Search results for "MULT"
showing 10 items of 17528 documents
Analysis of substrate binding in individual active sites of bifunctional human ATIC
2018
Aminoimidazolecarboxamide ribonucleotide formyl transferase (AICARFT): Inosine monophosphate cyclohydrolase (IMPCH, collectively called ATIC) is a bifunctional enzyme that catalyses the penultimate and final steps in the purine de novo biosynthesis pathway. The bifunctional protein is dimeric and each monomer contains two different active sites both of which are capable of binding nucleotide substrates, this means to a potential total of four distinct binding events might be observed. Within this work we used a combination of site-directed and truncation mutants of ATIC to independently investigate the binding at these two sites using calorimetry. A single S10W mutation is sufficient to blo…
Identification of factors involved in dimorphism and pathogenicity of Zymoseptoria tritici
2017
A forward genetics approach was applied in order to investigate the molecular basis of morphological transition in the wheat pathogenic fungus Zymoseptoria tritici. Z. tritici is a dimorphic plant pathogen displaying environmentally regulated morphogenetic transition between yeast-like and hyphal growth. Considering the infection mode of Z. tritici, the switching to hyphal growth is essential for pathogenicity allowing the fungus the host invasion through natural openings like stomata. We exploited a previously developed Agrobacterium tumefaciens-mediated transformation (ATMT) to generate a mutant library by insertional mutagenesis including more than 10,000 random mutants. To identify gene…
Coupling News Sentiment with Web Browsing Data Improves Prediction of Intra-Day Price Dynamics
2015
The new digital revolution of big data is deeply changing our capability of understanding society and forecasting the outcome of many social and economic systems. Unfortunately, information can be very heterogeneous in the importance, relevance, and surprise it conveys, affecting severely the predictive power of semantic and statistical methods. Here we show that the aggregation of web users' behavior can be elicited to overcome this problem in a hard to predict complex system, namely the financial market. Specifically, our in-sample analysis shows that the combined use of sentiment analysis of news and browsing activity of users of Yahoo! Finance greatly helps forecasting intra-day and dai…
Quality enhancement of multispectral images for skin cancer optical diagnostics
2018
Melanoma is the least common but deadliest skin cancer, accounting for only about 1% of all cases, but is the cause of the vast majority of skin cancer death. In some parts of the world, especially among western countries, melanoma is becoming more common every year. The detection of melanoma in early stage can be helpful to cure it. Unfortunately, long ques and high prices for dermatology service can result in the skin cancer diagnosis at its later stage, thus increasing the risk of mortality for the patient. It is important to provide a non-invasive optical device for primary care physicians to help diagnose different skin malformation based on obtained optical images. Such device will be…
Vitamin D in malaria: more hypotheses than clues
2019
Abstract Vitamin D is a secosteroid hormone regulating calcium and phosphate metabolism, immune response and brain development. Low blood 25(OH)D levels have been reported in patients affected by infectious diseases caused by parasites, including malaria. Despite the high effectiveness of antimalarials, malaria is burdened with high morbidity and mortality, and the search for additional therapies is rapidly growing. Furthermore, available preventive measures have proved to be barely effective so far. Finding new prevention and therapy tools is a matter of urgency. Studies on animal models and humans have hypothesized some mechanisms by which the hormone can influence malaria pathogenesis, a…
Quantitative super-resolution localization microscopy of DNA in situ using Vybrant® DyeCycle™ Violet fluorescent probe.
2016
Single Molecule Localization Microscopy (SMLM) is a recently emerged optical imaging method that was shown to achieve a resolution in the order of tens of nanometers in intact cells. Novel high resolution imaging methods might be crucial for understanding of how the chromatin, a complex of DNA and proteins, is arranged in the eukaryotic cell nucleus. Such an approach utilizing switching of a fluorescent, DNA-binding dye Vybrant® DyeCycle™ Violet has been previously demonstrated by us (Żurek-Biesiada et al., 2015) [1]. Here we provide quantitative information on the influence of the chemical environment on the behavior of the dye, discuss the variability in the DNA-associated signal density,…
Targeting RNA structure in SMN2 reverses spinal muscular atrophy molecular phenotypes
2018
Modification of SMN2 exon 7 (E7) splicing is a validated therapeutic strategy against spinal muscular atrophy (SMA). However, a target-based approach to identify small-molecule E7 splicing modifiers has not been attempted, which could reveal novel therapies with improved mechanistic insight. Here, we chose as a target the stem-loop RNA structure TSL2, which overlaps with the 5′ splicing site of E7. A small-molecule TSL2-binding compound, homocarbonyltopsentin (PK4C9), was identified that increases E7 splicing to therapeutic levels and rescues downstream molecular alterations in SMA cells. High-resolution NMR combined with molecular modelling revealed that PK4C9 binds to pentaloop conformati…
Collective properties of viral infectivity
2018
Individual virions typically fail to infect cells. Such decoupling between virions and infectious units is most evident in multicomponent and other segmented viruses, but is also frequent in non-segmented viruses. Despite being a well-known observation, the causes and implications of low single-virion infectivity often remain unclear. In principle, this can originate from intrinsic genetic and/or structural virion defects, but also from host infection barriers that limit early viral proliferation. Hence, viruses may have evolved strategies to increase the per-virion likelihood of establishing successful infections. This can be achieved by adopting spread modes that elevate the multiplicity …
Increased survival of honeybees in the laboratory after simultaneous exposure to low doses of pesticides and bacteria
2018
Recent studies of honeybees and bumblebees have examined combinatory effects of different stressors, as insect pollinators are naturally exposed to multiple stressors. At the same time the potential influences of simultaneously occurring agricultural agents on insect pollinator health remain largely unknown. Due to different farming methods, and the drift of applied agents and manure, pollinators are most probably exposed to insecticides but also bacteria from organic fertilizers at the same time. We orally exposed honeybee workers to sub-lethal doses of the insecticide thiacloprid and two strains of the bacterium Enterococcus faecalis, which can occur in manure from farming animals. Our re…
S-Aligner: Ultrascalable Read Mapping on Sunway Taihu Light
2017
The availability and amount of sequenced genomes have been rapidly growing in recent years because of the adoption of next-generation sequencing (NGS) technologies that enable high-throughput short-read generation at highly competitive cost. Since this trend is expected to continue in the foreseeable future, the design and implementation of efficient and scalable NGS bioinformatics algorithms are important to research and industrial applications. In this paper, we introduce S-Aligner–a highly scalable read mapper designed for the Sunway Taihu Light supercomputer and its fourth-generationShenWei many-core architecture (SW26010). S-Aligner employs a combination of optimization techniques to o…