206 research outputs found
Amyloid-like aggregates sequester numerous metastable proteins with essential cellular functions
Protein aggregation is linked with neurodegeneration and numerous other diseases by mechanisms that are not well understood. Here, we have analyzed the gain-of-function toxicity of artificial ÎČ sheet proteins that were designed to form amyloid-like fibrils. Using quantitative proteomics, we found that the toxicity of these proteins in human cells correlates with the capacity of their aggregates to promote aberrant protein interactions and to deregulate the cytosolic stress response. The endogenous proteins that are sequestered by the aggregates share distinct physicochemical properties: They are relatively large in size and significantly enriched in predicted unstructured regions, features that are strongly linked with multifunctionality. Many of the interacting proteins occupy essential hub positions in cellular protein networks, with key roles in chromatin organization, transcription, translation, maintenance of cell architecture and protein quality control. We suggest that amyloidogenic aggregation targets a metastable subproteome, thereby causing multifactorial toxicity and, eventually, the collapse of essential cellular functions. PaperFlick: © 2011 Elsevier Inc
Evaporative attachment of slow electrons to alkali nanoclusters
The abundance spectrum of Na^-_{n~7-140} anions formed by low energy electron
attachment to free nanoclusters is measured to be strongly and nontrivially
restructured with respect to the neutral precursor beam. This restructuring is
explained in quantitative detail by a general framework of evaporative
attachment: an electron is captured by the long-range polarization potential,
its energy is transferred into thermal vibrations, and dissipated by
evaporative cooling. The data also affirm a formulated relation between the
binding energies of cationic, neutral, and anionic clusters, and an adjustment
to the prior values of dimer evaporation energies.Comment: 9 pages, 3 figures, revise
Collecting Service-Based Maintainability Metrics from RESTful API Descriptions: Static Analysis and Threshold Derivation
While many maintainability metrics have been explicitly designed for
service-based systems, tool-supported approaches to automatically collect these
metrics are lacking. Especially in the context of microservices,
decentralization and technological heterogeneity may pose challenges for static
analysis. We therefore propose the modular and extensible RAMA approach
(RESTful API Metric Analyzer) to calculate such metrics from machine-readable
interface descriptions of RESTful services. We also provide prototypical tool
support, the RAMA CLI, which currently parses the formats OpenAPI, RAML, and
WADL and calculates 10 structural service-based metrics proposed in scientific
literature. To make RAMA measurement results more actionable, we additionally
designed a repeatable benchmark for quartile-based threshold ranges (green,
yellow, orange, red). In an exemplary run, we derived thresholds for all RAMA
CLI metrics from the interface descriptions of 1,737 publicly available RESTful
APIs. Researchers and practitioners can use RAMA to evaluate the
maintainability of RESTful services or to support the empirical evaluation of
new service interface metrics.Comment: Accepted at CSE/QUDOS workshop (collocated with ECSA 2020
Excited States of Proton-bound DNA/RNA Base Homo-dimers: Pyrimidines
We are presenting the electronic photo fragment spectra of the protonated
pyrimidine DNA bases homo-dimers. Only the thymine dimer exhibits a well
structured vibrational progression, while protonated monomer shows broad
vibrational bands. This shows that proton bonding can block some non radiative
processes present in the monomer.Comment: We acknowledge the use of the computing facility cluster GMPCS of the
LUMAT federation (FR LUMAT 2764
HLA-DRB1*07:01-HLA-DQA1*02:01-HLA-DQB1*02:02 haplotype is associated with a high risk of asparaginase hypersensitivity in acute lymphoblastic leukemia
Hypersensitivity reactions are the most frequent dose-limiting adverse reactions to Escherichia coli-derived asparaginase in pediatric acute lymphoblastic leukemia (ALL) patients. The aim of the present study was to identify associations between sequence-based Human Leukocyte Antigen Class II region alleles and asparaginase hypersensitivity in a Hungarian ALL population. Four-digit typing of HLA-DRB1 and HLA-DQB1 loci was performed in 359 pediatric ALL patients by using next-generation sequencing method. Based on genotypic data of the two loci, haplotype reconstruction was carried out. In order to investigate the possible role of the HLA-DQ complex, the HLA-DQA1 alleles were also inferred. Multivariate logistic regression analysis and a Bayesian network-based approach were applied to identify relevant genetic risk factors of asparaginase hypersensitivity. Patients with HLA-DRB1*07:01 and HLA-DQB1*02:02 alleles had significantly higher risk of developing asparaginase hypersensitivity compared to non-carriers [P=4.56Ă10â5; OR=2.86 (1.73â4.75) and P=1.85Ă10â4; OR=2.99 (1.68â5.31); n=359, respectively]. After haplotype reconstruction, the HLA-DRB1*07:01-HLA-DQB1*02:02 haplotype was associated with an increased risk. After inferring the HLA-DQA1 alleles the HLA-DRB1*07:01âHLA-DQA1*02:01âHLA-DQB1*02:02 haplotype was associated with the highest risk of asparaginase hypersensitivity [P=1.22Ă10â5; OR=5.00 (2.43â10.29); n=257]. Significantly fewer T-cell ALL patients carried the HLA-DQB1*02:02 allele and the associated haplotype than did pre-B-cell ALL patients (6.5%; vs. 19.2%, respectively; P=0.047). In conclusion, we identified a haplotype in the Human Leukocyte Antigen Class II region associated with a higher risk of asparaginase hypersensitivity. Our results confirm that variations in HLA-D region might influence the development of asparaginase hypersensitivity
Developmental and evolutionary assumptions in a study about the impact of premature birth and low income on motherâinfant interaction
In order to study the impact of premature
birth and low income on motherâinfant interaction, four Portuguese samples were gathered: full-term, middle-class (n=99); premature, middle-class (n=63); full-term, low income (n=22); and premature, low income (n=21). Infants were filmed in a free play situation with their mothers, and the results were scored using the CARE Index. By means of multinomial regression analysis, social economic status (SES) was found to be the best predictor of maternal sensitivity and infant cooperative behavior within a set of medical and social factors. Contrary to the expectations of the cumulative risk perspective, two factors of risk (premature birth together with low SES) were as negative
for motherâinfant interaction as low SES solely. In this study, as previous studies have shown, maternal sensitivity and infant cooperative behavior were highly correlated, as was maternal control with infant compliance. Our results further indicate that, when maternal lack of responsiveness
is high, the infant displays passive behavior, whereas when the maternal lack of responsiveness is medium, the infant
displays difficult behavior. Indeed, our findings suggest that, in these cases, the link between types of maternal and infant interactive behavior is more dependent on the degree of maternal lack of responsiveness than it is on birth status
or SES. The results will be discussed under a developmental and evolutionary reasonin
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