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1.
Cell ; 187(8): 1907-1921.e16, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38552624

RESUMO

Hydroxyproline-rich glycoproteins (HRGPs) are a ubiquitous class of protein in the extracellular matrices and cell walls of plants and algae, yet little is known of their native structures or interactions. Here, we used electron cryomicroscopy (cryo-EM) to determine the structure of the hydroxyproline-rich mastigoneme, an extracellular filament isolated from the cilia of the alga Chlamydomonas reinhardtii. The structure demonstrates that mastigonemes are formed from two HRGPs (a filament of MST1 wrapped around a single copy of MST3) that both have hyperglycosylated poly(hydroxyproline) helices. Within the helices, O-linked glycosylation of the hydroxyproline residues and O-galactosylation of interspersed serine residues create a carbohydrate casing. Analysis of the associated glycans reveals how the pattern of hydroxyproline repetition determines the type and extent of glycosylation. MST3 possesses a PKD2-like transmembrane domain that forms a heteromeric polycystin-like cation channel with PKD2 and SIP, explaining how mastigonemes are tethered to ciliary membranes.


Assuntos
Chlamydomonas reinhardtii , Cílios , Glicoproteínas , Cílios/química , Glicoproteínas/química , Glicosilação , Hidroxiprolina/química , Plantas/metabolismo , Chlamydomonas reinhardtii/química
2.
Cell ; 186(13): 2880-2896.e17, 2023 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-37327785

RESUMO

Sperm motility is crucial to reproductive success in sexually reproducing organisms. Impaired sperm movement causes male infertility, which is increasing globally. Sperm are powered by a microtubule-based molecular machine-the axoneme-but it is unclear how axonemal microtubules are ornamented to support motility in diverse fertilization environments. Here, we present high-resolution structures of native axonemal doublet microtubules (DMTs) from sea urchin and bovine sperm, representing external and internal fertilizers. We identify >60 proteins decorating sperm DMTs; at least 15 are sperm associated and 16 are linked to infertility. By comparing DMTs across species and cell types, we define core microtubule inner proteins (MIPs) and analyze evolution of the tektin bundle. We identify conserved axonemal microtubule-associated proteins (MAPs) with unique tubulin-binding modes. Additionally, we identify a testis-specific serine/threonine kinase that links DMTs to outer dense fibers in mammalian sperm. Our study provides structural foundations for understanding sperm evolution, motility, and dysfunction at a molecular level.


Assuntos
Motilidade dos Espermatozoides , Cauda do Espermatozoide , Masculino , Animais , Bovinos , Cauda do Espermatozoide/química , Cauda do Espermatozoide/metabolismo , Sêmen , Microtúbulos/metabolismo , Axonema/química , Espermatozoides , Mamíferos
3.
Molecules ; 29(13)2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38999102

RESUMO

Activated carbon has an excellent porous structure and is considered a promising adsorbent and electrode material. In this study, activated carbon fibers (ACFs) with abundant microporous structures, derived from natural cotton fibers, were successfully synthesized at a certain temperature in an Ar atmosphere and then activated with KOH. The obtained ACFs were characterized by field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), elemental analysis, nitrogen and carbon dioxide adsorption-desorption analysis, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and N2 adsorption-desorption measurement. The obtained ACFs showed high porous qualities and had a surface area from 673 to 1597 m2/g and a pore volume from 0.33 to 0.79 cm3/g. The CO2 capture capacities of prepared ACFs were measured and the maximum capture capacity for CO2 up to 6.9 mmol/g or 4.6 mmol/g could be achieved at 0 °C or 25 °C and 1 standard atmospheric pressure (1 atm). Furthermore, the electrochemical capacitive properties of as-prepared ACFs in KOH aqueous electrolyte were also studied. It is important to note that the pore volume of the pores below 0.90 nm plays key roles to determine both the CO2 capture ability and the electrochemical capacitance. This study provides guidance for designing porous carbon materials with high CO2 capture capacity or excellent capacitance performance.

4.
BMC Nurs ; 23(1): 425, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38918776

RESUMO

BACKGROUND: Nurses often face challenges such as inadequate welfare protection, injustice, and workplace adversity including violence, bullying, and sexual harassment. In this context, providing sufficient support to nurses is crucial for the promotion of their professional well-being. This study examines the direct and indirect effects of perceived organizational support on nurses' well-being, particularly highlighting the mediating roles of professional quality of life and the perception of decent work. METHODS: A cross-sectional survey design was employed in this study. Convenience sampling was used to survey 792 nurses from five tertiary A-grade hospitals in Shanxi Province in January 2024. Data collection tools included a custom demographic survey, the Perceived Organizational Support Scale, Professional Quality of Life Scale, Decent Work Perception Scale, and Nurse Occupational Well-being Questionnaire. Descriptive statistics, correlation analysis, and mediation effect analyses were performed. RESULTS: The findings demonstrate that perceived organizational support has a direct impact on nurses' occupational well-being (ß = 0.323, p < 0.001). Additionally, professional quality of life and the perception of decent work play chain mediating roles between perceived organizational support and nurses' well-being (ß = 0.019, BootLLCI = 0.010, BootULCI = 0.030). CONCLUSIONS: This study highlighted the importance of organizational support in enhancing nurses' well-being. Professional quality of life and decent work were key mediators. Healthcare institutions should prioritize support measures to improve nurses' well-being. Future research should explore additional mediators and mechanisms to develop effective strategies for nursing policymakers and administrators.

5.
Anal Chem ; 95(4): 2253-2259, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36638820

RESUMO

Double spike (DS) method has been extensively used in determining stable isotope ratios of many elements. However, challenges remain in obtaining high-precision isotope data for ultra-trace elements owing to the limitations of instrumental signal-to-noise ratios and the systematics of precision of DS-based measurements. Here, the DS-standard addition (SA) (DSSA) technique is proposed to improve measurements of isotope compositions of ultra-trace elements in natural samples. According to the U-shaped relationship between DS measurement uncertainty and the spike/sample ratio, theoretical equations and an error propagation model (EPM) were constructed comprehensively. In our method, a spiked secondary standard solution with a high, precisely known spike/sample ratio is mixed with samples such that the mixtures have spike/sample ratios within the optimal range. The abundances of the samples relative to the added standards (sample fraction; fspl) and the samples' isotope ratios can then be obtained exactly using a standard DS data reduction routine and the isotope binary mixing model. The accuracy and precision of the DSSA approach were verified by measurements of cadmium and molybdenum isotopes at as low as 5 ng levels. Compared with traditional DS measurements, the sample size for isotope analysis is reduced to 1/6-1/5 of the original with no loss of measurement precision. The optimal mixing range fspl = 0.15-0.5 is recommended. The DSSA method can be extended to isotope measurement of more than 33 elements where the DS method is applicable, especially for the ultra-trace elements such as platinum group and rare earth element isotopes.

6.
Mol Cell ; 57(5): 925-935, 2015 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-25620561

RESUMO

Replication and transcription of influenza virus genome mainly depend on its RNA-dependent RNA polymerase (RdRP), composed of the PA, PB1, and PB2 subunits. Although extensively studied, the underlying mechanism of the RdRP complex is still unclear. Here we report the biochemical characterization of influenza RdRP subcomplex comprising PA, PB1, and N terminus of PB2, which exist as dimer in solution and can assemble into a tetramer state, regulated by vRNA promoter. Using single-particle cryo-electron microscopy, we have reconstructed the RdRP tetramer complex at 4.3 Å, highlighting the assembly and interfaces between monomers within the tetrameric structure. The individual RdRP subcomplex contains all the characterized motifs and appears as a cage-like structure. High-throughput mutagenesis profiling revealed that residues involved in the oligomer state formation are critical for viral life cycle. Our results lay a solid base for understanding the mechanism of replication of influenza and other negative-stranded RNA viruses.


Assuntos
Microscopia Crioeletrônica/métodos , Orthomyxoviridae/enzimologia , RNA Polimerase Dependente de RNA/ultraestrutura , Proteínas Virais/ultraestrutura , Sequência de Aminoácidos , Animais , Linhagem Celular , Células HEK293 , Humanos , Imageamento Tridimensional , Modelos Moleculares , Dados de Sequência Molecular , Mutação , Orthomyxoviridae/genética , Multimerização Proteica , Estrutura Quaternária de Proteína , Estrutura Terciária de Proteína , Subunidades Proteicas/química , Subunidades Proteicas/genética , Subunidades Proteicas/metabolismo , RNA Polimerase Dependente de RNA/química , RNA Polimerase Dependente de RNA/genética , Homologia de Sequência de Aminoácidos , Proteínas Virais/química , Proteínas Virais/genética
7.
J Clin Immunol ; 42(8): 1672-1684, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35849269

RESUMO

PURPOSE: CD81 deficiency is an extremely rare primary immunodeficiency disease characterized by severe and recurrent infections, IgA-related nephropathy, and profound hypogammaglobulinemia. Only one patient has been reported so far, and the pathogenesis remains unclear. Here, we identified a new case of CD81 deficiency and described its pathogenesis. METHODS: We analyzed the clinical, genetic, and immunological features of the patient with CD81 deficiency, and explored the pathogenesis of her antibody deficiencies. RESULTS: The major manifestation of this patient was unexpectedly not recurrent infections but IgA nephropathy with aberrant serum galactose-deficient IgA1. Whole-exome sequencing revealed novel biallelic mutations in CD81 gene that abolished the surface expression of CD81. B cells from the patient lack membrane CD19 and showed reduced switched memory B cells and transitional B cells. Decreased expression of key molecules pY and pBTK in BCR signaling were demonstrated by confocal microscopy. RNA sequencing revealed that genes associated with BCR signaling and immunoglobulins were downregulated in CD81-deficient B cells. In addition, the patient showed increased frequency of T follicular helper cells that biased to Th1-like subsets. CONCLUSION: We reported the second patient with CD81 deficiency in the world and illustrated aberrant BCR signaling in the patient, therefore helping to unravel the mechanism of antibody deficiency in CD81-deficient patients.


Assuntos
Glomerulonefrite por IGA , Tetraspanina 28 , Feminino , Humanos , Antígenos CD19/metabolismo , Linfócitos B , China , Glomerulonefrite por IGA/diagnóstico , Glomerulonefrite por IGA/genética , Glomerulonefrite por IGA/metabolismo , Imunoglobulina A/genética , Mutação , Tetraspanina 28/genética
8.
Anal Chem ; 93(20): 7449-7455, 2021 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-33974413

RESUMO

Stable isotope ratios are widely used to solve environmental, geological, medical, and forensic problems. The double spike technique is considered to be one of the most robust and efficient methods to correct for instrumental mass bias and isotopic fractionation that may occur during sample preparation. However, various hidden errors can arise from data processing and have been largely overlooked in previous studies. Several of these hidden errors were investigated in this work using measurement and synthetic data. Double spike inversion of chromium isotope raw data from 1116 natural samples demonstrated that averaging raw isotope ratios before double spike inversion can add significant errors to inverted isotope values, and such errors can be 1.5 times larger than the true analytical precision. Synthetic data were used to investigate the errors on inverted Cr isotope data caused by spike:analyte ratio and Fe-Ti-V interferences, and the following threshold values are recommended to minimize such errors: 54Crspike/52Crsample ratio greater than 0.5, 56Fe/52Cr less than 0.2, 49Ti/52Cr less than 0.04, and 51V/52Cr less than 1. Sample preparation can potentially lead to large errors in inverted Cr isotope data if preparation-induced isotope fractionation deviates from the exponential law used in the double spike inversion, but such errors can be minimized by achieving >70% Cr yield. Our findings provide important insights for the double spike inversion procedure and assessing the reliability of inverted isotope data for not only the chromium isotope system but also other elements commonly analyzed using the double spike technique.


Assuntos
Fracionamento Químico , Isótopos , Cromo , Isótopos do Cromo , Reprodutibilidade dos Testes
9.
Anal Chem ; 92(1): 1463-1469, 2020 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-31766840

RESUMO

High-sensitivity and high-precision (2 SD ≤ 0.06‰) measurement of chromium (Cr) isotopes at the 10 ng level was successfully carried out using double spike multiple-collector inductively couple plasma mass spectrometry (MC-ICP-MS). To enhance the signal sensitivity and stability, the Aridus II desolvating nebulizer system was improved by placing its waste gas trap bottle in an ice chamber (5 °C cold trap). This setup, beyond Cr isotope analysis, can be applied to most heavy metal isotope measurements. The sensitivity of the 52Cr signal is ≥300 V mg-1 L (with a 1011Ω amplifier and a 110 µL min-1 uptake rate), an enhancement of ≥1.5 times compared to the Aridus II without the cold trap. In addition, the relative standard deviation of the 52Cr signal varied ≤4% over 8 h, demonstrating high stability. The δ53Cr values of common geological reference materials determined using 10 ng of Cr are in excellent agreement with results measured at 25 ng and 50 ng and are consistent with previous determinations, validating the accurate and precise Cr isotope ratio measurements. An empirical method is proposed to correct for the residual (after subtraction) effect of Fe interference on δ53Cr determination. This method relies on a linear relationship between the [Fe]/[Cr] and δ53Cr shift within one analytical session. Finally, we report the δ53Cr values of 19 new reference materials, ranging from -0.44‰ to 0.49‰. Among them, GSS-7 (-0.44 ± 0.02‰, 2 SD, n = 5), GSS-4 (0.48 ± 0.02‰, 2 SD, n = 5), and GSD-10 (0.49 ± 0.05‰, 2 SD, n = 5) can be used as candidate reference materials for interlaboratory comparisons to complement existing ones that are mostly isotopically unfractionated from the bulk silicate earth.

10.
Phytopathology ; 109(6): 972-982, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30714883

RESUMO

Plant survival in the terrestrial ecosystem is influenced by both beneficial and harmful microbes. Trichoderma spp. are a group of filamentous fungi that promote plant growth and resistance to harmful microbes. Previously, we showed that the genus Trichoderma could effectively suppress Fusarium wilt in cucumber. However, the mechanisms that underlie the effects of the genus Trichoderma on plant defense have not been fully substantiated. Two essential metabolic pathways, such as the ascorbate (AsA)-glutathione (GSH) cycle and the oxidative pentose phosphate pathway (OPPP), have been shown to participate in plant tolerance to biotic stressors; nevertheless, the involvement of these pathways in Trichoderma-induced enhanced defense remains elusive. Here, we show that Trichoderma harzianum could alleviate oxidative and nitrostative stress by minimizing reactive oxygen species (ROS; hydrogen peroxide and superoxide) and reactive nitrogen species (nitric oxide [NO]) accumulation, respectively, under Fusarium oxysporum infection in cucumber roots. The genus Trichoderma enhanced antioxidant potential to counterbalance the overproduced ROS and attenuated the transcript and activity of NO synthase and nitrate reductase. The genus Trichoderma also stimulated S-nitrosylated glutathione reductase activity and reduced S-nitrosothiol and S-nitrosylated glutathione content. Furthermore, the genus Trichoderma enhanced AsA and GSH concentrations and activated their biosynthetic enzymes, γ-GCS and l-galactono-1,4-lactone dehydrogenase. Interestingly, the genus Trichoderma alleviated Fusarium-inhibited activity of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase, enzymes involved in the OPPP. Such positive regulation of the key enzymes indicates the adequate maintenance of the AsA-GSH pathway and the OPPP, which potentially contributed to improve redox balance, energy flow, and defense response. Our study advances the current knowledge of Trichoderma-induced enhanced defense against F. oxysporum in cucumber.


Assuntos
Cucumis sativus , Fusarium , Doenças das Plantas/microbiologia , Trichoderma , Raízes de Plantas , Espécies Reativas de Oxigênio
11.
J Cell Physiol ; 234(1): 433-442, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29932226

RESUMO

Breast cancer is known as the most prevalent cancer in women worldwide, and has an undeniable negative impact on public health, both physically, and mentally. This study aims to investigate the effects of toll-like receptor 4 (TLR4) gene silencing on proliferation and apoptosis of human breast cancer cells to explore for a new theoretical basis for its treatment. TLR4 small interference RNA (siRNA) fragment recombinant plasmids were constructed, including TLR4 siRNA-1, TLR4 siRNA-2, and TLR4 siRNA-3. Human breast cancer MCF-7 and MDA-MB-231 cells were assigned into blank, negative control (NC), TLR4 siRNA-1, TLR4 siRNA-2, and TLR4 siRNA-3 groups. MCF-7 and MDA-MB-231 cell growth was detected by MTT assay. Apoptosis and cell cycle were determined by flow cytometry. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis were conducted to determine the expression of TLR4, CDK4, cyclin D1, Livin, Bcl-2, p53, c-FLIP, and caspase-3. In comparison with the NC and blank groups, the TLR4 siRNA-1, TLR4 siRNA-2, and TLR4 siRNA-3 groups showed decreased the expression of TLR4, inhibited proliferation of MCF-7 and MDA-MB-231 cells and promoted MCF-7 and MDA-MB-231 cell apoptosis, and the cells were blocked in G1 phase. In comparison with the NC and blank groups, in the TLR4 siRNA-1, TLR4 siRNA-2, and TLR4 siRNA-3 groups, siRNA-TLR4 significantly increased expression of p53 and caspase-3 in MCF-7 and MDA-MB-231 cells, while it decreased the expressions of CDK4, cyclinD1, Livin, Bal-2, and c-FLIP. The study demonstrates that TLR4 gene silencing inhibits proliferation and induces apoptosis of MCF-7 and MDA-MB-231 cells.


Assuntos
Neoplasias da Mama/genética , Proliferação de Células/genética , Proteínas de Neoplasias/genética , Receptor 4 Toll-Like/genética , Apoptose/genética , Neoplasias da Mama/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Humanos , Células MCF-7 , Interferência de RNA , Receptor 4 Toll-Like/antagonistas & inibidores
12.
Guang Pu Xue Yu Guang Pu Fen Xi ; 36(9): 2894-2900, 2016 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-30084622

RESUMO

Porphyrin is a kind of photosensitizer for photodynamic therapy of cancer. Many porphyrin derivatives have been used in clinical treatment. Human Serum Albumin (HSA) is the carrier of drug transportation. Therefore, investigation on the interaction of porphyrin with HSA is very important to understand the pharmacokinetic of the porphyrin. In this paper, a new water-soluble carboxyl porphyrins, meso-tetrakis(carboxyl) zinc(Ⅱ) porphyrin (2-Zn), was synthesized and characterized. Its interaction with human serum albumin (HSA)was investigated by UV-Vis absorption spectra, fluorescence spectra, circular dichroism (CD) spectra and molecular modeling. The results indicated that the fluorescence quenching of HSA by 2-Zn was a static process with the quenching constants are 1.96×104 L·mol-1 (298 K) and 1.37×104 L·mol-1 (310 K) and the binding constants were calculated to be 1.93×104 L·mol-1 (298 K) and 1.50×104 L·mol-1 (310 K). According to the Van't Hoff equation, the thermodynamic parameters were characterized by negative enthalpy (ΔH=-16.132 kJ·mol-1) and positive entropy (ΔS=27.905 J·mol-1·K-1), which indicated that 2-Zn binds with HSA mainly via electrostatic interaction along with the hydrogen bonding and hydrophobic interaction. Site marker competitive binding experiment confirmed that 2-Zn mainly binds at site Ⅱ. The distance between HSA and the receptor (2-Zn) and the efficiency energy transfer were obtained to be 4.01 nm and 0.163 respectively, based on the Forster theory on resonance energy transfer. Synchronous fluorescence, absorption and CD spectroscopy showed that the interaction of HSA with 2-Zn induced a conformational change of protein, and the amount of α-helical structures were decrease. Furthermore, the binding details between 2-Zn and HSA were further studied with the molecular docking, which was in good agreement with the site marker competitive binding experiments and thermodynamic parameters.


Assuntos
Água/química , Sítios de Ligação , Dicroísmo Circular , Transferência de Energia , Fluorescência , Humanos , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Modelos Moleculares , Simulação de Acoplamento Molecular , Porfirinas , Ligação Proteica , Albumina Sérica , Albumina Sérica Humana , Espectrometria de Fluorescência , Termodinâmica , Zinco
13.
Luminescence ; 30(7): 1045-54, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25736221

RESUMO

The DNA binding of amphiphilic iron(III) 2,17-bis(sulfonato)-5,10,15-tris(pentafluorophenyl)corrole complex (Fe-SC) was studied using spectroscopic methods and viscosity measurements. Its nuclease-like activity was examined by using pBR322 DNA as a target. The interaction of Fe-SC with human serum albumin (HSA) in vitro was also examined using multispectroscopic techniques. Experimental results revealed that Fe-SC binds to ct-DNA via an outside binding mode with a binding constant of 1.25 × 10(4) M(-1). This iron corrole also displays good activity during oxidative DNA cleavage by hydrogen peroxide or tert-butyl hydroperoxide oxidants, and high-valent (oxo)iron(V,VI) corrole intermediates may play an important role in DNA cleavage. Fe-SC exhibits much stronger binding affinity to site II than site I of HSA, indicating a selective binding tendency to HSA site II. The HSA conformational change induced by Fe-SC was confirmed by UV/Vis and CD spectroscopy.


Assuntos
DNA Super-Helicoidal/química , Compostos Férricos/química , Porfirinas/química , Albumina Sérica/química , Ácidos Sulfônicos/química , Tensoativos/química , Clivagem do DNA , Fluorescência , Humanos , Estrutura Molecular , Viscosidade
14.
bioRxiv ; 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38562900

RESUMO

Motile cilia have essential cellular functions in development, reproduction, and homeostasis. Genetic causes for motile ciliopathies have been identified, but the consequences on cellular functions beyond impaired motility remain unknown. Variants in CCDC39 and CCDC40 cause severe disease not explained by loss of motility. Using human cells with pathological variants in these genes, Chlamydomonas genetics, cryo-electron microscopy, single cell RNA transcriptomics, and proteomics, we identified perturbations in multiple cilia-independent pathways. Absence of the axonemal CCDC39/CCDC40 heterodimer results in loss of a connectome of over 90 proteins. The undocked connectome activates cell quality control pathways, switches multiciliated cell fate, impairs microtubule architecture, and creates a defective periciliary barrier. Both cilia-dependent and independent defects are likely responsible for the disease severity. Our findings provide a foundation for reconsidering the broad cellular impact of pathologic variants in ciliopathies and suggest new directions for therapies.

15.
PLoS Genet ; 6(1): e1000806, 2010 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-20072603

RESUMO

Osteoporosis is a major public health problem. It is mainly characterized by low bone mineral density (BMD) and/or low-trauma osteoporotic fractures (OF), both of which have strong genetic determination. The specific genes influencing these phenotypic traits, however, are largely unknown. Using the Affymetrix 500K array set, we performed a case-control genome-wide association study (GWAS) in 700 elderly Chinese Han subjects (350 with hip OF and 350 healthy matched controls). A follow-up replication study was conducted to validate our major GWAS findings in an independent Chinese sample containing 390 cases with hip OF and 516 controls. We found that a SNP, rs13182402 within the ALDH7A1 gene on chromosome 5q31, was strongly associated with OF with evidence combined GWAS and replication studies (P = 2.08x10(-9), odds ratio = 2.25). In order to explore the target risk factors and potential mechanism underlying hip OF risk, we further examined this candidate SNP's relevance to hip BMD both in Chinese and Caucasian populations involving 9,962 additional subjects. This SNP was confirmed as consistently associated with hip BMD even across ethnic boundaries, in both Chinese and Caucasians (combined P = 6.39x10(-6)), further attesting to its potential effect on osteoporosis. ALDH7A1 degrades and detoxifies acetaldehyde, which inhibits osteoblast proliferation and results in decreased bone formation. Our findings may provide new insights into the pathogenesis of osteoporosis.


Assuntos
Aldeído Desidrogenase/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Osteoporose/genética , Idoso , Povo Asiático/genética , Densidade Óssea , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose/fisiopatologia , Polimorfismo de Nucleotídeo Único , População Branca/genética
16.
Nat Struct Mol Biol ; 29(5): 483-492, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35578023

RESUMO

A pair of extensively modified microtubules form the central apparatus (CA) of the axoneme of most motile cilia, where they regulate ciliary motility. The external surfaces of both CA microtubules are patterned asymmetrically with large protein complexes that repeat every 16 or 32 nm. The composition of these projections and the mechanisms that establish asymmetry and longitudinal periodicity are unknown. Here, by determining cryo-EM structures of the CA microtubules, we identify 48 different CA-associated proteins, which in turn reveal mechanisms for asymmetric and periodic protein binding to microtubules. We identify arc-MIPs, a novel class of microtubule inner protein, that bind laterally across protofilaments and remodel tubulin structure and lattice contacts. The binding mechanisms utilized by CA proteins may be generalizable to other microtubule-associated proteins. These structures establish a foundation to elucidate the contributions of individual CA proteins to ciliary motility and ciliopathies.


Assuntos
Axonema , Microtúbulos , Axonema/metabolismo , Cílios/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Microtúbulos/metabolismo , Tubulina (Proteína)/metabolismo
17.
Environ Sci Pollut Res Int ; 29(43): 64721-64731, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35474432

RESUMO

High gravity technology, as a process intensification technology, has demonstrated the great advantages in the field of gas purification on account of its excellent mass transfer efficiency and energy-efficient, but it is rarely applied in the field of nitrogen oxides (NOx) purification of marine diesel engine exhaust. In this paper, a high-gravity bowl-shaped-disk rotating bed (HBRB) without catalytic was designed for diesel exhaust after-treatment. A diesel oxidation catalyst (DOC) was installed in the front of the HBRB to regenerate more nitrogen dioxide (NO2) easily reduced by urea. A bench test of a 6-cylinder marine diesel engine with the HBRB was carried out. The effects of the HBRB speeds, urea concentrations, and engine operating conditions on NOx purification efficiency in engine exhaust were experimentally investigated. The experimental result indicates that the maximum NOx removal efficiency of the HBRB can reach 69.1%. The improvement of the NOx removal efficiency is not obvious at the HBRB speed of over 1500 r/min. The pre-oxidation degree of nitric oxide (NO) and urea concentration largely affect the NOx removal efficiency. The HBRB has great potential in marine diesel engine exhaust denitration.


Assuntos
Hipergravidade , Emissões de Veículos , Gasolina , Óxido Nítrico , Dióxido de Nitrogênio/análise , Óxidos de Nitrogênio/análise , Ureia
18.
Medicine (Baltimore) ; 100(13): e24875, 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33787577

RESUMO

BACKGROUND: In recent years, with the accelerated pace of life, diet, environmental problems occur frequently. External factors are easily to cause endocrine disorders and hormone sensitivity of breast tissue, which can lead to mammary hyperplasia. The incidence rate of hyperplasia of mammary glands is increasing year by year, and the age of onset is also getting lower and lower. If not treated in time, there is a crisis of breast cancer.Clinical studies have found that auricular point pressing therapy is widely used in clinical treatment of mammary hyperplasia recently, but the efficacy of massage in the treatment of mammary hyperplasia has not been systematically reviewed. The purpose of this study is to explore the efficacy, safety and effectiveness of auricular point pressing therapy in the treatment of hyperplasia of mammary glands. METHODS: We will search PubMed, Web of Science, Cochrane Library, EMBASE, Wan fang Database, Chinese Scientific Journal Database, CNKI, VIP, and Chinese Biomedical Literature Database. The retrieval date was January 10, 2021. RevMan 5.3 software was used to evaluate the quality and risk of included studies. The efficacy, recurrence rate, and symptom score of breast hyperplasia were analyzed, and the results were observed and measured. RESULTS: This study will be from the clinical efficiency, improvement rate, pain symptoms disappear rate, tumor size improvement rate, and other aspects of the existing evidence for a high quality synthesis, as well as auricular point pressing therapy adverse events. CONCLUSION: the conclusion of this review will provide the basis for judging whether auricular point pressing therapy is safe and effective in the treatment of hyperplasia of mammary glands. ETHICS AND DISSEMINATION: This systematic will evaluate the effectiveness and safety of auricular point pressing therapy in the treatment of hyperplasia of mammary glands. As all data used in this systematic review and meta-analysis have been published, ethical approval is not required for this review. PROTOCOL REGISTRATION NUMBER: INPLASY202110028.


Assuntos
Pontos de Acupuntura , Doenças Mamárias/terapia , Glândulas Mamárias Humanas/patologia , Massagem/métodos , Doenças Mamárias/patologia , Ensaios Clínicos como Assunto , Pavilhão Auricular , Feminino , Humanos , Hiperplasia/terapia , Metanálise como Assunto , Projetos de Pesquisa , Revisões Sistemáticas como Assunto , Resultado do Tratamento
19.
Sci Total Environ ; 783: 147126, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34088147

RESUMO

Black shale contains abundant pyrite and organic matter that are susceptible to weathering when exposed to the air. In the process of weathering, acid mine drainage can be produced, and a range of toxic trace elements including Cr can be released and transported into rivers, groundwater and soils, potentially leading to severe environmental pollution. In order to study Cr migration and Cr isotopic fractionation during black shale weathering, we sampled metalliferous black shales and cherts from two weathering profiles at Shadi and Yutangba from the Permian Maokou Formation in Enshi Prefecture. The unweathered samples in Shadi and Yutangba have high Cr contents (1562 µg/g and 643 µg/g, respectively), and highly fractionated Cr isotopic compositions (2.04 ± 0.11‰ and 1.91 ± 0.09‰, respectively, expressed as δ53Cr). The narrow range of authigenic δ53Cr in these unweathered shales suggests that the δ53Cr value of the seawater was relatively stable during the period of deposition. Strongly weathered shales in Shadi and Yutangba both display significant Cr losses compared to the unweathered counterparts. Their average δ53Cr values are 1.75 ± 0.12‰ and 1.85 ± 0.39‰ for Shadi and Yutangba, respectively, which are isotopically lighter than fresh samples. This indicates that heavier Cr isotopes are preferentially leached into fluids, leaving the residues enriched in lighter isotopes during black shale weathering. However, the δ53Cr values of the samples close to the water table are higher than those of the unaltered ones, which can be explained by adsorption or quantitative reduction of Cr(VI) near the water table. The fact that Cr isotopes are fractionated during black shale weathering may complicate the application of δ53Cr in polluted samples to identify the Cr sources in areas with exposed black shales. The δ53Cr of seepage water can be measured and treated as a more realistic source signal.

20.
Avian Dis ; 65(2): 261-268, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34412457

RESUMO

The resistance to serum complement-mediated killing is a vital virulence property of microbial pathogens. Complement factor H (FH) is a key negative regulator of the complement alternative pathway (AP) that prevents formation and accelerates the decay of AP C3 convertase and acts as a cofactor in the inactivation of C3b. Pathogens can recruit host FH through their surface proteins to escape the clearance of the complement system. Riemerella anatipestifer could also evade the complement system attack to achieve host infection, but the mechanism is still unclear. In this study, the R. anatipestifer proteins that could interact with FH in host serum were screened and analyzed, and the functions were determined. Affinity chromatography with a Ni-nitrilotriacetic acid Sefinose column and mass spectrometry identified three outer membrane proteins (Omp) of R. anatipestifer, Omp54, Omp53, and Omp24, as potential FH-binding proteins. We then successfully conducted the prokaryotic expression and polyclonal antibody preparation of three candidate proteins. Indirect immunofluorescence assay showed that three candidate proteins were all present in R. anatipestifer. The affinity blotting assay, anti-serum-inhibiting assay, and serum bactericidal assay presented evidence that Omp24 could bind FH. Moreover, FH bound to Omp24 was associated with resistance to the alternative pathway and functional for R. anatipestifer survival in the normal duck serum. These results suggested that R. anatipestifer Omp24 was a FH-binding protein and the interaction with FH blocked the alternative pathway. Recruitment of complement regulatory proteins may facilitate better R. anatipestifer resistance to this vital line of host defense.


Artículo regular­El factor H del complemento de pato se une a la proteína de la membrana externa Omp24 de Riemerella anatipestifer La resistencia a la destrucción mediada por el complemento sérico es una propiedad vital para la virulencia de los patógenos microbianos. El factor de complemento H (FH) es un regulador negativo clave de la vía alterna del complemento (AP) que previene la formación y acelera la descomposición de la C3 convertasa de la vía alterna y actúa como cofactor en la inactivación de C3b. Los patógenos pueden reclutar factor H del huésped a través de sus proteínas de superficie para escapar de la destrucción por el sistema del complemento. Riemerella anatipestifer también pudo evadir el ataque del sistema del complemento para lograr la infección del huésped, pero el mecanismo aún no está claro. En este estudio, se seleccionaron y analizaron las proteínas de R. anatipestifer que podrían interactuar con el factor H en el suero del huésped y se determinaron las funciones. La cromatografía de afinidad con una columna de sefinosa de Ni-NTA y la espectrometría de masas identificaron tres proteínas de la membrana externa de R. anatipestifer, Omp54, Omp53 y Omp24, como posibles proteínas que se unen al factor H. Posteriormente, se llevó a cabo con éxito la expresión procariota y la preparación de anticuerpos policlonales de las tres proteínas candidatas. El ensayo de inmunofluorescencia indirecta mostró que las tres proteínas candidatas estaban presentes en R. anatipestifer. El ensayo de transferencia para afinidad, el ensayo anti-inhibidor del suero y el ensayo bactericida sérico presentaron evidencia de que la proteína Omp24 podría unirse al factor H. Además, el factor H unido a la proteína Omp24 se asoció con resistencia a la vía alterna y funcional para la supervivencia de R. anatipestifer en el suero de pato normal. Estos resultados sugirieron que la proteína Omp24 de R. anatipestifer era una proteína de unión al factor H y que la interacción con este factor bloqueaba la vía alterna del complemento. El reclutamiento de proteínas reguladoras del complemento puede facilitar una mejor resistencia de R. anatipestifer a esta línea vital de defensa del huésped.


Assuntos
Proteínas da Membrana Bacteriana Externa/metabolismo , Fator H do Complemento/metabolismo , Riemerella/metabolismo , Sequência de Aminoácidos , Animais , Proteínas da Membrana Bacteriana Externa/química , Cromatografia de Afinidade/veterinária , Patos , Técnica Indireta de Fluorescência para Anticorpo/veterinária , Camundongos , Coelhos , Riemerella/imunologia
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