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71.
Kirk A. J. Stephenson Julia Zhu Adrian Dockery Laura Whelan Toms Burke Jacqueline Turner James J. OByrne G. Jane Farrar David J. Keegan 《International journal of molecular sciences》2022,23(2)
Although rare, inherited retinal degenerations (IRDs) are the most common reason for blind registration in the working age population. They are highly genetically heterogeneous (>300 known genetic loci), and confirmation of a molecular diagnosis is a prerequisite for many therapeutic clinical trials and approved treatments. First-tier genetic testing of IRDs with panel-based next-generation sequencing (pNGS) has a diagnostic yield of ≈70–80%, leaving the remaining more challenging cases to be resolved by second-tier testing methods. This study describes the phenotypic reassessment of patients with a negative result from first-tier pNGS and the rationale, outcomes, and cost of second-tier genetic testing approaches. Removing non-IRD cases from consideration and utilizing case-appropriate second-tier genetic testing techniques, we genetically resolved 56% of previously unresolved pedigrees, bringing the overall resolve rate to 92% (388/423). At present, pNGS remains the most cost-effective first-tier approach for the molecular assessment of diverse IRD populations Second-tier genetic testing should be guided by clinical (i.e., reassessment, multimodal imaging, electrophysiology), and genetic (i.e., single alleles in autosomal recessive disease) indications to achieve a genetic diagnosis in the most cost-effective manner. 相似文献
72.
Alexander Balatskiy Ilia Ozhimalov Maria Balatskaya Alexandra Savina Julia Filatova Natalia Kalinina Vladimir Popov Vsevolod Tkachuk 《International journal of molecular sciences》2022,23(3)
The local development of atherosclerotic lesions may, at least partly, be associated with the specific cellular composition of atherosclerosis-prone regions. Previously, it was demonstrated that a small population of immature vascular smooth muscle cells (VSMCs) expressing both CD146 and neuron-glial antigen 2 is postnatally sustained in atherosclerosis-prone sites. We supposed that these cells may be involved in atherogenesis and can continuously respond to angiotensin II, which is an atherogenic factor. Using immunohistochemistry, flow cytometry, wound migration assay xCELLigence system, and calcium imaging, we studied the functional activities of immature VSMCs in vitro and in vivo. According to our data, these cells do not express nestin, CD105, and the leptin receptor. They are localized in atherosclerosis-prone regions, and their number increases with age, from 5.7% to 23%. Immature VSMCs do not migrate to low shear stress areas and atherosclerotic lesions. They also do not have any unique response to angiotensin II. Thus, despite the localization of immature VSMCs and the presence of the link between their number and age, our study did not support the hypothesis that immature VSMCs are directly involved in the formation of atherosclerotic lesions. Additional lineage tracing studies can clarify the fate of these cells during atherogenesis. 相似文献
73.
Amalia Ruiz-Serrano Christina N. Boyle Josep M. Monn Rodríguez Julia Günter Agnieszka E. Jucht Svende Pfundstein Andreas M. Bapst Thomas A. Lutz Roland H. Wenger Carsten C. Scholz 《International journal of molecular sciences》2022,23(3)
Dysregulated energy metabolism is a major contributor to a multitude of pathologies, including obesity and diabetes. Understanding the regulation of metabolic homeostasis is of utmost importance for the identification of therapeutic targets for the treatment of metabolically driven diseases. We previously identified the deubiquitinase OTUB1 as substrate for the cellular oxygen sensor factor-inhibiting HIF (FIH) with regulatory effects on cellular energy metabolism, but the physiological relevance of OTUB1 is unclear. Here, we report that the induced global deletion of OTUB1 in adult mice (Otub1 iKO) elevated energy expenditure, reduced age-dependent body weight gain, facilitated blood glucose clearance and lowered basal plasma insulin levels. The respiratory exchange ratio was maintained, indicating an unaltered nutrient oxidation. In addition, Otub1 deletion in cells enhanced AKT activity, leading to a larger cell size, higher ATP levels and reduced AMPK phosphorylation. AKT is an integral part of insulin-mediated signaling and Otub1 iKO mice presented with increased AKT phosphorylation following acute insulin administration combined with insulin hypersensitivity. We conclude that OTUB1 is an important regulator of metabolic homeostasis. 相似文献
74.
Anna Stauff Julia Schnapka Frank Heckel Reinhard Matissek 《European Journal of Lipid Science and Technology》2020,122(7)
Mineral oil hydrocarbons (MOH) are present in many fats and oils as well as foods prepared thereof. A survey of mineral oil saturated hydrocarbons (MOSH) and mineral oil aromatic hydrocarbons (MOAH) in different types of vegetable fats and oils is reported. Contents of MOSH/MOAH were quantified using liquid chromatography online‐coupled to gas chromatography with flame‐ionization detection (LC‐GC‐FID). Cocoa butter (n = 142) showed levels from <LOQ (2.5 mg kg?1) to 162 mg kg?1 ΣMOSH (sum of C10–C50) and <LOQ to 55 mg kg?1 ΣMOAH, in palm oil (n = 21) ΣMOSH were quantified from <LOQ to 124 mg kg?1 and ΣMOAH from <LOQ to 39 mg kg?1. Sunflower oil showed lower levels: ΣMOSH were determined in the range of <LOQ to 17 mg kg?1 and MOAH were not observed at all. A possible influence of deodorization and a subsequent minimization of MOSH/MOAH was investigated. Systematic model‐experiments were performed on laboratory scale using spiked cocoa butter. Significant minimization of volatile MOH subfractions ≤C24 were observed at a deodorization temperature of 210 °C. Deodorization can be considered as an important processing step to reduce or even remove volatile MOSH/MOAH ≤C24. Practical Applications: Regardless of their possible entry routes into the food chain, volatile fractions of MOSH/MOAH can be removed by deodorizing vegetable fats and oils. This model‐study identifies the temperatures of deodorization that provide a significant improvement toward minimization of undesired MOSH/MOAH. 相似文献
75.
Characterization of products from fast and isothermal hydrothermal liquefaction of microalgae 下载免费PDF全文
Julia L. Faeth Phillip E. Savage Jacqueline M. Jarvis Amy M. McKenna Phillip E. Savage 《American Institute of Chemical Engineers》2016,62(3):815-828
We investigated nonisothermal (fast) and nominally isothermal hydrothermal liquefaction (HTL) of Nannochloropsis sp. microalgae for the production of biocrude. Biocrude yields ranged from 36 to 45 wt % (dry weight), with fast HTL with low mass loading giving the highest yield. This condition also gave the biocrude with the lowest heating value, which indicates there are compromises to be made between biocrude quantity and quality. The aqueous phase and biocrude product fractions were characterized using elemental analysis and Fourier transform ion cyclotron resonance mass spectrometry (FT‐ICR MS). This detailed level of analysis identified more than 30,000 unique molecular products. The aqueous phase products included compounds with the same molecular formulae as known herbicides, which may inform efforts in genetic engineering of algae and/or bacteria for cultivation on the aqueous phase. This detailed molecular‐level characterization provides some clues regarding the types of reactions that may take place during HTL. © 2016 American Institute of Chemical Engineers AIChE J, 62: 815–828, 2016 相似文献
76.
Application of β-Sitosterol + γ-Oryzanol-Structured Organogel as Migration Barrier in Filled Chocolate Products 下载免费PDF全文
Alexandra Wendt Karin Abraham Christin Wernecke Julia Pfeiffer Eckhard Flöter 《Journal of the American Oil Chemists' Society》2017,94(9):1131-1140
Oil migration in filled pralines is a phenomenon that is highly correlated with the occurrence of chocolate bloom. In this study the potential to suppress or prevent oil migration by incorporation of sterol/sterolster-structured organogels was evaluated. Different quantities, 2.5 or 14% (w/w), of gel with structurant levels of either 10 or 25% (w/w) were studied in a layered model system. The gel was either a part of the nougat or of the chocolate phase, or as a separate layer. Samples were monitored regularly for a period of 24 weeks at storage temperatures of 10, 18 and 28 °C. The amount of migrated oil was determined via DSC analysis of a surface sample. The results indicate that, despite the additional oil brought into the system via the oleogel, the level of oil found in the chocolate layer is reduced through the presence of the gel. In particular, the three-layer system and gelled chocolate appear to be promising routes to either suppress oil migration or improve nutritional profiles by incorporation of liquid oils. 相似文献
77.
Dr. Jessica S. Kelsey Dr. Tamas Geczy Nancy E. Lewin Dr. Noemi Kedei Colin S. Hill Julia S. Selezneva Christopher J. Valle Wonhee Woo Dr. Inna Gorshkova Dr. Peter M. Blumberg 《Chembiochem : a European journal of chemical biology》2014,15(8):1131-1144
The C1 domain, which represents the recognition motif on protein kinase C for the lipophilic second messenger diacylglycerol and its ultrapotent analogues, the phorbol esters, has emerged as a promising therapeutic target for cancer and other indications. Potential target selectivity is markedly enhanced both because binding reflects ternary complex formation between the ligand, C1 domain, and phospholipid, and because binding drives membrane insertion of the C1 domain, permitting aspects of the C1 domain surface outside the binding site, per se, to influence binding energetics. Here, focusing on charged residues identified in atypical C1 domains which contribute to their loss of ligand binding activity, we showed that increasing charge along the rim of the binding cleft of the protein kinase C δ C1 b domain raises the requirement for anionic phospholipids. Correspondingly, it shifts the selectivity of C1 domain translocation to the plasma membrane, which is more negatively charged than internal membranes. This change in localization is most pronounced in the case of more hydrophilic ligands, which provide weaker membrane stabilization than do the more hydrophobic ligands and thus contributes an element to the structure–activity relations for C1 domain ligands. Coexpressing pairs of C1‐containing constructs with differing charges each expressing a distinct fluorescent tag provided a powerful tool to demonstrate the effect of increasing charge in the C1 domain. 相似文献
78.
Crespo JF Retzek M Foetisch K Sierra-Maestro E Cid-Sanchez AB Pascual CY Conti A Feliu A Rodriguez J Vieths S Scheurer S 《Molecular nutrition & food research》2006,50(3):282-290
Oranges are clinically relevant allergenic foods. To date, orange allergens have not been characterized in detail. The study is aimed at analyzing the sensitization profile in orange-sensitized subjects with and without clinical allergy, and to identify orange allergens. Fifty-six sensitized subjects with self-reported reactions to orange were grouped into reactors (anaphylaxis or multiple episodes of immediate reactions and/or positive challenge tests) and non-reactors (negative open food challenge tests). Allergens were characterized by IgE immunoblotting, N-terminal sequencing, IgE-inhibition assays, and mediator release assays were performed to determine the allergenic potency of orange profilin. Of 56 subjects, 23 were classified as orange allergic showing mainly an oral allergy syndrome. Of 23 subjects classified as orange allergic, 22 were sensitized to profilin, Cit s 2. In patients with mono-sensitization to profilin in vitro histamine releases up to 75% from basophils were induced using orange extract and purified plant profilins. Of the allergic patients 78% were sensitized to germin-like protein, Cit s 1. Both allergens showed retained IgE reactivity in heat-processed orange juice. Interestingly, subjects with and without clinical allergy showed a comparable sensitization profile. Profilin and germin-like proteins are major orange allergens. The potential clinical relevance of orange profilin was indicated by its strong capacity to release histamine from basophils. However, a predominant sensitization to both allergens in subjects without symptoms also indicates a high frequency of clinically insignificant sensitization. 相似文献
79.
The concept of data in the humanistic academy carries a heavycultural freight: as a reductionist yet efficient representationof complex textual significance. Far from being an inventionof the digital age, this conception of the role of quantificationhas a prehistory whose terms continue to resonate in moderndebates about digital editing and digitally mediated scholarship.This essay explores these terms and the anxieties they reflect,concluding that digital representation is no less textuallyand methodologically rich, and no less a production of knowledge,than its print counterpart. 相似文献
80.
In this paper, a scheduling problem that occurs in potash mining is introduced, where a block excavation sequence has to be found taking into account a limited number of underground machines as well as safety-related restrictions. The aim is to minimize the maximum completion time of excavations, i.e., the makespan. The resulting problem can be transformed into a hybrid flow shop scheduling problem with reentry, unrelated machines, and job-precedences. A mixed-integer linear model is presented and small-scale instances are solved with CPLEX. In order to tackle medium- and large-scale instances heuristically, a basic and an advanced multi-start algorithm are developed, based on a specific priority rule-based construction procedure. In addition, a modified version of the Giffler and Thompson procedure is applied. Computational experiments are conducted on problem instances derived from real-world data in order to evaluate the performances of the proposed solution procedures. 相似文献