ≤ 0.001) and a peak EED of 0.58 cm (area under the curve 0.608 [95% CI 0.540–0.676]; p = 0.002) as best predictive values for outcome discrimination. Conclusions: Compared with absolute peak PHE volume, peak EED represents a promising edema measure in patients with ICH that is largely hematoma volume-independent and nevertheless associated with functional outcome. [ABSTRACT FROM AUTHOR]

Segmenting liver tumors in CT scans plays a vital role in medical analysis planning. The clinicians require a detailed 3D understanding of the tumor's location and liver anatomy, to decide about the proper surgical resection approach. Manual segmentation requires a lot of efforts and time also it depends on the expertise of clinicians. An automatic U-net based method for liver tumors delineation in CT images is proposed. It relies on employing attention-based processes to enhance the performance of U-net. Hard attention and soft attention are used to orient the U-net in learning the intended features from the target CT scans. Soft attention mechanisms, spatial and channel attentions, are employed to help in extracting the long-range relationships and allow the network to successfully distinguish tumors from the surrounding parenchyma. The paper addressed the use of region based active contour implemented using Chan and Vese approach as postprocessing step to improve the predicted segmented tumors. The proposed approach is validated using a challenging big LiTS datasets. The achieved Dice score for the segmenting of liver tumors is 0.81 which shows a superior performance compared to other proposed method in the state of art. The suggested method was successful in discriminating liver tumors from surrounding tissue in heterogeneous CT scans, taking the advantage from the important preprocessing enhancement step. The method demonstrates its generalizability and reliability to be used for automatic analysis of the liver tumors in daily clinical practice. Also, the method proved its ability to achieve high accuracy in detecting stroke that proves its ability to be utilized as clinical tool for a preoperative clinical planning. [ABSTRACT FROM AUTHOR]

Development of primordial germ cells (PGCs) is required for reproduction. During PGC development in mammals, major epigenetic remodeling occurs, which is hypothesized to establish an epigenetic landscape for sex-specific germ cell differentiation and gametogenesis. In order to address the role of embryonic ectoderm development (EED) and histone 3 lysine 27 trimethylation (H3K27me3) in this process, we created an EED conditional knockout mouse and show that EED is essential for regulating the timing of sex-specific PGC differentiation in both ovaries and testes, as well as X chromosome dosage decompensation in testes. Integrating chromatin and whole genome bisulfite sequencing of epiblast and PGCs, we identified a poised repressive signature of H3K27me3/DNA methylation that we propose is established in the epiblast where EED and DNMT1 interact. Thus, EED joins DNMT1 in regulating the timing of sex-specific PGC differentiation during the critical window when the gonadal niche cells specialize into an ovary or testis.

The kernel search optimizer (KSO) is a recent metaheuristic optimization algorithm that is based on kernel theory, eliminating the need for hyper-parameter adjustments, and demonstrating excellent global search capabilities. However, the original KSO exhibits insufficient accuracy in local search, and there is a high probability that it may fail to achieve local optimization in complex tasks. Therefore, this paper proposes a multi-strategy enhanced KSO (MSKSO) to enhance the local search ability of the KSO. The MSKSO combines several control strategies, including chaotic initialization, chaotic local search mechanisms, the high-altitude walk strategy (HWS), and the Levy flight (LF), to effectively balance exploration and exploitation. The MSKSO is compared with ten well-known algorithms on 50 benchmark test functions to validate its performance, including single-peak, multi-peak, separable variable, and non-separable variable functions. Additionally, the MSKSO is applied to two real engineering economic emission dispatch (EED) problems in power systems. Experimental results demonstrate that the performance of the MSKSO nearly optimizes that of other well-known algorithms and achieves favorable results on the EED problem. These case studies verify that the MSKSO outperforms other algorithms and can serve as an effective optimization tool. [ABSTRACT FROM AUTHOR]

EED is a core component of polycomb repressive complex 2 (PRC2) with EZH2 and SUZ12. PRC2 has H3K27 methyltransferase activity (HMTase) that catalyzes the addition of up to three methyl groups on histone 3 at lysine residue 27 (H3K27). Germline heterozygous variants in EED, SUZ12, and EZH2 have been identified in patients with overgrowth and multiple dysmorphic features. The clinical manifestations of these syndromes significantly overlap: generalized overgrowth, intellectual disability, and scoliosis. To date, 11 unrelated patients have been published with missense variants in EED at highly conserved amino acids. We report three affected members in a family with a previously reported missense variant. All three affected members manifested very similarly, and this represents a homogenous clinical phenotype associated with EED related intellectual disability and overgrowth. This disorder is appropriately called Cohen‐Gibson syndrome. [ABSTRACT FROM AUTHOR]

Inhibition of the Embryonic Ectoderm Development (EED) subunit in Polycomb Repressive Complex 2 (PRC2) can inhibit tumor growth. In this paper, we selected six experimentally designed EED competitive Inhibitors of the triazolopyrimidine derivatives class. We investigated the difference in the binding mode of the natural substrate to the Inhibitors and the effects of differences in the parent nuclei, heads, and tails of the Inhibitors on the inhibitory capacity. The results showed that the binding free energy of this class of Inhibitors was close to or lower compared to the natural substrate, providing an energetic basis for competitive inhibition. For the Inhibitors, the presence of a strong negatively charged group at the 6-position of the parent nucleus or the 8′-position of the head would make the hydrogen atom on the head imino group prone to flip, resulting in the vertical movement of the parent nucleus, which significantly decreased the inhibitory ability. When the 6-position of the parent nucleus was a nonpolar group, the parent nucleus would move horizontally, slightly decreasing the inhibitory ability. When the 8′-position of the head was methylene, it formed an intramolecular hydrophobic interaction with the benzene ring on the tail, resulting in a significant increase in inhibition ability. [ABSTRACT FROM AUTHOR]

ABSTRAK Pembangkit Listrik Tenaga Uap Batu bara menghasilkan zat SO2, CO2, NO2, dan partikel yang merupakan emisi dari proses pembakarannya. Emisi tersebut menyebabkan peningkatan efek pemanasan global, kerusakan lingkungan, dan merusak kesehatan. Dikarenakan pembangkit batu bara masih banyak digunakan di Indonesia maka Economic Emission Dispatch yang dikombinasikan dengan algoritma Whale Optimization Algorithm menjadi solusi dalam pengurangan emisi pembangkit listrik. Dengan cara memasukkan nilai weighted sum pada fungsi biaya dan emisi agar dapat dilihat pembangkit mana yang memiliki kadar emisi lebih rendah untuk memenuhi beban listrik yang dibutuhkan. Pada simulasi tersebut didapatkan pengurangan kadar emisi sebesar 12,73% dibandingkan tanpa menggunakan weighted sum dengan algortima WOA. Hal ini mampu untuk membantu program pemerintah dalam mengurangi emisi karbon agar tidak melebihi standar emisi yang telah ditetapkan sesuai dengan Peraturan Menteri Nomor P.15/MENLHK/SETJEN/KUM.1/4/2019. Kata kunci: PLTU batu bara, emisi, EED, WOA, weighted sum ABSTRACT Coal-fired power plants produce SO2, CO2, NO2, and particulate matter as emissions from the combustion process. These emissions cause increased global warming effects, environmental damage, and damage to health. coal plants are still widely used in Indonesia, Economic Emission Dispatch combined with the Whale Optimization Algorithm is a solution for reducing power plant emissions. By entering the weighted sum value in the cost and emission functions, it can be seen which plants have lower emission levels to meet the required electricity load. The simulation obtained a reduction in emission levels of 12.73% compared to not using weighted sum with the WOA algorithm. This method is able to help government programs in reducing carbon emissions so as not to exceed the emission standards that have been set in accordance with Peraturan Menteri Nomor P.15/MENLHK/SETJEN/ KUM.1/4/2019. Keywords: coal power plant, emission, EED, WOA, weighted sum

Weaver syndrome (WS), an overgrowth/intellectual disability syndrome (OGID), is caused by pathogenic variants in the histone methyltransferase EZH2, which encodes a core component of the Polycomb repressive complex-2 (PRC2). Using genome-wide DNA methylation (DNAm) data for 187 individuals with OGID and 969 control subjects, we show that pathogenic variants in EZH2 generate a highly specific and sensitive DNAm signature reflecting the phenotype of WS. This signature can be used to distinguish loss-of-function from gain-of-function missense variants and to detect somatic mosaicism. We also show that the signature can accurately classify sequence variants in EED and SUZ12, which encode two other core components of PRC2, and predict the presence of pathogenic variants in undiagnosed individuals with OGID. The discovery of a functionally relevant signature with utility for diagnostic classification of sequence variants in EZH2, EED, and SUZ12 supports the emerging paradigm shift for implementation of DNAm signatures into diagnostics and translational research.

Background: Brain tumours are the leading cause of cancer-related death in children, and there is no effective treatment. A growing body of evidence points to deregulated epigenetics as a tumour driver, particularly in paediatric cancers as they have relatively few genomic alterations, and key driver mutations have been identified in histone 3 (H3). Cancer stem cells (CSC) are implicated in tumour development, relapse and therapy resistance and thus particularly important to target. We therefore aimed to identify novel epigenetic treatment targets in CSC derived from H3-mutated high-grade glioma (HGG) through a CRISPR-Cas9 knockout screen. Results: The knockout screen identified more than 100 novel genes essential for the growth of CSC derived from paediatric HGG with H3K27M mutation. We successfully validated 12 of the 13 selected hits by individual knockout in the same two CSC lines, and for the top six hits we included two additional CSC lines derived from H3 wild-type paediatric HGG. Knockout of these genes led to a significant decrease in CSC growth, and altered stem cell and differentiation markers. Conclusions: The screen robustly identified essential genes known in the literature, but also many novel genes essential for CSC growth in paediatric HGG. Six of the novel genes (UBE2N, CHD4, LSM11, KANSL1, KANSL3 and EED) were validated individually thus demonstrating their importance for CSC growth in H3-mutated and wild-type HGG. These genes should be further studied and evaluated as novel treatment targets in paediatric HGG. [ABSTRACT FROM AUTHOR]

In this paper, a multi-objective modified seagull optimization algorithm (MOMSOA) is proposed to handle multi-objective environmental economic power dispatch (EED) problems. The algorithm utilizes logistic map to randomize the parameter u, which increases the diversity of the algorithm and speeds up the convergence rate. Besides, the mutation operator is combined to enlarge the range of the search and to avoid falling into the local optimum. The exploration as well as exploitation capabilities for MOSOA are balanced by non-linearizing the original linear parameter A through a cosine dynamic variation strategy. Furthermore, with the assistance of a unique constraint handling approach and non-inferior sorting, MOMSOA can obtain a set of uniform Pareto optimal solution (POS). In order to verify the effectiveness of MOMSOA, experiments were conducted on diverse test systems including IEEE30-Bus, IEEE57-Bus and IEEE118-Bus test systems. During the experimental process, MOSOA and MOPSO/MODE are compared with MOMSOA. Eight trials were conducted, and optimized objective functions include fuel cost, fuel cost with valve point effect, power loss and pollution emission. The results of experiments demonstrate that the proposed MOMSOA can obtain more uniform Pareto fronts (PFs) and optimal best compromise solution (BCS). Finally, two metrics that measure the performance of multi-objective algorithms, SP and HV, are employed to evaluate the results of each algorithm, and the results reveal that solutions obtained by MOMSOA are the most uniform, with the broadest diversity and the best convergence. [ABSTRACT FROM AUTHOR]

Inhibition of the Embryonic Ectoderm Development (EED) subunit in Polycomb Repressive Complex 2 (PRC2) can inhibit tumor growth. In this paper, we selected six experimentally designed EED competitive Inhibitors of the triazolopyrimidine derivatives class. We investigated the difference in the binding mode of the natural substrate to the Inhibitors and the effects of differences in the parent nuclei, heads, and tails of the Inhibitors on the inhibitory capacity. The results showed that the binding free energy of this class of Inhibitors was close to or lower compared to the natural substrate, providing an energetic basis for competitive inhibition. For the Inhibitors, the presence of a strong negatively charged group at the 6-position of the parent nucleus or the 8′-position of the head would make the hydrogen atom on the head imino group prone to flip, resulting in the vertical movement of the parent nucleus, which significantly decreased the inhibitory ability. When the 6-position of the parent nucleus was a nonpolar group, the parent nucleus would move horizontally, slightly decreasing the inhibitory ability. When the 8′-position of the head was methylene, it formed an intramolecular hydrophobic interaction with the benzene ring on the tail, resulting in a significant increase in inhibition ability.

Background and purpose: Continuous efforts have been made to move towards maintaining the beneficial anti‐inflammatory functions of glucocorticoids (GCs) while minimizing side effects. Here, we investigated the selective glucocorticoid receptor (GR) modulator‐like properties of a plant‐derived compound caesaldekarin e (CA‐e). Experimental approach: The therapeutic efficacy of CA‐e was evaluated in several mouse models, including dextran sulfate sodium‐induced colitis, ovalbumin‐induced lung allergic inflammation, imiquimod‐induced psoriasis‐like skin inflammation and skin atrophy. The action of CA‐e targeting the GR was analysed using molecular docking, cellular thermal shift assays and microscale thermophoresis. Other methods included DNA–protein pull‐down assays and mass spectrometry. Key results: CA‐e selectively inhibited positive GC response element ((+) GRE)‐mediated direct transactivation while maintaining and even enhancing the anti‐inflammatory effects of treatment with dexamethasone. CA‐e, alone and in combination with dexamethasone, efficiently alleviated inflammation in several mouse models with milder side effects compared with dexamethasone alone. Mechanistically, CA‐e inhibited the formation of dimers by binding to the dimerization interface located in the ligand‐binding domain of GR and facilitated embryonic ectoderm development that is involved in the regulation of transcriptional repression to compete for binding to (+) GRE, eventually leading to the repression of (+) GRE‐regulated genes. In addition, CA‐e repressed NF‐κB‐dependent genes by enhancing the interaction between GR and p65. Conclusions and implications: Our results reveal that CA‐e is a novel GR modulator with strong potency to attenuate the side effects of GC therapy and can be used as a potential molecular tool for deciphering GR signalling. [ABSTRACT FROM AUTHOR]

Ovarian organoids, based on female germline stem cells (FGSCs), are nowadays widely applied for reproductive medicine screening and exploring the potential mechanisms during mammalian oogenesis. However, there are still key issues that urgently need to be resolved in ovarian organoid technology, one of which is to establish a culture system that effectively expands FGSCs in vitro, as well as maintaining the unipotentcy of FGSCs to differentiate into oocytes. Here, FGSCs were EED226 treated and processed for examination of proliferation and differentiation in vitro. According to the results, EED226 specifically increased FGSC survival by decreasing the enrichment of H3K27me3 on Oct4 promoter and exon, as well as enhancing OCT4 expression and inhibiting P53 and P63 expression. Notably, we also found that FGSCs with EED226 treatment differentiated into more oocytes during oogenesis in vitro, and the resultant oocytes maintained a low level of P63 versus control at early stage development. These results demonstrated that inhibition of EED activity appeared to promote the survival of FGSCs and markedly inhibited their apoptosis during in vitro differentiation. As a result of our study, we propose an effective culture strategy to culture FGSCs and obtain oocytes in vitro, which provides a new vision for oogenesis in vitro.

Modulations in melanin synthesis and distribution caused by underlying genetic variants are considered to be majorly responsible for the inter-personal human pigmentation variation. In the publicly available Color Genes dataset, 171 cloned murine loci are documented to be involved with alterations in mice coat color. We hypothesize that the human orthologues of these 171 loci may also be implicated towards human pigmentation variation through their polymorphic variants. We used several freely available bioinformatic tools and designed a predictive pipeline to prioritize the Single Nucleotide Variants (SNVs) within and in the vicinity of the 171 human orthologues, according to their functional potential. The genes associated with the prioritized SNVs were annotated a potential function in the pigmentation pathway, based on extensive literature review and assessment of protein–protein interaction networks. Our analyses could prioritize 77 candidate SNVs including 10 non-synonymous SNVs, 45 synonymous SNVs and 22 regulatory SNVs associated with 46 genes that can potentially contribute towards human pigmentation variation. Our study, thus outlines a comprehensive bioinformatic pipeline using freely available web-tools that can be utilized in similar kind of studies dealing with other complex human traits and diseases where individual nucleotide variant imparts subtle functional roles in regulating the phenotype. [ABSTRACT FROM AUTHOR]

Background: Bovine milk is a beneficial ingredient in teh treatment of malnutrition., Objectives: Our objectives were to determine the effect of dietary milk protein and milk carbohydrate on the intestinal permeability, fecal 16S rRNA gene configuration, and fecal metabolomics of children with moderate malnutrition., Methods: This was a randomized, double-blind, controlled trial among 413 children with wasting in rural Sierra Leone who received 1 of the following 4 supplementary foods, which differed in sources of protein and carbohydrate: milk protein and milk carbohydrate (MPMC), milk protein and vegetable carbohydrate (MPVC), vegetable protein and milk carbohydrate (VPMC), or a control group consuming entirely vegetable-based food (VPVC). After 4 wk, urine and stool were collected from participants enrolled with mid-upper arm circumference of <12.1 cm. Urine was analyzed for lactulose excretion (%L). Stool samples were subjected to both 16S rRNA gene analysis to assess β-diversity and untargeted metabolomic abundance., Results: Among the 386 children who completed permeability testing, the mean difference (95% CI) in %L excretion as compared with VPVC was 0.01 (-0.05, 0.07) for MPMC, 0.05 (-0.01, 0.11) for MPVC, and 0.01 (-0.05, 0.07) for VPMC. Of the 374 children who provided a stool sample that was analyzed, the β-diversity among bacterial taxa was similar between dietary groups (P > 0.05 for all comparisons). No significant differences between dietary groups were seen among the 20 most abundant bacterial taxa. Among the 5769 unique metabolomic features identified, greater flavonoid levels in VPVC were seen., Conclusions: Abnormal intestinal permeability do not improve with 4 wk of supplementary feeding. Fecal rRNA do not differ with consumption of different diets. This trial was registered at clinicaltrials.gov as NCT04216043., Competing Interests: Conflict of interest MJM received funding from the Danish Dairy Research Foundation for this work and is an Associate Editor at the American Journal of Clinical Nutrition. All other authors report no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Polycomb repressive complex 2 (PRC2) is an evolutionarily conserved epigenetic modifier responsible for tri-methylation of lysine 27 on histone H3 (H3K27me3). Previous studies have linked PRC2 to invariant natural killer T (iNKT) cell development, but its physiological and precise role remained unclear. To address this, we conditionally deleted Eed, a core subunit of PRC2, in mouse T cells. The results showed that Eed-deficient mice exhibited a severe reduction in iNKT cell numbers, particularly NKT1 and NKT17 cells, while conventional T cells and NKT2 cells remained intact. Deletion of Eed disrupted iNKT cell differentiation, leading to increased cell death, which was accompanied by a severe reduction in H3K27me3 levels and abnormal expression of Zbtb16 , Cdkn2a , and Cdkn1a . Interestingly, Eed-deficient mice were highly susceptible to acetaminophen-induced liver injury and inflammation in an iNKT cell-dependent manner, highlighting the critical role of Eed-mediated H3K27me3 marks in liver-resident iNKT cells. These findings provide further insight into the epigenetic orchestration of iNKT cell-specific transcriptional programs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Guo, Ohki, Kawano, Kong, Ohno, Honda, Kanno and Yasuda.)

Background: Validated biomarkers could catalyze environmental enteric dysfunction (EED) research., Objectives: Leveraging an EED histology scoring system, this multicountry analysis examined biomarker associations with duodenal histology features among children with EED. We also examined differences in 2-h compared with 1-h urine collections in the lactulose rhamnose (LR) dual sugar test., Methods: Three cohorts of undernourished children unresponsive to nutrition intervention underwent esophagogastroduodenoscopy and duodenal biopsies. Histopathology scores were compared to fecal calprotectin (CAL), myeloperoxidase (MPO), neopterin (NEO), and urinary LR ratio and lactulose percentage recovery. Log-transformed biomarkers were used in linear regressions adjusted for age, center, and sample collection-biopsy time interval in multivariable models., Results: Data on >1 biomarker were available for 120 Bangladeshi (CAL, MPO, NEO, and LR), 63 Pakistani (MPO, NEO, and LR), and 63 Zambian children (CAL). Median age at endoscopy was similar (19 mo) across centers. Median sample collection prior to endoscopy was consistent with each center's study design: 2 wk in Bangladesh (urine and stool) and Zambia (stool), and 6 (urine) and 11 (stool) mo in Pakistan. In multivariable models, intraepithelial lymphocytes were associated with CAL (exponentiated [exp.] coefficient: 1.19; 95% confidence interval [CI]: 1, 1.41), intramucosal Brunner's glands with MPO (exp. coefficient: 1.33; 95% CI: 1.05, 1.69) and NEO (exp. coefficient: 1.37; 95% CI: 1.1, 1.7), and chronic inflammation with NEO (exp. coefficient: 1.61; 95% CI: 1.17, 2.17). Intraepithelial lymphocytes were associated with lactulose % recovery (exp. coefficient: 1.22; 95% CI: 1.05, 1.41). LR recovery was substantially lower in 1-h collections than in 2-h collections., Conclusions: Four commonly used markers of enteric dysfunction were associated with specific histologic features. One-hour urine collection may be insufficient to reflect small bowel permeability in LR testing. While acknowledging the challenges with obtaining relevant tissue, these findings form the basis for further EED biomarker validation research., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Polycomb repressive complex 2 (PRC2) is a multicomponent complex with methyltransferase activity that catalyzes trimethylation of histone H3 at lysine 27 (H3K27me3). Interaction of the epigenetic reader protein EED with EZH2, a catalytic unit of PRC, allosterically stimulates PRC2 activity. In this study, we investigated the role and underlying mechanism of the PRC2 in acute kidney injury (AKI) by using EED226, a highly selective PRC2 inhibitor, to target EED. Administration of EED226 improved renal function, attenuated renal pathological changes, and reduced renal tubular cell apoptosis in a murine model of cisplatin‐induced AKI. In cultured renal epithelial cells, treatment with either EED226 or EED siRNA also ameliorated cisplatin‐induced apoptosis. Mechanistically, EED226 treatment inhibited cisplatin‐induced phosphorylation of p53 and FOXO3a, two transcriptional factors contributing to apoptosis, and preserved expression of Sirtuin 3 and PGC1α, two proteins associated with mitochondrial protection in vivo and in vitro. EED226 was also effective in enhancing renal tubular cell proliferation, suppressing expression of multiple inflammatory cytokines, and reducing infiltration of macrophages to the injured kidney. These data suggest that inhibition of the PRC2 activity by targeting EED can protect against cisplatin‐induced AKI by promoting the survival and proliferation of renal tubular cells and inhibiting inflammatory response. [ABSTRACT FROM AUTHOR]

Epigenetic modifications by polycomb repressive complex (PRC) molecules appear to play a role in the tumorigenesis and aggressiveness of neuroblastoma (NB). Embryonic ectoderm development (EED) is a member of the PRC2 complex that binds to the H3K27me3 mark deposited by EZH2 via propagation on adjacent nucleosomes. We herein investigated the molecular roles of EED in MYCN-amplified NB cells using EED-knockdown (KD) shRNAs, EED-knockout sgRNAs, and the EED small molecule inhibitor EED226. The suppression of EED markedly inhibited NB cell proliferation and flat and soft agar colony formation. A transcriptome analysis using microarrays of EED-KD NB cells indicated the de-repression of cell cycle-regulated and differentiation-related genes. The results of a GSEA analysis suggested that inhibitory cell cycle-regulated gene sets were markedly up-regulated. Furthermore, an epigenetic treatment with the EED inhibitor EED226 and the HDAC inhibitors valproic acid/SAHA effectively suppressed NB cell proliferation and colony formation. This combined epigenetic treatment up-regulated cell cycle-regulated and differentiation-related genes. The ChIP sequencing analysis of histone codes and PRC molecules suggested an epigenetic background for the de-repression of down-regulated genes in MYCN-amplified/PRC2 up-regulated NB.

• Dysregulated PRC2 links tumor development with an EZH2 inhibitor approved in the market. • EED is an attractive drug target associated with PRC2 potentially mitigating challenges posed by EZH2 inhibitors. • Advances, challenges and opportunities in drug discovery targeting EED are discussed. • Novel approaches developing EED allosteric inhibitors and PROTAC degraders are briefly described. • EED inhibitors disrupting EED–EZH2 protein–protein interactions are also discussed. EED within the PRC2 complex is crucial for chromatin regulation particularly in tumor development, making its inhibition a promising epigenetic therapeutic strategy. Significant advancement in PRC2 inhibitor development has been achieved with an approved EZH2 inhibitor in the market and with others in the clinical trials. However, current EZH2 inhibitors are limited to specific blood cancers and encounter therapeutic resistance. EED stabilizes PRC2 complex and enhances its activity through unique allosteric mechanisms, thereby acting as both a scaffold protein and a recognizer of H3K27me3 making it an attractive drug target. This review provides an overview of epigenetic therapeutic strategies targeting EED, including allosteric inhibitors, PPI inhibitors, and PROTACs, together with brief discussions on the relevant challenges, opportunities, and future directions. [ABSTRACT FROM AUTHOR]

MAK683 (N-((5-fluoro-2,3-dihydrobenzofuran-4-yl)methyl)-8-(2-methylpyridin-3-yl)-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine) is a potent and orally bioavailable EED inhibitor for the potential treatment in oncology. Pharmacokinetics (PK) in preclinical species are characterised by low to moderate plasma clearances, high oral exposure, and moderate to high oral bioavailability at the dose of 1–2 mg/kg. A species comparison of the metabolic pathways of MAK683 has been made using [14C]MAK683 incubations with liver microsomes and hepatocytes from rat, dog, cynomolgus monkey, and human. Overall, the in vitro hepatic metabolism pathway of MAK683 in all five species was very complex. A total of 60 metabolites with 19 metabolites >1.5% of the total integrated area in the radiochromatogram of at least one species were identified in five species (rat, mouse, dog, monkey, and human). The primary in vitro hepatic oxidative metabolism pathway identified in humans involved 2-hydroxylation of the dihydrofuran ring to form alcohol (M28), which was in a chemical equilibrium favouring the formation of its aldehyde form. The aldehyde was then oxidised to the carboxylic acid metabolite (M26) or reduced to the O-hydroxyethylphenol (M29). N-dealkylation (M1), 3-hydroxylation of the dihydrofuran ring (M27), N-oxidation of the pyridine moiety (M53), and sulphate conjugation of M28 to form M19 were also important biotransformation pathways in human hepatocytes. The above major human hepatic metabolic pathways were also observed across the animal species (rat, mouse, dog, and monkey) mostly providing precursors for the formation of other metabolites via further oxygenation, glucuronidation, and sulphation pathways. No human-specific metabolites were observed. In addition, in vivo biotransformation was also conducted in bile-duct cannulated (BDC) rat. The metabolism in BDC rat was similar to those observed the in vitro hepatocytes. [ABSTRACT FROM AUTHOR]

Cohen–Gibson syndrome is a rare genetic disorder, characterized by fetal or early childhood overgrowth and mild to severe intellectual disability. It is caused by heterozygous aberrations in EED, which encodes an evolutionary conserved polycomb group (PcG) protein that forms the polycomb repressive complex‐2 (PRC2) together with EZH2, SUZ12, and RBBP7/4. In total, 11 affected individuals with heterozygous pathogenic variants in EED were reported, so far. All variants affect a few key residues within the EED WD40 repeat domain. By trio exome sequencing, we identified the heterozygous missense variant c.581A > G, p.(Asn194Ser) in exon 6 of the EED‐gene in an individual with moderate intellectual disability, overgrowth, and epilepsy. The same pathogenic variant was detected in 2 of the 11 previously reported cases. Epilepsy, however, was only diagnosed in one other individual with Cohen–Gibson syndrome before. Our findings further confirm that the WD40 repeat domain represents a mutational hotspot; they also expand the clinical spectrum of Cohen–Gibson syndrome and highlight the clinical variability even in individuals with the same pathogenic variant. Furthermore, they indicate a possible association between Cohen–Gibson syndrome and epilepsy. [ABSTRACT FROM AUTHOR]

The Polycomb Repressive Complex 2 (PRC2) regulates corticogenesis, yet the consequences of mutations to this epigenetic modifier in the mature brain are poorly defined. Importantly, PRC2 core genes are haploinsufficient and causative of several human neurodevelopmental disorders. To address the role of PRC2 in mature cortical structure and function, we conditionally deleted the PRC2 gene Eed from the developing mouse dorsal telencephalon. Adult homozygotes displayed smaller forebrain structures. Single-nucleus transcriptomics revealed that glutamatergic neurons were particularly affected, exhibiting dysregulated gene expression profiles, accompanied by aberrations in neuronal morphology and connectivity. Remarkably, homozygous mice performed well on challenging cognitive tasks. In contrast, while heterozygous mice did not exhibit clear anatomical or behavioral differences, they displayed dysregulation of neuronal genes and altered neuronal morphology that was strikingly different from homozygous phenotypes. Collectively, these data reveal how alterations to PRC2 function shape the mature brain and reveal a dose-specific role for PRC2 in determining glutamatergic neuron identity., (© The Author(s) 2024. Published by Oxford University Press.)

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In a two-year field experiment, six different weed control methods were studied. The methods were: use of the herbicide glyphosate (GL), use of herbicides based on acetic acid (AA), pelargonic acid (PA) and citrus essential oil (EO), mowing weeds with a thread trimmer (TT) and flaming of weeds with fire (FL). Alternative methods of weed control were significantly less effective than the use of herbicide glyphosate. Due to the lower efficiency of alternative methods, large yield losses have occurred, on average, 31 % at AA, 30.6 % at PA, 22.7 % at EO, 5.4 % at TT and 12.9 % at FL in two years. The cost of carrying out controls with alternative methods was significantly higher than the cost of GL. AA it was higher by 3.2-times, in PA by 7.1-times, in EO by 3.8-times, in TT by 3.8- times and in FL by 5.8-times on average in two years. To achieve a comparable control efficiency of GL, five applications of alternative preparations per year have to be performed, or four times mowing of weeds or five weed flaming operations per year.

Low enthalpy geothermal resources play an essential role in climate change mitigation. When ensuring the correct future operation of ground-source heat pump systems, an accurate design is mandatory. In this sense, different methodologies can be implemented. Although using sophisticated software constitutes the most optimal solution, its implementation is sometimes inviable in certain projects (the increase of the initial investment required is not justified in small plants). This work is focused on evaluating and comparing procedures used in the design of shallow geothermal systems. Thus, the research includes a simple method based on manual calculations, the Climasoft free application, Earth Energy Designer (EED) software, and the new geothermal tool GES-CAL developed by researchers from the TIDOP Research Group (University of Salamanca). The objective is to evaluate this new software and compare the results of all the detailed methodologies. This comparison derives from applying these tools in the calculation of the same case study (a single-family house placed in Ávila, Spain). Results show that the easiest methods involve oversized well-field schemas that also mean higher initial investments. Regarding GES-CAL, it is considered an accurate and valid alternative for the design of all heat exchanger configurations, especially for those installations placed in the region of Ávila. However, EED is recommended to calculate high-power geothermal systems that require an exhaustive analysis of the ground and the heat carrier fluid behaviour.

MANET-IoT networks are currently being focus developed and expected to become popular in next-generation mobile networks due to their simplicity and efficiency in solving real problems in a wide range of areas such as smart agriculture, smart health care, intelligent traffic, military, entertainment, and smart cities. Because of the nature of mobile network nodes, saving energy for MANET is always a complicated problem. In this paper, we proposed a saving energy routing protocol that uses an integrated routing metric from hops number and remaining energy metrics for decision-making to selects a fit route. Besides, we evaluate the performance of the proposed protocol on NS2 simulation software. Simulation results demonstrated the proposed protocol improves the network lifetime and network performance parameters compared to traditional protocols. [ABSTRACT FROM AUTHOR]

Enhancer of zeste homolog 2 (EZH2) is a histone lysine methyltransferase that is overexpressed in many cancers. Numerous EZH2 inhibitors have been developed as anticancer agents, but recent studies have also focused on protein–protein interaction (PPI) between embryonic ectoderm development (EED) and EZH2 as a novel drug discovery target. Because EED indirectly enhances EZH2 enzymatic activity, EED-EZH2 PPI inhibitors suppress the methyltransferase activity and inhibit cancer growth. By contrast to the numerous promising EZH2 inhibitors, there are a paucity of EED-EZH2 PPI inhibitors reported in the literature. Here, we aimed to discover novel EED-EZH2 PPI inhibitors by first identifying possible binders of EED using an in-house knowledge-based in silico fragment mapping method. Next, 3D pharmacophore models were constructed from the arrangement pattern of the potential binders mapped onto the EED surface. In all, 16 compounds were selected by 3D pharmacophore-based virtual screening followed by docking-based virtual screening. In vitro evaluation revealed that five of these compounds exhibited inhibitory activities. This study has provided structural insights into the discovery and the molecular design of novel EED-EZH2 PPI inhibitors using an in silico fragment mapping method. [ABSTRACT FROM AUTHOR]

Purpose: To compare the incidence and clinical characteristics of retinal detachments (RDs) diagnosed in a tertiary eye emergency department (EED) during the COVID-19 pandemic and in the corresponding period of the previous 4 years. Methods: EED consultations performed from February 21, 2020 (first national case of COVID-19 infection) to May 3, 2020 (end of lockdown imposed by national Government) and for the same date range of 2016– 2019 (pre-COVID-19 period), and with a confirmed diagnosis of RD were collected and reviewed. The following demographical and clinical features have been analyzed: age, gender, etiology of RD, macular involvement, best corrected visual acuity (BCVA), and duration of experienced symptoms. Results: Eighty-two subjects (20.5± 1.0 eyes/year) were diagnosed with RD in the pre-COVID-19 period, compared to 12 patients in the COVID-19 period (− 41.5%). During the pandemic, patients complained symptoms for a median of 8.5 days (IQR, 1.7– 15 days) before the EED consultation, while in the pre-COVID-19 period, they declared they had been symptomatic for 2 days (IQR, 1– 4 days) (p=0.037); macula-off RD raised from 56% to 75% and no one reported trauma as a triggering event. Conclusion: During the COVID-19 pandemic, the rate of RD diagnosed in our EED decreased significantly and patients waited longer before asking for an ophthalmologic examination. These findings are probably due to the fear of contracting the COVID-19 infection attending hospital environments. Even if emergency departments are often misused by people suffering non-urgent conditions, patients complaining of sudden visual loss, visual field defects, or phosphenes should always and promptly attend an EED visit to prevent a worse prognosis. [ABSTRACT FROM AUTHOR]

Abstract: The Polycomb Repressive complex 2 (PRC2) maintains a repressive chromatin state and silences many genes, acting as methylase on histone tails. This enzyme was found overexpressed in many types of cancer. In this work, we have set up a Computer‐Aided Drug Design approach based on the allosteric modulation of PRC2. In order to minimize the possible bias derived from using a single set of coordinates within the protein‐ligand complex, a dynamic workflow was developed. In details, molecular dynamic was used as tool to identify the most significant ligand‐protein interactions from several crystallized protein structures. The identified features were used for the creation of dynamic pharmacophore models and docking grid constraints for the design of new PRC2 allosteric modulators. Our protocol was retrospectively validated using a dataset of active and inactive compounds, and the results were compared to the classic approaches, through ROC curves and enrichment factor. Our approach suggested some important interaction features to be adopted for virtual screening performance improvement. [ABSTRACT FROM AUTHOR]

High Campylobacter prevalence during early childhood has been associated with stunting and environmental enteric dysfunction (EED), especially in low resource settings. This study assessed the prevalence, diversity, abundance, and co-occurrence of Campylobacter spp. in stools from children in a rural area of eastern Ethiopia and their association with microbiome, diarrhea, and EED in children. Stool samples (n = 100) were collected from randomly selected children (age range: 360–498 days) in five kebeles in Haramaya District, Ethiopia. Diarrhea, compromised gut permeability, and gut inflammation were observed in 48, 45, and 57% of children, respectively. Campylobacter prevalence and species diversity were assessed using PCR and meta-total RNA sequencing (MeTRS). The prevalence of Campylobacter spp. in the children's stools was 50% (41–60%) by PCR and 88% (80–93.6%) by MeTRS (P < 0.01). Further, seven Campylobacter species (Campylobacter jejuni, Campylobacter upsaliensis, Campylobacter hyointestinalis, Campylobacter coli, Campylobacter sp. RM6137, uncultured Campylobacter sp., and Campylobacter sp. RM12175) were detected by MeTRS in at least 40% of children stools in high abundance (>1.76-log read per million per positive stool sample). Four clusters of Campylobacter species (5–12 species per cluster) co-occurred in the stool samples, suggesting that Campylobacter colonization of children may have occurred through multiple reservoirs or from a reservoir in which several Campylobacter species may co-inhabit. No associations between Campylobacter spp., EED, and diarrhea were detected in this cross-sectional study; however, characteristic microbiome profiles were identified based on the prevalence of Campylobacter spp., EED severity, and diarrhea. Forty-seven bacterial species were correlated with Campylobacter, and 13 of them also correlated with gut permeability, gut inflammation and/or EED severity. Forty-nine species not correlated with Campylobacter were correlated with gut permeability, gut inflammation, EED severity and/or diarrhea. This study demonstrated that (1) in addition to C. jejuni and C. coli, multiple non-thermophilic Campylobacter spp. (i.e., Campylobacter hyointestinalis, Campylobacter fetus, and Campylobacter concisus) were frequently detected in the children's stools and (2) the Campylobacter, gut permeability, gut inflammation, EED severity, and diarrhea were associated with characteristic microbiome composition. Additional spatial and longitudinal studies are needed to identify environmental reservoirs and sources of infection of children with disparate Campylobacter species and to better define their associations with EED in low-income countries.

BackgroundAtrial fibrillation (AF) is accompanied by progressive epicardial fibrosis, dissociation of electrical activity between the epicardial layer and the endocardial bundle network, and transmural conduction (breakthroughs). However, causal relationships between these phenomena have not been demonstrated yet. Our goal was to test the hypothesis that epicardial fibrosis suffices to increase endo–epicardial dissociation (EED) and breakthroughs (BT) during AF.MethodsWe simulated the effect of fibrosis in the epicardial layer on EED and BT in a detailed, high-resolution, three-dimensional model of the human atria with realistic electrophysiology. The model results were compared with simultaneous endo–epicardial mapping in human atria. The model geometry, specifically built for this study, was based on MR images and histo-anatomical studies. Clinical data were obtained in four patients with longstanding persistent AF (persAF) and three patients without a history of AF.ResultsThe AF cycle length (AFCL), conduction velocity (CV), and EED were comparable in the mapping studies and the simulations. EED increased from 24.1 ± 3.4 to 56.58 ± 6.2% (p < 0.05), and number of BTs per cycle from 0.89 ± 0.55 to 6.74 ± 2.11% (p < 0.05), in different degrees of fibrosis in the epicardial layer. In both mapping data and simulations, EED correlated with prevalence of BTs. Fibrosis also increased the number of fibrillation waves per cycle in the model.ConclusionA realistic 3D computer model of AF in which epicardial fibrosis was increased, in the absence of other pathological changes, showed increases in EED and epicardial BT comparable to those in longstanding persAF. Thus, epicardial fibrosis can explain both phenomena.

Sonic hedgehog (Shh) signaling is essential for proliferation of cerebellar granule neuron progenitors (CGNPs) and its misregulation is linked to various disorders, including the cerebellar cancer medulloblastoma (MB). We recently identified RNF220, a ubiquitin E3 ligase promoting K63-linked polyubiquitylation and nuclear exportation of Gli transcription factors, as an Shh/Gli regulator involved in ventral neural patterning. Here, we report that RNF220 is required for the proliferation of CGNPs and Daoy cells (an Shh-grouped MB cell line), working as a positive regulator of Shh signaling. Mechanistic investigation demonstrated that RNF220 promotes Shh target gene expression by targeting the PRC2 component EED, and alters levels of epigenetic modification marks on Shh target promoters. We provided evidence that RNF220+/-; Ptch1+/- mice showed lower spontaneous MB occurrence compared with Ptch1+/- mice. Furthermore, in human clinical MB samples, RNF220 expression correlated well with that of GAB1, an Shh-group MB marker. Our findings provide new insights into the epigenetic regulation of Shh signaling and identify RNF220 as a potential new diagnostic marker and therapeutic target for Shh-group MB [ABSTRACT FROM AUTHOR]

Neurospora crassa contains a minimal Polycomb repression system, which provides rich opportunities to explore Polycomb-mediated repression across eukaryotes and enables genetic studies that can be difficult in plant and animal systems. Polycomb Repressive Complex 2 is a multi-subunit complex that deposits mono-, di-, and trimethyl groups on lysine 27 of histone H3, and trimethyl H3K27 is a molecular marker of transcriptionally repressed facultative heterochromatin. In mouse embryonic stem cells and multiple plant species, H2A.Z has been found to be colocalized with H3K27 methylation. H2A.Z is required for normal H3K27 methylation in these experimental systems, though the regulatory mechanisms are not well understood. We report here that Neurospora crassa mutants lacking H2A.Z or SWR-1, the ATP-dependent histone variant exchanger, exhibit a striking reduction in levels of H3K27 methylation. RNA-sequencing revealed downregulation of eed, encoding a subunit of PRC2, in an hH2Az mutant compared to wild type, and overexpression of EED in a ΔhH2Az;Δeed background restored most H3K27 methylation. Reduced eed expression leads to region-specific losses of H3K27 methylation, suggesting that differential dependence on EED concentration is critical for normal H3K27 methylation at certain regions in the genome. [ABSTRACT FROM AUTHOR]

Background: Atrial fibrillation (AF) is accompanied by progressive epicardial fibrosis, dissociation of electrical activity between the epicardial layer and the endocardial bundle network, and transmural conduction (breakthroughs). However, causal relationships between these phenomena have not been demonstrated yet. Our goal was to test the hypothesis that epicardial fibrosis suffices to increase endo–epicardial dissociation (EED) and breakthroughs (BT) during AF. Methods: We simulated the effect of fibrosis in the epicardial layer on EED and BT in a detailed, high-resolution, three-dimensional model of the human atria with realistic electrophysiology. The model results were compared with simultaneous endo–epicardial mapping in human atria. The model geometry, specifically built for this study, was based on MR images and histo-anatomical studies. Clinical data were obtained in four patients with longstanding persistent AF (persAF) and three patients without a history of AF. Results: The AF cycle length (AFCL), conduction velocity (CV), and EED were comparable in the mapping studies and the simulations. EED increased from 24.1 ± 3.4 to 56.58 ± 6.2% (p < 0.05), and number of BTs per cycle from 0.89 ± 0.55 to 6.74 ± 2.11% (p < 0.05), in different degrees of fibrosis in the epicardial layer. In both mapping data and simulations, EED correlated with prevalence of BTs. Fibrosis also increased the number of fibrillation waves per cycle in the model. Conclusion: A realistic 3D computer model of AF in which epicardial fibrosis was increased, in the absence of other pathological changes, showed increases in EED and epicardial BT comparable to those in longstanding persAF. Thus, epicardial fibrosis can explain both phenomena. [ABSTRACT FROM AUTHOR]

Polycomb repressive complex 2 (PRC2) mediates histone H3K27me3 methylation and the stable transcriptional repression of a number of gene expression programs involved in the control of cellular identity during development and differentiation. Here, we report on the generation and on the characterization of a zebrafish line harboring a null allele of eed, a gene coding for an essential component of the PRC2. Homozygous eed-deficient mutants present a normal body plan development but display strong defects at the level of the digestive organs, such as reduced size of the pancreas, hepatic steatosis, and a loss of the intestinal structures, to die finally at around 10–12 days post fertilization. In addition, we found that PRC2 loss of function impairs neuronal differentiation in very specific and discrete areas of the brain and increases larval activity in locomotor assays. Our work highlights that zebrafish is a suited model to study human pathologies associated with PRC2 loss of function and H3K27me3 decrease.

Abstract Background Polycomb repressive complex 2 (PRC2) catalyzes histone H3K27me3, which marks many transcriptionally silent genes throughout the mammalian genome. Although H3K27me3 is associated with silenced gene expression broadly, it remains unclear why some but not other PRC2 target genes require PRC2 and H3K27me3 for silencing. Results Here we define the transcriptional and chromatin features that predict which PRC2 target genes require PRC2/H3K27me3 for silencing by interrogating imprinted mouse X-chromosome inactivation. H3K27me3 is enriched at promoters of silenced genes across the inactive X chromosome. To abrogate PRC2 function, we delete the core PRC2 protein EED in F1 hybrid trophoblast stem cells (TSCs), which undergo imprinted inactivation of the paternally inherited X chromosome. Eed –/– TSCs lack H3K27me3 and Xist lncRNA enrichment on the inactive X chromosome. Despite the absence of H3K27me3 and Xist RNA, only a subset of the inactivated X-linked genes is derepressed in Eed –/– TSCs. Unexpectedly, in wild-type (WT) TSCs these genes are transcribed and are enriched for active chromatin hallmarks on the inactive-X, including RNA PolII, H3K27ac, and H3K36me3, but not the bivalent mark H3K4me2. By contrast, PRC2 targets that remain repressed in Eed –/– TSCs are depleted for active chromatin characteristics in WT TSCs. Conclusions A comparative analysis of transcriptional and chromatin features of inactive X-linked genes in WT and Eed –/– TSCs suggests that PRC2 acts as a brake to prevent induction of transcribed genes on the inactive X chromosome, a mode of PRC2 function that may apply broadly.

Nowadays, the power system is faced with some new changes from low-carbon approaches, though these approaches have proved to be effective in developing low-carbon electricity. Specifically, wind power integration and carbon trading influence the traditional economic emission dispatch (EED) mode, allowing for the disturbance of wind power uncertainties and the fluctuation of carbon trading price. Aiming at the above problems, this study firstly builds a stochastic EED model in the form of chance-constrained programming associated with wind power reliability. Next, wind power features are deduced from the statistic characteristics of wind speed, and thus the established model is converted to a deterministic form. After that, an auxiliary decision-making method based on the technique for order preference by similarity to an ideal solution (TOPSIS) is designed to draw the optimal solution based upon the specific requirements of carbon emission control. The simulation results eventually indicate that the minimization of fuel costs and carbon emissions comes at the expense of wind power reliability. Meanwhile, carbon emission reduction can be effectively realized by carbon trading rather than a substantial increase in fuel costs, and carbon trading may help to improve power generation efficiency. Furthermore, carbon trading prices could be determined by the demands of carbon emission reduction and power generation efficiency improvement.

Numerous molecular processes conduct epigenetic regulation of protein transcription to maintain cell specification. In this review, we discuss molecular mechanisms of the Polycomb group of proteins and its enzymatic role in epigenetics. More specifically, we focus on the Polycomb repressive complex 2 (PRC2) and the effects of its repressive marker. We have compiled information regarding the biological structure and how that impacts the stability of the complex. In addition, we examined functions of the individual core proteins of PRC2 in relation to the accessory proteins that interact with the complex. Lastly, we discuss the implications of unregulated and downregulated PRC2 activity in Alzheimer's disease and cancer and possible methods of treatment related to PRC2 regulation. [ABSTRACT FROM AUTHOR]