Examinando por Autor "Stich, Michael"

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A biphasic model of lifespan in nematode Caenorhabditis elegans worm
(The Royal Society, 2023) Mulla, Suhayl; Ludlam, Adele R.; Elragig, Aiman; Slack, Cathy; Balklava, Zita; Stich, Michael; Cheong, Alex
Ageing research focuses on identifying lifespan modifiers and understanding and appropriately interpreting their effects. One of the most relevant quantities being studied is the shape of the survival curve that can reveal crucial information on the mechanism of action. Here, we introduce a bilogistic model to describe the shape of the lifespan curves of Caenorhabditis elegans populations. Using the corrected Akaike information criterion and the RMSE as goodness-of-fit tests, we show that the bilogistic model provides a better fit to the experimental data from nematode worms than other mathematical models and can identify and confirm biphasic lifespan data. Our parametric model offers a method to interpret replicate experiments data in terms of the shape parameters of the lifespan curve and enables robust statistical analysis of intra- and inter-group variance. We apply the model to novel lifespan data from C. elegans and Drosophila melanogaster and provide a rational statistical analysis of lifespan modifiers such as temperature and daf-16/FOXO mutation.
Association of novel monomethine cyanine dyes with bacteriophage MS2: A fluorescence study
(Elsevier, 2020-03-15) Vus, Kateryna; Tarabara, Uliana; Balklava, Zita; Nerukh, Dmitry; Stich, Michael; Laguta, Anna; Vodolazkaya, Natalya; Mchedlov-Petrossyan, Nikolay O.; Farafonov, Vladimir; Kriklya, Nika; Gorbenko, Galyna; Trusova, Valeriya; Zhytniakivska, Olga; Kurutos, Atanas; Gadjev, Nikolai; Deligeorgiev, Todor
Novelmonomethine cyanine dyes Cl-YO, F-YO, Cl-YO-Et, Cl-YO-Bu, and YO-Pent were evaluated as agents to detect and characterise a small virus, the MS2 bacteriophage, using the dye and virus intrinsic fluorescence, kinetic and thermal properties, chemical denaturation, and molecular docking and quantum chemistry modelling. The examined compounds demonstrated enhanced fluorescence responses and high affinities (~1 μM−1) for the intact bacteriophage at physiological ionic strength. The linear Scatchard plots revealed the existence of one binding mode for most dyes. Strong evidence that the cyanines bind to the bacteriophage external surface were obtained, although the possibility of the dye penetration through the virus shell and subsequent complexation with the viral RNA was also tested. The main arguments in favour of the former were that i) the fluorescence of theMS2-bound fluorophores decreased under the influence of protein denaturants, urea and guanidine hydrochloride; ii) the fluorescence responses of the dyes toMS2 and bovine serumalbumin were similar; and (iii) one order of magnitude higher sensitivity of the dyes to the yeast RNA was found. Simple docking studies suggested that one cyaninemolecule is trapped in a cleft formed by three proteins composing the virus shell. Significant role of electrostatic forces in the stabilisation of the dye-MS2 complexes at low ionic strength (10 mM) was demonstrated, while the influence of steric, hydrophobic, and van-der-Waals interactions was expected to increase at physiological ionic strength. The spectral properties of the novel cyanine dyes compared to other fluorophores demonstrated higher sensitivity of the cyanines to MS2, rendering them promising agents for the investigation of the changes in the virus structure under the influence of heat (Cl-YO-Et, Cl-YO-Bu), denaturants (Cl-YO, FYO), and ionic strength (all the compounds).
Complete Virion Simulated: All-Atom Model of an MS2 Bacteriophage with Native Genome
(ACS, 2023-10-19) Farafonov, Vladimir S.; Stich, Michael; Nerukh, Dmitry A.
For the first time, a complete all-atom molecular dynamics (MD) model of a virus, bacteriophage MS2, in its entirety, including a protein outer shell, native genomic RNA with necessary divalent ions, and surrounding explicit aqueous solution with ions at physiological concentration, was built. The model is based on an experimentally measured cryo-EM structure, which was substantially augmented by reconstructing missing or low-resolution parts of the measured density (where the atomistic structure cannot be fit unambiguously). The model was tested by a quarter of a microsecond MD run, and various biophysical characteristics are obtained and analyzed. The developed methodology of building the model can be used for reconstructing other large biomolecular structures when experimental data are fragmented and/or of varying resolution, while the model itself can be used for studying the biology of MS2, including the dynamics of its interaction with the host bacteria.
Ejercicios de Matemáticas II
(2023-01-16) Campos, Cédric M.; Iagar, Razvan G.; Latorre Balado, Marta; Puertas Centeno, David; Stich, Michael; Toranzo, Elio V.
Colección de ejercicios de la asignatura de Matemáticas II de diferentes titulaciones de la Escuela Superior de Ciencias Experimentales y Tecnología (ESCET) de la Universidad Rey Juan Carlos (URJC).
Elixhauser comorbidity method in predicting death of Spanish inpatients with asplenia and pneumococcal pneumonia
(BioMed Central, 2024-06-20) Gea-Izquierdo, Enrique; Ruiz-Urbaez, Rossana; Hernández-Barrera, Valentín; Stich, Michael; Gil-de-Miguel , Ángel
Background Pneumococcal pneumonia (PP) is a serious infection caused by Streptococcus pneumoniae (pneumococcus), with a wide spectrum of clinical manifestations. The aim of this study was to analyze the comorbidity factors that influenced the mortality in patients with asplenia according to PP. Methods Discharge reports from the Spanish Minimum Basic Data Set (MBDS) was used to retrospectively analyze patients with asplenia and PP, from 1997 to 2021. Elixhauser Comorbidity Index (ECI) was calculated to predict in-hospital mortality (IHM). Results 97,922 patients with asplenia were included and 381 cases of PP were identified. The average age for men was 63.87 years and for women 65.99 years. In all years, ECI was larger for splenectomized than for non-splenectomized patients, with men having a higher mean ECI than women. An association was found between risk factors ECI, splenectomy, age group, sex, pneumococcal pneumonia, and increased mortality (OR = 0.98; 95% CI: 0.97–0.99; p < 0.001). The IHM increased steadily with the number of comorbidities and index scores in 1997–2021. Conclusions Asplenia remain a relevant cause of hospitalization in Spain. Comorbidities reflected a great impact in patients with asplenia and PP, which would mean higher risk of mortality.
Estimation of Nanoparticle’s Surface Electrostatic Potential in Solution Using Acid−Base Molecular Probes. III. Experimental Hydrophobicity/Hydrophilicity and Charge Distribution of MS2 Virus Surface
(American Chemical Society, 2022-10-05) Vodolazkaya, Natalya; Nikolskaya, Marina; Laguta, Anna; Farafonov, Vladimir; Balklava, Zita; Stich, Michael; Mchedlov-Petrossyan, Nikolay; Nerukh, Dmitry
MS2 bacteriophage is often used as a model for evaluating pathogenic viruses’ behaviour in aqueous solution. However, the questions of the virus surface’s hydrophilic/hydrophobic balance, the charge distribution, and the binding mechanism are open. Using dynamic light scattering method and laser Doppler electrophoresis the hydrodynamic diameter and the zeta-potential of the virus particles were measured at their concentration of 5x10^11 particles per mL and ionic strength 0.03 M. The values were found to be 30 nm and −29 or −34 mV (by Smoluchowski or Ohshima approximations) respectively. MS2 bacteriophage surface was also investigated using a series of acid-base indicator dyes of various charge type, size, and structure. Their spectral and acid-base properties (pKa) are very sensitive to microenvironment in aqueous solution including containing nano-particles. The electrostatic potential of the surface Ψ was estimated using the common formula: Ψ =59x(pKa^i − pKa) in mV at 25 °C. The Ψ values were −50 mV and +10 mV respectively, which indicate the ‘mosaic’ way of the charge distribution on the surface. These data are in good agreement with the obtained zeta-potential values and provide even more information about the virus surface. It was found that the surface of the MS2 virus is hydrophilic in solution in contrast to commonly accepted hypothesis of hydrophobicity of virus particles. No hydrophobic interactions between various molecular probes and the capsid were observed.
Exámenes de Matemáticas II
(2023-01-16) Campos, Cédric M.; Iagar, Razvan G.; Latorre Balado, Marta; Puertas Centeno, David; Stich, Michael; Toranzo, Elio V.
Colección de exámenes de la asignatura de Matemáticas II de diferentes titulaciones de la Escuela Superior de Ciencias Experimentales y Tecnología (ESCET) de la Universidad Rey Juan Carlos (URJC).
Influence of various colloidal surfactants on the stability of MS2 bacteriophage suspension. The charge distribution on the PCV2 virus surface
(Elsevier, 2023-10-01) Vodolazkaya, Natalya; Laguta, Anna; Farafonov, Vladimir; Nikolskaya, Marina; Balklava, Zita; Khayat, Reza; Stich, Michael; Mchedlov-Petrossyan, Nikolay; Nerukh, Dmitry
To understand virus stability in aqueous solutions, the colloidal nanostructure and properties of a model virus, the MS2 bacteriophage, have been investigated by studying the effect of the addition of electrolytes and various colloidal surfactants to its water solution at physiological conditions. The charge of the virus particles influences their colloidal properties. It was found that the ζ-potential value is reduced from –35 mV to –10 mV in 0.01 M CaCl2 and 0.1 M NaCl solutions as well as at higher electrolytes concentrations, while the size of the MS2 aggregates was about 600 ÷ 900 nm with individual particles of size around 30 nm also recorded. The 2 : 1 electrolyte causes destabilization of MS2 bacteriophage particles in an aqueous solution at a lower concentration. The addition of cationic, anionic, and non-ionic colloidal surfactants below and above critical micelle concentration to MS2 bacteriophage suspension caused the destabilization of MS2 particles. We also investigated the capsid’s surface of another virus, PCV2, using dynamic light scattering and laser Doppler electrophoresis. The hydrodynamic diameter and the ζ-potential of PCV2 empty capsid were found to be equal to 22 ± 1 nm and -41± 4 mV (using Ohshima approximations). The electrostatic potential of the surface was measured using acid-base probes and found to be equal to -91 ± 3 and +14 ± 2 mV for positively and negatively charged probes respectively, which indicate the ‘mosaic’ way of the charge distribution on the surface, similar to MS2′s surface studied previously. Our data provide new information about the virus surface, the complex process of virus aggregation-disaggregation and virus capsid disassembly.
Lecture notes Algebra
(2023-09-05) Marriaga, Misael E.; Stich, Michael
Lecture notes for the course Algebra (Ingeniería Biomédica)
Notas de Matemáticas II
(2022-12-20) Campos, Cédric M.; Iagar, Razvan G.; Latorre Balado, Marta; Puertas Centeno, David; Stich, Michael; Toranzo, Elio V.
Estas notas integran los contenidos genéricos impartidos en la asignatura de Matemáticas II de diferentes titulaciones de la Escuela Superior de Ciencias Experimentales y Tecnología (ESCET) de la Universidad Rey Juan Carlos (URJC).
Reconstruction and validation of entire virus model with complete genome from mixed resolution cryo-EM density
(The Royal Society of Chemistry, 2022-04-12) Farafonov, Vladimir S.; Stich, Michael; Nerukh, Dmitry
It is very difficult to reconstruct computationally a large biomolecular complex in its biological entirety from experimental data. The resulting atomistic model should not contain gaps structurally and it should yield stable dynamics. We, for the first time, reconstruct from the published incomplete cryo-EM density a complete MS2 virus at atomistic resolution, that is, the capsid with the genome, and validate the result by all atom molecular dynamics with explicit water. The available experimental data includes a high resolution protein capsid and an inhomogeneously resolved genome map. For the genomic RNA, apart from 16 hairpins with atomistic resolution, the strands near the capsid’s inner surface were resolved up to the nucleic backbone level, and the innermost density was completely unresolved. As a result, only 242 nucleotides (out of 3569) were positioned, while only a fragmented backbone was outlined for the rest of the genome, making a detailed model reconstruction necessary. For model reconstruction, in addition to the available atomistic structure information, we extensively used the predicted secondary structure of the genome (base pairing). The technique was based on semi-automatic building of relatively large strands of RNA with subsequent manual positioning over the traced backbone. The entire virus structure (capsid + genome) was validated by a molecular dynamics run in physiological solution with ions at standard conditions confirming the stability of the model.