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21.
Andreas Brodehl Alexey Meshkov Roman Myasnikov Anna Kiseleva Olga Kulikova Brbel Klauke Evgeniia Sotnikova Caroline Stanasiuk Mikhail Divashuk Greta Marie Pohl Maria Kudryavtseva Karin Klingel Brenda Gerull Anastasia Zharikova Jan Gummert Sergey Koretskiy Stephan Schubert Elena Mershina Anna Grtner Polina Pilus Kai Thorsten Laser Valentin Sinitsyn Sergey Boytsov Oxana Drapkina Hendrik Milting 《International journal of molecular sciences》2021,22(7)
About 50% of patients with arrhythmogenic cardiomyopathy (ACM) carry a pathogenic or likely pathogenic mutation in the desmosomal genes. However, there is a significant number of patients without positive familial anamnesis. Therefore, the molecular reasons for ACM in these patients are frequently unknown and a genetic contribution might be underestimated. Here, we used a next-generation sequencing (NGS) approach and in addition single nucleotide polymor-phism (SNP) arrays for the genetic analysis of two independent index patients without familial medical history. Of note, this genetic strategy revealed a homozygous splice site mutation (DSG2–c.378+1G>T) in the first patient and a nonsense mutation (DSG2–p.L772X) in combination with a large deletion in DSG2 in the second one. In conclusion, a recessive inheritance pattern is likely for both cases, which might contribute to the hidden medical history in both families. This is the first report about these novel loss-of-function mutations in DSG2 that have not been previously identi-fied. Therefore, we suggest performing deep genetic analyses using NGS in combination with SNP arrays also for ACM index patients without obvious familial medical history. In the future, this finding might has relevance for the genetic counseling of similar cases. 相似文献
22.
Dr. Heike M. Kropp Dr. Samra Ludmann Dr. Kay Diederichs Dr. Karin Betz Dr. Andreas Marx 《Chembiochem : a European journal of chemical biology》2021,22(21):3060-3066
With increasing temperature, nucleobases in DNA become increasingly damaged by hydrolysis of exocyclic amines. The most prominent damage includes the conversion of cytosine to uracil and adenine to hypoxanthine. These damages are mutagenic and put the integrity of the genome at risk if not repaired appropriately. Several archaea live at elevated temperatures and thus, are exposed to a higher risk of deamination. Earlier studies have shown that DNA polymerases of archaea have the property of sensing deaminated nucleobases in the DNA template and thereby stalling the DNA synthesis during DNA replication providing another layer of DNA damage recognition and repair. However, the structural basis of uracil and hypoxanthine sensing by archaeal B-family DNA polymerases is sparse. Here we report on three new crystal structures of the archaeal B-family DNA polymerase from Thermococcus kodakarensis (KOD) DNA polymerase in complex with primer and template strands that have extended single stranded DNA template 5’-overhangs. These overhangs contain either the canonical nucleobases as well as uracil or hypoxanthine, respectively, and provide unprecedented structural insights into their recognition by archaeal B-family DNA polymerases. 相似文献
23.
The influence of nonsolvent, crystallinity of the polymer film, and addition of dodecane (a poor solvent for the polymer and for the nonsolvent) on the morphology of polylactides films has been investigated and was related to phase separation behavior. Both amorphous poly‐DL ‐lactide (PDLLA) and crystalline poly‐L ‐lactide (PLLA) were dissolved in dichloromethane, and subsequently films were made by immersion in nonsolvent baths. PDLLA gave dense films without any internal structure, since the structure was not solidified by crystallization or glassification. PLLA films show varying structure depending on the nonsolvent. With methanol, asymmetric morphologies were observed as a result from combined liquid‐liquid demixing and crystallization, while with water symmetric spherulitic structures were formed. As a next step, dodecane was added, which is not miscible with the nonsolvent, and we found it to have a strong influence on the morphology of the films. The PDLLA films with dodecane did not collapse: a closed cell structure was obtained. In PLLA films, dodecane speeds up phase separation and induces faster crystallization in the films, and the porosity, size of the pores, and interconnectivity increased. When the PLLA solutions were subjected to a heat pretreatment, crystallization could be postponed, which yielded a cellular structure around dodecane, which did not contain spherulites anymore. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 104: 959–971, 2007 相似文献
24.
25.
Karin Yaccato Alfred Hagemeyer Andreas Lesik Anthony Volpe Henry Weinberg 《Topics in Catalysis》2004,(1):127-132
High-throughput synthesis and screening methods have been developed for the discovery of highly active lead compounds for the selective catalytic reduction as well as direct decomposition of NO in the temperature range 200–300 °C. The discovery libraries for primary screening consisted of 16 × 16 catalyst arrays on 4in. square quartz wafers. Catalysts were prepared by robotic liquid dispensing techniques and screened for catalytic activity in Symyx' scanning mass spectrometer. The scanning mass spectrometer is a fast serial screening tool that uses flat wafer catalyst surfaces, local laser heating, a scanning/sniffing nozzle and a quadrupolar mass spectrometer to compare relative catalytic activities. The feed consisted of NO/NH3 mixtures with optional O2 cofeed and Kr as the internal standard in Ar carrier gas. QMS detection allowed for tracking of H2O, N2, NO, O2, N2O and Kr. Screening protocols for catalytic materials encompassed metal precursors and carriers for supported vanadia systems, extensive doping of V2O5/TiO2, and broad screening of mixed redox metal oxides and supported base and noble metal systems. More than 500 samples could be screened in a single day. Active hits (high NO consumption accompanied by corresponding N2 production) identified in discovery libraries were re-synthesized as focus libraries for lead confirmation and further optimization. These libraries used shallower compositional gradients, for example 56 points (compositions) per ternary, with four 56-point ternaries per 4in. wafer. Broad screening ternaries were generally 8 or 15 points. The focus libraries more clearly reveal the trends and provide guidelines for secondary screening and scale-up. High conversions were achieved in scanning mass spectrometer so the scalability risk is small for the short contact time reactions. 相似文献
26.
Roderick Bloem Krishnendu Chatterjee Karin Greimel Thomas A. Henzinger Georg Hofferek Barbara Jobstmann Bettina Könighofer Robert Könighofer 《Acta Informatica》2014,51(3-4):193-220
Systems should not only be correct but also robust in the sense that they behave reasonably in unexpected situations. This article addresses synthesis of robust reactive systems from temporal specifications. Existing methods allow arbitrary behavior if assumptions in the specification are violated. To overcome this, we define two robustness notions, combine them, and show how to enforce them in synthesis. The first notion applies to safety properties: If safety assumptions are violated temporarily, we require that the system recovers to normal operation with as few errors as possible. The second notion requires that, if liveness assumptions are violated, as many guarantees as possible should be fulfilled nevertheless. We present a synthesis procedure achieving this for the important class of GR(1) specifications, and establish complexity bounds. We also present an implementation of a special case of robustness, and show experimental results. 相似文献
27.
Chengyun Yue J. Milton Harris Per-Erik Hellberg Karin Bergstrom 《Journal of the American Oil Chemists' Society》1996,73(7):841-845
A series of noncyclic acetal-linked cleavable surfactants were simply prepared by condensation of aldehydes with poly(ethylene
glycol) monomethyl ethers. All of the products were characterized by1H nuclear magnetic resonance. Their hydrophile-lipophile balance, surface tension, cloud point, critical micelle concentration,
and foam height were determined. Hydrolysis kinetic studies, followed by gas chromatography, showed that they had higher hydrolytic
reactivity in acidic solution than cyclic acetal-linked cleavable surfactants. 相似文献
28.
The mechanical properties of moist samples of fine, polydisperse powders are investigated by measuring the tensile strength by a diametrical compression test and the stress—strain relationship of samples exposed to uniaxial compression. The strengths determined by the two methods correlate well. The strength of moist samples compressed to porosities comparable to the level of intragranular porosities achieved by granulation in high-speed mixers is shown to be influenced significantly by particle interactions in addition to mobile liquid bondings. For a particular material the strength is controlled mainly by porosity and liquid saturation. It is shown that the effect of a growing liquid saturation is to reduce particle interactions and thus to facilitate densification during granulation. The deformability of moist samples, which is dependent on strength and deformation behaviour, is assessed for lactose and dicalcium phosphate. 相似文献
29.
Maria Luz Fernandez A. Karin Conde Laura R. Ruiz Carlos Montano John Ebner Donald J. McNamara 《Lipids》1995,30(7):619-626
To test the effects of exchanging dietary complex and simple carbohydrate for fat calories on lipoprotein metabolism, guinea
pigs were fed two different fat/carbohydrate ratios: 2.5∶58% (w/w) or 25∶29% (w/w) with either sucrose or starch as the carbohydrate
source. Animals fed high-fat had higher plasma low-density lipoprotein (LDL) and hepatic cholesterol concentrations than animals
fed low-fat diets (P<0.01). The cholesteryl ester content per particle was higher, and the number of triacylglycerol (TAG) molecules was lower
in very low density lipoprotein (VLDL) and LDL from animals fed high-fat diets. Intake of high-fat/sucrose resulted in higher
plasma LDL concentrations than intake of high-fat/starch, and animals fed low-fat/starch had the highest plasma TAG concentrations
associated with VLDL particles containing more TAG molecules, as well as a TAG-enriched LDL. The activity of plasma lecithin
cholesteryl:acyl transferase (LCAT) was highest in animals fed high-fat/sucrose, and heart lipoprotein lipase (LPL) activity
was higher in animals fed high-fat diets. Hepatic apoprotein B/E (apo B/E) receptor number (Bmax) was increased 21% with low-fat diets (P<0.01). These results suggest that the hypercholesterolemia induced by high-fat and by sucrose intake are associated with
a higher plasma LCAT activity which results in a cholesteryl ester-enriched VLDL which, by the action of LPL, might be more
readily converted to LDL through the delipidation cascade leading to downregulation of hepatic apo B/E receptors. The hypertriglyceridemia
associated with low-fat intake may result from increased production of VLDL TAG, which would explain the increased TAG content
and the higher TAG/CE ratio of VLDL from animals fed the low-fat/starch diet. 相似文献
30.
Hong?ZhangEmail author Lars?Saaby?Pedersen Dorther?Kristensen Jens?Adler-Nissen Hans?Christian Holm 《Journal of the American Oil Chemists' Society》2004,81(7):653-658
Lipozyme TL IM-catalyzed interesterification for the modification of margarine fats was carried out in a batch reactor at
70°C with a lipase dosage of 4%. Solid fat content (SFC) was used to monitor the reaction progress. Lipase-catalyzed interesterification,
which led to changes in the SFC, was assumed to be a first-order reversible reaction. Accordingly, the change in SFC vs. reaction
time was described by an exponential model. The model contained three parameters, each with a particular physical or chemical
meaning: (i) the initial SFC (SFC0), (ii) the change in SFC (ΔSFC) from the initial to the equilibrium state, and (iii) the reaction rate constant value (k). SFCo and ΔSFC were related to only the types of blends and the blend ratios. The rate constant k was related to lipase activity on a given oil blend. Evaluation of the model was carried out with two groups of oil blends,
i.e., palm stearin/coconut oil in weight ratios of 90∶10, 80∶20, and 70∶30, and soybean oil/fully hydrogenated soybean oil
in weight ratios of 80∶20, 65∶35, and 50∶50. Correlation coefficients higher than 0.99 between the experimental and predicted
values were observed for SFC at temperatures above 30°C. The model is useful for predicting changes in the SFC during lipase-catalyzed
interesterification with a selected group of oil blends. It also can be used to control the process when particular SFC values
are targeted. 相似文献