RESUMEN
BACKGROUND: Histone H3K4 tri-methylation (H3K4me3) catalyzed by Set1/COMPASS, is a prominent epigenetic mark found in promoter-proximal regions of actively transcribed genes. H3K4me3 relies on prior monoubiquitination at the histone H2B (H2Bub) by Rad6 and Bre1. Swd2/Cps35, a Set1/COMPASS component, has been proposed as a key player in facilitating H2Bub-dependent H3K4me3. However, a more comprehensive investigation regarding the relationship among Rad6, Swd2, and Set1 is required to further understand the mechanisms and functions of the H3K4 methylation. RESULTS: We investigated the genome-wide occupancy patterns of Rad6, Swd2, and Set1 under various genetic conditions, aiming to clarify the roles of Set1 and Rad6 for occupancy of Swd2. Swd2 peaks appear on both the 5' region and 3' region of genes, which are overlapped with its tightly bound two complexes, Set1 and cleavage and polyadenylation factor (CPF), respectively. In the absence of Rad6/H2Bub, Set1 predominantly localized to the 5' region of genes, while Swd2 lost all the chromatin binding. However, in the absence of Set1, Swd2 occupancy near the 5' region was impaired and rather increased in the 3' region. CONCLUSIONS: This study highlights that the catalytic activity of Rad6 is essential for all the ways of Swd2's binding to the transcribed genes and Set1 redistributes the Swd2 to the 5' region for accomplishments of H3K4me3 in the genome-wide level.
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N-Metiltransferasa de Histona-Lisina , Histonas , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Histonas/metabolismo , Histonas/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , N-Metiltransferasa de Histona-Lisina/metabolismo , N-Metiltransferasa de Histona-Lisina/genética , Metilación , Adenosina Trifosfatasas/metabolismo , Adenosina Trifosfatasas/genética , Enzimas Ubiquitina-Conjugadoras/metabolismo , Enzimas Ubiquitina-Conjugadoras/genéticaRESUMEN
(1) Background: There is a paucity of data regarding the validity of rapid antibody testing for SARS-CoV-2 vaccine response in homeless people worldwide. The objective of this study was to evaluate a rapid SARS-CoV-2 IgM/IgG antibody detection kit as a qualitative screen for vaccination in homeless people. (2) Methods: This study included 430 homeless people and 120 facility workers who had received one of BNT162b2, mRNA-1273, AZD1222/ChAdOx1, or JNJ-78436735/AD26.COV2.5 vaccines. They were tested for IgM/IgG antibodies to the SARS-CoV-2 spike protein with the STANDARD™ Q COVID-19 IgM/IgG Plus Test (QNCOV-02C). ELISA/competitive inhibition ELISA (CI-ELISA) was subsequently run to assess the validity of the serological antibody test. (3) Results: The sensitivity of homeless people was 43.5%. The status of homelessness was related to a lower agreement between serological antibody testing and CI-ELISA (adjusted OR (aOR), 0.35; 95% CI, 0.18-0.70). However, the Heterologous boost vaccine presented higher agreement between serological antibody testing and CI-ELISA (adjusted OR (aOR), 6.50; 95% CI, 3.19-13.27). (4) Conclusions: This study found weak agreement between the rapid IgG results and confirmatory CI-ELISA testing in homeless people. However, it can be used as a screening test for the acceptance of homeless people with heterologous boost vaccination in facilities.
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COVID-19 , Personas con Mala Vivienda , Humanos , Vacunas contra la COVID-19 , Vacuna BNT162 , Ad26COVS1 , ChAdOx1 nCoV-19 , Prueba de COVID-19 , COVID-19/diagnóstico , COVID-19/epidemiología , COVID-19/prevención & control , SARS-CoV-2 , Anticuerpos Antivirales , Inmunoglobulina G , Inmunoglobulina MRESUMEN
An 8-year-old female pre-metamorphic axolotl (Ambystoma mexicanum) was examined for a suspected anterior lens luxation. Slit-lamp biomicroscopy revealed two lens-like structures in the anterior chamber of the right eye (OD), each with cataractous change. Ultrasound biomicroscopy and optical coherence tomography (OCT) were performed without sedation, and revealed small lenticular structures each with distinct nuclei and cortices. Although a distinct connection of the two lenticular structures could not be definitively ruled out, the structures appeared separate. Each of the lenticular structures was closely associated with its respective iris leaflet. This report demonstrates application of advanced imaging for diagnostic use in axolotl ophthalmology, showing that imaging of the lens can be performed without sedation, topical anesthetic, nor contact gel with high diagnostic quality. Although two distinct lenses were diagnosed with no historical evidence of trauma, the small sizes of each lenticular structure, with no detectable connection between them, are suggestive of a possible regenerative abnormality. This report opens discussion for the regenerative capabilities of the pre-metamorphic adult axolotl and possible implementations of their use in regenerative medicine research for the development of future therapies.
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Cristalino , Lentes , Femenino , Animales , Ambystoma mexicanum , Microscopía Acústica/veterinaria , Tomografía de Coherencia Óptica/veterinariaRESUMEN
Cell identity is determined by the transcriptional regulation of a cell-type-specific gene group. The Paf1 complex (Paf1C), an RNA polymerase II-associating factor, is an important transcriptional regulator that not only participates in transcription elongation and termination but also affects transcription-coupled histone modifications and chromatin organisation. Recent studies have shown that Paf1C is involved in the expression of genes required for self-renewal and pluripotency in stem cells and tumorigenesis. In this review, we focused on the role of Paf1C as a critical transcriptional regulator in cell fate decisions. Paf1C affects the pluripotency of stem cells by regulating the expression of core transcription factors such as Oct4 and Nanog. In addition, Paf1C directly binds to the promoters or distant elements of target genes, thereby maintaining the pluripotency in embryonic stem cells derived from an early stage of the mammalian embryo. Paf1C is upregulated in cancer stem cells, as compared with that in cancer cells, suggesting that Paf1C may be a target for cancer therapy. Interestingly, Paf1C is involved in multiple developmental stages in Drosophila, zebrafish, mice and even humans, thereby displaying a trend for the correlation between Paf1C and cell fate. Thus, we propose that Paf1C is a critical contributor to cell differentiation, cell specification and its characteristics and could be employed as a therapeutic target in developmental diseases.
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Células Madre Embrionarias , Factores de Transcripción , Animales , Humanos , Ratones , Núcleo Celular/metabolismo , Células Madre Embrionarias/metabolismo , Mamíferos/metabolismo , Proteínas Nucleares/genética , Factores de Transcripción/genética , Pez Cebra/metabolismoRESUMEN
Salmonella Typhimurium is a Gram-negative facultative pathogen that causes a range of diseases, from mild gastroenteritis to severe systemic infection in a variety of animal hosts. S. Typhimurium regulates virulence gene expression by a silencing mechanism using nucleoid-associated proteins such as Histone-like Nucleoid Structuring protein (H-NS) silencing. We hypothesize that the posttranslational modification, specifically protein acetylation, of proteins in gene silencing systems could affect the pathogenic gene expression of S. Typhimurium. Therefore, we created acetylation-deficient mutant by deleting two genes, pat and pta, which are involved in the protein acetylation pathway. We observed that the pat and pta deletion attenuates mouse virulence and also decreases Salmonella's replication within macrophages. In addition, the Δpat Δpta strain showed a decreased expression of the horizontally-acquired virulence genes, mgtC, pagC, and ugtL, which are highly expressed in low Mg2+. The decreased virulence gene expression is possibly due to higher H-NS occupancy to those promoters because the pat and pta deletion increases H-NS occupancy whereas the same mutation decreases occupancy of RNA polymerase. Our results suggest that Pat- and Pta-mediated protein acetylation system promotes the expression of virulence genes by regulating the binding affinity of H-NS in S. Typhimurium.
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Regulación Bacteriana de la Expresión Génica , Salmonella typhimurium , Acetilación , Animales , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Expresión Génica , Ratones , Procesamiento Proteico-Postraduccional , Virulencia/genéticaRESUMEN
Candida albicans is an opportunistic human fungal pathogen that exists in normal flora but can cause infection in immunocompromised individuals. The transition to pathogenic C. albicans requires a change of various gene expressions. Because histone-modifying enzymes can regulate gene expression, they are thought to control the virulence of C. albicans. Indeed, the absence of H3 lysine 4 (H3K4) methyltransferase Set1 has been shown to reduce the virulence of C. albicans; however, Set1-regulated genes responsible for this attenuated virulence phenotype remain unknown. Here, we demonstrated that Set1 positively regulates the expression of mitochondrial protein genes by methylating H3K4. In particular, levels of cellular mitochondrial reactive oxygen species (ROS) were higher in Δset1 than in the wild-type due to the defect of those genes' expression. Set1 deletion also increases H2O2 sensitivity and prevents proper colony formation when interacting with macrophage in vitro, consistent with its attenuated virulence in vivo. Together, these findings suggest that Set1 is required to regulate proper cellular ROS production by positively regulating the expression of mitochondrial protein genes and subsequently sustaining mitochondrial membrane integrity. Consequently, C. albicans maintains proper ROS levels via Set1-mediated transcriptional regulation, thus establishing a rapid defense against external ROS generated by the host.
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Candida albicans , Proteínas de Saccharomyces cerevisiae , Candida albicans/genética , Candida albicans/metabolismo , N-Metiltransferasa de Histona-Lisina/genética , N-Metiltransferasa de Histona-Lisina/metabolismo , Peróxido de Hidrógeno/farmacología , Metilación , Proteínas Mitocondriales/metabolismo , Especies Reactivas de Oxígeno , Proteínas de Saccharomyces cerevisiae/genética , VirulenciaRESUMEN
Bacterial mRNAs often harbor upstream open reading frames (uORFs) in the 5' untranslated regions (UTRs). Translation of the uORF usually affects downstream gene expression at the levels of transcription and/or translation initiation. Unlike other uORFs mostly located in the 5' UTR, we discovered an 8-amino-acid ORF, designated mgtQ, in the intergenic region between the mgtC virulence gene and the mgtB Mg2+ transporter gene in the Salmonella mgtCBRU operon. Translation of mgtQ promotes downstream mgtB Mg2+ transporter expression at the level of translation by releasing the ribosome-binding sequence of the mgtB gene that is sequestered in a translation-inhibitory stem-loop structure. Interestingly, mgtQ Asp2 and Glu5 codons that induce ribosome destabilization are required for mgtQ-mediated mgtB translation. Moreover, the mgtQ Asp and Glu codons-mediated mgtB translation is counteracted by the ribosomal subunit L31 that stabilizes ribosome. Substitution of the Asp2 and Glu5 codons in mgtQ decreases MgtB Mg2+ transporter production and thus attenuates Salmonella virulence in mice, likely by limiting Mg2+ acquisition during infection.IMPORTANCE Translation initiation regions in mRNAs that include the ribosome-binding site (RBS) and the start codon are often sequestered within a secondary structure. Therefore, to initiate protein synthesis, the mRNA secondary structure must be unfolded to allow the RBS to be accessible to the ribosome. Such unfolding can be achieved by various mechanisms that include translation of a small upstream open reading frame (uORF). In the intracellular pathogen Salmonella enterica serovar Typhimurium, translation of the Mg2+ transporter mgtB gene is enhanced by an 8-amino-acid upstream ORF, namely, mgtQ, that harbors Asp and Glu codons, which are likely to destabilize ribosome during translation. Translation of the mgtQ ORF promotes the formation of a stem-loop mRNA structure sequestering anti-RBS and thus releases the mgtB RBS. Because mgtQ-mediated MgtB Mg2+ transporter production is required for Salmonella virulence, this pathogen seems to control the virulence determinant production exquisitely via this uORF during infection.
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Proteínas de Transporte de Catión/genética , Proteínas de Transporte de Catión/metabolismo , ADN Intergénico , Magnesio/metabolismo , Sistemas de Lectura Abierta , Biosíntesis de Proteínas , Salmonella typhimurium/genética , Regiones no Traducidas 5' , Regulación Bacteriana de la Expresión Génica , Operón , Salmonella typhimurium/metabolismo , Salmonella typhimurium/patogenicidad , Virulencia , Factores de VirulenciaRESUMEN
Protein lysine acetylation influences many physiological functions, such as gene regulation, metabolism, and disease in eukaryotes. Although little is known about the role of lysine acetylation in bacteria, several reports have proposed its importance in various cellular processes. Here, we discussed the function of the protein lysine acetylation and the post-translational modifications (PTMs) of histone-like proteins in bacteria focusing on Salmonella pathogenicity. The protein lysine residue in Salmonella is acetylated by the Pat-mediated enzymatic pathway or by the acetyl phosphate-mediated non-enzymatic pathway. In Salmonella, the acetylation of lysine 102 and lysine 201 on PhoP inhibits its protein activity and DNA-binding, respectively. Lysine acetylation of the transcriptional regulator, HilD, also inhibits pathogenic gene expression. Moreover, it has been reported that the protein acetylation patterns significantly differ in the drug-resistant and -sensitive Salmonella strains. In addition, nucleoid-associated proteins such as histone-like nucleoid structuring protein (H-NS) are critical for the gene silencing in bacteria, and PTMs in H-NS also affect the gene expression. In this review, we suggest that protein lysine acetylation and the post-translational modifications of H-NS are important factors in understanding the regulation of gene expression responsible for pathogenicity in Salmonella.
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Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Regulación Bacteriana de la Expresión Génica , Lisina/metabolismo , Salmonella/genética , Salmonella/metabolismo , Acetilación , Bacterias/genética , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Silenciador del Gen , Procesamiento Proteico-Postraduccional , Salmonella typhimurium/genética , Salmonella typhimurium/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , VirulenciaRESUMEN
The Baeg-nyong cave is a limestone cave which has been nominated as the first critical zone observatory (CZO) in South Korea. Moonmilk is a well-known speleothem composed of various carbonate minerals. To characterize moonmilk from the Baeg-nyong cave, we performed mineralogical analyses and applied high-throughput 16S rRNA gene sequencing to analyze the microbial communities, including bacteria and fungi, of dry and wet moonmilk samples. The results showed that the dry and wet moonmilk samples had different and atypical crystal structures, although they were predominantly composed of CaCO3. Furthermore, metagenomic data revealed that the dry and wet moonmilk samples collected from an oligotrophic environment had completely different bacterial communities when compared to the outside soil, and there was a difference in bacterial communities even between dry and wet moonmilk specimens. Fungal communities, however, did not differ significantly between dry and wet moonmilk samples. This study is the first metagenomic analysis of two different types of moonmilk with different physical properties and the first report on the microbial diversity of moonmilk from a cave in the first CZO in South Korea.
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Histone modifications affect transcription by changing the chromatin structure. In particular, histone H3 lysine 4 trimethylation (H3K4me3) is one of the most recognized epigenetic marks of active transcription. While many studies have provided evidence of the correlation between H3K4me3 and active transcription, details regarding the mechanism involved remain unclear. The first study on the broad H3K4me3 domain was reported in 2014; subsequently, the function of this domain has been studied in various cell types. In this review, we summarized the recent studies on the role of the broad H3K4me3 domain in transcription, development, memory formation, and several diseases, including cancer and autoimmune diseases. The broadest H3K4me3 domains are associated with increased transcriptional precision of cell-type-specific genes related to cell identity and other essential functions. The broad H3K4me3 domain regulates maternal zygotic activation in early mammalian development. In systemic autoimmune diseases, high expression of immune-responsive genes requires the presence of the broad H3K4me3 domain in the promoter-proximal regions. Transcriptional repression of tumor-suppressor genes is associated with the shortening of the broad H3K4me3 domains in cancer cells. Additionally, the broad H3K4me3 domain interacts with the super-enhancer to regulate cancer-associated genes. During memory formation, H3K4me3 breadth is regulated in the hippocampus CA1 neurons. Taken together, these findings indicate that H3K4me3 breadth is essential for the regulation of the transcriptional output across multiple cell types.
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Metilación de ADN , Enfermedad/genética , Epigénesis Genética , Regulación de la Expresión Génica , Histonas/química , Transcripción Genética , Animales , Código de Histonas , HumanosRESUMEN
BACKGROUND: Streptomyces seoulensis has contributed to the discovery and initiation of extensive research into nickel superoxide dismutase (NiSOD), a unique type of superoxide dismutase found in actinomycetes. Still so far, there is no information about whole genome sequence of this strain. OBJECTIVE: To investigate complete genome sequence and perform bioinformatic analyses for genomic functions related with nickel-associated genes. METHODS: DNA was extracted using the Wizard Genomic DNA Purification Kit then sequenced using a Pacific Biosciences SMRT cell 8Pac V3 DNA Polymerase Binding Kit P6 with the PacBiov2 RSII platform. We assembled the PacBio long-reads with the HGAP3 pipeline. RESULTS: We obtained complete genome sequence of S. seoulensis, which comprises a 6,339,363 bp linear chromosome. While analyzing the genome to annotate the genomic function, we discovered the nickel-associated genes. We observed that the sodN gene encoding for NiSOD is located adjacent to the sodX gene, which encodes for the nickel-type superoxide dismutase maturation protease. In addition, several nickel-associated genes and gene clusters-nickel-responsive regulator, nickel uptake transporter, nickel-iron [NiFe]-hydrogenase and other putative genes were also detected. Strain specific genes were discovered through a comparative analysis of S. coelicolor and S. griseus. Further bioinformatic analyses revealed that this strain encodes at least 22 putative biosynthetic gene clusters, thereby implying that S. seoulensis has the potential to produce novel bioactive compounds. CONCLUSION: We annotated the genome and determined nickel-associated genes and gene clusters and discovered biosynthetic gene clusters for secondary metabolites implying that S. seoulensis produces novel types of bioactive compounds.
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Genoma Bacteriano , Streptomyces/genética , Superóxido Dismutasa/genética , Genómica , Familia de Multigenes , Níquel/metabolismo , Secuenciación Completa del GenomaRESUMEN
OBJECTIVE: This study evaluated gender differences in the relationship between psychiatric distress and subjective tinnitus severity. METHODS: This cross-sectional study included 134 female and 114 male patients who visited the otology outpatient clinic at Seoul St. Mary's Hospital for tinnitus from February to July 2015. Patients completed a series of instruments, including the Tinnitus Handicap Inventory, Beck Depression Inventory, Korean version of Brief Encounter Psychosocial Instrument (BEPSI-K), and visual analogue scales assessing various tinnitus characteristics (loudness, awareness, annoyance, and effect on life). RESULTS: Tinnitus severity did not significantly differ between the gender groups (p=0.632), and it correlated significantly with tinnitus characteristics and psychiatric distress. Partial correlations between tinnitus severity and depressive symptoms were stronger in males (r=0.411, pï¼0.01) than in females (r=0.304, pï¼0.01) while controlling for duration of tinnitus and tinnitus characteristics. However, stress (BEPSI-K) was positively correlated with tinnitus severity in only males (r=0.463, pï¼0.01). A multiple regression analysis revealed that effect of tinnitus on life, depressive symptoms, and stress were significantly associated with tinnitus severity in males, whereas only tinnitus annoyance and depressive symptoms were associated with tinnitus severity in females. CONCLUSION: Tinnitus severity was significantly correlated with depressive symptoms and stress, and there were gender differences in the relationship between tinnitus severity and psychiatric components. It is necessary to be vigilant of psychiatric symptoms among patients with tinnitus who visit the otology outpatient clinic, especially for male patients.
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Ribosome often stalls on mRNA sequences harboring consecutive proline codons. Elongation factor P (EF-P) is required for the stalled ribosome to continue translation and thus the absence of EF-P affects translation of the associated open reading frame. Here we report that EF-P controls translation of the mgtA gene encoding a Mg2+ -transporting ATPase from the intracellualr pathogen Salmonella enterica serovar Typhimurium. EF-P's effect on mgtA translation is dependent on the 550th and 551st proline codons in the coding region and thus substitution of those proline codons eliminates EF-P-mediated control of MgtA protein without affecting the Mg2+ -transporting activity of the mgtA gene. The Pro550 and Pro551-substituted mgtA gene promotes Salmonella's intramacrophage survival and mouse virulence, suggesting that EF-P-mediated translational control of the mgtA gene is required for Salmonella pathogenesis.
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Adenosina Trifosfatasas/metabolismo , Proteínas Bacterianas/metabolismo , Regulación Bacteriana de la Expresión Génica , Proteínas de Transporte de Membrana/metabolismo , Factores de Elongación de Péptidos/metabolismo , Biosíntesis de Proteínas , Infecciones por Salmonella/microbiología , Salmonella typhimurium/metabolismo , Adenosina Trifosfatasas/química , Adenosina Trifosfatasas/genética , Secuencias de Aminoácidos , Animales , Proteínas Bacterianas/química , Proteínas Bacterianas/genética , Femenino , Eliminación de Gen , Humanos , Magnesio/metabolismo , Proteínas de Transporte de Membrana/química , Proteínas de Transporte de Membrana/genética , Ratones , Factores de Elongación de Péptidos/genética , Salmonella typhimurium/química , Salmonella typhimurium/genéticaRESUMEN
There is a paucity of data regarding the differentiating characteristics of patients with laboratory-confirmed and those negative for Middle East respiratory syndrome coronavirus (MERS-CoV) in South Korea. This hospital-based retrospective study compared MERS-CoV-positive and MERS-CoV-negative patients. A total of seven positive patients and 55 negative patients with a median age of 43 years (P = 0.845) were included. No statistical differences were observed with respect to their sex and the presence of comorbidities. At the time of admission, headache (28.6% vs. 3.6%; odds ratio [OR], 10.60; 95% confidence interval [CI], 1.22-92.27), myalgia (57.1% vs. 9.1%; OR, 13.33; 95% CI, 2.30-77.24), and diarrhea (57.1% vs. 14.5%; OR, 7.83; 95% CI, 1.47-41.79) were common among MERS-CoV-positive patients. MERS-CoV-positive patients were more likely to have a low platelet count (164 ± 76.57 vs. 240 ± 79.87) and eosinophil (0.27 ± 0.43 vs. 2.13 ± 2.01; P = 0.003). Chest radiography with diffuse bronchopneumonia was more frequent in MERS-CoV-positive patients than in negative patients (100% vs. 62.5%; P = 0.491). The symptoms of headache, myalgia, and diarrhea, as well as laboratory characteristics, including low platelet counts and eosinophil, and chest X-ray showing diffuse bronchopneumonia might enhance the ability to detect patients in South Korea infected with MERS-CoV.
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Infecciones por Coronavirus/diagnóstico , Adulto , Anciano , Infecciones por Coronavirus/sangre , Infecciones por Coronavirus/epidemiología , Brotes de Enfermedades , Femenino , Hospitales , Humanos , Masculino , Persona de Mediana Edad , Coronavirus del Síndrome Respiratorio de Oriente Medio/aislamiento & purificación , República de Corea/epidemiología , Estudios Retrospectivos , Esputo/virologíaRESUMEN
Histone H2B ubiquitination mediated by the Rad6/Bre1 complex is crucial for regulating the stability and reassembly of the nucleosome. To understand the regulatory mechanisms of H2B ubiquitination, we explored proteins related to the Rad6/Bre1 complex. Interestingly, we observed that the stability of Lge1, reported to be a cofactor of Bre1, is greatly reduced in the absence of Bre1. The stability of Lge1 did require the middle fragment of Bre1 containing a coiled-coil structure, but not its E3 ligase activity. Additionally, we found that Lge1 is involved in the 'writing' step of H2B ubiquitination. Our data suggest that Bre1 mediates H2B ubiquitination more precisely by maintaining the stability of Lge1 as well as through its role as a known E3 ligase.
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Histonas/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Factores de Transcripción/metabolismo , Ubiquitinación , Estabilidad Proteica , Saccharomyces cerevisiae/metabolismo , Ubiquitina-Proteína Ligasas/metabolismoRESUMEN
Candida albicans is a major pathogenic fungus in humans, and meets at first the innate immune cells, such as macrophages, in its host. One important strategy of the host cell to kill C. albicans is to produce reactive oxygen species (ROS) by the macrophages. In response to ROS produced by the macrophages, C. albicans operates its defense mechanisms against them by expressing its oxidative stress response genes. Although there have been many research studies explaining the specific transcription factors and the expression of the oxidative stress genes in C. albicans, the regulation of the oxidative stress genes by chromatin structure is little known. Epigenetic regulation by the chromatin structure is very important for the regulation of eukaryotic gene expression, including the chromatin structure dynamics by histone modifications. Among various histone modifications, histone acetylation is reported for its direct relationship to the regulation of gene expression. Recent studies reported that histone acetyltransferases regulate genes to respond to the oxidative stress in C. albicans. In this review, we introduce all histone acetyltransferases that C. albicans contains and some papers that explain how histone acetyltransferases participate in the oxidative stress response in C. albicans.
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Candida albicans/enzimología , Candida albicans/metabolismo , Histona Acetiltransferasas/metabolismo , Estrés Oxidativo/genética , Candida albicans/patogenicidad , Candidiasis/microbiología , Epigénesis Genética , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Regulación Fúngica de la Expresión Génica , Inestabilidad Genómica , Interacciones Huésped-Patógeno/fisiología , Macrófagos/metabolismo , Macrófagos/microbiología , Especies Reactivas de Oxígeno/metabolismo , Factores de Transcripción/genética , Virulencia/genéticaRESUMEN
The selection of oxide materials for catalyzing the oxygen evolution reaction in acid-based electrolyzers must be guided by the proper balance between activity, stability and conductivity-a challenging mission of great importance for delivering affordable and environmentally friendly hydrogen. Here we report that the highly conductive nanoporous architecture of an iridium oxide shell on a metallic iridium core, formed through the fast dealloying of osmium from an Ir25Os75 alloy, exhibits an exceptional balance between oxygen evolution activity and stability as quantified by the activity-stability factor. On the basis of this metric, the nanoporous Ir/IrO2 morphology of dealloyed Ir25Os75 shows a factor of ~30 improvement in activity-stability factor relative to conventional iridium-based oxide materials, and an ~8 times improvement over dealloyed Ir25Os75 nanoparticles due to optimized stability and conductivity, respectively. We propose that the activity-stability factor is a key "metric" for determining the technological relevance of oxide-based anodic water electrolyzer catalysts.
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Inheritance of the apolipoprotein E4 (apoE4) genotype has been identified as the major genetic risk factor for late onset Alzheimer's disease (AD). Studies have shown that apoE, apoE4 in particular, binds to amyloid-ß (Aß) peptides at residues 12-28 of Aß and this binding modulates Aß accumulation and disease progression. We have previously shown in several AD transgenic mice lines that blocking the apoE/Aß interaction with Aß12-28 P reduced Aß and tau-related pathology, leading to cognitive improvements in treated AD mice. Recently, we have designed a small peptoid library derived from the Aß12-28 P sequence to screen for new apoE/Aß binding inhibitors with higher efficacy and safety. Peptoids are better drug candidates than peptides due to their inherently more favorable pharmacokinetic properties. One of the lead peptoid compounds, CPO_Aß17-21 P, diminished the apoE/Aß interaction and attenuated the apoE4 pro-fibrillogenic effects on Aß aggregation in vitro as well as apoE4 potentiation of Aß cytotoxicity. CPO_Aß17-21 P reduced Aß-related pathology coupled with cognitive improvements in an AD APP/PS1 transgenic mouse model. Our study suggests the non-toxic, non-fibrillogenic peptoid CPO_Aß17-21 P has significant promise as a new AD therapeutic agent which targets the Aß related apoE pathway, with improved efficacy and pharmacokinetic properties.
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Enfermedad de Alzheimer/tratamiento farmacológico , Péptidos beta-Amiloides/metabolismo , Apolipoproteínas E/metabolismo , Fármacos Neuroprotectores/uso terapéutico , Peptoides/uso terapéutico , Animales , Línea Celular Tumoral , Cognición , Femenino , Humanos , Masculino , Ratones , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/farmacocinética , Peptoides/química , Peptoides/farmacocinética , Unión ProteicaRESUMEN
BACKGROUND: Several studies have shown that family meals promote a well-balanced and healthier diet and weight status. Metabolic syndrome is related to eating behavior. This study investigated the association between eating family meals and the prevalence of metabolic syndrome. METHODS: This cross-sectional study included 4,529 subjects who participated in the Korea National Health and Nutrition Examination Survey IV and V (2007-2012). A self-reported questionnaire was used to assess dietary status. Metabolic syndrome was defined according to the guidelines of the modified version of the National Cholesterol Education Program Adult Treatment Panel III. We compared the overall quality of dietary intake in family meal. RESULTS: Nutritional adequacy ratios for energy, protein, calcium, vitamin A, vitamin B1, vitamin B2, vitamin C, niacin, and potassium, and the mean adequacy ratio were significantly higher in the family meal group (P<0.05). The prevalence of metabolic syndrome was lower in the family meal group (P<0.05). However, we observed no significant association between eating family meals and the prevalence of metabolic syndrome. CONCLUSION: This study demonstrated that eating family meals appeared to be associated with nutrient adequacy. However, we observed no significant differences in prevalence of metabolic syndrome between the 2 groups.
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Since Li4Ti5O12 as a promising anode material in lithium-ion batteries (LIBs) has a poor rate performance due to low electronic conductivity, a doping of Li4Ti5O12 with heterogeneous atoms has been considered to overcome this problem. Herein, we report that there is an upper limit of doping level to maintain the zero strain characteristics of Li4Ti5O12 lattice during charge/discharge process. By using synchrotron studies, it was revealed that the Li+ diffusivity was maximized at a certain doping level for which the conductivity was markedly increased with maintaining the zero strain characteristics. However, with more doses of dopants over the upper limit, the lattice shrank and therefore the Li+ diffusivity decreased, although the electronic conductivity was further increased in comparison with the optimal doping level.