PCAF promotes R-loop resolution via histone acetylation.

R-loops cause genome instability, disrupting normal cellular functions. Histone acetylation, particularly by p300/CBP-associated factor (PCAF), is essential for maintaining genome stability and regulating cellular processes. Understanding how R-loop formation and resolution are regulated is important because dysregulation of these processes can lead to multiple diseases, including cancer. This study explores the role of PCAF in maintaining genome stability, specifically for R-loop resolution. We found that PCAF depletion promotes the generation of R-loop structures, especially during ongoing transcription, thereby compromising genome stability. Mechanistically, we found that PCAF facilitates histone H4K8 acetylation, leading to recruitment of the a double-strand break repair protein (MRE11) and exonuclease 1 (EXO1) to R-loop sites. These in turn recruit Fanconi anemia (FA) proteins, including FANCM and BLM, to resolve the R-loop structure. Our findings suggest that PCAF, histone acetylation, and FA proteins collaborate to resolve R-loops and ensure genome stability. This study therefore provides novel mechanistic insights into the dynamics of R-loops as well as the role of PCAF in preserving genome stability. These results may help develop therapeutic strategies to target diseases associated with genome instability.

R-loops are harmful DNA-RNA hybrid structures that cause genome instability, disrupting normal cell functions. This study explored the role of the protein PCAF in resolving R-loops to maintain genome stability. The researchers found that depleting PCAF leads to increased R-loop formation, especially during transcription, compromising the genome. Mechanistically, PCAF facilitates histone acetylation, recruiting proteins like MRE11, EXO1, FANCM and BLM to R-loop sites. These proteins collaborate to resolve R-loop structures. The findings suggest that PCAF, histone acetylation, and these repair proteins work together to untangle R-loops and preserve genome integrity. Understanding this process provides insights into R-loop dynamics and PCAF's role in genome maintenance, potentially leading to therapeutic strategies for diseases associated with genome instability, such as cancer.

Notes of Five Wood-Decaying Fungi from Juwangsan National Park in Korea.

Wood-decaying fungi are essential decomposers in forest ecosystems. They decompose wood substrates by producing various lignocellulolytic enzymes, which have significant industrial and medical applications. A survey was conducted at the Juwangsan National Park from 2018 to 2019 to determine the diversity of macrofungi in Korea. Five previously unrecorded wood-decaying polyporoid and corticioid fungi were identified among the collected specimens: Eichleriella sinensis, Hymenochaete anomala, Hyphoderma subsetigerum, Lyomyces orientalis, and Pseudowrightoporia crassihypha. These species were identified based on morphological, molecular, and phylogenetic analyses of the internal transcribed spacer (ITS) and nuclear large subunit rDNA (nLSU) region. In this study, we provide detailed macro- and micro-morphological figures with phylogenetic trees to support the discovery of five new species in Korea.

Mass spectrometry-guided isolation of thiodiketopiperazines from an EtOAc-extract of Setosphaeria rostrata culture medium and their anti-skin aging effects on TNF-α-induced human dermal fibroblasts.

Using mass spectrometry (MS)-guided isolation methods, a new thiodiketopiperazine derivative (1) and exserohilone (2) were isolated from an EtOAc-extract of Setosphaeria rostrata culture medium. The chemical structure of the new compound was elucidated by MS and NMR spectroscopy, and the absolute configurations were established by the quantum mechanical calculations of electronic circular dichroism. All isolated compounds were examined for their effects on reactive oxygen species (ROS) production, matrix metalloproteinase 1 (MMP-1) secretion, and procollagen type I α1 secretion in tumor necrosis factor (TNF)-α-induced human dermal fibroblasts. Compound 1 and exserohilone (2) exhibited the inhibition of TNF-α-induced ROS generation and MMP-1 secretion. Additionally, compound 1 and exserohilone (2) increased the procollagen type I α1 secretion. Compound 1 docked computationally into the active site of MMP-1 (-6.0 kcal/mol).

Evaluation of the adsorption performance and thermal treatment-associated regeneration of adsorbents for formaldehyde removal.

Indoor air pollution remains a major concern, with formaldehyde (HCHO) a primary contributor due to its long emission period and associated health risks, including skin allergies, coughing, and bronchitis. This study evaluated the adsorption performance and economic efficiency of various adsorbents (biochar, activated carbon, zeolites A, X, and Y) selected for HCHO removal. The impact of thermal treatment on adsorbent regeneration was also assessed. The experimental apparatus featured an adsorption column and HCHO concentration meter with an electrochemical sensor designed for adsorption analysis. Zeolite X exhibited the highest adsorption performance, followed by zeolite A, zeolite Y, activated carbon, and biochar. All adsorbents displayed increased HCHO removal rates with an extended length/diameter (L/D) ratio of the adsorption column. Zeolite A demonstrated the highest economic efficiency, followed by zeolite X, activated carbon, zeolite Y, and biochar. Higher L/D ratios improved economic efficiency and prolonged the replacement cycle (the optimal timing for adsorbent replacement to maintain high adsorption performance). Sensitivity analysis of adsorbent regeneration under varying thermal treatment conditions (150, 120, and 80°C) and durations (60, 45, and 30 min) revealed minimal changes in adsorption efficiency (±3%). The results indicated the potential of adsorbent regeneration under energy-efficient thermal treatment conditions (80°C, 30 min). In conclusion, this study underscores the importance of a comprehensive assessment, considering factors such as adsorption performance, replacement cycle, economic efficiency, and regeneration performance for the selection of optimal adsorbents for HCHO adsorption and removal.Implications: This study underscores the importance of adsorption technology for the removal of formaldehyde and similar volatile organic compounds (VOCs), highlighting the potential of alternative adsorbents, such as environmentally friendly biochar, in addition to traditional strategies, such as activated carbon and zeolites. Our findings demonstrate the feasibility of adsorbent regeneration under energy-efficient thermal treatment conditions. These results hold promise for improving indoor air quality, reducing environmental pollutants, and enhancing responses to air contaminants like fine dust and VOCs.

Tenacibaculum tangerinum sp. nov., isolated from a tidal flat sediment.

An orange-coloured bacterium, designated as strain GRR-S3-23T, was isolated from a tidal flat sediment collected from Garorim Bay, Chuncheongbuk-do, Republic of Korea. Cells of GRR-S3-23T were aerobic, Gram-stain-negative, rod-shaped and motile. GRR-S3-23T grew at 18-40 °C (optimum, 30 °C), pH 7.0-9.0 (optimum, pH 7.0) and with 2-4 % NaCl (optimum, 2-3 % w/v). Results of 16S rRNA gene sequence analysis indicated that GRR-S3-23T was closely related to Tenacibaculum aiptasiae a4T (97.6 %), followed by Tenacibaculum aestuarii SMK-4T (97.5 %), Tenacibaculum mesophilum MBIC 1140T (97.4 %), Tenacibaculum singaporense TLL-A2T (97.3 %), Tenacibaculum crassostreae JO-1T (97.2 %),and Tenacibaculum sediminilitoris YKTF-3T (97.1 %). The average amino acid identity values between GRR-S3-23T and the related strains were 86.8-72.8 %, the average nucleotide identity values were 83.3-74.1 %, and the digital DNA-DNA hybridization values were 27.0-19.6 %. GRR-S3-23T possessed menaquinone-6 (MK-6) as major respiratory quinone and had summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c, 20.6 %) and iso-C15 : 1G (10.8 %) as major fatty acids (>10.0 %). The polar lipid profiles of GRR-S3-23T contained phosphatidylethanolamine, one unidentified aminolipid, one unidentified aminophospholipid, three unidentified lipids, one unidentified glycolipid and four unidentified phospholipids. The DNA G+C content of GRR-S3-23T was 33.7%. On the basis of the results of the polyphasic analysis involving phylogenetic, phylogenomic, physiological and chemotaxonomic analyses described in this study, GRR-S3-23T is considered to represent a novel species within the genus Tenacibaculum, for which the name Tenacibaculum tangerinum is proposed. The type strain is GRR-S3-23T (=KCTC 102029T=KACC 23271T=JCM 36353T).

APOBEC3B regulates R-loops and promotes transcription-associated mutagenesis in cancer.

The single-stranded DNA cytosine-to-uracil deaminase APOBEC3B is an antiviral protein implicated in cancer. However, its substrates in cells are not fully delineated. Here APOBEC3B proteomics reveal interactions with a surprising number of R-loop factors. Biochemical experiments show APOBEC3B binding to R-loops in cells and in vitro. Genetic experiments demonstrate R-loop increases in cells lacking APOBEC3B and decreases in cells overexpressing APOBEC3B. Genome-wide analyses show major changes in the overall landscape of physiological and stimulus-induced R-loops with thousands of differentially altered regions, as well as binding of APOBEC3B to many of these sites. APOBEC3 mutagenesis impacts genes overexpressed in tumors and splice factor mutant tumors preferentially, and APOBEC3-attributed kataegis are enriched in RTCW motifs consistent with APOBEC3B deamination. Taken together with the fact that APOBEC3B binds single-stranded DNA and RNA and preferentially deaminates DNA, these results support a mechanism in which APOBEC3B regulates R-loops and contributes to R-loop mutagenesis in cancer.

The impact of circulatory arrest with selective antegrade cerebral perfusion on brain functional connectivity and postoperative cognitive function.

Aortic surgery is one of the most challenging types of surgeries, which is possibly related to cognitive sequelae. We aimed to investigate the changes in resting-state functional connectivity (rsFC) associated with intraoperative circulatory arrest (CA) in aortic surgery, exploring the relationship between the altered connectivity and postoperative cognitive functions. Thirty-eight patients participated in this study (14 with CA, 24 without). Functional magnetic resonance imaging was scanned on the fifth day after surgery or after the resolution of delirium if it was developed. We assessed the differences in the development of postoperative cognitive changes and rsFC between patients with and without CA. The occurrence of postoperative delirium and postoperative cognitive dysfunction was not significantly different between the patients with and without the application of CA. However, patients with CA showed increased in posterior cingulate cortex-based connectivity with the right superior temporal gyrus, right precuneus, and right hippocampus, and medial prefrontal cortex-based connectivity with the dorsolateral prefrontal cortex. The application of moderate hypothermic CA with unilateral antegrade cerebral perfusion is unlikely to affect aspects of postoperative cognitive changes, whereas it may lead to increased rsFC of the default mode network at a subclinical level following acute brain insults.

Sphingomicrobium sediminis sp. nov., isolated from marine sediment in the Republic of Korea.

A Gram-stain-negative, rod-shaped, bright-orange coloured bacterium without flagellum, designated as strain GRR-S6-50T, was isolated from a tidal flat of Garorim bay, Taean-gun, Chungcheongbuk-do, Republic of Korea. Cells grew aerobically at 20-37 °C (optimum, 30 °C), pH 7.0-10.0 (optimum, pH 7.0) and with 1-5 % (w/v) NaCl (optimum, 3 %). The 16S rRNA gene sequence analysis demonstrated that strain GRR-S6-50T was closely related to Sphingomicrobium aestuariivivum AH-M8T with a sequence similarity of 97.80 % followed by Sphingomicrobium astaxanthinifaciens CC-AMO-30BT (97.44 %), Sphingomicrobium marinum CC- AMZ-30MT (97.16 %), Sphingomicrobium arenosum CAU 1457T (96.37 %), Sphingomicrobium flavum CC-AMZ-30NT (95.31 %) and Sphingomicrobium lutaoense CC-TBT-3T (95.23 %). The average nucleotide identity and digital DNA-DNA hybridization values with related strains ranged from 74.5 to 77.3% and 21.1 to 35.0 %, respectively. The G+C content of strain GRR-S6-50T was 63.30 mol%. The strain has ubiquinone-10 as the predominant respiratory quinone and the major fatty acids were C18 : 3 ω6c (54.57 %) and C17 : 1 ω6c (10.58 %). The polar lipids consisted of phosphatidylethanolamine, phosphatidylglycerol, three unidentified lipids and one glycolipid. On the basis of the results of phylogenetic, phenotypic and chemotaxonomic studies, strain GRR-S6-50T is regarded to represent a novel species within the genus Sphingomicrobium, for which the name Sphingomicrobium sediminis sp. nov. (KACC 22562T=KCTC 92123T=JCM 35084T) is proposed.

Clinical and Mechanistic Implications of R-Loops in Human Leukemias.

Genetic mutations or environmental agents are major contributors to leukemia and are associated with genomic instability. R-loops are three-stranded nucleic acid structures consisting of an RNA-DNA hybrid and a non-template single-stranded DNA. These structures regulate various cellular processes, including transcription, replication, and DSB repair. However, unregulated R-loop formation can cause DNA damage and genomic instability, which are potential drivers of cancer including leukemia. In this review, we discuss the current understanding of aberrant R-loop formation and how it influences genomic instability and leukemia development. We also consider the possibility of R-loops as therapeutic targets for cancer treatment.

Relationship between body mass index and risk of delirium in an intensive care unit.

OBJECTIVE: Delirium in the intensive care unit (ICU) is a common and critical condition that leads to poor prognosis in older patients, but the association between body mass index (BMI) and the incidence of delirium remains unclear. METHODS: We retrospectively analyzed 5,622 patients admitted to the ICU of a tertiary referral hospital between 2013 and 2022. We collected sociodemographic data, vital signs, laboratory results, and delirium scale scores. We subdivided the patients into four categories: underweight (<18.5 kg/m2), normal weight (18.5-22.9 kg/m2), overweight (23-24.9 kg/m2), and obese (>25 kg/m2). The primary outcome was the incidence of delirium according to the BMI categories. We performed multivariable logistic regression analysis, adjusted for sex, age, past smoking and alcohol history, benzodiazepine use, and laboratory abnormalities. RESULTS: Among the 5,622 patients in the ICU (mean age, 72.9 years; male, 60.1%; mean BMI, 24.2 kg/m2), the incidence of delirium was 19.0% (1,069 patients). The mean modified incidence of delirium was higher among underweight patients (odds ratio [OR]=1.51, confidence interval [CI]=1.07-2.12, p = 0.02) than among normal-weight patients. Overweight and obese status were not independently associated with delirium (OR=0.90, CI=0.70-1.17, p = 0.43; OR= 0.97; CI=0.77-1.21, p = 0.78, respectively). The area under the receiver-operating characteristic curve of the multivariable logistic regression model was 0.71 (95% CI=0.69-0.73). CONCLUSIONS: Underweight status is an independent risk factor for delirium in the ICU. Additional caution is required when evaluating underweight patients for delirium. Obese or overweight status are not associated with delirium, providing evidence for the obesity paradox.

Delirium-related factors and their prognostic value in patients undergoing craniotomy for brain metastasis.

Background: Delirium is characterized by acute brain dysfunction. Although delirium significantly affects the quality of life of patients with brain metastases, little is known about delirium in patients who undergo craniotomy for brain metastases. This study aimed to identify the factors influencing the occurrence of delirium following craniotomy for brain metastases and determine its impact on patient prognosis. Method: A total of 153 patients who underwent craniotomy for brain metastases between March 2013 and December 2020 were evaluated for clinical and radiological factors related to the occurrence of delirium. Statistical analysis was conducted by dividing the patients into two groups based on the presence of delirium, and statistical significance was confirmed by adjusting the clinical characteristics of the patients with brain metastases using propensity score matching (PSM). The effect of delirium on patient survival was subsequently evaluated using Kaplan-Meier analysis. Results: Of 153 patients, 14 (9.2%) had delirium. Age (P = 0.002), sex (P = 0.007), and presence of postoperative hematoma (P = 0.001) were significantly different between the delirium and non-delirium groups. When the matched patients (14 patients in each group) were compared using PSM, postoperative hematoma showed a statistically significant difference (P = 0.036) between the delirium and non-delirium groups. Kaplan-Meier survival analysis revealed that the delirium group had poorer prognosis (log-rank score of 0.0032) than the non-delirium group. Conclusion: In addition to the previously identified factors, postoperative hematoma was identified as a strong predictor of postoperative delirium. Also, the negative impact of delirium on patient prognosis including low survival rate was confirmed.

Risk of developing depression from endocrine treatment: A nationwide cohort study of women administered treatment for breast cancer in South Korea.

Background: Although previous studies demonstrated no association between depression and tamoxifen in patients with breast cancer, there is still a limited amount of long-term follow-up data. This study aimed to evaluate the relationship between endocrine treatment and the risk of depression. Methods: This nationwide population-based cohort study used data obtained over a 14-year period (January 2007 to December 2021) from the Korean National Health Insurance claims database. All female patients with breast cancer were included. We examined the incidence of depression in patients who underwent endocrine treatment, and those who did not undergo endocrine treatment constituted the control group. Results: The data from 11,109 patients who underwent endocrine treatment and 6,615 control patients between 2009 and 2010 were analyzed. After performing matching for comorbidities and age, both groups comprised 6,532 patients. The median follow-up were 119.71 months. Before and after matching was performed, the endocrine treatment was not a significant risk factor for developing depression (p=0.7295 and p=0.2668, respectively), nor was it a significant factor for an increased risk for suicide attempt (p=0.6381 and p=0.8366, respectively). Conclusions: Using a real-world population-based cohort, this study demonstrated that there is no evidence that the endocrine treatment increases the risk of depression.

Aurantiacibacter sediminis sp. nov., a marine bacterium isolated from a tidal flat.

A yellow-coloured bacterium, designated as strain JGD-13T, was isolated from a tidal flat in the Republic of Korea. Cells were Gram-stain-negative, aerobic, non-flagellated and rod-shaped. Growth was observed at 4-42 °C (optimum, 30 °C), at pH 6.0-12.0 (pH 7.0-8.0) and at 1-7 % (w/v) NaCl concentration (3 %). The 16S rRNA gene sequence analysis indicated that strain JGD-13T was closely related to Aurantiacibacter gangjinensis K7-2T with a sequence similarity of 98.2 %, followed by Aurantiacibacter aquimixticola JSSK-14T (98.1 %), Aurantiacibacter atlanticus s21-N3T (97.6 %), Aurantiacibacter zhengii V18T (97.6 %) and Aurantiacibacter luteus KA37T (97.5 %). The average nucleotide identity and digital DNA-DNA hybridization values with related strains were 70.3-76.2 % and 18.5-20.3 %. The genomic DNA G+C content was 60.2 mol%. Phylogenetic analysis using the maximum-likelihood method showed that strain JGD-13T formed a clade with A. aquimixticola JSSK-14T and A. gangjinensis K7-2T. The major fatty acids were summed feature 8 (39.7 %) and C17 : 1 ω6c (14.4 %). The predominant respiratory quinone was ubiquinone-10. The polar lipids were phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, one sphingoglycolipid and three unidentified lipids. On the basis of phylogenetic, phenotypic and chemotaxonomic characteristics, strain JGD-13T represents a novel species within the genus Aurantiacibacter, for which the name Aurantiacibacter sediminis JGD-13Tsp. nov. is proposed. The type strain is JGD-13T (=KCTC 72892T=KACC 21676T=JCM 33995T).

Best available technique for the recovery of marine benthic communities in a gravel shore after the oil spill: A mesocosm-based sediment triad assessment.

Ecotoxicological effects of spilled oils are well documented, but study of recovery of marine benthic communities is limited. Long-term recovery of hard bottom communities during physical and biological remediations after a spill was monitored. A 60-day experiment was conducted using a mesocosm with monitoring of eight endpoints by use of the sediment quality triad (SQT). First, physical treatment of hot water + high pressure flushing maximally removed residual oils (max=93%), showing the greatest recovery among SQT variables (mean=72%). Physical cleanup generally involved adverse effects such as depression of the microphytobenthic community during the initial period. Next, biological treatments, such as fertilizer, emulsifier, enzyme and augmentation of the microbes, all facilitated removal of oil (max=66%) enhancing ecological recovery. Analysis of the microbiome confirmed that oil-degrading bacteria, such as Dietzia sp. and Rosevarius sp. were present. A mixed bioremediation, including fertilizer + multi-enzyme + microbes (FMeM) maximized efficacy of remediation as indicated by SQT parameters (mean=47%). Natural attenuation with "no treatment" showed comparable recovery to other remediations. Considering economic availability, environmental performance, and technical applicability, of currently available techniques, combined treatments of physical removal via hand wiping followed by FMeM could be most effective for recovery of the rocky shore benthic community.

Halomonas getboli sp. nov., a halotolerant bacteria isolated from a salt flat.

A novel Gram-stain-negative, rod-shaped, cream-coloured, motile, halotolerant bacterium, designated as YJPS3-2T, was isolated from saltern sediment of the Yellow sea in Yongyu-do, Republic of Korea. Strain YJPS3-2T grew at pH 5.0-10.0 (optimum, pH 7.0), 4-40 °C (optimum, 30 °C) and with 1-15% (w/v) NaCl (optimum 3 %). The 16S rRNA gene sequence analysis indicated that strain YJPS3-2T was closely related to those of Halomonas halophila F5-7T (98.75 %), Halomonas salina F8-11T (98.74 %), Halomonas smyrnensis AAD6T (98.66 %), Halomonas organivorans G-16.1T (98.34 %), Halomonas koreensis SS20T (97.98 %) and Halomonas beimenensis NTU-107T (96.93 %). The average nucleotide identity and digital DNA-DNA hybridization values between YJPS3-2T and related type strains were 86.9-91.6 % and 32.0-44.8 %. Strain YJPS3-2T was characterized as having Q-9 as the predominant respiratory quinone and the principal fatty acids (>10 %) were C16 : 0 (31.4 %), C19 : 0 ω8c cyclo (16.3 %), C17 : 0 cyclo (11.9 %) and C12 : 0 3-OH (10.4 %). The polar lipids consisted of phosphatidylcholine, diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylglycerol. The DNA G+C content of strain YJPS3-2T is 68.1mol %. Based on the polyphasic taxonomic evidence presented in this study, YJPS3-2T should be classified as representing a novel species within the genus Halmonas, for which name Halomonas getboli is proposed, with the type strain YJPS3-2T (= KCTC 92124T=KACC 22561T=JCM 35085T).

Raphani Semen (Raphanus sativus L.) Ameliorates Alcoholic Fatty Liver Disease by Regulating De Novo Lipogenesis.

In this study, we investigated the pharmacological effect of a water extract of Raphani Semen (RSWE) on alcoholic fatty liver disease (AFLD) using ethanol-induced AFLD mice (the NIAAA model) and palmitic acid (PA)-induced steatosis HepG2 cells. An RSWE supplement improved serum and hepatic triglyceride (TG) levels of AFLD mice, as well as their liver histological structure. To explore the molecular action of RSWE in the improvement of AFLD, we investigated the effect of RSWE on four major pathways for lipid homeostasis in the liver: free fatty acid transport, lipogenesis, lipolysis, and ß-oxidation. Importantly, RSWE decreased the mRNA expression of de novo lipogenesis-related genes, such as Srebf1, Cebpa, Pparg, and Lpin1, as well as the protein levels of these factors, in the liver of AFLD mice. That these actions of RSWE affect lipogenesis was confirmed using PA-induced steatosis HepG2 cells. Overall, our findings suggest that RSWE has the potential for improvement of AFLD by inhibiting de novo lipogenesis.

USP39 promotes non-homologous end-joining repair by poly(ADP-ribose)-induced liquid demixing.

Mutual crosstalk among poly(ADP-ribose) (PAR), activated PAR polymerase 1 (PARP1) metabolites, and DNA repair machinery has emerged as a key regulatory mechanism of the DNA damage response (DDR). However, there is no conclusive evidence of how PAR precisely controls DDR. Herein, six deubiquitinating enzymes (DUBs) associated with PAR-coupled DDR were identified, and the role of USP39, an inactive DUB involved in spliceosome assembly, was characterized. USP39 rapidly localizes to DNA lesions in a PAR-dependent manner, where it regulates non-homologous end-joining (NHEJ) via a tripartite RG motif located in the N-terminus comprising 46 amino acids (N46). Furthermore, USP39 acts as a molecular trigger for liquid demixing in a PAR-coupled N46-dependent manner, thereby directly interacting with the XRCC4/LIG4 complex during NHEJ. In parallel, the USP39-associated spliceosome complex controls homologous recombination repair in a PAR-independent manner. These findings provide mechanistic insights into how PAR chains precisely control DNA repair processes in the DDR.

Bromodomain proteins: protectors against endogenous DNA damage and facilitators of genome integrity.

Endogenous DNA damage is a major contributor to mutations, which are drivers of cancer development. Bromodomain (BRD) proteins are well-established participants in chromatin-based DNA damage response (DDR) pathways, which maintain genome integrity from cell-intrinsic and extrinsic DNA-damaging sources. BRD proteins are most well-studied as regulators of transcription, but emerging evidence has revealed their importance in other DNA-templated processes, including DNA repair and replication. How BRD proteins mechanistically protect cells from endogenous DNA damage through their participation in these pathways remains an active area of investigation. Here, we review several recent studies establishing BRD proteins as key influencers of endogenous DNA damage, including DNA-RNA hybrid (R-loops) formation during transcription and participation in replication stress responses. As endogenous DNA damage is known to contribute to several human diseases, including neurodegeneration, immunodeficiencies, cancer, and aging, the ability of BRD proteins to suppress DNA damage and mutations is likely to provide new insights into the involvement of BRD proteins in these diseases. Although many studies have focused on BRD proteins in transcription, evidence indicates that BRD proteins have emergent functions in DNA repair and genome stability and are participants in the etiology and treatment of diseases involving endogenous DNA damage.

A new α-pyrone from Arthrinium pseudosinense culture medium and its estrogenic activity in MCF-7 cells.

A new α-pyrone analog, arthrifuranone A (1) was isolated from an EtOAc-extract of Arthrinium pseudosinense culture medium. The isolation workflow was guided by a Molecular Networking-based dereplication strategy. The chemical structure of the new compound was elucidated using MS and NMR spectroscopic techniques, and the absolute configuration was established by the Mosher's method and gauge-including atomic orbital NMR chemical shift calculations, followed by DP4 + analysis. The isolated compound was evaluated for its estrogenic activity using the MCF-7 estrogen responsive human breast cancer cells. Compound 1 showed estrogenic activity by increasing the proliferation of MCF-7 cells at the concentration of 3.125 µM via phosphorylation of estrogen receptor-α.

Novosphingobium aureum sp. nov., a marine bacterium isolated from salt flat sediment.

A Gram-stain-negative, aerobic, pale yellow-coloured, rod-shaped marine bacterium designated strain YJ-S2-02T was isolated from salt flat sediment sampled in Yongyu-do, Republic of Korea. Strain YJ-S2-02T grew at pH 6.0-9.0 (optimum, pH 7.0), 10-40 °C (optimum, 30 °C) and with optimum 1 % (w/v) NaCl. The 16S rRNA gene sequence analysis indicated that strain YJ-S2-02T was closely related to Novosphingobium naphthalenivorans NBRC 102051T (97.8 %) followed by Novosphingobium mathurense SM117T (97.5 %), Novosphingobium indicum H25T (97.3 %), Novosphingobium pentaromativorans US6-1T (96.8 %), Novosphingobium fontis STM-14T (96.6 %), Novosphingobium endophyticum EGI60015T (96.5 %), Novosphingobium naphthae D39T (96.5 %) and Novosphingobium malaysiense MUSC 273T (95.9 %). The average nucleotide identity and estimated DNA-DNA hybridization values between YJ-S2-02T and related type strains were 77.0-77.9 % and 19.1-24.0 %. Strain YJ-S2-02T was characterized as having Q-10 as the predominant respiratory quinone and the principal fatty acids (>10 %) were summed feature 8 (C18 : 1 ω6c/ω7c, 20.7 %), C18 : 3 ω6c (16.3 %) and C17 : 1 ω6c (11.8 %). The polar lipids consisted of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, sphingolipids and two unidentified lipids. The DNA G+C content of strain YJ-S2-02T was 65.6 mol%. On the basis of the polyphasic taxonomic evidence presented in this study, YJ-S2-02T should be classified as representing a novel species within the genus Novosphingobium, for which name Novosphingobium aureum is proposed, with the type strain YJ-S2-02T (=KACC 21677T =KCTC 72891T=JCM 33996T).