Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 376
Filtrar
Mais filtros

Base de dados
Tipo de documento
Intervalo de ano de publicação
1.
Mol Cell ; 80(2): 327-344.e8, 2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-32966758

RESUMO

Stabilization of stalled replication forks is a prominent mechanism of PARP (Poly(ADP-ribose) Polymerase) inhibitor (PARPi) resistance in BRCA-deficient tumors. Epigenetic mechanisms of replication fork stability are emerging but remain poorly understood. Here, we report the histone acetyltransferase PCAF (p300/CBP-associated) as a fork-associated protein that promotes fork degradation in BRCA-deficient cells by acetylating H4K8 at stalled replication forks, which recruits MRE11 and EXO1. A H4K8ac binding domain within MRE11/EXO1 is required for their recruitment to stalled forks. Low PCAF levels, which we identify in a subset of BRCA2-deficient tumors, stabilize stalled forks, resulting in PARPi resistance in BRCA-deficient cells. Furthermore, PCAF activity is tightly regulated by ATR (ataxia telangiectasia and Rad3-related), which phosphorylates PCAF on serine 264 (S264) to limit its association and activity at stalled forks. Our results reveal PCAF and histone acetylation as critical regulators of fork stability and PARPi responses in BRCA-deficient cells, which provides key insights into targeting BRCA-deficient tumors and identifying epigenetic modulators of chemotherapeutic responses.


Assuntos
Proteína BRCA1/deficiência , Proteína BRCA2/deficiência , Enzimas Reparadoras do DNA/metabolismo , Replicação do DNA , Exodesoxirribonucleases/metabolismo , Histonas/metabolismo , Proteína Homóloga a MRE11/metabolismo , Fatores de Transcrição de p300-CBP/metabolismo , Acetilação/efeitos dos fármacos , Sequência de Aminoácidos , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Proteína BRCA1/metabolismo , Proteína BRCA2/metabolismo , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Replicação do DNA/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Lisina/metabolismo , Modelos Biológicos , Mutação/genética , Fosforilação/efeitos dos fármacos , Fosfosserina/metabolismo , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Ligação Proteica/efeitos dos fármacos , Fatores de Transcrição de p300-CBP/química , Fatores de Transcrição de p300-CBP/genética
2.
Genes Dev ; 33(23-24): 1751-1774, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31753913

RESUMO

Bromodomain proteins (BRD) are key chromatin regulators of genome function and stability as well as therapeutic targets in cancer. Here, we systematically delineate the contribution of human BRD proteins for genome stability and DNA double-strand break (DSB) repair using several cell-based assays and proteomic interaction network analysis. Applying these approaches, we identify 24 of the 42 BRD proteins as promoters of DNA repair and/or genome integrity. We identified a BRD-reader function of PCAF that bound TIP60-mediated histone acetylations at DSBs to recruit a DUB complex to deubiquitylate histone H2BK120, to allowing direct acetylation by PCAF, and repair of DSBs by homologous recombination. We also discovered the bromo-and-extra-terminal (BET) BRD proteins, BRD2 and BRD4, as negative regulators of transcription-associated RNA-DNA hybrids (R-loops) as inhibition of BRD2 or BRD4 increased R-loop formation, which generated DSBs. These breaks were reliant on topoisomerase II, and BRD2 directly bound and activated topoisomerase I, a known restrainer of R-loops. Thus, comprehensive interactome and functional profiling of BRD proteins revealed new homologous recombination and genome stability pathways, providing a framework to understand genome maintenance by BRD proteins and the effects of their pharmacological inhibition.


Assuntos
Instabilidade Genômica , Estruturas R-Loop , Reparo de DNA por Recombinação/genética , Fatores de Transcrição/genética , Acetilação , Linhagem Celular , Quebras de DNA de Cadeia Dupla , DNA Topoisomerases Tipo I/metabolismo , DNA Topoisomerases Tipo II/metabolismo , Células HEK293 , Células HeLa , Humanos , Transativadores/metabolismo , Fatores de Transcrição/análise , Ubiquitinação , Fatores de Transcrição de p300-CBP/genética , Fatores de Transcrição de p300-CBP/metabolismo
3.
Nucleic Acids Res ; 52(15): 8643-8660, 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-38936834

RESUMO

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.


Assuntos
Instabilidade Genômica , Histonas , Estruturas R-Loop , Fatores de Transcrição de p300-CBP , Acetilação , Histonas/metabolismo , Histonas/genética , Fatores de Transcrição de p300-CBP/metabolismo , Fatores de Transcrição de p300-CBP/genética , Humanos , Exodesoxirribonucleases/metabolismo , Exodesoxirribonucleases/genética , Reparo do DNA , Enzimas Reparadoras do DNA
4.
Compr Psychiatry ; 129: 152445, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38154288

RESUMO

BACKGROUND: Cognitive impairments occur on a continuous spectrum in multiple cognitive domains showing individual variability of the deteriorating patterns; however, often, cognitive domains are studied separately. METHODS: The present study investigated aging individual variations of cognitive abilities and related resting-state functional connectivity (rsFC) using data-driven approach. Cognitive and neuroimaging data were obtained from 62 elderly outpatients with cognitive decline. Principal component analysis (PCA) was conducted on the cognitive data to determine patterns of cognitive performance, then data-driven whole-brain connectome multivariate pattern analysis (MVPA) was applied on the neuroimaging data to discover neural regions associated with the cognitive characteristic. RESULTS: The first component (PC1) delineated an overall decline in all domains of cognition, and the second component (PC2) represented a compensatory relationship within basic cognitive functions. MVPA indicated rsFC of the cerebellum lobule VIII and insula with the default-mode network, frontoparietal network, and salience network inversely correlated with PC1 scores. Additionally, PC2 score was related to rsFC patterns with temporal pole and occipital cortex. CONCLUSIONS: The featured primary cognitive characteristic depicted the importance of the cerebellum and insula connectivity patterns in of the general cognitive decline. The findings also discovered a secondary characteristic that communicated impaired interactions within the basic cognitive function, which was independent from the impairment severity.


Assuntos
Disfunção Cognitiva , Imageamento por Ressonância Magnética , Adulto , Humanos , Idoso , Imageamento por Ressonância Magnética/métodos , Envelhecimento/psicologia , Encéfalo/diagnóstico por imagem , Cognição , Disfunção Cognitiva/diagnóstico por imagem
5.
Artigo em Inglês | MEDLINE | ID: mdl-37074128

RESUMO

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.


Assuntos
Ácidos Graxos , Água do Mar , Ácidos Graxos/química , Água do Mar/microbiologia , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Composição de Bases , DNA Bacteriano/genética , Técnicas de Tipagem Bacteriana , Sedimentos Geológicos/microbiologia , República da Coreia
6.
Int J Syst Evol Microbiol ; 73(12)2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38117208

RESUMO

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).


Assuntos
Ácidos Graxos , Tenacibaculum , Composição de Bases , Ácidos Graxos/química , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , DNA Bacteriano/genética , Técnicas de Tipagem Bacteriana
7.
Nucleic Acids Res ; 49(19): 11083-11102, 2021 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-34614178

RESUMO

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.


Assuntos
Reparo do DNA por Junção de Extremidades , DNA Ligase Dependente de ATP/genética , Proteínas de Ligação a DNA/genética , DNA/genética , Poli(ADP-Ribose) Polimerases/genética , Proteases Específicas de Ubiquitina/genética , Motivos de Aminoácidos , Ciclo Celular/genética , Linhagem Celular , Linhagem Celular Tumoral , DNA/metabolismo , Quebras de DNA de Cadeia Dupla , DNA Ligase Dependente de ATP/metabolismo , Proteínas de Ligação a DNA/metabolismo , Endopeptidases/genética , Endopeptidases/metabolismo , Fator de Iniciação 3 em Eucariotos/genética , Fator de Iniciação 3 em Eucariotos/metabolismo , Fibroblastos/citologia , Fibroblastos/metabolismo , Regulação da Expressão Gênica , Células HEK293 , Humanos , Osteoblastos/citologia , Osteoblastos/metabolismo , Poli Adenosina Difosfato Ribose/metabolismo , Poli(ADP-Ribose) Polimerases/metabolismo , Reparo de DNA por Recombinação , Transdução de Sinais , Spliceossomos , Ubiquitina Tiolesterase/genética , Ubiquitina Tiolesterase/metabolismo , Proteases Específicas de Ubiquitina/metabolismo
8.
Proc Natl Acad Sci U S A ; 117(31): 18439-18447, 2020 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-32675241

RESUMO

In mammals, repressive histone modifications such as trimethylation of histone H3 Lys9 (H3K9me3), frequently coexist with DNA methylation, producing a more stable and silenced chromatin state. However, it remains elusive how these epigenetic modifications crosstalk. Here, through structural and biochemical characterizations, we identified the replication foci targeting sequence (RFTS) domain of maintenance DNA methyltransferase DNMT1, a module known to bind the ubiquitylated H3 (H3Ub), as a specific reader for H3K9me3/H3Ub, with the recognition mode distinct from the typical trimethyl-lysine reader. Disruption of the interaction between RFTS and the H3K9me3Ub affects the localization of DNMT1 in stem cells and profoundly impairs the global DNA methylation and genomic stability. Together, this study reveals a previously unappreciated pathway through which H3K9me3 directly reinforces DNMT1-mediated maintenance DNA methylation.


Assuntos
DNA (Citosina-5-)-Metiltransferase 1/metabolismo , Metilação de DNA , Heterocromatina/metabolismo , Histonas/metabolismo , DNA (Citosina-5-)-Metiltransferase 1/genética , Heterocromatina/genética , Histonas/química , Histonas/genética , Humanos , Lisina/genética , Lisina/metabolismo , Metilação , Processamento de Proteína Pós-Traducional
9.
Int J Mol Sci ; 24(6)2023 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-36983041

RESUMO

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.


Assuntos
Leucemia , Estruturas R-Loop , Humanos , Transcrição Gênica , Reparo do DNA , RNA/genética , Replicação do DNA , Leucemia/genética , Instabilidade Genômica
10.
Psychol Med ; 52(7): 1296-1305, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-32880252

RESUMO

BACKGROUND: Social anxiety disorder (SAD) is characterized by anxiety regarding social situations, avoidance of external social stimuli, and negative self-beliefs. Virtual reality self-training (VRS) at home may be a good interim modality for reducing social fears before formal treatment. This study aimed to find neurobiological evidence for the therapeutic effect of VRS. METHODS: Fifty-two patients with SAD were randomly assigned to a VRS or waiting list (WL) group. The VRS group received an eight-session VRS program for 2 weeks, whereas the WL group received no intervention. Clinical assessments and functional magnetic resonance imaging scanning with the distress and speech evaluation tasks were repeatedly performed at baseline and after 3 weeks. RESULTS: The post-VRS assessment showed significantly decreased anxiety and avoidance scores, distress index, and negative evaluation index for 'self', but no change in the negative evaluation index for 'other'. Patients showed significant responses to the distress task in various regions, including both sides of the prefrontal regions, occipital regions, insula, and thalamus, and to the speech evaluation task in the bilateral anterior cingulate cortex. Among these, significant neuronal changes after VRS were observed only in the right lingual gyrus and left thalamus. CONCLUSIONS: VRS-induced improvements in the ability to pay attention to social stimuli without avoidance and even positively modulate emotional cues are based on functional changes in the visual cortices and thalamus. Based on these short-term neuronal changes, VRS can be a first intervention option for individuals with SAD who avoid society or are reluctant to receive formal treatment.


Assuntos
Fobia Social , Realidade Virtual , Ansiedade , Transtornos de Ansiedade , Medo , Humanos , Fobia Social/terapia
11.
Int J Syst Evol Microbiol ; 72(12)2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36748432

RESUMO

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).


Assuntos
Halomonas , Cloreto de Sódio , Ácidos Graxos/química , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , DNA Bacteriano/genética , Composição de Bases , Filogenia , Técnicas de Tipagem Bacteriana
12.
Artigo em Inglês | MEDLINE | ID: mdl-35666678

RESUMO

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).


Assuntos
Rhodobacteraceae , Água do Mar , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Ácidos Graxos/química , Fosfolipídeos/química , Filogenia , RNA Ribossômico 16S/genética , Água do Mar/microbiologia , Análise de Sequência de DNA
13.
Microb Ecol ; 83(2): 436-446, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34003315

RESUMO

Invasion of Spartina spp. in tidal salt marshes may affect the function and characteristics of the ecosystem. Previous studies reported that the invasion alters biogeochemical and microbial processes in marsh ecosystems, yet our knowledge of changing archaeal community due to the invasion is still limited, whereas archaeal communities play a pivotal role in biogeochemical cycles within highly reduced marsh soils. In this study, we aimed to illustrate the influences of the Spartina anglica invasion on soil archaeal community and the depth profile of the influences. The relative abundance of archaeal phyla demonstrated that the invasion substantially shifted the characteristics of tidal salt marsh from marine to terrestrial soil only in surface layer, while the influences indirectly propagated to the deeper soil layer. In particular, two archaeal phyla, Asgardaeota and Diapherotrites, were strongly influenced by the invasion, indicating a shift from marine to terrestrial archaeal communities. The shifts in soil characteristics spread to the deeper soil layer that results in indirect propagation of the influences of the invasion down to the deeper soil, which was underestimated in previous studies. The changes in the concentration of dissolved organic carbon and salinity were the substantial regulating factors for that. Therefore, changes in biogeochemical and microbial characteristics in the deep soil layer, which is below the root zone of the invasive plant, should be accounted for a more accurate illustration of the consequences of the invasion.


Assuntos
Solo , Áreas Alagadas , Archaea , Ecossistema , Espécies Introduzidas , Poaceae/fisiologia
14.
Crit Rev Biochem Mol Biol ; 54(3): 208-241, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31164001

RESUMO

Modulation of chromatin templates in response to cellular cues, including DNA damage, relies heavily on the post-translation modification of histones. Numerous types of histone modifications including phosphorylation, methylation, acetylation, and ubiquitylation occur on specific histone residues in response to DNA damage. These histone marks regulate both the structure and function of chromatin, allowing for the transition between chromatin states that function in undamaged condition to those that occur in the presence of DNA damage. Histone modifications play well-recognized roles in sensing, processing, and repairing damaged DNA to ensure the integrity of genetic information and cellular homeostasis. This review highlights our current understanding of histone modifications as they relate to DNA damage responses (DDRs) and their involvement in genome maintenance, including the potential targeting of histone modification regulators in cancer, a disease that exhibits both epigenetic dysregulation and intrinsic DNA damage.


Assuntos
Dano ao DNA , Reparo do DNA , Código das Histonas , Animais , Cromatina/genética , Epigênese Genética , Instabilidade Genômica , Histonas/genética , Humanos , Neoplasias/genética
15.
Artigo em Inglês | MEDLINE | ID: mdl-34328829

RESUMO

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).


Assuntos
Ácidos Graxos , Cloreto de Sódio , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Ácidos Graxos/química , Fosfolipídeos , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Sphingomonadaceae , Ubiquinona
16.
Int J Syst Evol Microbiol ; 71(12)2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34874248

RESUMO

A yellow-coloured bacterium, designated strain JGD-16T, was isolated from a tidal flat in Janggu-do, Garorim Bay, Taean-gun, Chungcheongbuk-do, Republic of Korea. Cells were Gram-stain-negative, aerobic, non-flagellated and short ovoid to coccoid-shaped. Growth was observed at 10-37 °C (optimum, 30 °C), pH 6.0-9.0 (pH 8.0) and with 1-5% (w/v) NaCl (2%). Results of 16S rRNA gene sequence analysis indicated that strain JGD-16T was closely related to Altererythrobacter xiamenensis LY02T (97.1 %), Altererythrobacter aurantiacus O30T (96.3 %), Altererythrobacter ishigakiensis JPCCMB0017T (95.8 %), Altererythrobacter epoxidivorans JCS350T (95.7 %) and Altererythrobacter insulae BPTF-M16T (95.3%). Phylogenomic analysis using the maximum-likelihood algorithm showed that strain JGD-16T formed a clade with the genus Altererythrobacter. The genomic DNA G+C content was 57.8 mol%. The predominant respiratory quinone was ubiquinone-10. The major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, a sphingoglycolipid, an unidentified glycolipid and an unidentified lipid. The major fatty acids were C18:1 ω7c (31.5 %) and C18:3 ω6c (19.6 %). On the basis of its phylogenomic, physiological and chemotaxonomical characteristics, strain JGD-16T represents a novel species within the genus Altererythrobacter, for which the name Altererythrobacter lutimaris JGD-16Tsp. nov. is proposed. The type strain is JGD-16T (=KCTC 72632T=KACC 21405T=JCM 33750T). We also propose the reclassification of Altererythrobacter deserti as Tsuneonella deserti comb. nov., Altererythrobacter estronivorus as Croceicoccus estronivorus comb. nov. and Altererythrobacter muriae as Alteripontixanthobacter muriae comb. nov.


Assuntos
Alphaproteobacteria/classificação , Filogenia , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Ácidos Graxos/química , Fosfolipídeos/química , Pigmentação , RNA Ribossômico 16S/genética , República da Coreia , Análise de Sequência de DNA , Ubiquinona/análogos & derivados , Ubiquinona/química
17.
Bioorg Chem ; 114: 105064, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34134032

RESUMO

Eight new naphtho[1,2-c]furan derivatives (1-8) along with six known analogues (9-14) were isolated from culture medium of the basidiomycete Basidioradulum radula. The structures of these compounds were identified using spectroscopic analysis, and their absolute configurations were resolved using X-ray diffraction, ECD, and VCD. Compounds 7 and 14 inhibited the cell viability of human prostate cancer DU-145 cells with IC50 values of 7.54 ± 0.03 µM and 5.04 ± 0.03 µM, respectively. At 8 µM, compounds 7 and 14 increased the percentage of apoptotic cells and upregulated the protein expression related to the apoptosis caspase pathways in DU-145 cells. Furthermore, the hallmarks of cells undergoing apoptosis, such as chromatin condensation, were also observed at this concentration. However, compound 7 and 14 showed no effect on the proliferation of splenocytes isolated from cyclophosphamide-induce immunosuppressed mice.


Assuntos
Antineoplásicos/farmacologia , Basidiomycota/química , Animais , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ciclofosfamida , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Estrutura Molecular , Baço/efeitos dos fármacos , Relação Estrutura-Atividade , Células Tumorais Cultivadas
18.
Addict Biol ; 26(3): e12916, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-32365424

RESUMO

Impulsivity and emotion dysregulation have been known to be risk factors for Internet gaming disorder (IGD), but their underlying neural mechanisms are not yet fully understood. Given that the prefrontal cortex has a key role in higher order cognition and addiction, the present study aimed to investigate emotional influences on response inhibition in situations with different cognitive demands. A total of 41 young male adults (20 with and 21 without IGD) were scanned while performing two versions of an emotional go/no-go task with demands on low and high working memory load. Patients with IGD showed a failure in response inhibition and increased activation of widespread brain regions, including prefrontal, motor-sensory, parietal, occipital, insula, and striatal regions across tasks. Among these regions, involvement of the dorsolateral prefrontal cortex and ventral striatum was observed only during the task with high demands on working memory. Moreover, it was also only during the high-load task that interaction between response inhibition and emotional states was observed in the dorsomedial prefrontal cortex, with observations revealing that its alteration in patients with IGD was associated with number of hours spent on Internet gaming. Our findings highlight a failure of response inhibition and dysfunction within the inhibitory control network. The special significance of our study is that dysfunctional dorsomedial prefrontal cortex may mediate abnormal emotional influences on response inhibition in patients with IGD.


Assuntos
Emoções , Comportamento Impulsivo , Transtorno de Adição à Internet/fisiopatologia , Córtex Pré-Frontal/fisiopatologia , Jogos de Vídeo/psicologia , Adulto , Mapeamento Encefálico/métodos , Humanos , Transtorno de Adição à Internet/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Masculino , Córtex Pré-Frontal/diagnóstico por imagem , Adulto Jovem
19.
Proc Natl Acad Sci U S A ; 115(49): 12365-12370, 2018 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-30442660

RESUMO

Organic matter is responsible for the generation of hydrocarbons during the thermal maturation of source rock formation. This geochemical process engenders a network of organic hosted pores that governs the flow of hydrocarbons from the organic matter to fractures created during the stimulation of production wells. Therefore, it can be reasonably assumed that predictions of potentially recoverable confined hydrocarbons depend on the geometry of this pore network. Here, we analyze mesoscale structures of three organic porous networks at different thermal maturities. We use electron tomography with subnanometric resolution to characterize their morphology and topology. Our 3D reconstructions confirm the formation of nanopores and reveal increasingly tortuous and connected pore networks in the process of thermal maturation. We then turn the binarized reconstructions into lattice models including information from atomistic simulations to derive mechanical and confined fluid transport properties. Specifically, we highlight the influence of adsorbed fluids on the elastic response. The resulting elastic energy concentrations are localized at the vicinity of macropores at low maturity whereas these concentrations present more homogeneous distributions at higher thermal maturities, due to pores' topology. The lattice models finally allow us to capture the effect of sorption on diffusion mechanisms with a sole input of network geometry. Eventually, we corroborate the dominant impact of diffusion occurring within the connected nanopores, which constitute the limiting factor of confined hydrocarbon transport in source rocks.

20.
Neuroimage ; 217: 116929, 2020 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-32413461

RESUMO

Self-respect is a practical way to promote life satisfaction through gratifying basic psychological needs, whereas self-criticism is associated with life dissatisfaction. The goal of the present study was to investigate the effect of two positive and negative self-talks on the functional connectome with respect to life satisfaction and its relationships with basic psychological needs. Forty-eight individuals with low life satisfaction (LLS, n â€‹= â€‹24) and with high life satisfaction (HLS, n â€‹= â€‹24) were scanned using functional magnetic resonance imaging at a baseline state and during and after self-respect or self-criticism tasks. Functional connectivity analysis was conducted to identify the modulatory effects of the tasks on the self-referential, default mode, and reward-motivation networks. We found that self-respect changed only the connection between the posterior cingulate cortex (PCC) and frontoparietal network, whereas self-criticism changed almost all of the connections examined. The group x condition interaction effect of self-respect was identified only in connection between the PCC and left ventrolateral prefrontal cortex, while that of self-criticism was observed in various connections based on the ventromedial prefrontal cortex and nucleus accumbens. In respect to basic psychological needs, functional connectivity after self-criticism was significant in predicting the needs of autonomy and relatedness only in the LLS group, whereas functional connectivity after self-respect could predict the needs of autonomy and competence only in the HLS group. Overall, self-criticism produces more noticeable negative changes in the brain than the positive changes of self-respect. Individuals with low life satisfaction may be more vulnerable to be negatively affected not only by self-criticism but also self-respect than individuals with high life satisfaction. The satisfaction of basic psychological needs can play a mediating role in the effects of self-talk tasks differently concerning life satisfaction.


Assuntos
Vias Neurais/fisiologia , Satisfação Pessoal , Autoimagem , Algoritmos , Conectoma , Ego , Feminino , Giro do Cíngulo/diagnóstico por imagem , Giro do Cíngulo/fisiologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Motivação/fisiologia , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiologia , Vias Neurais/diagnóstico por imagem , Testes Neuropsicológicos , Núcleo Accumbens/diagnóstico por imagem , Núcleo Accumbens/fisiologia , Autonomia Pessoal , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/fisiologia , Recompensa , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA