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2.
Biophys Chem ; 293: 106933, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36508984

RESUMEN

There is complete attenuation of fusion and infection mediated by HIV gp160 with gp41 subunit with V2E mutation, and also V2E dominance with WT/V2E mixtures. V2E is at the N-terminus of the ∼25-residue fusion peptide (Fp) which likely binds the target membrane. In this study, large V2E attenuation and dominance were observed for vesicle fusion induced by FP_HM, a large gp41 ectodomain construct with Fp followed by hyperthermostable hairpin with N- and C-helices, and membrane-proximal external region (Mper). FP_HM is a trimer-of-hairpins, the final gp41 structure during fusion. Vesicle fusion and helicity were measured for FP_HM using trimers with different fractions (f's) of WT and V2E proteins. Reductions in FP_HM fusion and helicity vs. fV2E were quantitatively-similar to those for gp160-mediated fusion and infection. Global fitting of all V2E data supports 6 WT gp41 (2 trimers) required for fusion. These data are understood by a model in which the ∼25 kcal/mol free energy for initial membrane apposition is compensated by the thermostable hairpin between the Fp in target membrane and Mper/transmembrane domain in virus membrane. The data support a structural model for V2E dominance with a membrane-bound Fp with antiparallel ß sheet and interleaved strands from the two trimers. Relative to fV2E = 0, a longer Fp sheet is stabilized with small fV2E because of salt-bridge and/or hydrogen bonds between E2 on one strand and C-terminal Fp residues on adjacent strands, like R22. A longer Fp sheet results in shorter N- and C-helices, and larger separation during membrane apposition which hinders fusion.


Asunto(s)
Infecciones por VIH , Fusión de Membrana , Humanos , Conformación Proteica en Lámina beta , Secuencia de Aminoácidos , Péptidos/genética , Infecciones por VIH/metabolismo , Mutación , Proteína gp41 de Envoltorio del VIH/genética , Proteína gp41 de Envoltorio del VIH/química , Proteína gp41 de Envoltorio del VIH/metabolismo
3.
Micromachines (Basel) ; 13(11)2022 Nov 19.
Artículo en Inglés | MEDLINE | ID: mdl-36422454

RESUMEN

Cable-driven manipulators, characterized by slender arms, dexterous motion, and controllable stiffness, have great prospects for application to capture on-orbit satellites. However, it is difficult to achieve effective motion planning and stiffness control of cable-driven manipulators because of the coupled relationships between cable lengths, joint angles, and reaction forces. Therefore, a convolutional dynamic-jerk-planning algorithm is devised for impedance control of variable-stiffness cable-driven manipulators. First, a variable-stiffness cable-driven manipulator with universal modules and rotary quick-change modules is designed to overcome difficulties related to disassembly, installation, and maintenance. Second, a convolutional dynamic-jerk-planning algorithm is devised to overcome the discontinuity and shock problems of the manipulator's velocity during intermittent control processes. The algorithm can also make acceleration smooth by setting jerk dynamically, reducing acceleration shock and ensuring the stable movement of the cable-driven manipulator. Third, the stiffness of the cable-driven manipulator is further optimized by compensating for the position and velocity of drive cables by employing position-based impedance control. Finally, the prototype of the variable-stiffness cable-driven manipulator is developed and tested. The convolutional dynamic-jerk-planning algorithm is used to plan the desired velocity curves for velocity control experiments of the cable-driven manipulator. The results verify that the algorithm can improve the acceleration smoothness, thereby making movement smooth and reducing vibrations. Furthermore, stiffness control experiments verify that the cable-driven manipulator has ideal variable stiffness capabilities.

4.
Nat Commun ; 13(1): 3119, 2022 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-35701397

RESUMEN

The distribution range, time-varying characteristics, and sources of lunar water are still controversial. Here we show the Chang'E-5 in-situ spectral observations of lunar water under Earth's magnetosphere shielding and relatively high temperatures. Our results show the hydroxyl contents of lunar soils in Chang'E-5 landing site are with a mean value of 28.5 ppm, which is on the weak end of lunar hydration features. This is consistent with the predictions from remote sensing and ground-based telescopic data. Laboratory analysis of the Chang'E-5 returned samples also provide critical clues to the possible sources of these hydroxyl contents. Much less agglutinate glass contents suggest a weak contribution of solar wind implantation. Besides, the apatite present in the samples can provide hydroxyl contents in the range of 0 to 179 ± 13 ppm, which shows compelling evidence that, the hydroxyl-containing apatite may be an important source for the excess hydroxyl observed at this young mare region.

5.
Nature ; 600(7887): 59-63, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34666339

RESUMEN

Mare volcanics on the Moon are the key record of thermo-chemical evolution throughout most of lunar history1-3. Young mare basalts-mainly distributed in a region rich in potassium, rare-earth elements and phosphorus (KREEP) in Oceanus Procellarum, called the Procellarum KREEP Terrane (PKT)4-were thought to be formed from KREEP-rich sources at depth5-7. However, this hypothesis has not been tested with young basalts from the PKT. Here we present a petrological and geochemical study of the basalt clasts from the PKT returned by the Chang'e-5 mission8. These two-billion-year-old basalts are the youngest lunar samples reported so far9. Bulk rock compositions have moderate titanium and high iron contents  with KREEP-like rare-earth-element and high thorium concentrations. However, strontium-neodymium isotopes indicate that these basalts were derived from a non-KREEP mantle source. To produce the high abundances of rare-earth elements and thorium, low-degree partial melting and extensive fractional crystallization are required. Our results indicate that the KREEP association may not be a prerequisite for young mare volcanism. Absolving the need to invoke heat-producing elements in their source implies a more sustained cooling history of the lunar interior to generate the Moon's youngest melts.

6.
Drug Des Devel Ther ; 15: 2551-2562, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34163141

RESUMEN

PURPOSE: To evaluate the bioequivalence and safety of two formulations of 25 mg tenofovir alafenamide tablets in Chinese healthy male and female subjects under fed and fasting conditions. PATIENTS AND METHODS: This was a randomized, open-label, single-center, crossover study consisting of a fasting trial with two periods and a fed trial with four periods. In total, 42 healthy subjects were enrolled in the fasting trial and 32 healthy subjects were enrolled in the fed trial. In each period, blood samples for pharmacokinetic analysis were collected until 72 hours post-dose. The plasma concentrations of tenofovir alafenamide and tenofovir were measured and noncompartmental analysis was used to determine pharmacokinetic parameters. Throughout the entire study, subjects' safety was monitored by assessment of physical examinations, vital signs, 12-lead electrocardiography, clinical laboratory parameters, and treatment emergent adverse events (TEAEs). RESULTS: Forty subjects completed the fasting trial and 32 subjects completed the fed trial. The 90% confidence intervals (CIs) of the geometric mean ratios for AUC0-t, AUC0-∞, and Cmax for the two formulations were within 80.00% to 125.00%, which met the bioequivalence acceptance criteria. The study drugs were well tolerated by all subjects. CONCLUSION: This study demonstrated that the test formulation of 25 mg tenofovir alafenamide tablets was bioequivalent to the formulation marketed under the brand name VEMLIDY® in healthy Chinese male and female subjects under fasting and fed conditions.


Asunto(s)
Alanina/administración & dosificación , Antivirales/administración & dosificación , Interacciones Alimento-Droga , Tenofovir/análogos & derivados , Adolescente , Adulto , Alanina/farmacocinética , Alanina/toxicidad , Antivirales/farmacocinética , Antivirales/toxicidad , Área Bajo la Curva , Estudios Cruzados , Ayuno , Femenino , Humanos , Masculino , Persona de Mediana Edad , Comprimidos , Tenofovir/administración & dosificación , Tenofovir/farmacocinética , Tenofovir/toxicidad , Equivalencia Terapéutica , Adulto Joven
7.
PLoS One ; 15(8): e0237881, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32817641

RESUMEN

At present, the identification of honeysuckle aroma depends on experienced tasters, which results in inconsistencies due to human error. The key odorants have the potential to distinguish the different species and evaluate the quality of honeysuckle. Hence, in this study, a more scientific approach was applied to distinguish various honeysuckles. The volatile compounds of different species and parts of honeysuckle were separately extracted by headspace-solid phase microextraction (HS-SPME) and solvent assisted flavor evaporation (SAFE). Compounds with greater volatility such as aldehydes, limonene, γ-terpinene, and terpinolene were preferentially extracted by HS-SPME. As a complementary extraction method to HS-SPME, SAFE was found to recover comparatively more polar compounds such as eugenol, decanoic acid, and vanillin. Subsequently, key odorants with the highest flavour dilution (FD) factors were detected by aroma extract dilution analysis (AEDA). These were benzaldehyde, 4-ethylphenol, decanoic acid, vanillin, 3-methyl-2-butenal, and ß-ionone in honeysuckle flowers and γ-octalactone, 4-ethyl phenol, and vanillin in honeysuckle stem. Finally, principal component analysis (PCA) was conducted to analyze not only the key odorants of species and parts of honeysuckle but also their different origins. The results of PCA suggested that the species of honeysuckle contributed much more to variations in aroma rather than their origins. In conclusion, the application of the key odorants combined with PCA was demonstrated as a valid approach to differentiate species, origins, and parts of honeysuckle.


Asunto(s)
Lonicera/química , Odorantes/análisis , Olfatometría/métodos , Microextracción en Fase Sólida/métodos , Cromatografía de Gases y Espectrometría de Masas/métodos , Lonicera/clasificación , Lonicera/metabolismo , Solventes/química
8.
Inorg Chem ; 57(7): 3761-3774, 2018 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-29521502

RESUMEN

A series of homoleptic mononuclear 8-coordinate FeII and CoII compounds, [FeII(L2)2](ClO4)2 (2), [FeII(L3)2](ClO4)2 (3), [FeII(L4)2](ClO4)2 (4), [CoII(L1)2](ClO4)2 (5), [CoII(L2)2](ClO4)2 (6), [CoII(L3)2](ClO4)2 (7), and [CoII(L4)2](ClO4)2 (8) (L1 and L2 are 2,9-dialkylcarboxylate-1,10-phenanthroline ligands; L3 and L4 are 6,6'-dialkylcarboxylate-2,2'-bipyridine ligands), have been obtained, and their crystal structures have been determined by X-ray crystallography. The metal center in all of these compounds has an oversaturated coordination number of 8, which is completed by two neutral homoleptic tetradentate ligands and is unconventional in 3d-metal compounds. These compounds are further characterized by electronic spectroscopy, cyclic voltammetry (CV), and magnetic measurements. CV measurements of these complexes in MeCN solution exhibit rich redox properties. Magnetic measurements on these compounds demonstrate that the observed single-ion magnetic (SIM) behavior in the previously reported [FeII(L1)2](ClO4)2 (1) is not a contingent case, since all of the 8-coordinate compounds 2-8 exhibit interesting slow magnetic relaxation under applied direct current fields.

9.
J Org Chem ; 82(17): 9198-9203, 2017 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-28749668

RESUMEN

A copper-catalyzed three-component reaction of methyl ketones, organic azides, and various one-carbon (C1) donors was developed that provides 4-acyl-1,2,3-triazoles in moderate to good yields. While DMF, DMA, TMEDA, or DMSO can serve as the C1 donor, best yields were obtained using DMF. The transformation is proposed to proceed via an oxidative C-H/C-H cross-dehydrogenative coupling followed by an oxidative 1,3-dipolar cycloaddition.

10.
J Org Chem ; 82(12): 6163-6171, 2017 06 16.
Artículo en Inglés | MEDLINE | ID: mdl-28558242

RESUMEN

An efficient copper-catalyzed C-N bond formation by N-H/C-H cross-dehydrogenative coupling (CDC) between NH-1,2,3-triazoles and N,N-dialkylamides has been developed. The method provided N-amidoalkylated 1,2,3-triazoles with moderate to high yields, and the reactions showed high N2-selectivities when 4,5-disubstituted NH-1,2,3-triazoles served as the substrates.

11.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 33(4): 471-476, 2017 Apr.
Artículo en Chino | MEDLINE | ID: mdl-28395716

RESUMEN

Objective To investigate the effect of insulin-like growth factor 1 (IGF-1) on the proliferation and differentiation potential of human periodontal ligament stem cells (hPDLSCs). Methods The hPDLSCs were isolated by the limited dilution method. Surface markers of hPDLSCs were detected by flow cytometry. Cell clones were tested by crystal violet staining. The hPDLSCs were induced into osteoblasts and adipogenic by osteogenic and adipogenic medium. The influence of different concentrations of IGF-1 (1, 10, 30, 50, 100 ng/mL) on hPDLSCs was analyzed by CCK-8 assay. The expressions of collagen I α1 (Col1α1), collagen III α1 (Col3α1), runt-related transcription factor 2 (Runx2), bone sialoprotein (BSP), osteopontin (OPN), cementum protein 1 (CEMP1) and scleraxis (SCXA) were compared by means of real-time PCR. Col1, Col3, SCXA, Runx2 and CEMP1 protein expressions were determined by Western blotting. Results The hPDLSCs obtained by the limited dilution were positive for CD105 (95.4%), CD90 (96.1%) and negative for CD34 (1.58%), CD45 (1.74%). Single colonies were observed after cells were plated at low density by crystal violet staining. Alizarinred-positive mineral deposits and oil red O-positive cells indicated that the cultured cells had osteogenic and adipogenic potential. Proliferative potential of hPDLSCs was enhanced by IGF-1 in a dose-dependent manner. Real-time PCR showed that IGF-1 enhanced the expressions of Col1α1, Col3α1 and SCXA, while no significant change was found in the expressions of Runx2, BSP, OPN and CEMP1. Western blot analysis showed that the expressions of Col1, Col3 and SCXA increased significantly. Conclusion IGF-1 promotes proliferation and collagen synthesis of hPDLSCs, which further accelerates the differentiation into periodontal ligament fibroblast cells.


Asunto(s)
Diferenciación Celular , Proliferación Celular , Fibroblastos/citología , Factor I del Crecimiento Similar a la Insulina/metabolismo , Ligamento Periodontal/citología , Células Madre/citología , Adolescente , Adulto , Células Cultivadas , Colágeno Tipo I/metabolismo , Femenino , Fibroblastos/metabolismo , Humanos , Factor I del Crecimiento Similar a la Insulina/genética , Masculino , Ligamento Periodontal/metabolismo , Células Madre/metabolismo , Adulto Joven
12.
Chem Commun (Camb) ; 53(9): 1474-1477, 2017 Jan 26.
Artículo en Inglés | MEDLINE | ID: mdl-28083575

RESUMEN

The synthesis and structure of an 8-coordinate Fe(ii) compound [FeII(L1)2](ClO4)2 (1) with a [FeN4O4] core are reported. 1 exhibits uni-axial anisotropy for which a slow magnetic relaxation is observed under 1.4 kOe dc field. It is the first example of an 8-coordinate Fe(ii) complex exhibiting field-induced single-molecule magnet (SMM) behaviour.

13.
Dalton Trans ; 45(21): 8790-4, 2016 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-27143486

RESUMEN

Two dinuclear dysprosium complexes with the Dy(iii) ions bridged by the neutral bipyrimidine (BPYM) ligand were synthesized and magnetically characterized. They crystallized in a monoclinic and triclinic crystal system, respectively, with almost the same structural core, only differing in the lattice solvent molecules. Alternating current (ac) susceptibility measurements revealed that they exhibit significant slow relaxation of magnetization until 25 K in the absence of a dc field. The single and double relaxation processes were assigned to one and two types of Dy(iii) environments in the two dimmers, respectively, with barriers of 266 and 345 K under zero field conditions. The magnetic hysteresis loops of 1 and 2 were both observed up to 2.5 K.

14.
Endocrine ; 52(2): 296-304, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26403613

RESUMEN

The purpose of the study was to evaluate the effect of removing iodized salt on children's goiter prevalence in high iodine area (HIA). A total of 452 and 459 children aged 8-10 years old were selected by simple random sampling method before and after removing iodized salt from their diet in three towns with median water iodine content of 150-300 µg/l in Hengshui city of Hebei province of China. Their goiter status was judged using the thyroid volume (Tvol) reference for body surface area recommended by the WHO. After removing iodized salt, children's overall median urinary iodine content (MUIC) decreased from 518 (IQR 347,735) µg/l to 416 µg/l (IQR 274,609). Children's MUIC across sex and age group decreased significantly. The overall goiter prevalence in the three towns significantly decreased from 32.96 % (149/452) to 6.54 % (30/459) (P < 0.001). The goiter prevalence in 8-, 9-, and 10-year-old children decreased, respectively, from 38.04 % (35/92), 30.57 % (59/193), and 32.93 % (55/167) to 6.10 % (10/164), 6.75 % (11/163), and 6.82 % (9/132). The goiter prevalence in boys and girls decreased from 34.01 % (83/244) and 31.73 % (66/208) to 6.19 % (14/225) and 6.87 % (16/234), respectively. The decreases in children's goiter prevalence across gender and age groups were all statistically significant. The present study revealed that children's goiter prevalence decreased significantly after removing iodized salt from their diet for about one and half years in the HIA in Hebei province.


Asunto(s)
Bocio/prevención & control , Yodo/orina , Cloruro de Sodio Dietético/efectos adversos , Niño , China/epidemiología , Agua Potable/química , Femenino , Bocio/diagnóstico por imagen , Bocio/epidemiología , Bocio/orina , Humanos , Yodo/efectos adversos , Masculino , Prevalencia , Glándula Tiroides/diagnóstico por imagen , Ultrasonografía
15.
Wei Sheng Yan Jiu ; 44(3): 393-7, 2015 May.
Artículo en Chino | MEDLINE | ID: mdl-26137616

RESUMEN

OBJECTIVE: To explore the changes of goiter prevalence of children living in areas with high iodine in drinking water after removing iodized salt from their diet. METHODS: Three towns with median water iodine of 150 - 300 µg/L were selected randomly in Hengshui city of Hebei province of China. A total of 452 and 459 children in the 3 towns were randomly selected to measure thyroid volume by ultrasound before and after removing iodized salt, respectively. Their goiter status was judged using the criteria of age-specific thyroid volume recommended by the WHO. RESULTS: After removing iodized salt, the overall goiter prevalence in the three towns significantly decreased from 24.56% (111/452) to 5.88% (27/459) (P < 0.01). The goiter prevalence in 8, 9 and 10 year-old children decreased respectively from 33.70% (31/92), 23.32% (45/193) and 20.96% (35/167) to 6.10% (10/164), 5.52% (9/163) and 6.06% (8/132). The goiter prevalence in boys and girls decreased from 27.05% (66/244) and 21.63% (45/208 ) to 6.66% (15/226 ) and 5.15% (12/233), respectively. The decreases in children's goiter prevalence across gender and age group were all significant. CONCLUSION: Children's goiter prevalence decreased significantly after removing iodized salt from their diet for about one and half years in the HIA in Hebei province.


Asunto(s)
Agua Potable/química , Bocio/diagnóstico por imagen , Cloruro de Sodio Dietético/uso terapéutico , Glándula Tiroides/diagnóstico por imagen , Niño , China/epidemiología , Dieta , Femenino , Bocio/epidemiología , Humanos , Yoduros , Yodo , Masculino , Estado Nutricional , Prevalencia , Valores de Referencia , Medio Social , Ultrasonografía , Agua
16.
Zhonghua Yu Fang Yi Xue Za Zhi ; 49(4): 356-61, 2015 Apr.
Artículo en Chino | MEDLINE | ID: mdl-26081546

RESUMEN

OBJECTIVE: Using the thyroid volume criteria for body surface area (BSA) to assess more precisely the effectiveness of removing iodized salt on the goiter status of children living in areas with excessive iodine in drinking water. METHODS: Three towns with median water iodine (MWI) of 150-300 µg/L were selected by simple random method in Hengshui city of Hebei province of China in May of 2010. A total of 452 and 459 children in the 3 towns were randomly selected to measure thyroid volume by ultrasound. Iodized salt was removed in July of 2010. In October of 2013, 459 children in these 3 towns were selected by simple random method to measure their thyroid volume by ultrasound again. Their goiter status was judged using the criteria of thyroid volume for BSA recommended by the WHO. RESULTS: After removing iodized salt, the overall BSA specific goiter prevalence in the three towns significantly decreased from 33% (149/452) to 6% (30/459) (χ² = 100.64, P < 0.001). The BSA specific goiter prevalence in 8, 9 and 10 year-old children decreased respectively from 38% (35/92), 31% (59/193) and 33% (55/167) to 6% (10/164), 7% (11/163) and 7% (9/132) (χ² values were 41.35, 31.66, 29.79, P < 0.001). The BSA specific goiter prevalence in boys and girls decreased from 34% (83/244) and 32% (66/208) to 6% (14/225) and 7% (16/234) (χ² values were 55.01, 45.06, P < 0.001) respectively. CONCLUSION: The BSA specific children's goiter prevalence decreased significantly after removing iodized salt from their diet in the HIA in Hebei province.


Asunto(s)
Agua Potable , Bocio , Yodo , Cloruro de Sodio Dietético , Superficie Corporal , Niño , China , Dieta , Femenino , Humanos , Masculino , Prevalencia , Agua
17.
J Am Chem Soc ; 137(24): 7548-51, 2015 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-26039158

RESUMEN

The ∼25 N-terminal "HAfp" residues of the HA2 subunit of the influenza virus hemagglutinin protein are critical for fusion between the viral and endosomal membranes at low pH. Earlier studies of HAfp in detergent support (1) N-helix/turn/C-helix structure at pH 5 with open interhelical geometry and N-helix/turn/C-coil structure at pH 7; or (2) N-helix/turn/C-helix at both pHs with closed interhelical geometry. These different structures led to very different models of HAfp membrane location and different models of catalysis of membrane fusion by HAfp. In this study, the interhelical geometry of membrane-associated HAfp is probed by solid-state NMR. The data are well-fitted to a population mixture of closed and semiclosed structures. The two structures have similar interhelical geometries and are planar with hydrophobic and hydrophilic faces. The different structures of HAfp in detergent vs membrane could be due to the differences in interaction with the curved micelle vs flat membrane with better geometric matching between the closed and semiclosed structures and the membrane. The higher fusogenicity of longer sequences and low pH is correlated with hydrophobic surface area and consequent increased membrane perturbation.


Asunto(s)
Detergentes/química , Glicoproteínas Hemaglutininas del Virus de la Influenza/química , Hemaglutininas Virales/química , Orthomyxoviridae/química , Secuencia de Aminoácidos , Animales , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Gripe Humana/virología , Micelas , Modelos Moleculares , Datos de Secuencia Molecular , Resonancia Magnética Nuclear Biomolecular , Infecciones por Orthomyxoviridae/virología , Estructura Secundaria de Proteína
18.
J Magn Reson ; 253: 154-65, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25797012

RESUMEN

Rotational-echo double-resonance (REDOR) solid-state NMR is applied to probe the membrane locations of specific residues of membrane proteins. Couplings are measured between protein (13)CO nuclei and membrane lipid or cholesterol (2)H and (31)P nuclei. Specific (13)CO labeling is used to enable unambiguous assignment and (2)H labeling covers a small region of the lipid or cholesterol molecule. The (13)CO-(31)P and (13)CO-(2)H REDOR respectively probe proximity to the membrane headgroup region and proximity to specific insertion depths within the membrane hydrocarbon core. One strength of the REDOR approach is use of chemically-native proteins and membrane components. The conventional REDOR pulse sequence with 100 kHz (2)H π pulses is robust with respect to the (2)H quadrupolar anisotropy. The (2)H T1's are comparable to the longer dephasing times (τ's) and this leads to exponential rather than sigmoidal REDOR buildups. The (13)CO-(2)H buildups are well-fitted to A×(1-e(-γτ)) where A and γ are fitting parameters that are correlated as the fraction of molecules (A) with effective (13)CO-(2)H coupling d=3γ/2. The REDOR approach is applied to probe the membrane locations of the "fusion peptide" regions of the HIV gp41 and influenza virus hemagglutinin proteins which both catalyze joining of the viral and host cell membranes during initial infection of the cell. The HIV fusion peptide forms an intermolecular antiparallel ß sheet and the REDOR data support major deeply-inserted and minor shallowly-inserted molecular populations. A significant fraction of the influenza fusion peptide molecules form a tight hairpin with antiparallel N- and C-α helices and the REDOR data support a single peptide population with a deeply-inserted N-helix. The shared feature of deep insertion of the ß and α fusion peptide structures may be relevant for fusion catalysis via the resultant local perturbation of the membrane bilayer. Future applications of the REDOR approach may include samples that contain cell membrane extracts and use of lower temperatures and dynamic nuclear polarization to reduce data acquisition times.


Asunto(s)
Membrana Celular/química , Membrana Celular/ultraestructura , Membrana Dobles de Lípidos/química , Proteínas de la Membrana/química , Proteínas de la Membrana/ultraestructura , Resonancia Magnética Nuclear Biomolecular/métodos , Sitios de Unión , Técnicas de Sonda Molecular , Unión Proteica
19.
Br J Nutr ; 113(1): 114-9, 2015 Jan 14.
Artículo en Inglés | MEDLINE | ID: mdl-25366513

RESUMEN

The impact of removing iodised salt on children's goitre status in a high-iodine area (HIA) remains unclear. The aim of the present study was to explore the changes in the prevalence of goitre in children after removing iodised salt from their diet. For this purpose, three towns with the median water iodine content of 150-300 µg/l were selected randomly in Hengshui City, Hebei Province, China. A total of 452 and 459 children were randomly selected from the three towns in order to measure thyroid volume by ultrasound before and after removing iodised salt, respectively. Their goitre status was judged using the criteria of age-specific thyroid volume recommended by the WHO. After removing iodised salt, the overall median urinary iodine content (MUIC) of children decreased from 518 (interquartile range (IQR) 347-735) to 416 (IQR 274-609) µg/l. The MUIC of children across sex and age group decreased significantly except for the age group of 9 years. The overall prevalence of goitre in the three towns significantly decreased from 24·56% (n 111/452) to 5·88% (n 27/459) (P< 0·001). Goitre prevalence in children aged 8-10 years decreased from 33·70% (n 31/92), 23·32% (n 45/193) and 20·96% (n 35/167) to 6·10% (n 10/164), 5·52% (n 9/163) and 6·06% (n 8/132), respectively. Goitre prevalence in boys and girls decreased from 27·05% (n 66/244) and 21·63% (n 45/208) to 6·66% (n 15/226) and 5·15% (n 12/233), respectively. The decreases in the prevalence of goitre in children across sex and age group were all statistically significant. The present study revealed that goitre prevalence in children decreased significantly after removing iodised salt from their diet for about 1·5 years in the HIA in Hebei Province.


Asunto(s)
Agua Potable/química , Bocio/epidemiología , Yodo/orina , Cloruro de Sodio Dietético/orina , Niño , China/epidemiología , Dieta , Femenino , Bocio/diagnóstico por imagen , Humanos , Yodo/administración & dosificación , Masculino , Estado Nutricional , Prevalencia , Cloruro de Sodio Dietético/administración & dosificación , Glándula Tiroides/diagnóstico por imagen , Ultrasonografía
20.
Biochemistry ; 54(3): 677-84, 2015 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-25531389

RESUMEN

Membrane locations of peptides and proteins are often critical to their functions. Solid-state rotational-echo double-resonance (REDOR) nuclear magnetic resonance is applied to probe the locations of two peptides via peptide (13)CO to lipid (2)H distance measurements. The peptides are KALP, an α-helical membrane-spanning peptide, and HFP, the ß-sheet N-terminal fusion peptide of the HIV gp41 fusion protein that plays an important role in HIV-host cell membrane fusion. Both peptides are shown to have at least two distinct locations within the hydrocarbon core of gel-phase membranes. The multiple locations are attributed to snorkeling of lysine side chains for KALP and to the distribution of antiparallel ß-sheet registries for HFP. The relative population of each location is also quantitated. To the best of our knowledge, this is the first clear experimental support of multiple peptide locations within the membrane hydrocarbon core. These data are for gel-phase membranes, but the approach should work for liquid-ordered membranes containing cholesterol and may be applicable to liquid-disordered membranes with appropriate additional analysis to take into account protein and lipid motion. This paper also describes the methodological development of (13)CO-(2)H REDOR using the lyophilized I4 peptide that is α-helical and (13)CO-labeled at A9 and (2)Hα-labeled at A8. The I4 spins are well-approximated as an ensemble of isolated (13)CO-(2)H spin pairs each separated by 5.0 Å with a 37 Hz dipolar coupling. A pulse sequence with rectangular 100 kHz (2)H π pulses results in rapid and extensive buildup of REDOR (ΔS/S0) with a dephasing time (τ). The buildup is well-fit by a simple exponential function with a rate of 24 Hz and an extent close to 1. These parameter values reflect nonradiative transitions between the (2)H spin states during the dephasing period. Each spin pair spends approximately two-thirds of its time in the (13)CO-(2)H (m = ±1) states and approximately one-third of its time in the (13)CO-(2)H (m = 0) state and contributes to the ΔS/S0 buildup during the former but not the latter time segments.


Asunto(s)
Membrana Celular/química , Deuterio/química , Hidrocarburos/química , Lípidos/química , Espectroscopía de Resonancia Magnética/métodos , Péptidos/química , Transición de Fase , Secuencia de Aminoácidos , Isótopos de Carbono , Geles , Datos de Secuencia Molecular , Rotación
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