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1.
Nat Commun ; 13(1): 6299, 2022 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-36272978

RESUMO

Inhibition of γ-secretase activity represents a potential therapeutic strategy for Alzheimer's disease (AD). MRK-560 is a selective inhibitor with higher potency for Presenilin 1 (PS1) than for PS2, the two isoforms of the catalytic subunit of γ-secretase, although the underlying mechanism remains elusive. Here we report the cryo-electron microscopy (cryo-EM) structures of PS1 and PS2-containing γ-secretase complexes with and without MRK-560 at overall resolutions of 2.9-3.4 Å. MRK-560 occupies the substrate binding site of PS1, but is invisible in PS2. Structural comparison identifies Thr281 and Leu282 in PS1 to be the determinant for isoform-dependent sensitivity to MRK-560, which is confirmed by swapping experiment between PS1 and PS2. By revealing the mechanism for isoform-selective inhibition of presenilin, our work may facilitate future drug discovery targeting γ-secretase.


Assuntos
Secretases da Proteína Precursora do Amiloide , Presenilina-1/genética , Presenilina-1/metabolismo , Secretases da Proteína Precursora do Amiloide/metabolismo , Presenilina-2 , Microscopia Crioeletrônica , Isoformas de Proteínas
2.
PLoS Pathog ; 18(6): e1010599, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35658050

RESUMO

Regulation of chromatin structure and accessibility determines the transcription activities of genes, which endows the host with function-specific patterns of gene expression. Upon viral infection, the innate immune responses provide the first line of defense, allowing rapid production of variegated antiviral cytokines. Knowledge on how chromatin accessibility is regulated during host defense against viral infection remains limited. Our previous work found that the nuclear matrix protein SAFA surveilled viral RNA and regulated antiviral immune genes expression. However, how SAFA regulates the specific induction of antiviral immune genes remains unknown. Here, through integration of RNA-seq, ATAC-seq and ChIP-seq assays, we found that the depletion of SAFA specifically decreased the chromatin accessibility, activation and expression of virus induced genes. And mutation assays suggested that the RNA-binding ability of SAFA was essential for its function in regulating antiviral chromatin accessibility. RIP-seq results showed that SAFA exclusively bound with antiviral related RNAs following viral infection. Further, we combined the CRISPR-Cas13d mediated RNA knockdown system with ATAC-qPCR, and demonstrated that the binding between SAFA and according antiviral RNAs specifically mediated the openness of the corresponding chromatin and following robust transcription of antiviral genes. Moreover, knockdown of these associated RNAs dampened the accessibility of related genes in an extranuclear signaling pathway dependent manner. Interestingly, VSV infection cleaved SAFA protein at the C-terminus which deprived its RNA binding ability for immune evasion. Thus, our results demonstrated that SAFA and the interacting RNA products collaborated and remodeled chromatin accessibility to facilitate antiviral innate immune responses.


Assuntos
Antivirais , Viroses , Cromatina/genética , Interações Hospedeiro-Patógeno/genética , Humanos , Imunidade Inata/genética , RNA Viral
3.
Proc Natl Acad Sci U S A ; 119(15): e2119429119, 2022 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-35377791

RESUMO

Charge density waves (CDWs) have been observed in nearly all families of copper-oxide superconductors. But the behavior of these phases across different families has been perplexing. In La-based cuprates, the CDW wavevector is an increasing function of doping, exhibiting the so-called Yamada behavior, while in Y- and Bi-based materials the behavior is the opposite. Here, we report a combined resonant soft X-ray scattering (RSXS) and neutron scattering study of charge and spin density waves in isotopically enriched La1.8−xEu0.2SrxCuO4 over a range of doping 0.07≤x≤0.20. We find that the CDW amplitude is temperature independent and develops well above experimentally accessible temperatures. Further, the CDW wavevector shows a nonmonotonic temperature dependence, exhibiting Yamada behavior at low temperature with a sudden change occurring near the spin ordering temperature. We describe these observations using a Landau­Ginzburg theory for an incommensurate CDW in a metallic system with a finite charge compressibility and spin-CDW coupling. Extrapolating to high temperature, where the CDW amplitude is small and spin order is absent, our analysis predicts a decreasing wavevector with doping, similar to Y and Bi cuprates. Our study suggests that CDW order in all families of cuprates forms by a common mechanism.

4.
Proc Natl Acad Sci U S A ; 119(12): e2122292119, 2022 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-35298330

RESUMO

Aberrant cleavage of amyloid precursor protein (APP) by γ-secretase is closely associated with Alzheimer's disease (AD). γ-secretase activating protein (GSAP) specifically promotes γ-secretase­mediated cleavage of APP. However, the underlying mechanism remains enigmatic. Here, we demonstrate that the 16-kDa C-terminal fragment of GSAP (GSAP-16K) undergoes phase separation in vitro and forms puncta-like condensates in cells. GSAP-16K exerts dual modulation on γ-secretase cleavage; GSAP-16K in dilute phase increases APP­C-terminal 99-residue fragment (C99) cleavage toward preferred production of ß-amyloid peptide 42 (Aß42), but GSAP-16K condensates reduce APP-C99 cleavage through substrate sequestration. Notably, the Aß42/Aß40 ratio is markedly elevated with increasing concentrations of GSAP-16K. GSAP-16K stably associates with APP-C99 through specific sequence elements. These findings mechanistically explain GSAP-mediated modulation of γ-secretase activity that may have ramifications on the development of potential therapeutics.


Assuntos
Doença de Alzheimer , Secretases da Proteína Precursora do Amiloide , Doença de Alzheimer/metabolismo , Secretases da Proteína Precursora do Amiloide/metabolismo , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Humanos , Fragmentos de Peptídeos/metabolismo
5.
Environ Technol ; 43(15): 2270-2277, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33428535

RESUMO

An electrochemiluminescence (ECL) aptasensor was prepared to detect Pb2+ with nitrogen-doped carbon quantum dots (NCQDs) as ECL materials. To prepare the working electrode, NCQDs with carboxyl groups were loaded on a glassy carbon electrode (GCE) and then Pb2+ aptamers were covalently bound to the NCQDs to form a stable GCE/NCQDs/aptamers. On addition of Pb2+, the chain aptamers change to a pb2+ G-quadruplex conformation, which lead to a large decrease in the ECL intensity. The variation of intensity and the logarithm of the Pb2+ concentration had a good linear relationship (R2 = 0.998). The detection range was wide (50 pM to 387.9 nM) with a low detection limit (18.9 pM). In interference experiments, the ECL Pb2+ aptasensor did not suffer from interference and it had good stability. The NCQDs ECL aptasensor can detect Pb2+ quickly and accurately, and provides a fast and efficient method for detection of Pb2+. Compared with literatures, the Pb2+ aptasensor has simpler preparation process, lower cost; furthermore, it is more environmentally friendly.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Pontos Quânticos , Aptâmeros de Nucleotídeos/metabolismo , Técnicas Biossensoriais/métodos , Carbono , Técnicas Eletroquímicas/métodos , Eletrodos , Chumbo , Medições Luminescentes , Nitrogênio
6.
Phys Rev Lett ; 127(2): 027602, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34296905

RESUMO

How superconductivity interacts with charge or nematic order is one of the great unresolved issues at the center of research in quantum materials. Ba_{1-x}Sr_{x}Ni_{2}As_{2} (BSNA) is a charge ordered pnictide superconductor recently shown to exhibit a sixfold enhancement of superconductivity due to nematic fluctuations near a quantum phase transition (at x_{c}=0.7) [1]. The superconductivity is, however, anomalous, with the resistive transition for 0.4

9.
RNA Biol ; 18(11): 1608-1621, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-33596778

RESUMO

RNA and protein are interconnected biomolecules that can influence each other's life cycles and functions through physical interactions. Abnormal RNA-protein interactions lead to cell dysfunctions and human diseases. Therefore, mapping networks of RNA-protein interactions is crucial for understanding cellular processes and pathogenesis of related diseases. Different practical protein-centric methods for studying RNA-protein interactions have been reported, but few robust RNA-centric methods exist. Here, we developed CRISPR-based RNA proximity proteomics (CBRPP), a new RNA-centric method to identify proteins associated with an endogenous RNA of interest in native cellular context without pre-editing of the target RNA, cross-linking or RNA-protein complexes manipulation in vitro. CBRPP is based on a fusion of dCas13 and proximity-based labelling (PBL) enzyme. dCas13 can deliver PBL enzyme to the target RNA with high specificity, while PBL enzyme labels the surrounding proteins of the target RNA, which are then identified by mass spectrometry.


Assuntos
Espectrometria de Massas/métodos , Mapeamento de Interação de Proteínas , Proteínas de Ligação a RNA/metabolismo , RNA/metabolismo , Biotinilação , Células HEK293 , Humanos , Ligação Proteica , RNA/genética , Proteínas de Ligação a RNA/genética , Coloração e Rotulagem
10.
Theranostics ; 11(7): 3196-3212, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33537082

RESUMO

Resistance to chemotherapy is a long-standing problem in the management of cancer, and cancer stem cells are regarded as the main source of this resistance. This study aimed to investigate metallothionein (MT)-1G involvement in the regulation of cancer stemness and provide a strategy to overcome chemoresistance in pancreatic ductal adenocarcinoma (PDAC). Methods: MT1G was identified as a critical factor related with gemcitabine resistance in PDAC cells by mRNA microarray. Its effects on PDAC stemness were evaluated through sphere formation and tumorigenicity. LC-MS/MS analysis of conditional medium revealed that activin A, a NF-κB target, was a major protein secreted from gemcitabine resistant PDAC cells. Both loss-of-function and gain-of-function approaches were used to validate that MT1G inhibited NF-κB-activin A pathway. Orthotopic pancreatic tumor model was employed to explore the effects on gemcitabine resistance with recombinant follistatin to block activin A. Results: Downregulation of MT1G due to hypermethylation of its promoter is related with pancreatic cancer stemness. Secretome analysis revealed that activin A, a NF-κB target, was highly secreted by drug resistant cells. It promotes pancreatic cancer stemness in Smad4-dependent or independent manners. Mechanistically, MT1G negatively regulates NF-κB signaling and promotes the degradation of NF-κB p65 subunit by enhancing the expression of E3 ligase TRAF7. Blockade of activin A signaling with follistatin could overcome gemcitabine resistance. Conclusions: MT1G suppresses PDAC stemness by limiting activin A secretion via NF-κB inhibition. The blockade of the activin A signaling with follistatin may provide a promising therapeutic strategy for overcoming gemcitabine resistance in PDAC.


Assuntos
Ativinas/metabolismo , Metalotioneína/metabolismo , Células-Tronco Neoplásicas/metabolismo , Animais , Carcinoma Ductal Pancreático/patologia , Linhagem Celular Tumoral , China , Cromatografia Líquida , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Humanos , Metalotioneína/genética , Camundongos Endogâmicos C57BL , Camundongos Nus , NF-kappa B/metabolismo , Células-Tronco Neoplásicas/fisiologia , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Transdução de Sinais/efeitos dos fármacos , Espectrometria de Massas em Tandem , Fator de Transcrição RelA/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Cell Host Microbe ; 29(2): 222-235.e4, 2021 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-33388094

RESUMO

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic poses an unprecedented public health crisis. Evidence suggests that SARS-CoV-2 infection causes dysregulation of the immune system. However, the unique signature of early immune responses remains elusive. We characterized the transcriptome of rhesus macaques and mice infected with SARS-CoV-2. Alarmin S100A8 was robustly induced in SARS-CoV-2-infected animal models as well as in COVID-19 patients. Paquinimod, a specific inhibitor of S100A8/A9, could rescue the pneumonia with substantial reduction of viral loads in SARS-CoV-2-infected mice. Remarkably, Paquinimod treatment resulted in almost 100% survival in a lethal model of mouse coronavirus infection using the mouse hepatitis virus (MHV). A group of neutrophils that contributes to the uncontrolled pathological damage and onset of COVID-19 was dramatically induced by coronavirus infection. Paquinimod treatment could reduce these neutrophils and regain anti-viral responses, unveiling key roles of S100A8/A9 and aberrant neutrophils in the pathogenesis of COVID-19, highlighting new opportunities for therapeutic intervention.


Assuntos
Alarminas/farmacologia , Antivirais/farmacologia , Neutrófilos/efeitos dos fármacos , SARS-CoV-2/efeitos dos fármacos , Animais , COVID-19/metabolismo , COVID-19/virologia , Modelos Animais de Doenças , Feminino , Humanos , Macaca mulatta , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neutrófilos/metabolismo , Transcriptoma , Carga Viral
12.
Cell ; 184(2): 521-533.e14, 2021 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-33373587

RESUMO

Development of γ-secretase inhibitors (GSIs) and modulators (GSMs) represents an attractive therapeutic opportunity for Alzheimer's disease (AD) and cancers. However, how these GSIs and GSMs target γ-secretase has remained largely unknown. Here, we report the cryoelectron microscopy (cryo-EM) structures of human γ-secretase bound individually to two GSI clinical candidates, Semagacestat and Avagacestat, a transition state analog GSI L685,458, and a classic GSM E2012, at overall resolutions of 2.6-3.1 Å. Remarkably, each of the GSIs occupies the same general location on presenilin 1 (PS1) that accommodates the ß strand from amyloid precursor protein or Notch, interfering with substrate recruitment. L685,458 directly coordinates the two catalytic aspartate residues of PS1. E2012 binds to an allosteric site of γ-secretase on the extracellular side, potentially explaining its modulating activity. Structural analysis reveals a set of shared themes and variations for inhibitor and modulator recognition that will guide development of the next-generation substrate-selective inhibitors.


Assuntos
Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Secretases da Proteína Precursora do Amiloide/química , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Preparações Farmacêuticas/química , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/farmacologia , Alanina/análogos & derivados , Alanina/farmacologia , Sequência de Aminoácidos , Secretases da Proteína Precursora do Amiloide/ultraestrutura , Azepinas/farmacologia , Sítios de Ligação , Microscopia Crioeletrônica , Células HEK293 , Humanos , Modelos Biológicos , Modelos Moleculares , Oxidiazóis/química , Oxidiazóis/farmacologia , Presenilina-1/química , Presenilina-1/metabolismo , Ligação Proteica/efeitos dos fármacos , Conformação Proteica , Relação Estrutura-Atividade , Especificidade por Substrato/efeitos dos fármacos , Sulfonamidas/química , Sulfonamidas/farmacologia
13.
Nature ; 565(7738): 192-197, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30598546

RESUMO

Aberrant cleavage of Notch by γ-secretase leads to several types of cancer, but how γ-secretase recognizes its substrate remains unknown. Here we report the cryo-electron microscopy structure of human γ-secretase in complex with a Notch fragment at a resolution of 2.7 Å. The transmembrane helix of Notch is surrounded by three transmembrane domains of PS1, and the carboxyl-terminal ß-strand of the Notch fragment forms a ß-sheet with two substrate-induced ß-strands of PS1 on the intracellular side. Formation of the hybrid ß-sheet is essential for substrate cleavage, which occurs at the carboxyl-terminal end of the Notch transmembrane helix. PS1 undergoes pronounced conformational rearrangement upon substrate binding. These features reveal the structural basis of Notch recognition and have implications for the recruitment of the amyloid precursor protein by γ-secretase.


Assuntos
Secretases da Proteína Precursora do Amiloide/metabolismo , Secretases da Proteína Precursora do Amiloide/ultraestrutura , Microscopia Crioeletrônica , Receptores Notch/metabolismo , Receptores Notch/ultraestrutura , Sequência de Aminoácidos , Secretases da Proteína Precursora do Amiloide/química , Precursor de Proteína beta-Amiloide/química , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Humanos , Camundongos , Modelos Moleculares , Ligação Proteica , Receptores Notch/química , Especificidade por Substrato
14.
Science ; 363(6428)2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30630874

RESUMO

Cleavage of amyloid precursor protein (APP) by the intramembrane protease γ-secretase is linked to Alzheimer's disease (AD). We report an atomic structure of human γ-secretase in complex with a transmembrane (TM) APP fragment at 2.6-angstrom resolution. The TM helix of APP closely interacts with five surrounding TMs of PS1 (the catalytic subunit of γ-secretase). A hybrid ß sheet, which is formed by a ß strand from APP and two ß strands from PS1, guides γ-secretase to the scissile peptide bond of APP between its TM and ß strand. Residues at the interface between PS1 and APP are heavily targeted by recurring mutations from AD patients. This structure, together with that of γ-secretase bound to Notch, reveal contrasting features of substrate binding, which may be applied toward the design of substrate-specific inhibitors.


Assuntos
Secretases da Proteína Precursora do Amiloide/química , Precursor de Proteína beta-Amiloide/química , Domínio Catalítico , Proteólise , Doença de Alzheimer/metabolismo , Microscopia Crioeletrônica , Humanos , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Receptores Notch/química
15.
Acta Biomater ; 50: 556-565, 2017 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-28069511

RESUMO

The effect of widely different corrosion rates of Mg alloys on four parameters of interest for in vivo characterization was evaluated: (1) the effectiveness of transdermal H2 measurements with an electrochemical sensor for noninvasively monitoring biodegradation compared to the standard techniques of in vivo X-ray imaging and weight loss measurement of explanted samples, (2) the chemical compositions of the corrosion layers of the explanted samples by XPS, (3) the effect on animal organs by histology, and (4) the accumulation of corrosion by-products in multiple organs by ICP-MS. The in vivo biodegradation of three magnesium alloys chosen for their widely varying corrosion rates - ZJ41 (fast), WKX41 (intermediate) and AZ31 (slow) - were evaluated in a subcutaneous implant mouse model. Measuring H2 with an electrochemical H2 sensor is a simple and effective method to monitor the biodegradation process in vivo by sensing H2 transdermally above magnesium alloys implanted subcutaneously in mice. The correlation of H2 levels and biodegradation rate measured by weight loss shows that this non-invasive method is fast, reliable and accurate. Analysis of the insoluble biodegradation products on the explanted alloys by XPS showed all of them to consist primarily of Mg(OH)2, MgO, MgCO3 and Mg3(PO4)2 with ZJ41 also having ZnO. The accumulation of magnesium and zinc were measured in 9 different organs by ICP-MS. Histological and ICP-MS studies reveal that there is no significant accumulation of magnesium in these organs for all three alloys; however, zinc accumulation in intestine, kidney and lung for the faster biodegrading alloy ZJ41 was observed. Although zinc accumulates in these three organs, no toxicity response was observed in the histological study. ICP-MS also shows higher levels of magnesium and zinc in the skull than in the other organs. STATEMENT OF SIGNIFICANCE: Biodegradable devices based on magnesium and its alloys are promising because they gradually dissolve and thereby avoid the need for subsequent removal by surgery if complications arise. In vivo biodegradation rate is one of the crucial parameters for the development of these alloys. Promising alloys are first evaluated in vivo by being implanted subcutaneously in mice for 1month. Here, we evaluated several magnesium alloys with widely varying corrosion rates in vivo using multiple characterization techniques. Since the alloys biodegrade by reacting with water forming H2 gas, we used a recently demonstrated, simple, fast and noninvasive method to monitor the biodegradation process by just pressing the tip of a H2 sensor against the skin above the implant. The analysis of 9 organs (intestine, kidney, spleen, lung, heart, liver, skin, brain and skull) for accumulation of Mg and Zn revealed no significant accumulation of magnesium in these organs. Zinc accumulation in intestine, kidney and lung was observed for the faster corroding implant ZJ41. The surfaces of explanted alloys were analyzed to determine the composition of the insoluble biodegradation products. The results suggest that these tested alloys are potential candidates for biodegradable implant applications.


Assuntos
Implantes Absorvíveis , Ligas/química , Técnicas Eletroquímicas/métodos , Hidrogênio/análise , Magnésio/química , Espectroscopia Fotoeletrônica , Espectrofotometria Atômica , Animais , Camundongos Nus , Distribuição Tecidual , Raios X , Zinco/análise
16.
Anal Chem ; 86(9): 4354-61, 2014 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-24673177

RESUMO

A Nafion film loaded with novel catalyst-free multiwalled carbon nanotubes (MWCNTs) was used to modify a glassy carbon (GC) electrode to detect trace concentrations of metal ions, with europium ion (Eu(3+)) as a model. The interaction between the sidewalls of MWCNTs and the hydrophobic backbone of Nafion allows the MWCNTs to be dispersed in Nafion, which was then coated as a thin film on the GC electrode surface. The electrochemical response to Eu(3+) was found to be ∼10 times improved by MWCNT concentrations between 0.5 and 2 mg/mL, which effectively expanded the electrode surface into the Nafion film and thereby reduced the diffusion distance of Eu(3+) to the electrode surface. At low MWCNT concentrations of 0.25 and 0.5 mg/mL, no significant improvement in signal was obtained compared with Nafion alone. Scanning electron microscopy and electrochemical impedance spectroscopy were used to characterize the structure of the MWCNT-Nafion film, followed by electrochemical characterization with Eu(3+) via cyclic voltammetry and preconcentration voltammetry. Under the optimized conditions, a linear range of 1-100 nM with a calculated detection limit of 0.37 nM (signal/noise = 3) was obtained for determination of Eu(3+) by Osteryoung square-wave voltammetry after a preconcentration time of 480 s.

17.
Artigo em Chinês | MEDLINE | ID: mdl-24358747

RESUMO

OBJECTIVE: To understand the changes of schistosomiasis endemic situation and water body security in the Changsha City section of the Xiangjiang River. METHODS: The prevention and control measures of schistosomiasis, the status of Oncomelania hupensis snails in the marshlands, and the schistosome infection rates of residents on the both sides of the river and boat fishermen were investigated from 2003 to 2012. The schistosome infectivity of the water body was investigate by the method of sentry mice. RESULTS: The snail area decreased from 471 hm(2) in 2003 to 28.81 hm(2) in 2012 with the decline rate of 93.88%. Through the environmental modification, no living snails were found in 9 marshlands among the 11 marshlands, and the density of snails was below 0.006/0.1 m(2) in the other 2 marshlands, but no infected snails were found for 7 years. The original snail habitats of Juzhou scenic area were completely modified and no living snails were found from 2008. In the area, no domestic animals were pastured and the schistosome infectivity of the water body was negative with the sentry mouse method for 10 years. In 2003, the schistosome infection rate was 3.63% in the residents, but no new infections were found in original residents after 2010. CONCLUSION: The endemic situation of schistosomiasis of the Changsha City section of the Xiangjiang River has reached the standards of schistosomiasis transmission controlled and the water body of Juzhou scenic area is safe.


Assuntos
Reservatórios de Doenças/parasitologia , Rios/parasitologia , Esquistossomose/epidemiologia , Caramujos/parasitologia , Adolescente , Adulto , Idoso , Animais , Criança , China/epidemiologia , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Schistosoma/isolamento & purificação , Schistosoma/fisiologia , Esquistossomose/parasitologia , Caramujos/crescimento & desenvolvimento , Adulto Jovem
18.
Acta Biomater ; 9(11): 9211-9, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23871945

RESUMO

Understanding Mg corrosion is important to the development of biomedical implants made from Mg alloys. Mg corrodes readily in aqueous environments, producing H2, OH- and Mg2+. The rate of formation of these corrosion products is especially important in biomedical applications where they can affect cells and tissue near the implant. We have developed a corrosion characterization system (CCS) that allows realtime monitoring of the solution soluble corrosion products OH-, Mg2+, and H2 during immersion tests commonly used to study the corrosion of Mg materials. Instrumentation was developed to allow the system to also record electrochemical impedance spectra simultaneously in the same solution to monitor changes in the Mg samples. We demonstrated application of the CCS by observing the corrosion of Mg (99.9%) in three different corrosion solutions: NaCl, HEPES buffer, and HEPES buffer with NaCl at 37°C for 48 h. The solution concentrations of the corrosion products measured by sensors correlated with the results using standard weight loss measurements to obtain corrosion rates. This novel approach gives a better understanding of the dynamics of the corrosion process in realtime during immersion tests, rather than just providing a corrosion rate at the end of the test, and goes well beyond the immersion tests that are commonly used to study the corrosion of Mg materials. The system has the potential to be useful in systematically testing and comparing the corrosion behavior of different Mg alloys, as well as protective coatings.


Assuntos
Espectroscopia Dielétrica/métodos , Técnicas Eletroquímicas/instrumentação , Magnésio/química , Corrosão , Dureza , Hidrogênio/análise , Concentração de Íons de Hidrogênio , Íons/análise , Magnésio/análise , Peso Molecular , Potenciometria , Soluções , Espectrofotometria Atômica , Água/química
19.
Anal Chem ; 84(1): 241-6, 2012 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-22035288

RESUMO

A label-free biosensor for Escherichia coli (E. coli) ORN 178 based on faradaic electrochemical impedance spectroscopy (EIS) was developed. α-Mannoside or ß-galactoside was immobilized on a gold disk electrode using a self-assembled monolayer (SAM) via a spacer terminated in a thiol functionality. Impedance measurements (Nyquist plot) showed shifts due to the binding of E. coli ORN 178, which is specific for α-mannoside. No significant change in impedance was observed for E. coli ORN 208, which does not bind to α-mannoside. With increasing concentrations of E. coli ORN 178, electron-transfer resistance (R(et)) increases before the sensor is saturated. After the Nyquist plot of E. coli/mixed SAM/gold electrode was modeled, a linear relationship between normalized R(et) and the logarithmic value of E. coli concentrations was found in a range of bacterial concentration from 10(2) to 10(3) CFU/mL. The combination of robust carbohydrate ligands with EIS provides a label-free, sensitive, specific, user-friendly, robust, and portable biosensing system that could potentially be used in a point-of-care or continuous environmental monitoring setting.


Assuntos
Carboidratos/química , Espectroscopia Dielétrica/métodos , Escherichia coli/química , Microscopia Eletrônica de Varredura
20.
Artigo em Chinês | MEDLINE | ID: mdl-22379824

RESUMO

OBJECTIVE: To study a reliable, friendly environmental and sustainable Oncomelania snail control method in marshlands of the Xiangjiang River. METHODS: According to the special characteristics of the marshlands of the Xiangjiang River, smoothing and cultivating in beaches were applied for snail control. In sections with scarce distribution of snails, lowering parts of 4.4 beaches and raising other parts were added. RESULTS: Since 2003, the project has been practiced for 8 years. The average snail density declined by 99.83% with the simple smoothing beaches and then cultivation there. The average snail density declined by 100% with lowering parts of beaches and raising other parts and then cultivation. The schistosome infection rate was 0.31% with a declined rate of 93.84% in residents in 2006. The schistosome infection rate was 1.03% in 2010. The test result of water contamination was negative. CONCLUSIONS: The method of simple smoothing beaches and then cultivation can control the density of snails in marshlands and the method of lowering parts of beaches and raising other parts and then cultivation is more effective.


Assuntos
Controle de Pragas/métodos , Rios/parasitologia , Esquistossomose Japônica/prevenção & controle , Caramujos/crescimento & desenvolvimento , Animais , China , Humanos , Camundongos , Schistosoma japonicum/isolamento & purificação , Schistosoma japonicum/fisiologia , Esquistossomose Japônica/parasitologia , Caramujos/parasitologia , Saúde da População Urbana
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