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1.
G3 (Bethesda) ; 14(6)2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38526099

RESUMO

Cellular pathways that detect DNA damage are useful for identifying genes that suppress DNA damage, which can cause genome instability and cancer predisposition syndromes when mutated. We identified 199 high-confidence and 530 low-confidence DNA damage-suppressing (DDS) genes in Saccharomyces cerevisiae through a whole-genome screen for mutations inducing Hug1 expression, a focused screen for mutations inducing Ddc2 foci, and data from previous screens for mutations causing Rad52 foci accumulation and Rnr3 induction. We also identified 286 high-confidence and 394 low-confidence diverse genome instability-suppressing (DGIS) genes through a whole-genome screen for mutations resulting in increased gross chromosomal rearrangements and data from previous screens for mutations causing increased genome instability as assessed in a diversity of genome instability assays. Genes that suppress both pathways (DDS+ DGIS+) prevent or repair DNA replication damage and likely include genes preventing collisions between the replication and transcription machineries. DDS+ DGIS- genes, including many transcription-related genes, likely suppress damage that is normally repaired properly or prevent inappropriate signaling, whereas DDS- DGIS+ genes, like PIF1, do not suppress damage but likely promote its proper, nonmutagenic repair. Thus, induction of DNA damage markers is not a reliable indicator of increased genome instability, and the DDS and DGIS categories define mechanistically distinct groups of genes.


Assuntos
Dano ao DNA , Instabilidade Genômica , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/genética , Mutação , Genes Supressores , Reparo do DNA/genética , Genoma Fúngico
2.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-1007905

RESUMO

OBJECTIVE@#The aim of this study was to assess the impact of bisphenol A (BPA) and its substitute, bisphenol F (BPF), on the colonic fecal community structure and function of mice.@*METHODS@#We exposed 6-8-week-old male C57BL/6 mice to 5 mg/(kg∙day) and 50 μg/(kg∙day) of BPA or BPF for 14 days. Fecal samples from the colon were analyzed using 16S rRNA sequencing.@*RESULTS@#Gut microbiome community richness and diversity, species composition, and function were significantly altered in mice exposed to BPA or BPF. This change was characterized by elevated levels of Ruminococcaceae UCG-010 and Oscillibacter and decreased levels of Prevotella 9 and Streptococcus. Additionally, pathways related to carbohydrate and amino acid metabolism showed substantial enrichment.@*CONCLUSION@#Mice exposed to different BP analogs exhibited distinct gut bacterial community richness, composition, and related metabolic pathways. Considering the essential role of gut bacteria in maintaining intestinal homeostasis, our study highlights the intestinal toxicity of BPs in vertebrates.


Assuntos
Masculino , Animais , Camundongos , Microbioma Gastrointestinal , Camundongos Endogâmicos C57BL , RNA Ribossômico 16S/genética , Compostos Benzidrílicos/toxicidade , Bactérias/genética , Fenóis
3.
International Eye Science ; (12): 1723-1731, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-987898

RESUMO

AIM:To evaluate the agreement of corneal high-order aberrations from Topcon KR-1W, i.Profiler and OPD-Scan Ⅲ wavefront aberrometers in myopic adults.METHODS:A prospective clinical study. A total of 92 adult patients(92 eyes)with myopia in the department of optometry, the People's Hospital of Guangxi Zhuang Autonomous Region from June to August 2022 were enrolled. The third-order and fourth-order corneal aberrations at the pupil diameter of 4 and 6mm were measured by Topcon KR-1W, i.Profiler, and OPD-Scan Ⅲ, respectively. The difference and agreement of the three aberrometers were evaluated.RESULTS: The measurements at 6mm pupil diameter were all greater than those at 4mm pupil diameter. Although there were no statistical differences in the measurements of Z-44、Z-24 by the three aberrometers at 4 pupil diameter(P>0.05), there were statistical differences in other measurements(P<0.05). The aberration results measured by the three aberrometers were statistically different at the 6mm pupil diameter(P<0.05). The 95% limit of agreement(95%LoA)of the measurements of higher-order aberration, including the third-order aberrations at 4mm pupil diameter and the third-order and fourth-order aberrations at 6mm pupil diameter(except for the Z-24)were greater than 0.1μm. The concordance correlation coefficient(Pc)was lower than 0.90, indicating a poor consistency. The correlation coefficients of corneal higher-order aberrations were significantly different among the three aberrometers at 4 and 6mm pupil diameter(r4mm=0.215~0.805, P4mm<0.05; r6mm=0.561~0.916, P6mm<0.001).CONCLUSION:There were significant differences in the measurements of the third- and fourth-order corneal aberrations at 4 and 6mm pupil diameter among Topcon KR-1W, i.Profiler, and OPD-Scan Ⅲ, and the agreements were poor, so they are not interchangeably in clinical applications.

4.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1009830

RESUMO

OBJECTIVES@#To explore the etiology composition and outcomes of pediatric chronic critical illness (PCCI) in the pediatric intensive care unit (PICU).@*METHODS@#The children who were hospitalized in the PICU of Dongguan Children's Hospital Affiliated to Guangdong Medical University and met the diagnostic criteria for PCCI from January 2017 to December 2022 were included in the study. The etiology of the children was classified based on their medical records and discharge diagnoses. Relevant clinical data during hospitalization were collected and analyzed.@*RESULTS@#Among the 3 955 hospitalized children in the PICU from January 2017 to December 2022, 321 cases (8.12%) met the diagnostic criteria for PCCI. Among the 321 cases, the most common etiology was infection (71.3%, 229 cases), followed by unintentional injury (12.8%, 41 cases), postoperation (5.9%, 19 cases), tumors/immune system diseases (5.0%, 16 cases), and genetic and chromosomal diseases (5.0%, 16 cases). Among the 321 cases, 249 cases (77.6%) were discharged after improvement, 37 cases (11.5%) were discharged at the request of the family, and 35 cases (10.9%) died in the hospital. Among the deaths, infection accounted for 74% (26/35), unintentional injury accounted for 17% (6/35), tumors/immune system diseases accounted for 6% (2/35), and genetic and chromosomal diseases accounted for 3% (1/35). From 2017 to 2022, the proportion of PCCI in PICU diseases showed an increasing trend year by year (P<0.05). Among the 321 children with PCCI, there were 148 infants and young children (46.1%), 57 preschool children (17.8%), 54 school-aged children (16.8%), and 62 adolescents (19.3%), with the highest proportion in the infant and young children group (P<0.05). The in-hospital mortality rates of the four age groups were 14.9% (22/148), 8.8% (5/57), 5.6% (3/54), and 8.1% (5/62), respectively. The infant and young children group had the highest mortality rate, but there was no statistically significant difference among the four groups (P>0.05).@*CONCLUSIONS@#The proportion of PCCI in PICU diseases is increasing, and the main causes are infection and unintentional injury. The most common cause of death in children with PCCI is infection. The PCCI patient population is mainly infants and young children, and the in-hospital mortality rate of infant and young children with PCCI is relatively high.


Assuntos
Adolescente , Lactente , Pré-Escolar , Humanos , Criança , Estado Terminal , Prognóstico , Criança Hospitalizada , Doença Crônica , Unidades de Terapia Intensiva Pediátrica
5.
International Eye Science ; (12): 1377-1380, 2022.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-935017

RESUMO

AIM:To observe the clinical effect of ranibizumab combined with 577nm micropulse laser in the treatment of severe diabetic macular edema(DME). METHODS:There were 52 eyes of 52 patients diagnosed with severe DME who admitted to the People's Hospital of Guangxi Zhuang Autonomous Region from June 2016 to September 2019. The patients were randomly divided into the observation group(26 patients with 26 eyes, treated with ranibizumab combined with 577nm micropulse laser)and the control group(26 patients with 26 eyes, treated with ranibizumab alone). Patients in both groups received intravitreal injection of ranibizumab with “3+PRN” regimen. Followed up at 9mo after treatment to observe the central macular thickness(CMT), the best corrected visual acuity(BCVA)and the times of intravitreal injection of ranibizumab in the two groups.RESULTS:Compared with before treatment, the CMT and BCVA of the two groups were significantly improved at each time point after treatment(all P<0.001), but there was no difference between the two groups(P>0.05). During the follow-up period, the times of vitreous injection of ranibizumabin the observation group was significantly less than that in the control group(5.88±1.24 times vs 7.12±1.24 times, P=0.001). CONCLUSION:Both ranibizumab combined with 577nm micropulse laser and ranibizumab alone are effective in reducing edema and improving vision in patients with severe DME, but the combination therapy reduces the times of injection.

6.
Nat Commun ; 12(1): 5568, 2021 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-34552065

RESUMO

Eukaryotic DNA Mismatch Repair (MMR) involves redundant exonuclease 1 (Exo1)-dependent and Exo1-independent pathways, of which the Exo1-independent pathway(s) is not well understood. The exo1Δ440-702 mutation, which deletes the MutS Homolog 2 (Msh2) and MutL Homolog 1 (Mlh1) interacting peptides (SHIP and MIP boxes, respectively), eliminates the Exo1 MMR functions but is not lethal in combination with rad27Δ mutations. Analyzing the effect of different combinations of the exo1Δ440-702 mutation, a rad27Δ mutation and the pms1-A99V mutation, which inactivates an Exo1-independent MMR pathway, demonstrated that each of these mutations inactivates a different MMR pathway. Furthermore, it was possible to reconstitute a Rad27- and Msh2-Msh6-dependent MMR reaction in vitro using a mispaired DNA substrate and other MMR proteins. Our results demonstrate Rad27 defines an Exo1-independent eukaryotic MMR pathway that is redundant with at least two other MMR pathways.


Assuntos
Reparo de Erro de Pareamento de DNA , Exodesoxirribonucleases/metabolismo , Endonucleases Flap/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , DNA Ligases/metabolismo , DNA Fúngico/metabolismo , Exodesoxirribonucleases/genética , Endonucleases Flap/genética , Proteínas MutL/genética , Proteínas MutL/metabolismo , Mutação , Antígeno Nuclear de Célula em Proliferação/genética , Antígeno Nuclear de Célula em Proliferação/metabolismo , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/genética
7.
China Occupational Medicine ; (6): 329-333, 2021.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-923173

RESUMO

OBJECTIVE: To analyze the stability of test results of fingertip thermotactile perception threshold(TPT) among healthy individuals and the influencing factors of the TPT test. METHODS: Fifty healthy young volunteers aged 20-25 were selected as the study subjects using the convenience sampling method. The HVLab thermal aesthesiometer was used to perform the fingertip TPT test under the standard condition. Right index, middle, ring, little, left index and little fingers were tested. According to the method of random number table, we selected 25 subjects to receive second test after the interval of two weeks. RESULTS: Intraclass correlation coefficient(ICC) for cold threshold of right little finger was bigger than 0.75, suggesting the test-retest reliability was excellent. The ICC for hot threshold of six test fingers, cold threshold of right and left index fingers, right middle and left little finges was in the range of 0.60-0.74, indicating the test-retest reliability was good. However, the ICC for cold threshold of right ring finger was less than 0.40, and the test-retest reliability was poor. The hot threshold of right middle, ring and little fingers, and the cold threshold of left little finger of males were higher than those of females(all P<0.05). The cold threshold of right index and little fingers were lower than those of left hand in males(all P<0.05). The cold threshold of right middle and ring fingers were lower than that of the right index finger in females(all P<0.05). The cold threshold of right little finger was lower than those of right index, middle and ring fingers in females(all P<0.05). CONCLUSION: The stability of the fingertip TPT result is good in healthy young adults aged 20-25. The fingertip TPT test could be used for occupational health surveillance of workers exposed to hand-transmitted vibration. We should take into account the influence of gender, the right or left hand and different fingers when developing TPT reference values.

8.
Elife ; 92020 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-32762846

RESUMO

Foldback inversions, also called inverted duplications, have been observed in human genetic diseases and cancers. Here, we used a Saccharomyces cerevisiae genetic system that generates gross chromosomal rearrangements (GCRs) mediated by foldback inversions combined with whole-genome sequencing to study their formation. Foldback inversions were mediated by formation of single-stranded DNA hairpins. Two types of hairpins were identified: small-loop hairpins that were suppressed by MRE11, SAE2, SLX1, and YKU80 and large-loop hairpins that were suppressed by YEN1, TEL1, SWR1, and MRC1. Analysis of CRISPR/Cas9-induced double strand breaks (DSBs) revealed that long-stem hairpin-forming sequences could form foldback inversions when proximal or distal to the DSB, whereas short-stem hairpin-forming sequences formed foldback inversions when proximal to the DSB. Finally, we found that foldback inversion GCRs were stabilized by secondary rearrangements, mostly mediated by different homologous recombination mechanisms including single-strand annealing; however, POL32-dependent break-induced replication did not appear to be involved forming secondary rearrangements.


Assuntos
Inversão Cromossômica , Cromossomos Fúngicos/genética , Instabilidade Genômica , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/genética , Quebras de DNA de Cadeia Dupla , Rearranjo Gênico , Genoma Fúngico , Recombinação Homóloga
9.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-873503

RESUMO

@#Objective To analyze the treatment outcome and related influencing factors of Tibet- an nationality new smear-positive pulmonary tuberculosis patients in Qinghai Province,so as to provide evidence for tuberculosis control and treatment among Tibetan population. Methods Statistical analysis was conducted on 5 564 Tibetan nationality new smear-positive pulmonary tuberculosis cases in Qinghai province who were reported in the China Tuberculosis Information Management System and approved to receive treatment from 2008 to 2017. The main influencing factors were detected by unconditional Logistic regression model analysis,dependent variable was successful treatment or not,independent variables were other factors related to the treatment outcome. Results The treatment success rate of Tibetan nationality new smear-positive pulmonary tuberculosis cases was 87. 1% ( 4 848 /5 564) ,and the adverse outcome rate was 12. 9% ( 716 /5 564) . Unconditional Logistic regression model analysis indicated that non-full- course supervision management,living in agricultural and pastoral area,having severe disease,floating population,and age older than 60 years were risk factors of adverse outcome. The odds ratio( OR) 95% confidence interval( CI) of the above risk factors were 13. 044( 10. 671-15. 944) ,2. 305( 1. 703-3. 119) , 2. 090( 1. 346-3. 243) ,1. 967( 1. 443-2. 682) ,and 1. 909( 1. 410-2. 586) . Clinical consultation,farmers and herdsmen were protective factors. The OR( 95% CI) were 0. 451( 0. 375-0. 543) ,and 0. 786( 0. 627- 0. 985) . Conclusions Treatment success rate of Tibetan nationality new smear positive pulmonary tuberculosis cases was low. Therefore,the directly observed treatment short-course ( DOTS) strategy should be strictly implemented and the full-course supervision management should be strengthened to improve the treatment success rate. More attention should be paid to the elderly,severe,floating,agricultural and pastoral populations among the Tibetan population.

10.
Nat Struct Mol Biol ; 26(12): 1184, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31686054

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

11.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 31(3): 319-322, 2019 Jun 26.
Artigo em Chinês | MEDLINE | ID: mdl-31544417

RESUMO

OBJECTIVE: To assess the clinical significance of transient elastography (Fibroscan) in detection of clonorchiasis, so as to provide new insights into the assessment of therapeutic efficacy of deworming. METHODS: The liver stiffness measurement (LSM) values were measured in parasitologically diagnosed clonorchiasis patients using FibroScan before and after deworming, and the patients'age, gender, body mass index (BMI), duration of raw fish consumption and total amount of raw fish consumption were collected for correlation analyses. RESULTS: The clonorchiasis patients'age, gender, BMI, duration of raw fish consumption and total amount of raw fish consumption had no associations with pre-treatment LSM values (r/rs = 0.189, 0.073, 0.180; 0.071, -0.098, 0.033; 0.166, 0.309, 0.172; 0.235, 0.247, 0.209; 0.164, 0.277, 0.088; all P values > 0.05). There was a significant difference in the LSM values from the seventh, eighth and ninth intercostal space prior to deworming (F = 3.259, P < 0.05), and no significant difference was detected after deworming (F = 0.851, P > 0.05). The LSM values from the seventh, eighth and ninth intercostal space were significantly lower pre-deworming than post-deworming (t = 6.724, 5.603, 2.884; all P values < 0.05). CONCLUSIONS: FibroScan is feasible to assess the therapuetic efficacy of deworming in patients with clonorchiasis; however, measurement at various sites affects the LSM value.


Assuntos
Clonorquíase , Técnicas de Imagem por Elasticidade , Animais , Anti-Helmínticos/uso terapêutico , Índice de Massa Corporal , Clonorquíase/complicações , Clonorquíase/diagnóstico por imagem , Técnicas de Imagem por Elasticidade/normas , Feminino , Peixes/parasitologia , Humanos , Fígado/diagnóstico por imagem , Fígado/parasitologia , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/etiologia , Masculino , Alimentos Crus/parasitologia
12.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-818937

RESUMO

Objective To assess the clinical significance of transient elastography (Fibroscan) in detection of clonorchiasis, so as to provide new insights into the assessment of therapeutic efficacy of deworming. Methods The liver stiffness measurement (LSM) values were measured in parasitologically diagnosed clonorchiasis patients using FibroScan before and after deworming, and the patients’age, gender, body mass index (BMI), duration of raw fish consumption and total amount of raw fish consumption were collected for correlation analyses. Results The clonorchiasis patients’age, gender, BMI, duration of raw fish consumption and total amount of raw fish consumption had no associations with pre-treatment LSM values (r/rs = 0.189, 0.073, 0.180; 0.071, –0.098, 0.033; 0.166, 0.309, 0.172; 0.235, 0.247, 0.209; 0.164, 0.277, 0.088; all P values > 0.05). There was a significant difference in the LSM values from the seventh, eighth and ninth intercostal space prior to deworming (F = 3.259, P < 0.05), and no significant difference was detected after deworming (F = 0.851, P > 0.05). The LSM values from the seventh, eighth and ninth intercostal space were significantly lower pre-deworming than post-deworming (t = 6.724, 5.603, 2.884; all P values < 0.05). Conclusion FibroScan is feasible to assess the therapuetic efficacy of deworming in patients with clonorchiasis; however, measurement at various sites affects the LSM value.

13.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-818485

RESUMO

Objective To assess the clinical significance of transient elastography (Fibroscan) in detection of clonorchiasis, so as to provide new insights into the assessment of therapeutic efficacy of deworming. Methods The liver stiffness measurement (LSM) values were measured in parasitologically diagnosed clonorchiasis patients using FibroScan before and after deworming, and the patients’age, gender, body mass index (BMI), duration of raw fish consumption and total amount of raw fish consumption were collected for correlation analyses. Results The clonorchiasis patients’age, gender, BMI, duration of raw fish consumption and total amount of raw fish consumption had no associations with pre-treatment LSM values (r/rs = 0.189, 0.073, 0.180; 0.071, –0.098, 0.033; 0.166, 0.309, 0.172; 0.235, 0.247, 0.209; 0.164, 0.277, 0.088; all P values > 0.05). There was a significant difference in the LSM values from the seventh, eighth and ninth intercostal space prior to deworming (F = 3.259, P < 0.05), and no significant difference was detected after deworming (F = 0.851, P > 0.05). The LSM values from the seventh, eighth and ninth intercostal space were significantly lower pre-deworming than post-deworming (t = 6.724, 5.603, 2.884; all P values < 0.05). Conclusion FibroScan is feasible to assess the therapuetic efficacy of deworming in patients with clonorchiasis; however, measurement at various sites affects the LSM value.

14.
Nat Commun ; 9(1): 3680, 2018 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-30206225

RESUMO

Genome instability is associated with tumorigenesis. Here, we identify a role for the histone Htz1, which is deposited by the Swr1 chromatin-remodeling complex (SWR-C), in preventing genome instability in the absence of the replication fork/replication checkpoint proteins Mrc1, Csm3, or Tof1. When combined with deletion of SWR1 or HTZ1, deletion of MRC1, CSM3, or TOF1 or a replication-defective mrc1 mutation causes synergistic increases in gross chromosomal rearrangement (GCR) rates, accumulation of a broad spectrum of GCRs, and hypersensitivity to replication stress. The double mutants have severe replication defects and accumulate aberrant replication intermediates. None of the individual mutations cause large increases in GCR rates; however, defects in MRC1, CSM3 or TOF1 cause activation of the DNA damage checkpoint and replication defects. We propose a model in which Htz1 deposition and retention in chromatin prevents transiently stalled replication forks that occur in mrc1, tof1, or csm3 mutants from being converted to DNA double-strand breaks that trigger genome instability.


Assuntos
Adenosina Trifosfatases/metabolismo , Montagem e Desmontagem da Cromatina , Replicação do DNA , Instabilidade Genômica , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/citologia , Saccharomyces cerevisiae/genética , Ciclo Celular , Cromatina/metabolismo , Montagem e Desmontagem da Cromatina/efeitos dos fármacos , Cromossomos Fúngicos/genética , Dano ao DNA , Replicação do DNA/efeitos dos fármacos , Rearranjo Gênico/genética , Recombinação Homóloga/genética , Hidroxiureia/farmacologia , Modelos Biológicos , Mutação/genética , Saccharomyces cerevisiae/metabolismo , Estresse Fisiológico/efeitos dos fármacos
15.
Nat Struct Mol Biol ; 25(8): 650-659, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30061603

RESUMO

Eukaryotic DNA mismatch repair (MMR) involves both exonuclease 1 (Exo1)-dependent and Exo1-independent pathways. We found that the unstructured C-terminal domain of Saccharomyces cerevisiae Exo1 contains two MutS homolog 2 (Msh2)-interacting peptide (SHIP) boxes downstream from the MutL homolog 1 (Mlh1)-interacting peptide (MIP) box. These three sites were redundant in Exo1-dependent MMR in vivo and could be replaced by a fusion protein between an N-terminal fragment of Exo1 and Msh6. The SHIP-Msh2 interactions were eliminated by the msh2M470I mutation, and wild-type but not mutant SHIP peptides eliminated Exo1-dependent MMR in vitro. We identified two S. cerevisiae SHIP-box-containing proteins and three candidate human SHIP-box-containing proteins. One of these, Fun30, had a small role in Exo1-dependent MMR in vivo. The Remodeling of the Structure of Chromatin (Rsc) complex also functioned in both Exo1-dependent and Exo1-independent MMR in vivo. Our results identified two modes of Exo1 recruitment and a peptide module that mediates interactions between Msh2 and other proteins, and they support a model in which Exo1 functions in MMR by being tethered to the Msh2-Msh6 complex.


Assuntos
Reparo de Erro de Pareamento de DNA , Enzimas Reparadoras do DNA/metabolismo , Exodesoxirribonucleases/metabolismo , Proteína 2 Homóloga a MutS/metabolismo , Domínios e Motivos de Interação entre Proteínas , Sequência de Aminoácidos , Sequência Conservada , Humanos , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Homologia de Sequência de Aminoácidos
16.
PLoS Genet ; 14(3): e1007250, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29505562

RESUMO

Mms21, a subunit of the Smc5/6 complex, possesses an E3 ligase activity for the Small Ubiquitin-like MOdifier (SUMO). Here we show that the mms21-CH mutation, which inactivates Mms21 ligase activity, causes increased accumulation of gross chromosomal rearrangements (GCRs) selected in the dGCR assay. These dGCRs are formed by non-allelic homologous recombination between divergent DNA sequences mediated by Rad52-, Rrm3- and Pol32-dependent break-induced replication. Combining mms21-CH with sgs1Δ caused a synergistic increase in GCRs rates, indicating the distinct roles of Mms21 and Sgs1 in suppressing GCRs. The mms21-CH mutation also caused increased rates of accumulating uGCRs mediated by breakpoints in unique sequences as revealed by whole genome sequencing. Consistent with the accumulation of endogenous DNA lesions, mms21-CH mutants accumulate increased levels of spontaneous Rad52 and Ddc2 foci and had a hyper-activated DNA damage checkpoint. Together, these findings support that Mms21 prevents the accumulation of spontaneous DNA lesions that cause diverse GCRs.


Assuntos
Dano ao DNA/genética , Proteína SUMO-1/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/genética , Cromossomos Fúngicos , Reparo do DNA , DNA Polimerase Dirigida por DNA/genética , DNA Polimerase Dirigida por DNA/metabolismo , Endodesoxirribonucleases/genética , Endodesoxirribonucleases/metabolismo , Epistasia Genética , Exodesoxirribonucleases/genética , Exodesoxirribonucleases/metabolismo , Genoma Fúngico , Mutação , Proteína Rad52 de Recombinação e Reparo de DNA/metabolismo , RecQ Helicases/genética , RecQ Helicases/metabolismo , Proteína SUMO-1/genética , Proteínas de Saccharomyces cerevisiae/genética
17.
PLoS Genet ; 14(1): e1007170, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29320491

RESUMO

Defects in the genes encoding the Paf1 complex can cause increased genome instability. Loss of Paf1, Cdc73, and Ctr9, but not Rtf1 or Leo1, caused increased accumulation of gross chromosomal rearrangements (GCRs). Combining the cdc73Δ mutation with individual deletions of 43 other genes, including TEL1 and YKU80, which are involved in telomere maintenance, resulted in synergistic increases in GCR rates. Whole genome sequence analysis of GCRs indicated that there were reduced relative rates of GCRs mediated by de novo telomere additions and increased rates of translocations and inverted duplications in cdc73Δ single and double mutants. Analysis of telomere lengths and telomeric gene silencing in strains containing different combinations of cdc73Δ, tel1Δ and yku80Δ mutations suggested that combinations of these mutations caused increased defects in telomere maintenance. A deletion analysis of Cdc73 revealed that a central 105 amino acid region was necessary and sufficient for suppressing the defects observed in cdc73Δ strains; this region was required for the binding of Cdc73 to the Paf1 complex through Ctr9 and for nuclear localization of Cdc73. Taken together, these data suggest that the increased GCR rate of cdc73Δ single and double mutants is due to partial telomere dysfunction and that Ctr9 and Paf1 play a central role in the Paf1 complex potentially by scaffolding the Paf1 complex subunits or by mediating recruitment of the Paf1 complex to the different processes it functions in.


Assuntos
Instabilidade Genômica/genética , Proteínas Nucleares/fisiologia , Proteínas de Saccharomyces cerevisiae/fisiologia , Homeostase do Telômero/genética , Proteínas de Ciclo Celular/genética , Proteínas de Ligação a DNA/fisiologia , Peptídeos e Proteínas de Sinalização Intracelular/fisiologia , Proteínas Nucleares/genética , Organismos Geneticamente Modificados , Fenótipo , Ligação Proteica , Proteínas Serina-Treonina Quinases/fisiologia , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Telômero/metabolismo , Fatores de Elongação da Transcrição/genética
18.
Chinese Pharmacological Bulletin ; (12): 626-631, 2018.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-705098

RESUMO

Aim To explore the anti-psoriatic effects of honokiol on the mouse model induced by imiquimod and the underlying mechanism. Methods The mice were randomly divided into control group, model group, liposome solvent control group, dexamethasone positive group and honokiol high, medium, low dose groups. The progress of the disease was observed by the psoriasis area and severity index (PASI). The morphological changes of the skin cells were observed by HE staining, and epidermis thickness was meas-ured. The expression of IL-17, IL-23, JAK, STAT3, TNF-α and NF-κB was semi-quantitively analyzed by immunohistochemistry. Results Compared to model group, the scaling and thickness of honokiol treated groups were alleviated. Inflammatory infiltration and micro abscess were reduced. The expressions of IL-17, IL-23, JAK, STAT3, TNF-α and NF-κB in model group were higher than those in honokiol-high and honokiol-medium group in a dose-dependent manner. Conclusion Honokiol can inhibit imiquimod-induced psoriasis-like lesions in mice by inhibiting the IL-17/IL-23 inflammatory axis.

19.
Pol J Radiol ; 82: 152-160, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28392852

RESUMO

BACKGROUND: A systematic review and meta-analysis of all available publications was performed to evaluate the diagnostic accuracy of percutaneous transthoracic needle biopsy (PTNB) using a C-Arm Cone-Beam CT (CBCT) system in patients with lung nodules. MATERIAL/METHODS: Thedatabases of PUBMED, OVID, EBSCO, EMBASE, and China National Knowledge Infrastructure (CNKI) were systematically searched for relevant original articles on the diagnostic accuracy of CBCT-guided PTNB for the diagnosis of nodules in the lungs. Diagnostic indices including sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and diagnostic score (DS) were calculated. Moreover,summary receiver operating characteristic curves (SROC) were constructed with Stata (version 13.0), Rev Man (version 5.3), and Meta-disc (version 1.4) software. Other clinical indices such as incidence of complications were also recorded. RESULTS: Eight studies met the inclusion and exclusion criteria for the meta-analysis. The pooled sensitivity, specificity, PLR, NLR, DOR, DS, and SROC with 95% confidence intervals were 0.96 (0.93-0.98), 1.00 (0.91-1.00), 711.15 (9.48-53325.89), 0.04 (0.02-0.07), 16585.29 (284.88-9.7e+05), 9.72 (5.65-13.78), and 0.99 (0.97-0.99), respectively. The incidence of pneumothorax and hemorrhage was 10-29.27% and 1.22-47.25%, respectively. CONCLUSIONS: CBCT-guided PTNB has an acceptable rate of complications and is associated with a reasonable radiation exposure. Moreover, it is a highly accurate and safe technique for the diagnosis of lung nodules and can be recommended to be used in routine clinical practice.

20.
Journal of Medical Biomechanics ; (6): E384-E387, 2017.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-803893

RESUMO

Objective To study the effects on anterosuperior stability of the shoulder joint when the coracoacromial arch is damaged at different degrees. Methods Thirty-six specimens of the fresh frozen adult shoulder joints were randomly and evenly divided into 3 groups. Group 1, reserving integrity of the coracoacromial ligament of the shoulder joint; Group 2, dissecting half of the coracoacromial ligament attachment sector on the acromion; Group 3, grinding all the coracoacromial ligament attachment sector on the acromion. The specimens of the shoulder joint were fixed on test bench of the biomechanical testing machine. The axial pressure was applied on the humeral shaft, and the humeral head was pushed to move in anterosuperior direction. The displacement distance of the humeral head under 50 N pressure was then recorded. Results Under 50 N pressure, the displacement distance of the humeral head in Group 1, 2, 3 was (2.50±0.59), (5.38±0.71), (6.49±0.81) mm, respectively, which showed significantly statistic differences among 3 groups (P<0.05). Conclusions The damage to the coracoacromial arch will affect the anterosuperior stability of the shoulder joint. The greater damage to the coracoacromial arch will lead to the lower anterosuperior stability of the shoulder joint.

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