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2.
Bioresour Technol ; 401: 130733, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38670287

RESUMO

This study investigated the mediating effect of Triethanolamine on Fe@C-Rhodobacter sphaeroides hybrid photosynthetic system to achieve efficient biohydrogen production. The biocompatible Fe@C generates excited electrons upon exposure to light, releasing ferrum for nitrogenase synthesis, and regulating the pH of the fermentation environment. Triethanolamine was introduced to optimize the electron transfer chain, thereby improving system stability, prolonging electron lifespan, and facilitating ferrum corrosion. This, in turn, stimulated the lactic acid synthetic metabolic pathway of Rhodobacter sphaeroides, resulting in increased reducing power in the biohybrid system. The ternary coupling system was analyzed through the regulation of concentration, initial pH, and light intensity. The system achieved the highest total H2 production of 5410.9 mL/L, 1.29 times higher than the control (2360.5 mL/L). This research provides a valuable strategy for constructing ferrum-carbon-based composite-cellular biohybrid systems for photo-fermentation H2 production.


Assuntos
Etanolaminas , Hidrogênio , Luz , Rhodobacter sphaeroides , Rhodobacter sphaeroides/metabolismo , Hidrogênio/metabolismo , Etanolaminas/metabolismo , Etanolaminas/química , Ferro/química , Catálise , Concentração de Íons de Hidrogênio , Carbono , Fermentação , Fotossíntese
3.
Insights Imaging ; 15(1): 98, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38536581

RESUMO

OBJECTIVE: To systematically analyze the accuracy of ultrasonic techniques in assessing the nature of gastric contents and their volume. METHODS: English-language articles that used ultrasonic techniques to assess the nature of gastric contents and their volume in patients were selected. In eligible studies, data were recalculated and analyzed for forest plots and subject summary curves of operating characteristics (SROC). Study quality was assessed using the diagnostic accuracy study quality assessment tool QUADAS-2. Publication bias was tested using funnel plots. RESULTS: Nine articles with a total of 523 study subjects were identified for this review. All studies were feasibility studies. The sensitivity of ultrasound assessment of gastric contents ranged from 53 to 100% and the specificity from 48 to 99%. The combined analysis yielded an area under the working characteristic curve for subjects of 97% (95% confidence interval (CI), 95-98%), a sensitivity of 95% (95% CI, 84-99%), and a specificity of 88% (95% CI, 72-95%). There was a high degree of heterogeneity among the studies due to inter-operator differences and small sample sizes. CONCLUSION: Ultrasound techniques have high diagnostic accuracy in assessing the nature of gastric contents and their volume in patients. However, most of the studies were feasibility studies with small sample sizes, lacked standardization, and had high risk of bias. More studies are needed in the future to investigate the diagnostic performance of gastric ultrasound assessment techniques. CRITICAL RELEVANCE STATEMENT: Ultrasonography can be used to assess gastric contents, but standardized data integration and reporting are needed to account for the diagnostic capabilities of this technology. KEY POINTS: • Ultrasound is a safe and feasible tool for assessing gastric contents. • Ultrasound has good diagnostic performance for gastric contents. • There is still a certain heterogeneity within our analysis process; more research is needed in the future to improve our results.

4.
J Opt Soc Am A Opt Image Sci Vis ; 41(3): 543-549, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38437445

RESUMO

A kind of optical beam with a radially parabolic propagating manner and intensity decay inversely proportional to propagating distance in the far field is investigated. The initial complex amplitudes of this kind of beam have the form of a Gaussian function multiplied by a m/2-order modified Bessel function and a helical phase factor with topological charge m. The arguments for Bessel and Gauss parts in the propagating solutions of these beams are complex and symmetric as elegant Laguerre and Hermite Gaussian beams. As a result, the beams can be referred to as elegant modified Bessel Gauss (EMBG) beams. Similar to non-diffractive beams such as Bessel and Airy beams, the EMBG beams also carry infinite power due to a transversely slowly decaying tail of complex amplitude. The EMBG beams demonstrate intermediate propagating properties between non-diffractive and finite-power beams. Unlike non-diffractive beams that never spread their power and finite-power beams that always diverge in a linear manner and spread their power by inversely square law in the far field, the EMBG beams demonstrate a far-field parabolic propagating manner and decay their power by inversely linear law. In addition, the EMBG beams have total Gouy phase, which is only half of that of elegant Laguerre Gauss beams with the same topological charge, and have far-field intensity distributions regardless of the beam waist radius in the initial plane. The propagating and focusing properties of EMBG beams represent an intermediate status between the non-diffractive and finite-power beams.

5.
Int J Mol Sci ; 25(3)2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38338931

RESUMO

Cladosporium, a genus of ascomycete fungi in the Dematiaceae family, is primarily recognized as a widespread environmental saprotrophic fungus or plant endophyte. Further research has shown that the genus is distributed in various environments, particularly in marine ecosystems, such as coral reefs, mangroves and the polar region. Cladosporium, especially the marine-derived Cladosporium, is a highly resourceful group of fungi whose natural products have garnered attention due to their diverse chemical structures and biological activities, as well as their potential as sources of novel leads to compounds for drug production. This review covers the sources, distribution, bioactivities, biosynthesis and structural characteristics of compounds isolated from Cladosporium in the period between January 2000 and December 2022, and conducts a comparative analysis of the Cladosporium isolated compounds derived from marine and terrestrial sources. Our results reveal that 34% of Cladosporium-derived natural products are reported for the first time. And 71.79% of the first reported compounds were isolated from marine-derived Cladosporium. Cladosporium-derived compounds exhibit diverse skeletal chemical structures, concentrating in the categories of polyketides (48.47%), alkaloids (19.21%), steroids and terpenoids (17.03%). Over half of the natural products isolated from Cladosporium have been found to have various biological activities, including cytotoxic, antibacterial, antiviral, antifungal and enzyme-inhibitory activities. These findings testify to the tremendous potential of Cladosporium, especially the marine-derived Cladosporium, to yield novel bioactive natural products, providing a structural foundation for the development of new drugs.


Assuntos
Produtos Biológicos , Cladosporium , Produtos Biológicos/farmacologia , Ecossistema , Estudos Prospectivos , Fungos
6.
Org Lett ; 26(14): 2686-2690, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-37125782

RESUMO

Herein, we report a method that enables the synthesis of carbohydrate-DNA conjugates by radical addition. Key to the success is the use of readily available, bench-stable, and unprotected glycosyl sulfinates as precursors to glycosyl radicals. The redox neutral reaction proceeds under mild and simple conditions and tolerates a broad substrate scope. A small library of carbohydrate-DNA conjugates was prepared.


Assuntos
DNA , Glicosídeos , Oxirredução
7.
J Enzyme Inhib Med Chem ; 39(1): 2296695, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38111311

RESUMO

Photodynamic therapy (PDT) has been demonstrated to provide immediate relief of oesophageal cancer patients' re-obstruction and extend their lifespan. However, tumour regrowth may occur after PDT due to enhanced aerobic glycolysis. Previous research has confirmed the inhibitory effect of Dihydroartemisinin (DHA) on aerobic glycolysis. Therefore, the current study intends to investigate the function and molecular mechanism of DHA targeting tumour cell aerobic glycolysis in synergia PDT. The combined treatment significantly suppressed glycolysis in vitro and in vivo compared to either monotherapy. Exploration of the mechanism through corresponding experiments revealed that pyruvate kinase M2 (PKM2) was downregulated in treated cells, whereas overexpression of PKM2 nullified the inhibitory effects of DHA and PDT. This study proposes a novel therapeutic strategy for oesophageal cancer through DHA-synergized PDT treatment, targeting inhibit PKM2 to reduce tumour cell proliferation and metastasis.


Assuntos
Neoplasias Esofágicas , Fotoquimioterapia , Humanos , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/patologia , Glicólise , Piruvato Quinase/metabolismo
8.
Front Public Health ; 11: 1248551, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38026352

RESUMO

Background: Falls place a heavy burden on older adults and families, and there was little research on the relationship between falls and depressive symptoms among older adults in China. This study is designed to examine the association between falls and depressive symptoms in Chinese older adults. Methods: This study was based on 9,539 data sets from the China Health and Retirement Longitudinal Study (CHARLS) in 2018. The 10-item Center for Epidemiologic Studies-Depression Scale (CESD-10) was used to access depressive symptoms in older adults. A logistic regression model was used to calculate multivariate odds ratios (ORs) and 95% confidence intervals (CIs) for falls and depressive symptoms, adjusted for possible confounders. The Classification and regression tree (CART) demonstrates the prediction of the target variable values based on other variables. Results: In this study, 9,539 older people were selected: 60-69 years old accounted for 63.0%, 70-79 years old accounted for 29.7%, and 80 years old and above accounted for 7.3%. Male accounted for 49.7% and female for 50.3%. The rate of falls among older adults was 21.4%, and the rate of depressive symptoms was 33.9%. Adjusted ORs (OR = 1.37, 95% CI: 1.23, 1.53) showed a significant association between falls and depressive symptoms among older adults. Subgroup analysis revealed that this association was statistically significant across male (OR = 1.29, 95% CI: 1.23, 1.53) and female (OR = 1.42, 95% CI: 1.23, 1.64), 60-69 aged (OR = 1.38, 95% CI: 1.19, 1.60) and 70-79 aged (OR =1.42, 95% CI: 1.16, 1.74), rural (OR = 1.42, 95% CI: 1.25, 1.61), <15,000 CNY (OR = 1.35, 95% CI: 1.19, 1.54) and more than 25,000 CNY (OR = 1.42, 95% CI: 1.09, 1.85). Additionally, The CART model showed that the probability (73.0%) of falls was highest among older adults with depressive symptoms who self-rated poor health and female gender. Conclusions: This cross-sectional study demonstrated a significant association between falls and depressive symptoms in Chinese older adults. The findings provide some evidence and support for risk monitoring, screening for depressive symptoms, and early prevention in the high-risk older population.


Assuntos
Depressão , Aposentadoria , Idoso , Humanos , Pessoa de Meia-Idade , Acidentes por Quedas , China/epidemiologia , Estudos Transversais , Depressão/epidemiologia , Estudos Longitudinais , Idoso de 80 Anos ou mais
9.
Nat Chem Biol ; 2023 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-37945898

RESUMO

After the discovery of insulin, a century ago, extensive work has been done to unravel the molecular network regulating insulin secretion. Here we performed a chemical screen and identified AZD7762, a compound that potentiates glucose-stimulated insulin secretion (GSIS) of a human ß cell line, healthy and type 2 diabetic (T2D) human islets and primary cynomolgus macaque islets. In vivo studies in diabetic mouse models and cynomolgus macaques demonstrated that AZD7762 enhances GSIS and improves glucose tolerance. Furthermore, genetic manipulation confirmed that ablation of CHEK2 in human ß cells results in increased insulin secretion. Consistently, high-fat-diet-fed Chk2-/- mice show elevated insulin secretion and improved glucose clearance. Finally, untargeted metabolic profiling demonstrated the key role of the CHEK2-PP2A-PLK1-G6PD-PPP pathway in insulin secretion. This study successfully identifies a previously unknown insulin secretion regulating pathway that is conserved across rodents, cynomolgus macaques and human ß cells in both healthy and T2D conditions.

10.
BMC Neurol ; 23(1): 365, 2023 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-37817104

RESUMO

BACKGROUND: Gills de la Tourette syndrome (TS) is a childhood-onset neurodevelopmental disorder manifested by motor and vocal tics. Kleefstra syndrome 1 (KS1), a rare genetic disorder, is caused by haploinsufficiency of the EHMT1 gene and is characterized by intellectual disability (ID), childhood hypotonia, and distinctive facial features. Tourette-like syndrome in KS1 has rarely been reported. CASE PRESENTATION: Here we describe a 7-year-old girl presenting involuntary motor and vocal tics, intellectual disability, childhood hypotonia, and dysmorphic craniofacial appearances, as well as comorbidities including attention deficit-hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), and self-injurious behavior (SIB). The patient's CNV-seq testing revealed a de novo 320-kb deletion in the 9q34.3 region encompassing the EHMT1 gene. CONCLUSIONS: This is the first case reporting Tourette-like syndrome secondary to KS1 with a de novo microdeletion in the EHMT1 gene. Our case suggests TS with ID and facial anomalies indicate a genetic cause and broadens the phenotypic and genotypic spectrum of both TS and KS1.


Assuntos
Cardiopatias Congênitas , Deficiência Intelectual , Tiques , Síndrome de Tourette , Criança , Feminino , Humanos , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/genética , Histona-Lisina N-Metiltransferase/genética , Deficiência Intelectual/complicações , Deficiência Intelectual/genética , Hipotonia Muscular , Síndrome de Tourette/complicações , Síndrome de Tourette/genética
11.
Opt Express ; 31(19): 31221-31230, 2023 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-37710646

RESUMO

A complex phase space and ray method is proposed to present intuitive interpretation of unique intensity profiles, parabolic accelerating trajectories, and distinctive phase shifts of Airy beam and its exponentially decaying version (i.e., finite-energy Airy beam). In the complex phase space, finite-energy Airy beam manifests itself as a complex parabolic phase space curve (PSC) which represents a cluster of light rays with complex wave vectors. The complex ray cluster converges to a complex parabolic caustic curve in complex coordinate space. For infinite-energy Airy beam, phase space, PSC, light ray and caustic curve change to real values. In the paraxial condition, Airy beams can maintain parabolic form of PSC and keep constant ray density, which guarantees the non-diffraction property of Airy beam and approximate non-diffraction property of finite-energy Airy beam. From the evolution of vertexes of parabolic PSC along a parabolic trajectory in phase space, one can also give the parabolic caustic curve for Airy beam and the complex parabolic caustic curve for exponentially decaying Airy beam. Further, the special phase and decay factors in the propagating solution of complex amplitude of Airy beams can be directly derived from the phase shifts of light ray cluster along transverse and longitudinal directions. The proposed phase space and ray method can present intuitive comprehension to distinctive propagating characteristics of Airy beams including intensity and phase, without resort to solving wave equation or diffracting integral formula.

12.
Biomolecules ; 13(8)2023 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-37627256

RESUMO

Acrostalagmus is known for its ability to produce numerous bioactive natural products, making it valuable in drug development. This review provides information on the sources, distribution, chemical structure types, biosynthesis, and biological activities of the compounds isolated from the genus Acrostalagmus in the family Plectosphaerellaceae from 1969 to 2022. The results show that 50% of the compounds isolated from Acrostalagmus are new natural products, and 82% of the natural products derived from this genus are from the marine Acrostalagmus. The compounds isolated from Acrostalagmus exhibit diverse structures, with alkaloids being of particular importance, accounting for 56% of the natural products derived from this genus. Furthermore, within the alkaloid class, 61% belong to the epipolythiodioxopiperazine family, highlighting the significance of epipolythiodioxopiperazine as a key characteristic structure within Acrostalagmus. Seventy-two percent of natural products derived from Acrostalagmus display bioactivities, with 50% of the bioactive compounds exhibiting more significant or comparable activities than their positive controls. Interestingly, 89% of potent active compounds are derived from marine fungi, demonstrating their promising potential for development. These findings underscore Acrostalagmus, particularly the marine-derived genus Acrostalagmusas, a valuable source of new bioactive secondary metabolites, and emphasize the vast resource importance of the ocean.


Assuntos
Ascomicetos , Produtos Biológicos , Produtos Biológicos/farmacologia , Desenvolvimento de Medicamentos
13.
EMBO Rep ; 24(9): e55494, 2023 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-37493024

RESUMO

Human CST (CTC1-STN1-TEN1) is a ssDNA-binding complex that interacts with the replisome to aid in stalled fork rescue. We previously found that CST promotes telomere replication to maintain genomic integrity via G-quadruplex (G4) resolution. However, the detailed mechanism by which CST resolves G4s in vivo and whether additional factors are involved remains unclear. Here, we identify RECQ4 as a novel CST-interacting partner and show that RECQ4 can unwind G4 structures in vitro using a FRET assay. Moreover, G4s accumulate at the telomere after RECQ4 depletion, resulting in telomere dysfunction, including the formation of MTSs, SFEs, and TIFs, suggesting that RECQ4 is crucial for telomere integrity. Furthermore, CST is also required for RECQ4 telomere or chromatin localization in response to G4 stabilizers. RECQ4 is involved in preserving genomic stability by CST and RECQ4 disruption impairs restart of replication forks stalled by G4s. Overall, our findings highlight the essential roles of CST and RECQ4 in resolving G-rich regions, where they collaborate to resolve G4-induced replication deficiencies and maintain genomic homeostasis.


Assuntos
Replicação do DNA , Quadruplex G , Humanos , Proteínas de Ligação a Telômeros/genética , Homeostase do Telômero , Telômero/metabolismo
14.
Protein Cell ; 14(3): 165-179, 2023 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-37051671

RESUMO

Histone lysine methyltransferases (HKMTs) deposit methyl groups onto lysine residues on histones and play important roles in regulating chromatin structure and gene expression. The structures and functions of HKMTs have been extensively investigated in recent decades, significantly advancing our understanding of the dynamic regulation of histone methylation. Here, we review the recent progress in structural studies of representative HKMTs in complex with nucleosomes (H3K4, H3K27, H3K36, H3K79, and H4K20 methyltransferases), with emphasis on the molecular mechanisms of nucleosome recognition and trans-histone crosstalk by these HKMTs. These structural studies inform HKMTs' roles in tumorigenesis and provide the foundations for developing new therapeutic approaches targeting HKMTs in cancers.


Assuntos
Histonas , Nucleossomos , Histonas/metabolismo , Histona-Lisina N-Metiltransferase/química , Histona-Lisina N-Metiltransferase/genética , Histona-Lisina N-Metiltransferase/metabolismo , Lisina/química , Lisina/genética , Lisina/metabolismo , Metiltransferases/metabolismo , Metilação
15.
Angew Chem Int Ed Engl ; 62(16): e202218303, 2023 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-36760072

RESUMO

We herein report a method that enables the generation of glycosyl radicals under highly acidic conditions. Key to the success is the design and use of glycosyl sulfinates as radical precursors, which are bench-stable solids and can be readily prepared from commercial starting materials. This development allows the installation of glycosyl units onto pyridine rings directly by the Minisci reaction. We further demonstrate the utility of this method in the late-stage modification of complex drug molecules, including the anticancer agent camptothecin. Experimental studies provide insight into the reaction mechanism.

16.
Mar Drugs ; 21(2)2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36827168

RESUMO

Antarctic krill (Euphausia superba) of the Euphausiidae family comprise one of the largest biomasses in the world and play a key role in the Antarctic marine ecosystem. However, the study of E. superba-derived microbes and their secondary metabolites has been limited. Chemical investigation of the secondary metabolites of the actinomycetes Nocardiopsis sp. LX-1 (in the family of Nocardiopsaceae), isolated from E. superba, combined with molecular networking, led to the identification of 16 compounds a-p (purple nodes in the molecular network) and the isolation of one new pyrroline, nocarpyrroline A (1), along with 11 known compounds 2-12. The structure of the new compound 1 was elucidated by extensive spectroscopic investigation. Compound 2 exhibited broad-spectrum antibacterial activities against A. hydrophila, D. chrysanthemi, C. terrigena, X. citri pv. malvacearum and antifungal activity against C. albicans in a conventional broth dilution assay. The positive control was ciprofloxacin with the MIC values of <0.024 µM, 0.39 µM, 0.39 µM, 0.39 µM, and 0.20 µM, respectively. Compound 1 and compounds 7, 10, and 11 displayed antifungal activities against F. fujikuroi and D. citri, respectively, in modified agar diffusion test. Prochloraz was used as positive control and showed the inhibition zone radius of 17 mm and 15 mm against F. fujikuroi and D. citri, respectively. All the annotated compounds a-p by molecular networking were first discovered from the genus Nocardiopsis. Nocarpyrroline A (1) features an unprecedented 4,5-dihydro-pyrrole-2-carbonitrile substructure, and it is the first pyrroline isolated from the genus Nocardiopsis. This study further demonstrated the guiding significance of molecular networking in the research of microbial secondary metabolites.


Assuntos
Actinobacteria , Euphausiacea , Animais , Nocardiopsis , Euphausiacea/química , Actinomyces , Antifúngicos , Ecossistema , Pirróis , Regiões Antárticas
17.
Immunology ; 169(3): 245-259, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36814103

RESUMO

Cysteinyl aspartate specific proteinase (caspase)-6 belongs to the caspase family and plays a vital role in mediating cell death. Under certain conditions, three pathways of programmed cell death (PCD), including apoptosis, necroptosis and pyroptosis (PANoptosis), transform one way into another, with enormous therapeutic potential. Initially, scholars reported that caspase-6 is a caspase executor that mediates apoptosis. With the ceaseless exploration of the PCD types, studies have demonstrated that caspase-6 mediates pyroptosis by regulating gasdermin D and mediates necroptosis by regulating mixed lineage kinase domain-like. By regulating PANoptosis, caspase-6 plays a crucial role in tumorigenesis in humans and mediates anti-tumour immunity. Therefore, a comprehensive understanding of caspase-6 function in cancer via PANoptosis is important for the prevention and therapy of tumours. This article summarized the function of caspase-6 in PANoptosis and its impact on cancer development, providing targets and strategies for tumour treatment.


Assuntos
Apoptose , Neoplasias , Humanos , Caspase 6/metabolismo , Piroptose , Caspases/metabolismo , Caspase 8/metabolismo
18.
Curr Drug Metab ; 24(5): 353-366, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36683364

RESUMO

Framework nucleic acids (FNAs), which are a series of self-assembled DNA nanostructures, are highly versatile tools for engineering intelligent molecular delivery vehicles. Owing to their precise and controllable design and construction, excellent programmability and functionality, as well as favorable intercalation between DNA and small molecules, FNAs provide a promising approach for small molecule delivery. This review discusses the advantages, applications, and current challenges of FNAs for the delivery of small molecular cargo. First, the physicochemical and biological properties that make FNAs favorable for the transport of small molecules are introduced. Thereafter, the classification of loaded cargos and the mechanism of combination between small molecules and FNAs are summarized in detail, and recent research on FNA-based delivery systems and their applications are highlighted. Finally, the challenges and prospects of FNA nanocarriers are discussed to advance their exploitation and clinical adoption.


Assuntos
Nanoestruturas , Ácidos Nucleicos , Humanos , Ácidos Nucleicos/química , DNA , Nanoestruturas/química
19.
Anal Chem ; 94(44): 15261-15269, 2022 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-36282989

RESUMO

Lewy pathologies, which mainly consist of insoluble α-synuclein (α-syn) aggregates, are the hallmarks of Parkinson's disease and many other neurodegenerative diseases termed "synucleinopathies". Detection of Lewy pathologies with optical methods is of interest for preclinical studies, while the α-syn fluorescent probe is still in great demand. By rational design, we obtained a series of D-π-A-based trisubstituted alkenes with acceptable optical properties and high binding affinities to α-syn fibrils. Among these probes, FPQXN and TQXN-2 exhibited high binding affinities (6 and 8 nM, respectively), significant fluorescence enhancements (17.2- and 26.6-fold, respectively), and satisfying quantum yields (36.5% and 10.4%, respectively), which met the need for the in vitro neuropathological staining of Lewy pathologies in the PD brain sections. In addition, TQXN-2 showed great potential in fluorescent discrimination of Lewy pathologies and Aß plaques. Our research provides flexible tools for in vitro detection of α-syn aggregates and offers new structural frameworks for the further development of α-syn fluorescent probes.


Assuntos
Corantes Fluorescentes , Doença de Parkinson , Humanos , Corantes Fluorescentes/metabolismo , Alcenos/metabolismo , alfa-Sinucleína/química , Doença de Parkinson/metabolismo , Placa Amiloide/metabolismo , Encéfalo/metabolismo
20.
iScience ; 25(9): 104948, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36065180

RESUMO

Dumpy-30 (DPY30) is a conserved component of the mixed lineage leukemia (MLL) family complex and is essential for robust methyltransferase activity of MLL complexes. However, the biochemical role of DPY30 in stimulating methyltransferase activity of MLL complexes remains elusive. Here, we demonstrate that DPY30 plays a crucial role in regulating MLL1 activity through two complementary mechanisms: A nucleosome-independent mechanism and a nucleosome-specific mechanism. DPY30 functions as an ASH2L-specific stabilizer to increase the stability of ASH2L and enhance ASH2L-mediated interactions. As a result, DPY30 promotes the compaction and stabilization of the MLL1 complex, consequently increasing the HKMT activity of the MLL1 complex on diverse substrates. DPY30-stabilized ASH2L further acquires additional interfaces with H3 and nucleosomal DNA, thereby boosting the methyltransferase activity of the MLL1 complex on nucleosomes. These results collectively highlight the crucial and conserved roles of DPY30 in the complex assembly and activity regulation of MLL family complexes.

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