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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.
Laura K. Finnegan Naomi Chadderton Paul F. Kenna Arpad Palfi Michael Carty Andrew G. Bowie Sophia Millington-Ward G. Jane Farrar 《International journal of molecular sciences》2022,23(3)
The challenge of developing gene therapies for genetic forms of blindness is heightened by the heterogeneity of these conditions. However, mechanistic commonalities indicate key pathways that may be targeted in a gene-independent approach. Mitochondrial dysfunction and axon degeneration are common features of many neurodegenerative conditions including retinal degenerations. Here we explore the neuroprotective effect afforded by the absence of sterile alpha and Toll/interleukin-1 receptor motif-containing 1 (SARM1), a prodegenerative NADase, in a rotenone-induced mouse model of retinal ganglion cell loss and visual dysfunction. Sarm1 knockout mice retain visual function after rotenone insult, displaying preservation of photopic negative response following rotenone treatment in addition to significantly higher optokinetic response measurements than wild type mice following rotenone. Protection of spatial vision is sustained over time in both sexes and is accompanied by increased RGC survival and additionally preservation of axonal density in optic nerves of Sarm1−/− mice insulted with rotenone. Primary fibroblasts extracted from Sarm1−/− mice demonstrate an increased oxygen consumption rate relative to those from wild type mice, with significantly higher basal, maximal and spare respiratory capacity. Collectively, our data indicate that Sarm1 ablation increases mitochondrial bioenergetics and confers histological and functional protection in vivo in the mouse retina against mitochondrial dysfunction, a hallmark of many neurodegenerative conditions including a variety of ocular disorders. 相似文献
73.
Presented here is an investigation of the structure–property relationships of crosslinked networks using three bi-functional glycidyl ether aromatic epoxy resins, two bi-aryl and one tri-aryl, cured with bi- and tri-aryl amines. Subtle changes to the monomer chemistry including changing aromatic substitution patterns from meta to para, methylene to isopropyl and isopropyl to ether were explored. Changing an epoxy resin backbone from methylene to isopropyl enhances backbone rigidity thus increasing glass transition temperature (Tg), yield strength, and strain despite reducing modulus. Changing meta-substitution to para increases Tg and yield strain while leaving strength unaffected and reducing modulus. Changing isopropyl linkages to ether reduces modulus, strength, Tg, and yield strain reflecting increased molecular flexibility. Using three instead of two aromatic rings increases the molecular weight between crosslinks thereby decreasing Tg and yield strain while increasing modulus and strength. Despite the complexities of multiple systems for varying epoxy resins and amine hardeners, the effect upon network properties is explained in terms of short- and long-range molecular and segmental mobility, crosslink density, and equilibrium packing density. © 2020 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48874. 相似文献
74.
Additive manufacturing, sometimes referred to as 3D printing is a new, rapidly developing technology which has the potential to revolutionize fabrication of certain high value, complex products. Until now conventional elastomers have not been widely used in the additive manufacturing process. The goal of our work was to determine the feasibility of additive manufacturing using ink jet printing of elastomeric latex materials. Particle size, viscosity, and surface tension were measured for five different latex materials—poly(2‐chloro‐1,3‐butadiene), carboxylated styrene‐butadiene rubber, carboxylated butadiene‐acrylonitrile copolymer, natural rubber, and prevulcanized natural rubber. The XSBR latex was predicted as the one most likely to be printable. Printing trials carried out with the XSBR as the ink proved it to be printable, although technical problems of agglomeration and print head clogging need to be addressed and both the material and process need to be optimized for consistent printing to be achieved. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 42931. 相似文献
75.
Low rates of triacylglycerol (TAG) biosynthesis were observed in cell-free extracts ofCandida curvata, but rates were increased up to 10-fold by adding either α- or β-cyclodextrins. Spheroplasts, whole or gently disrupted,
had higher rates of incorporation of both [U-14C]glycerol 3-phosphate or [1-14C]oleate into triacylglycerol and the intermediates of its biosynthesis: lysophosphatic acid, phosphatidic acid and diacylglycerol.
Fatty acyl-CoA synthetase was highest with palmitate, oleate and linoleate but was some 6- to 8-fold lower with stearate.
Stearate and stearoyl-CoA were poorly incorporated into lipids. Subcellular fractionation of the spheroplasts into mitochondrial,
microsomal, lipid bodies and supernatant fractions diminished the rates of14C incorporation of oleate into triacylglycerol. By comparing the relative specific activities for each activity in each fraction,
the fatty acyl-CoA synthetase activity appeared mainly in the lipid bodies, and that for phosphatidic acid formation was mainly
in the mitochondrion; other activities were too weak and too dispersed for accurate assessment of their location. Recombining
all the subcellular fractions restored triacylglycerol synthesizing activity. Omitting any single fraction from the mixture
did not result in restoration of triacylglycerol synthesizing activity. Starvation of the yeast, which leads to utilization
of the endogenous lipid reserves, stimulated fatty acyl-CoA synthetase activity, but diminished phosphatidic acid and triacylglycerol
biosynthesis indicating probable induction of β-oxidation in the peroxisomes and repression of lipid biosynthesis. 相似文献
76.
简·欧文景观设计事务所 《风景园林》2017,24(3):59-65
<正>切尔西街游乐场位于悉尼市内东雷德福区中心地带,是散布在该区域内的一系列小型公园中的一个。这些公园作为城市的公共区域,在某种程度上犹如戏剧中的配角一般并不夺人眼球,却是城市格局中至关重要的一部分,成为强调道路网络的日常活动空间。附近有更大的公园和游乐场,承载更有活力的 相似文献
77.
Graphene nanosheets were synthesized in large quantities using a chemical approach. Field emission electron microscope observation revealed that loose graphene nanosheets agglomerated and crumpled naturally into shapes resembling flower-petals. High resolution transmission electron microscope analysis, Raman spectroscopy and ultraviolet-visible spectroscopy measurements confirmed the graphitic crystalline structure of the graphene nanosheets. The nanosheets exhibited an enhanced lithium storage capacity as anodes in lithium-ion cells and good cyclic performance. 相似文献
78.
Wilhelmina Kalt Shawna MacKinnon Jane McDonald Melinda Vinqvist Cheryl Craft Amy Howell 《Journal of the science of food and agriculture》2008,88(1):68-76
The concentrations and profiles of phenolics of selected fruit crops common in the Western diet, including several Vaccinium species, were examined to better understand how these crops may be useful sources of phenolic phytochemicals. Vaccinium fruit had a high phenolic concentration compared to non‐Vaccinium fruit. Some Vaccinium fruit were particularly rich in certain phenolic subgroups, especially anthocyanins and pro‐anthocyanidins. Among the pro‐anthocyanidin oligomers measured using fluorometric and mass spectroscopic detection, the trimers and tetramers were most abundant, while pro‐anthocyanidins with a degree of polymerization greater than 8 were least abundant. As biomedical studies determine which phenolic structures are associated with particular bioactivities, information on the phenolic concentration and profile of selected species will be useful in developing specific uses for fruit crops in human health. Methods were compared to assess the usefulness of simpler versus more sophisticated means of phenolic analysis. The phenolic components of fruit extracts were purified approximately 20‐fold, and not qualitatively altered, by C18 solid‐phase extraction. However, fruit extracts obtained from C18 solid‐phase extraction differed in their relative abundance of phenolic components. Colorimetric and HPLC‐DAD measures of phenolic concentration were correlated (R2 = 0.79), as was pro‐anthocyanidin concentration detected fluorometrically and by mass spectrometry (R2 = 0.44). Copyright © 2007 Crown in the right of Canada and Society of Chemical Industry 相似文献
79.
Jong-Tae Park Antonius Suwanto Irawan Tan Tommy Nuryanto Rudy Lukman Kan Wang Jay-lin Jane 《Food science and biotechnology》2014,23(1):125-132
An α-amylase gene was cloned from the thermophilic bacterium Bacillus subtilis isolated from Indonesian oil palm shell waste. The gene expressed an extracellular enzyme. Optimal hydrolysis conditions for the enzyme were 70°C and pH 6.0. The specific activity of the enzyme was 16.0 kU per mg of protein, which was higher than for other thermostable amylases. Hydrolytic products of the enzyme using starch and glycogen were mainly maltohexaose and maltopentaose. The enzyme had a K m value of 0.099 mg/mL for amylopectin, more than 10 times lower than for amylose. The catalytic efficiency of the enzyme using amylopectin was 39,200 mL/mg·s and was 3,270 mL/mg·s using amylose. The enzyme liquefied corn starch at pH 5.0, which was successfully converted to glucose using commercial glucoamylase and pullulanase without pH adjustment. The enzyme has advantages for industrial applications. 相似文献
80.
Humphreys Glyn W.; Wulff Melanie; Yoon Eun Young; Riddoch M. Jane 《Canadian Metallurgical Quarterly》2010,36(3):659
Two experiments are reported that use patients with visual extinction to examine how visual attention is influenced by action information in images. In Experiment 1 patients saw images of objects that were either correctly or incorrectly colocated for action, with the objects held by hands that were congruent or incongruent with those used premorbidly by the patients. The images were also shown from a 1st- and 3rd-person perspective. There was an overall reduction in extinction for objects colocated for action. In addition, there was an extra benefit when the objects were held in hands congruent with those used by the patients and when the objects were seen from a 1st-person perspective. This last result fits with an effect of motor simulation, over and above a purely visual effect based on positioning objects correctly for action. Experiment 2 showed that effects of hand congruence could emerge with images depicted from a 3rd-person perspective when patients saw themselves holding the objects. The data indicate 2 effects of action information on extinction: (a) an effect of colocating objects for action, which does not depend on a self-reference frame (a visual effect), and (b) an effect sensitive to object–hand congruence, which does depend on a self-reference frame (a motor-based effect). The self-reference frame is induced when stimuli are viewed from a 1st-person perspective and when an image of the self is seen from a 3rd-person perspective. Both visual and motor-based effects of action information facilitate the spread of attention across objects. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献