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1.
Opt Lett ; 49(3): 642-645, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38300079

RESUMEN

An optical needle is created using a radially polarized circular Airy beam with a conical angle, stemmed from the auto-focusing property of light beams. The utilization of the angular spectrum representation serves to illustrate the field distributions of the optical needle, and an explicit formula is provided to describe the angular spectrum of the light beam. The findings suggest that the optical needle exhibits a long depth of focus and well uniformity, and the full width at half maximum of the transverse field distribution is approximately 0.38 λ beyond the diffraction limit. The uniformity of the optical needle can be tailored by adjusting the width of the primary ring, the decay parameter, and the conical angle. Additionally, the depth of focus of the optical needle significantly improves as the radius of the primary ring increases while still maintaining well uniformity. It may find applications in high-resolution optical imaging and optical manipulation.

2.
Nano Lett ; 23(16): 7584-7592, 2023 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-37539848

RESUMEN

Optical bound states in the continuum (BICs) offer strong interactions with quantum emitters and have been extensively studied for manipulating spontaneous emission, lasing, and polariton Bose-Einstein condensation. However, the out-coupling efficiency of quasi-BIC emission, crucial for practical light-emitting devices, has received less attention. Here, we report an adaptable approach for enhancing quasi-BIC emission from a resonant monocrystalline silicon (c-Si) metasurface through lattice and multipolar engineering. We identify dual-BICs originating from electric quadrupoles (EQ) and out-of-plane magnetic dipoles, with EQ quasi-BICs exhibiting concentrated near-fields near the c-Si nanodisks. The enhanced fractional radiative local density of states of EQ quasi-BICs overlaps spatially with the emitters, promoting efficient out-coupling. Furthermore, coupling the EQ quasi-BICs with Rayleigh anomalies enhances directional emission intensity, and we observe inherent opposite topological charges in the multipolarly controlled dual-BICs. These findings provide valuable insights for developing efficient nanophotonic devices based on quasi-BICs.

3.
Opt Express ; 31(21): 34280-34291, 2023 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-37859188

RESUMEN

We propose a new method for fabricating hybrid metasurfaces by combining Mie and plasmonic resonances. Our approach involves obtaining an ultrasmooth gold film and separately structuring monocrystalline silicon (c-Si) nanoantenna arrays, which are then wet-transferred and finally immobilized onto the gold film. The experimental and simulation analysis reveals the importance of the native oxide layer of Si and demonstrates fascinating dispersion curves with nanogap resonances and bound states in the continuum. The localized field enhancements in the nanogap cavities result from the coupling between multipolar Mie resonances and their mirror images in the gold film. This effective method improves our understanding of hybrid modes and offers opportunities for developing active metasurfaces, such as depositing c-Si nanoantenna arrays onto stretchable polydimethylsiloxane substrates or electro-optic and piezoelectric sensitive lithium niobate films for potential applications in MEMS, LiDAR, and beyond.

4.
Mol Cell ; 58(5): 832-44, 2015 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-26028538

RESUMEN

The increase in multi-drug-resistant bacteria is limiting the effectiveness of currently approved antibiotics, leading to a renewed interest in antibiotics with distinct chemical scaffolds. We have solved the structures of the Thermus thermophilus 70S ribosome with A-, P-, and E-site tRNAs bound and in complex with either the aminocyclitol-containing antibiotic hygromycin A (HygA) or the nucleoside antibiotic A201A. Both antibiotics bind at the peptidyl transferase center and sterically occlude the CCA-end of the A-tRNA from entering the A site of the peptidyl transferase center. Single-molecule Förster resonance energy transfer (smFRET) experiments reveal that HygA and A201A specifically interfere with full accommodation of the A-tRNA, leading to the presence of tRNA accommodation intermediates and thereby inhibiting peptide bond formation. Thus, our results provide not only insight into the mechanism of action of HygA and A201A, but also into the fundamental process of tRNA accommodation during protein synthesis.


Asunto(s)
Aminoglicósidos/química , Antibacterianos/química , Cinamatos/química , Higromicina B/análogos & derivados , ARN de Transferencia/química , Subunidades Ribosómicas Grandes Bacterianas/química , Subunidades Ribosómicas Pequeñas Bacterianas/química , Aminoglicósidos/farmacología , Antibacterianos/farmacología , Cinamatos/farmacología , Cristalografía por Rayos X , Pruebas Antimicrobianas de Difusión por Disco , Farmacorresistencia Bacteriana , Escherichia coli/efectos de los fármacos , Enlace de Hidrógeno , Higromicina B/química , Higromicina B/farmacología , Modelos Moleculares , Conformación Proteica , Thermus thermophilus
5.
Clin Genet ; 102(5): 391-403, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35882632

RESUMEN

Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease. Highly penetrant copy number variants (CNVs) and genes related to the etiology of TOF likely exist with differences among populations. We aimed to identify CNV contributions to sporadic TOF cases in Han Chinese. Genomic DNA was extracted from peripheral blood in 605 subjects (303 sporadic TOF and 302 unaffected Han Chinese [Control] from cardiac centers in China) and analyzed by genome-wide association study (GWAS). The GWAS results were compared with existing Database of Genetic Variants. These CNVs were further validated by qPCR. Bioinformatics analyses were performed with protein-protein interaction (PPI) network and KEGG pathway enrichment. Across all chromosomes 119 novel "TOF-specific CNVs" were identified with prevalence of CNVs of 21.5% in chromosomes 1-20 and 37.0% including Chr21/22. In chromosomes 1-20, CNVs on 11q25 (encompasses genes ACAD8, B3GAT1, GLB1L2, GLB1L3, IGSF9B, JAM3, LOC100128239, LOC283177, MIR4697, MIR4697HG, NCAPD3, OPCML, SPATA19, THYN1, and VPS26B) and 14q32.33 (encompasses genes THYN1, OPCML, and NCAPD3) encompass genes most likely to be associated with TOF. Specific CNVs found on the chromosome 21 (6.3%) and 22(11.9%) were also identified in details. PPI network analysis identified the genes covering the specific CNVs related to TOF and the signaling pathways. This study for first time identified novel TOF-specific CNVs in the Han Chinese with higher frequency than in Caucasians and with 11q25 and 14q32.33 not reported in TOF of Caucasians. These novel CNVs identify new candidate genes for TOF and provide new insights into genetic basis of TOF.


Asunto(s)
Variaciones en el Número de Copia de ADN , Tetralogía de Fallot , Pueblo Asiatico/genética , Moléculas de Adhesión Celular/genética , ADN , Variaciones en el Número de Copia de ADN/genética , Proteínas Ligadas a GPI/genética , Estudio de Asociación del Genoma Completo , Humanos , Tetralogía de Fallot/genética
6.
Opt Express ; 30(2): 2143-2155, 2022 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-35209361

RESUMEN

Based on the full wave simulation and the Maxwell stress tensor theory, we demonstrate an enhanced transverse optical gradient force acting on Rayleigh particles immersed in a simple optical field formed by two linearly polarized plane waves. The optical gradient force acting on a conventional dielectric particle can be enhanced by two orders of magnitude via coating an extremely thin silver shell, whose thickness is only about one-tenth of the dielectric core. The analytical results based on the multipole expansion theory reveal that the enhanced optical gradient force comes mostly from the interaction between the incident field and the electric quadrupole excited in the core-shell particle. It is worth noting that the force expression within the dipole approximation commonly used for Rayleigh particles is invalid in our situation, even the particle is within the Rayleigh regime. In addition, both the optical potential energy and the optical trapping stiffness for the core-shell particle exhibit a great enhancement by two orders of magnitude stronger than a conventional dielectric particle and thus is favorable to a stable optical trapping. These results may extend the application range of optical tweezers and enrich optical manipulation techniques.

7.
Opt Lett ; 47(23): 6241-6244, 2022 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-37219217

RESUMEN

Based on the multipole expansion theory, we show that a transverse optical torque acting on a dipolar plasmonic spherical nanoparticle can be anomalously enhanced in two plane waves with linear polarization. Compared with a homogeneous Au nanoparticle, the transverse optical torque acting on an Au-Ag core-shell nanoparticle with an ultra-thin shell thickness can be dramatically enhanced by more than two orders of magnitude. Such enhanced transverse optical torque is dominated by the interaction between the incident optical field and the electric quadrupole excited in the dipolar core-shell nanoparticle. It is thus noted that the torque expression based on the dipole approximation usually used for dipolar particles is not available even in our dipolar case. These findings deepen the physical understanding of the optical torque (OT) and may have applications in optically driven rotation of plasmonic microparticles.

8.
Cell Mol Biol (Noisy-le-grand) ; 67(4): 135-142, 2022 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-35809293

RESUMEN

Spinal tuberculosis or tuberculous spondylitis is one of the most common types of skeletal tuberculosis. Complications of the spine and spinal cord tuberculosis include destruction of the vertebrae, deformity, and paraplegia. Since in some patients, the clinical manifestations of tuberculosis are unusual and timely diagnosis and treatment of this disease can prevent its serious consequences, so in the present study, some cases of rare manifestations of tuberculosis were investigated. The expression of the NF-κB gene in these patients was also evaluated. In this regard, 36 patients with spinal tuberculosis and 30 healthy individuals (as a control group) were assessed. Clinical symptoms, imaging, laboratory tests, pathology, and response to treatment related to patients with spinal tuberculosis and spinal cord tuberculosis were evaluated. NF-κB expression was also evaluated using the PCR technique in peripheral white blood cell samples. The obtained results were analyzed using SPSS ver. 16, χ2 and T-test statistical methods. Mann-Whitney U test and Kruskal-Wallis non-parametric tests were used to analyze non-parametric data. The results showed that out of 36 cases of spinal tuberculosis, 29 cases had spinal tuberculosis, five cases had tuberculous radiculomyelitis, one case had spinal intramedullary tuberculoma, and one case had syringomyelia. 52.78% of patients were male, and 70% of cases were observed between the ages of 35 and 55 years. Fever and back pain were seen in more than 80% of cases. The study of NF-κB expression in the control and case groups showed that the NF-κB expression in the case group increased compared to the control group. This increase was statistically significant (P = 0.0071). In general, in the present study, the methods of clinical diagnosis of spinal tuberculosis were evaluated. Also, the amount of NF-κB transcription factor was evaluated as an effective genetic factor in the diagnosis of this disease.


Asunto(s)
Tuberculosis de la Columna Vertebral , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , FN-kappa B/genética , FN-kappa B/metabolismo , Médula Espinal/metabolismo , Tuberculosis de la Columna Vertebral/complicaciones , Tuberculosis de la Columna Vertebral/diagnóstico , Tuberculosis de la Columna Vertebral/terapia
9.
Phys Rev Lett ; 125(7): 073901, 2020 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-32857552

RESUMEN

Lateral optical forces in a direction perpendicular to light propagation have attracted increasing interest in recent years. Up to now, all lateral forces can be attributed to the symmetry breaking in the lateral directions caused by either the morphology of the scatterer geometry or the optical fields impinging on the scatterer. Here we demonstrate, both numerically and analytically, that when an isotropic scatterer breaks the electric-magnetic symmetry, a new type of anomalous lateral force can be induced along the direction of translational invariance where the illumination striking the scatterer has no propagation, field gradient, or spin density vortex (Belinfante's spin momentum). Our analytical results are rigorous for an arbitrary size scatterer, ensuring the universality of our conclusion. Furthermore, the electric-magnetic symmetry-breaking-induced lateral force is comparable in magnitude to other components of the optical force and reversible in direction for different polarizations of the illuminating light, rendering it capable of practical optical manipulation as well as enriching the understanding of light-matter interaction.

10.
Opt Lett ; 43(9): 2086-2089, 2018 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-29714752

RESUMEN

Based on the full wave simulation, we demonstrate that a circularly polarized vector Airy beam can selectively transport small chiral particles along a curved trajectory via the chirality-tailored optical forces. The transverse optical forces can draw the chiral particles with different particle chirality towards or away from the intensity maxima of the beam, leading to the selective trapping in the transverse plane. The transversely trapped chiral particles are then accelerated along a curved trajectory of the Airy beam by the chirality-tailored longitudinal scattering force, rendering an alternative way to sort and/or transport chiral particles with specified helicity. Finally, the underlying physics of the chirality induced transverse trap and de-trap phenomena are examined by the analytical theory within the dipole approximation.

11.
Appl Microbiol Biotechnol ; 102(24): 10589-10601, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30276712

RESUMEN

Pactamycin, a structurally unique aminocyclitol natural product isolated from Streptomyces pactum, has potent antibacterial, antitumor, and anti-protozoa activities. However, its production yields under currently used culture conditions are generally low. To understand how pactamycin biosynthesis is regulated and explore the possibility of improving pactamycin production in S. pactum, we investigated the transcription regulations of pactamycin biosynthesis. In vivo inactivation of two putative pathway-specific regulatory genes, ptmE and ptmF, resulted in mutant strains that are not able to produce pactamycin. Genetic complementation using a cassette containing ptmE and ptmF integrated into the S. pactum chromosome rescued the production of pactamycin. Transcriptional analysis of the ΔptmE and ΔptmF strains suggests that both genes control the expression of the whole pactamycin biosynthetic gene cluster. However, attempts to overexpress these regulatory genes by introducing a second copy of the genes in S. pactum did not improve the production yield of pactamycin. We discovered that pactamycin biosynthesis is sensitive to phosphate regulation. Concentration of inorganic phosphate higher than 2 mM abolished both the transcription of the biosynthetic genes and the production of the antibiotic. Draft genome sequencing of S. pactum and bioinformatics studies revealed the existence of global regulatory genes, e.g., genes that encode a two-component PhoR-PhoP system, which are commonly involved in secondary metabolism. Inactivation of phoP did not show any significant effect to pactamycin production. However, in the phoP::aac(3)IV mutant, pactamycin biosynthesis is not affected by external inorganic phosphate concentration.


Asunto(s)
Proteínas Bacterianas/genética , Regulación Bacteriana de la Expresión Génica , Pactamicina/biosíntesis , Streptomyces/genética , Streptomyces/metabolismo , Proteínas Bacterianas/metabolismo , Duplicación de Gen , Perfilación de la Expresión Génica , Prueba de Complementación Genética , Genoma Bacteriano , Mutación , Operón , Fosfatos/metabolismo , Streptomyces/crecimiento & desarrollo
12.
Opt Express ; 25(19): 23238-23253, 2017 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-29041625

RESUMEN

Based on the generalized Lorenz-Mie theory and the Maxwell stress tensor approach we present the first rigorous full-wave solution of the optical forces acting on spherical microparticles immersed in a two-dimensional vector Airy beam beyond the paraxial approximation. The critical aspect lies in evaluating efficiently and accurately the partial wave expansion coefficients of the incident Airy beam, which are achieved by using the vector angular spectrum representation for a variety of polarizations. The optical field distributions are then simulated to show the self-accelerating and self-healing effects of the Airy beam. The dielectric and gold microparticles are shown to be trapped within the main lobe or the nearby side-lobes mostly by the transverse gradient optical force while driven forward along the parabolic trajectory of the Airy beam by the longitudinal scattering force. It is thus demonstrated theoretically that the vector Airy beam has the capability of precisely transporting both dielectric and metallic microparticles along the prespecified curved paths.

13.
J Xray Sci Technol ; 25(5): 813-829, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28527236

RESUMEN

Iterative reconstruction algorithms for computed tomography (CT) through total variation (TV) regularization can provide accurate and stable reconstruction results. TV minimization is the L1-norm of gradient-magnitude images and can be regarded as a convex relaxation method to replace the L0 norm. In this study, a fast and efficient algorithm, which is named a weighted difference of L1 and L2 (L1 - αL2) on the gradient minimization, was proposed and investigated. The new algorithm provides a better description of sparsity for the optimization-based algorithms than TV minimization algorithms. The alternating direction method is an efficient method to solve the proposed model, which is utilized in this study. Both simulations and real CT projections were tested to verify the performances of the proposed algorithm. In the simulation experiments, the reconstructions from the proposed method provided better image quality than TV minimization algorithms with only 7 views in 180 degrees, which is also computationally faster. Meanwhile, the new algorithm enabled to achieve the final solution with less iteration numbers.


Asunto(s)
Algoritmos , Procesamiento de Imagen Asistido por Computador/métodos , Tomografía Computarizada por Rayos X/métodos , Animales , Masculino , Modelos Biológicos , Fantasmas de Imagen , Conejos
14.
J Xray Sci Technol ; 25(3): 429-464, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28157114

RESUMEN

Nowadays, diversities of task-specific applications for computed tomography (CT) have already proposed multiple challenges for algorithm design of image reconstructions. Consequently, efficient algorithm design tool is necessary to be established. A fast and efficient algorithm design framework for CT image reconstruction, which is based on alternating direction method (ADM) with ordered subsets (OS), is proposed, termed as OS-ADM. The general ideas of ADM and OS have been abstractly introduced and then they are combined for solving convex optimizations in CT image reconstruction. Standard procedures are concluded for algorithm design which contain 1) model mapping, 2) sub-problem dividing and 3) solving, 4) OS level setting and 5) algorithm evaluation. Typical reconstruction problems are modeled as convex optimizations, including (non-negative) least-square, constrained L1 minimization, constrained total variation (TV) minimization and TV minimizations with different data fidelity terms. Efficient working algorithms for these problems are derived with detailed derivations by the proposed framework. In addition, both simulations and real CT projections are tested to verify the performances of two TV-based algorithms. Experimental investigations indicate that these algorithms are of the state-of-the-art performances. The algorithm instances show that the proposed OS-ADM framework is promising for practical applications.


Asunto(s)
Procesamiento de Imagen Asistido por Computador/métodos , Tomografía Computarizada por Rayos X/métodos , Algoritmos , Humanos , Fantasmas de Imagen
15.
Chembiochem ; 17(17): 1585-8, 2016 09 02.
Artículo en Inglés | MEDLINE | ID: mdl-27305101

RESUMEN

Pactamycin is a bacteria-derived aminocyclitol antibiotic with a wide-range of biological activity. Its chemical structure and potent biological activities have made it an interesting lead compound for drug discovery and development. Despite its unusual chemical structure, many aspects of its formation in nature remain elusive. Using a combination of genetic inactivation and metabolic analysis, we investigated the tailoring processes of pactamycin biosynthesis in Streptomyces pactum. The results provide insights into the sequence of events during the tailoring steps of pactamycin biosynthesis and explain the unusual production of various pactamycin analogues by S. pactum mutants. We also identified two new pactamycin analogues that have better selectivity indexes than pactamycin against malarial parasites.


Asunto(s)
Antibióticos Antineoplásicos/biosíntesis , Pactamicina/análogos & derivados , Pactamicina/biosíntesis , Streptomyces/metabolismo , Antibióticos Antineoplásicos/química , Conformación Molecular , Pactamicina/química , Streptomyces/genética
16.
Phys Chem Chem Phys ; 18(12): 8561-9, 2016 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-26948095

RESUMEN

Graphene is an excellent multi-functional platform for electrons, photons, and phonons due to exceptional electronic, photonic, and thermal properties. When combining its extraordinary mechanical characteristics with optical properties, graphene-based nanostructures can serve as an appealing platform for optomechanical applications at the nanoscale. Here, we demonstrate, using full-wave simulations, the emergence of extremely strong bipolar optical forces, or, optical binding and anti-binding, between a pair of coupled graphene nanoribbons, due to the remarkable confinement and enhancement of optical fields arising from the large effective mode indices. In particular, the binding and anti-binding forces, which are about two orders of magnitude stronger than that in metamaterials and high-Q resonators, can be tailored by selective excitation of either the even or the odd optical modes, achievable by tuning the relative phase of the lightwaves propagating along the two ribbons. Based on the coupled mode theory, we derive analytical formulae for the bipolar optical forces, which agree well with the numerical results. The attractive optical binding force F(y)(b) and the repulsive anti-binding force F(y)(a) exhibit a remarkably different dependence on the gap distance g between the nanoribbons and the Fermi energy E(F), in the forms of F(y)(b) ∝ 1/√(g³E(F)) and F(y)(a) ∝ 1/E(F)(2). With E(F) dynamically tunable by bias voltage, the bipolar forces may provide a flexible handle for active control of the nanoscale optomechanical effects, and also, might be significant for optoelectronic and optothermal applications as well.

17.
Appl Opt ; 55(19): 5095-101, 2016 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-27409196

RESUMEN

Tunable broadband optical field enhancements are demonstrated for graphene-based nanoscale slot waveguides, and the extremely strong field intensity inside the slot region is produced based on the ultrahigh effective mode index. Analytic formulas are obtained to reveal the dependence of enhanced optical fields and effective mode index on the gap distance, the Fermi energy, the width of nanoribbons, and the background medium. We show that most of the optical field is concentrated within the slot regions with the normalized power about up to 86%, and the averaged optical field intensity reaches 104 µm-2 for the slot waveguide with a 3 nm gap distance and 50 nm width. Meanwhile, the optical field enhancement effect is broadband at infrared frequencies and controlled by Fermi energy via bias electrical voltage for graphene.

18.
Opt Lett ; 40(23): 5530-3, 2015 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-26625043

RESUMEN

We demonstrate that a lateral optical force (LOF) can be induced on paired chiral nanoparticles with opposite handedness under the illumination of a linearly polarized plane wave. The LOFs on both chiral particles are equal and thus can move the pair sideways, with the direction depending on the separation between two particles, as well as the handedness of particle chirality. Analytical theory reveals that the LOF comes largely from the optical potential gradient established by the multiple scattering of light between the paired particles with asymmetric chirality. In addition, it is weakly dependent on the material loss of a particle, a feature of gradient force, while heavily dependent on the magnitude and handedness of particle chirality. The effect is expected to find applications in sorting and separating chiral dimers of different handedness.


Asunto(s)
Nanopartículas/química , Fenómenos Ópticos , Dimerización , Modelos Lineales , Modelos Moleculares , Conformación Molecular , Estereoisomerismo
19.
Vasa ; 44(4): 285-8, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-26314360

RESUMEN

BACKGROUND: Ischemic preconditioning (IPC) has many beneficial effects on the cardiovascular system. However, whether localized lower extremity IPC could be protective against the thrombogenic activity generated by lower extremity ischemia is unclear. MATERIAL AND METHODS: 41 male Sprague-Dawley rats were randomly assigned to either a IPC group or a sham group. The lower extremity blood inflow was previously treated with 4 cycles of 5 min ischemia followed by 5 min of reperfusion by clamping the abdominal aortic just before ligature of the left iliac vein(LIV) in the IPC group. Rats in the sham group had a 40-minute blank before left iliac vein ligation. The rats were euthanized at day 2 after ligation and the thrombosed LIV was carefully dissected out, while thrombi harvested from the LIV were measured with weight (g), length (mm) and weight/length (mg/mm). Influence of IPC on coagulation function was also tested. RESULTS: 21 and 20 rats were randomly assigned to einter the IPC group or the control group. Left iliac vein thrombosis was successfully generated in all 41 rats. IPC significantly protects the rats from experimental lower extremity thrombosis. Compared to control group, generated thrombus in rats in the IPC group showed significantly lower weight (2.73 ± 0.16 mg vs 1.82 ± 0.13 mg, P < 0.001), length (2.99 ± 0.17 mm vs 2.44 ± 0.08 mm, P < 0.009) and density (0.95 ± 0.05 mg/mm vs 0.75 ± 0.05 mg/mm, P = 0.01). Influence on coagulation function by IPC itself was not significant (P > 0.05). CONCLUSIONS: Our study demonstrated that localized lower extremity IPC could reduce DVT formation in rats in an in vivo experimental thrombosis model.


Asunto(s)
Precondicionamiento Isquémico/métodos , Extremidad Inferior/irrigación sanguínea , Trombosis de la Vena/prevención & control , Animales , Modelos Animales de Enfermedad , Masculino , Ratas , Ratas Sprague-Dawley
20.
J Am Chem Soc ; 136(12): 4565-74, 2014 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-24575817

RESUMEN

The marine Streptomyces sp. CNQ-617 produces two diastereomers, marineosins A and B. These are structurally related to alkyl prodiginines, but with a more complex cyclization and an unusual spiroaminal skeleton. We report the identification of the mar biosynthetic gene cluster and demonstrate production of marineosins through heterologous expression in a S. venezuelae host named JND2. The mar cluster shares the same gene organization and has high homology to the genes of the red cluster (which directs the biosynthesis of undecylprodiginine) but contains an additional gene, named marA. Replacement of marA in the JND2 strain leads to the accumulation of premarineosin, which is identical to marineosin with the exception that the middle pyrrole (Ring B) has not been reduced. The final step of the marineosin pathway is thus a MarA catalyzed reduction of this ring. Replacement of marG (a homologue of redG that directs undecylprodiginine cyclization to give streptorubin B) in the JND2 strain leads to the loss of all spiroaminal products and the accumulation of 23-hydroxyundecylprodiginine and a shunt product, 23-ketoundecylprodiginine. MarG thus catalyzes the penultimate step of the marineosin pathway catalyzing conversion of 23-hydroxyundecylprodiginine to premarineosin. The preceding steps of the biosynthetic marineosin pathway likely mirror that in the red-directed biosynthetic process, with the exception of the introduction of the hydroxyl functionality required for spiroaminal formation. This work presents the first experimentally supported scheme for biosynthesis of marineosin and provides a new biologically active molecule, premarineosin.


Asunto(s)
Antimaláricos/metabolismo , Familia de Multigenes , Pirroles/metabolismo , Compuestos de Espiro/metabolismo , Streptomyces/genética , Streptomyces/metabolismo , Antimaláricos/farmacología , Clonación Molecular , Resistencia a Múltiples Medicamentos/efectos de los fármacos , Oxidación-Reducción , Plasmodium falciparum/efectos de los fármacos , Prodigiosina/análogos & derivados , Prodigiosina/metabolismo , Pirroles/farmacología , Análisis de Secuencia , Homología de Secuencia de Ácido Nucleico , Compuestos de Espiro/farmacología
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