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991.
Hala Skayneh Batoul Jishi Rita Hleihel Maguy Hamie Rana El Hajj Carine Deleuze-Masquefa Pierre-Antoine Bonnet Marwan El Sabban Hiba El Hajj 《International journal of molecular sciences》2022,23(7)
Nucleophosmin-1 (NPM1) is a pleiotropic protein involved in numerous cellular processes. NPM1 shuttles between the nucleus and the cytoplasm, but exhibits a predominant nucleolar localization, where its fate and functions are exquisitely controlled by dynamic post-translational modifications (PTM). Sentrin/SUMO Specific Peptidase 3 (SENP3) and ARF are two nucleolar proteins involved in NPM1 PTMs. SENP3 antagonizes ARF-mediated NPM1 SUMOylation, to promote ribosomal biogenesis. In Acute Myeloid Leukemia (AML), NPM1 is frequently mutated, and exhibits an aberrant cytoplasmic localization (NPM1c). NPM1c mutations define a separate AML entity with good prognosis in some AML patients, rendering NPM1c as a potential therapeutic target. SENP3-mediated NPM1 de-SUMOylation induces resistance to therapy in NPM1c AML. Here, we demonstrate that the imidazoquinoxaline EAPB0503 prolongs the survival and results in selective reduction in the leukemia burden of NPM1c AML xenograft mice. Indeed, EAPB0503 selectively downregulates HDM2 expression and activates the p53 pathway in NPM1c expressing cells, resulting in apoptosis. Importantly, we unraveled that NPM1c expressing cells exhibit low basal levels of SUMOylation paralleled with high SENP3 and low ARF basal levels. EAPB0503 reverted these molecular players by inducing NPM1c SUMOylation and ubiquitylation, leading to its proteasomal degradation. EAPB0503-induced NPM1c SUMOylation is concurrent with SENP3 downregulation and ARF upregulation in NPM1c expressing cells. Collectively, these results provide a strong rationale for testing therapies modulating NPM1c post-translational modifications in the management of NPM1c AML. 相似文献
992.
Jana A. Hirsch Geoffrey F. Green Marc Peterson Daniel A. Rodriguez Penny Gordon-Larsen 《Journal of Urbanism》2017,10(2):181-197
While increasing evidence suggests an association between physical infrastructure in neighborhoods and health outcomes, relatively little research examines how neighborhoods change physically over time and how these physical improvements are spatially distributed across populations. This paper describes the change over 25 years (1985–2010) in bicycle lanes, off-road trails, bus transit service and parks, and spatial clusters of changes in these domains relative to neighborhood sociodemographics in four US cities that are diverse in terms of geography, size, and population. Across all four cities we identified increases in bicycle lanes, off-road trails, and bus transit service, with spatial clustering in these changes that related to neighborhood sociodemographics. Overall, we found evidence of positive changes in physical infrastructure commonly identified as supportive of physical activity. However, the patterning of infrastructure change by sociodemographic change encourages attention to the equity in infrastructure improvements across neighborhoods. 相似文献
993.
Alan L. Chaffee Galinda Lay Marc Marshall W. Roy Jackson Yi Fei T. Vincent Verheyen Steven G. Scott 《Fuel》2010,89(11):3241-3249
The structure of a suite of high-volatile, bituminous Surat Basin, Queensland coals has been investigated by a combination of analytical probes. These included elemental analyses, pyrolysis-gas chromatography-mass spectroscopy and Fourier transform infrared spectroscopy, together with a study of their liquefaction products in both tetralin and solvent free-tin catalysed hydrogenations. Samples were gathered across a 300 m depth interval intersected by the sampling well. Most techniques revealed clear but subtle differences in structure as a function of depth. The oils produced by solvent free-tin catalysed hydrogenation, however, showed very distinct dependence with depth and the waxy content, as indicated by 1H-NMR, could be correlated with the coal seam gas content. 相似文献
994.
Marc Flinders Darin Ray Angela Anderson Raymond A. Cutler 《Journal of the American Ceramic Society》2005,88(8):2217-2226
Silicon carbide, with single-edge precracked beam (SEPB) toughness greater than 7 MPa·m1/2 , was made by hot-pressing using Al–B–C (ABC) or Al–Y2 O3 (YAG) as additives. The hardness of SiC processed with a liquid phase was always less than SiC densified without a liquid phase despite having a similar or finer grain size. With increasing Al content, the ABC system changed from trans- to intergranular fracture with a drop in hardness and a two- to threefold increase in SEPB toughness. Strength and Weibull modulus for materials processed with a liquid phase were higher than those of solid-state densified SiC. Ballistic testing, however, did not show any improvement over SiC densified with B and C additives. Depth of penetration was controlled by hardness of the SiC-based materials, while V 50 values for 14.5 mm WC–Co cored projectiles were in the range of 720–750 m/s for all materials tested. 相似文献
995.
Abdelkader Kahouli Olivier Gallot‐Lavallée Pacal Rain Olivier Lesaint Christophe Guillermin Jean‐Marc Lupin 《应用聚合物科学杂志》2015,132(28)
The dielectric properties of two grades of bi‐oriented isotactic polypropylene were studied with a variety of techniques: breakdown field measurements, dielectric spectroscopy, thermally stimulated depolarization currents (Is), and direct‐current (dc) conduction I values. Standard polypropylene (STPP) and high‐crystallinity polypropylene (HCPP) films were investigated. Measurements were carried out over a wide temperature range (?150°C/+125°C). The breakdown fields in both materials showed a very small difference. On the other hand, the dielectric losses and dc conduction I values were significantly lower in HCPP. Both materials showed a decrease in the dielectric loss versus temperature in the range 20–90°C; this is favorable for application in alternating‐current power capacitors. The analysis of the dc I value allowed us to find evidence of two main conduction mechanisms: (1) below 80°C in both materials, a hopping mechanism due to the motion of electrons occurred in the amorphous phase, and (2) above 80°C, ionic conduction occurred in HCPP, and hopping conduction occurred in STPP. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42224. 相似文献
996.
Novel Tacrine‐Grafted Ugi Adducts as Multipotent Anti‐Alzheimer Drugs: A Synthetic Renewal in Tacrine–Ferulic Acid Hybrids
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Mohamed Benchekroun Dr. Manuela Bartolini Dr. Javier Egea Dr. Alejandro Romero Dr. Elena Soriano Dr. Marc Pudlo Vincent Luzet Prof. Vincenza Andrisano Dr. María‐Luisa Jimeno Dr. Manuela G. López Sarah Wehle Prof. Tijani Gharbi Prof. Bernard Refouvelet Lucía de Andrés Clara Herrera‐Arozamena Prof. Barbara Monti Prof. Maria Laura Bolognesi Prof. María Isabel Rodríguez‐Franco Prof. Dr. Michael Decker Prof. José Marco‐Contelles Dr. Lhassane Ismaili 《ChemMedChem》2015,10(3):523-539
Herein we describe the design, multicomponent synthesis, and biological, molecular modeling and ADMET studies, as well as in vitro PAMPA‐blood–brain barrier (BBB) analysis of new tacrine–ferulic acid hybrids (TFAHs). We identified (E)‐3‐(hydroxy‐3‐methoxyphenyl)‐N‐{8[(7‐methoxy‐1,2,3,4‐tetrahydroacridin‐9‐yl)amino]octyl}‐N‐[2‐(naphthalen‐2‐ylamino)2‐oxoethyl]acrylamide (TFAH 10 n ) as a particularly interesting multipotent compound that shows moderate and completely selective inhibition of human butyrylcholinesterase (IC50=68.2 nM ), strong antioxidant activity (4.29 equiv trolox in an oxygen radical absorbance capacity (ORAC) assay), and good β‐amyloid (Aβ) anti‐aggregation properties (65.6 % at 1:1 ratio); moreover, it is able to permeate central nervous system (CNS) tissues, as determined by PAMPA‐BBB assay. Notably, even when tested at very high concentrations, TFAH 10 n easily surpasses the other TFAHs in hepatotoxicity profiling (59.4 % cell viability at 1000 μM ), affording good neuroprotection against toxic insults such as Aβ1–40, Aβ1–42, H2O2, and oligomycin A/rotenone on SH‐SY5Y cells, at 1 μM . The results reported herein support the development of new multipotent TFAH derivatives as potential drugs for the treatment of Alzheimer′s disease. 相似文献
997.
We show that enriching logit mode choice model specification by mode attributes, socio economic variables and trip purpose
characteristics significantly improves model quality, and that Box-Cox transformations applied to model attributes imply an
asymmetry of the reaction curve, as well as more reasonable properties (diminishing marginal values of time savings, elasticities
and values of time that differ among the modes) than those of the linear logit model. Moreover, the model yielded very different
high speed rail market shares for Germany than results obtained with the usual linear utility functions.
Received: December 1996 / Accepted: April 1997 相似文献
998.
A method for characterising cook loss and water holding capacity in heat treated cod (Gadus morhua) muscle 总被引:1,自引:0,他引:1
Dagbjrn Skipnes Merete Lund
stby Marc E. Hendrickx 《Journal of food engineering》2007,80(4):1078-1085
The currently available methods for measuring water holding capacity (WHC) have been developed for raw material characterisation and have been applied to processed (cooked) muscle samples. The intrinsic shortcoming of the methods is that they do not allow rapid and uniform heating, which make them unsuitable for investigating the kinetics of cook loss and WHC. A new method and associated equipment (sample cups) for rapid and uniform heating that allows studying cook loss, water holding capacity and texture of fish samples was developed. After heating and cooling of samples in the sample cup it is feasible to gravimetrically determine the cook loss with a standard deviation within 30% of the total cook loss for minced samples. Both intact and coarsely minced muscle of farmed cod was used to investigate the abilities and limitations of the method with respect to WHC. 相似文献
999.
Influence of copigment derived from Tasmannia pepper leaf on Davidson's plum anthocyanins 总被引:1,自引:0,他引:1
Jensen MB López-de-Dicastillo Bergamo CA Payet RM Liu X Konczak I 《Journal of food science》2011,76(3):C447-C453
Davidson's plum (Davidsonia pruriens, F. Muell.), a native to Australian rainforests, large, crimson-red fruit, which superficially resembles plum, has been commercially cultivated in Australia since 1990s. The current production volume exceeds market demands therefore this study was designed to evaluate the suitability of Davidson's plum extract as a source of anthocyanin-based food colorant. The stability of the Davidson's plum extract towards heat treatment at 95 °C was higher than that of commercial mulberry colorant, but inferior to colorants derived from red cabbage and purple sweetpotato. An addition of a variety of phenolic acids significantly increased color intensity indicating the formation of copigmentation complexes. Commercial chlorogenic acid as well as extract from a native Australian herb rich in chlorogenic acid, Tasmannia pepper leaf (Tasmannia lanceolata, R. Br.), were both tested in model soft drink solutions subjected to light irradiation and heat treatment. In both cases, the addition of the copigment resulted in a lasting increase in color intensity. In conclusion, Davidson's plum extract can successfully be utilized as a source of natural food color. Extract from Tasmania pepper leaf can be used as a co-pigment for Davidson's plum anthocyanins. PRACTICAL APPLICATION: The color properties of an anthocyanin colorant derived from the native Australian fruit Davidson's plum are comparable to those of mulberry, which is currently applied as a food colorant in Australian food products. Utilization of Davidson's plum fruit as a source of natural color will allow the industry to increase the range of natural pigments and will create new opportunities for the emerging native food industry. 相似文献
1000.
In vitro β‐Carotene Bioaccessibility and Lipid Digestion in Emulsions: Influence of Pectin Type and Degree of Methyl‐Esterification
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Tina A.J. Verrijssen Stefanie Christiaens Sarah H.E. Verkempinck Jeroen Boeve Tara Grauwet Ann M. Van Loey Laura Salvia‐Trujillo Marc E. Hendrickx 《Journal of food science》2016,81(10):C2327-C2336
Citrus pectin (CP) and sugar beet pectin (SBP) were demethoxylated and fully characterized in terms of pectin properties in order to investigate the influence of the pectin degree of methyl‐esterification (DM) and the pectin type on the in vitro β‐carotene bioaccessibility and lipid digestion in emulsions. For the CP based emulsions containing β‐carotene enriched oil, water and pectin, the β‐carotene bioaccessibility, and lipid digestion were higher in the emulsions with pectin with a higher DM (57%; “CP57 emulsion”) compared to the emulsions with pectin with a lower DM (30%; “CP30 emulsion”) showing that the DM plays an important role. In contrast, in SBP‐based emulsions, nor β‐carotene bioaccessibility nor lipid digestion were dependent on pectin DM. Probably here, other pectin properties are more important factors. It was observed that β‐carotene bioaccessibility and lipid digestion were lower in the CP30 emulsion in comparison with the CP57, SBP32, and SBP58 emulsions. However, the β‐carotene bioaccessibility of CP57 emulsion was similar to that of the SBP emulsions, whereas the lipid digestion was not. It seems that pectin type and pectin DM (in case of CP) are determining which components can be incorporated into micelles. Because carotenoids and lipids have different structures and polarities, their incorporation may be different. This knowledge can be used to engineer targeted (digestive) functionalities in food products. If both high β‐carotene bioaccessibility and high lipid digestion are targeted, SBP emulsions are the best options. The CP57 emulsion can be chosen if high β‐carotene bioaccessibility but lower lipid digestion is desired. 相似文献