46 research outputs found
Molecular Simulation of the Binding of Nerve Growth Factor Peptide Mimics to the Receptor Tyrosine Kinase A
No full textAbstractNerve growth factor (NGF) mimics play an important role for therapies that target the receptor tyrosine kinase A (trkA). The N-terminal fragment of the NGF (N-term@NGF) was previously demonstrated to be an important determinant for affinity and specificity in the binding to trkA. Here we use a variety of computational tools (contact surface analysis and free energy predictions) to identify residues playing a key role for the binding to the receptor. Molecular dynamics simulations are then used to investigate the stability of complexes between trkA and peptides mimicking N-term@NGF. Steered molecular dynamics calculations are finally performed to investigate the process of detaching the peptide from the receptor. Three disruptive events are observed, the first involving the breaking of all intermolecular interactions except two salt bridges, which break subsequently
Amino acid empirical contact energy definitions for fold recognition in the space of contact maps
No full textAbstract Background Contradicting evidence has been presented in the literature concerning the effectiveness of empirical contact energies for fold recognition. Empirical contact energies are calculated on the basis of information available from selected protein structures, with respect to a defined reference state, according to the quasi-chemical approximation. Protein-solvent interactions are estimated from residue solvent accessibility. Results In the approach presented here, contact energies are derived from the potential of mean force theory, several definitions of contact are examined and their performance in fold recognition is evaluated on sets of decoy structures. The best definition of contact is tested, on a more realistic scenario, on all predictions including sidechains accepted in the CASP4 experiment. In 30 out of 35 cases the native structure is correctly recognized and best predictions are usually found among the 10 lowest energy predictions. Conclusion The definition of contact based on van der Waals radii of alpha carbon and side chain heavy atoms is seen to perform better than other definitions involving only alpha carbons, only beta carbons, all heavy atoms or only backbone atoms. An important prerequisite for the applicability of the approach is that the protein structure under study should not exhibit anomalous solvent accessibility, compared to soluble proteins whose structure is deposited in the Protein Data Bank. The combined evaluation of a solvent accessibility parameter and contact energy allows for an effective gross screening of predictive models.</p
The interplay of carbonate systems and volcanics: cues from the 3D model of the Sciliar platform (Dolomites, Southern Alps).
No full textExperimental test of seven widely-adopted MPPT algorithms
No full textIn these years the technology progress has allowed to increase renewable energies utilization and in the same time has contributed to raise large scale distributed generation applications. In particular the solar generation is growing and in the next future it will be always more considerable. Therefore it is important to optimize its production under different conditions (for example climatic situations), because the output characteristic of photovoltaic generators is nonlinear and changes with solar irradiation and cell's temperature. This paper presents a comparative study of seven widely-adopted MPPT algorithms; their performance is experimentally evaluated in presence of solar irradiance variations
Renal fibrosis and proteomics: Current knowledge and still key open questions for proteomic investigation
No full textRelación entre adicción a videojuegos, el trastorno de depresión y trastorno de depresión y ansiedad en adultos videojugadores de tipo competitivo de la ciudad de Cartago, Valle del Cauca, 2024
No full textEl objetivo general de la investigación es establecer la correlación entre la adicción a los videojuegos, el trastorno de ansiedad y trastorno de depresión en adultos gamers de tipo competitivo. La metodología fue cuantitativa y adoptó un enfoque correlacional. Participaron 30 individuos entre 18 y 385 años, de los cuales 22 fueron hombres y 8 fueron mujeres. Se aplicó la Escala de Adicción a los Videojuegos, el Cuestionario de Salud del Paciente (PHQ-9) y la Escala de Ansiedad Generalizada (GAD-7). El análisis estadístico se realizó con el software JAMOVI. Se encontró una prevalencia de 16.7% para adicción a los videojuegos, 13.3% de depresión severa y 30% de ansiedad en los participantes. En el nivel correlacional, la adicción a los videojuegos se asoció de forma positiva y moderada con la depresión (r=0.659, p<0.001) y de manera positiva y fuerte con la ansiedad (r=0.714, p<0.001). Se concluye que la adicción a los videojuegos guarda una relación directamente proporcional con la depresión y la ansiedad. Se recomienda realizar estudios con muestras más amplias.The general objective of the research is to establish the correlation between video game addiction, anxiety disorder and depression disorder in competitive adult gamers. The methodology was quantitative and adopted a correlational approach. 30 individuals between 18 and 385 years old participated, of which 22 were men and 8 were women. The Video Game Addiction Scale, the Patient Health Questionnaire (PHQ-9) and the Generalized Anxiety Scale (GAD-7) were applied. The statistical analysis was performed with the JAMOVI software. A prevalence of 16.7% for video game addiction, 13.3% for severe depression and 30% for anxiety was found in the participants. At the correlational level, video game addiction was positively and moderately associated with depression (r=0.659, p<0.001) and positively and strongly associated with anxiety (r=0.714, p<0.001). It is concluded that video game addiction is directly related to depression and anxiety. Studies with larger samples are recommended.Resumen -- Abstract -- Introducción -- Justificación -- Planteamiento del Problema -- Objetivos -- Objetivo general -- Objetivos específicos --Metodología -- Enfoque de investigación -- Diseño de investigación -- Población --Muestra -- Hipótesis -- Hipótesis de investigación -- Hipótesis nulas --Instrumentos -- Adicción a los videojuegos -- Depresión --Ansiedad -- Procedimiento -- Consideraciones éticas -- Plan de análisis --Marco Teórico -- Adicción a los videojuegos -- Depresión -- Ansiedad -- Resultados -- Características de la población -- Adicción a los videojuegos -- Depresión y ansiedad -- Relación entre adicción a los videojuegos, depresión y ansiedad -- Discusión -- Conclusiones -- Referencias BibliográficasPregradoPsicolog
Molekulare Mechanismen der cAMP-vermittelten Signaltransduktion
No full textDie vorliegende Dissertation basiert zwar auf meiner eingereichten kumulativen Dissertation, allerdings ohne die Original Artikel, die bei dem jeweiligen Verlag/Journal (ggf. kostenpflichtig) eingesehen werden können. Die bis zum Zeitpunkt meiner Dissertation noch nicht akzeptierten Manuskripte Publikation V und VI sind jetzt bei BMC veröffentlicht und finden sich unter: -----> Publikation VI - Moll, D., Prinz, A., Brendel, C. M., Berrera, M., Guske, K., Zaccolo, M., Genieser, H. G. and Herberg, F. W., "Biochemical characterization and cellular imaging of a novel, membrane permeable fluorescent cAMP analog", BMC Biochem 9, 18 (2008). -----> Publikation V - Bertinetti, D., Schweinsberg, S., Hanke, S. E., Schwede, F., Bertinetti, O., Drewianka, S., Genieser, H. G. and Herberg, F. W., "Chemical tools selectively target components of the PKA system", BMC Chem Biol 9 (1), 3 (2009)
mSphere of Influence: Compartmentalized cAMP signals in American trypanosomes
No full textABSTRACT Noelia Lander works on cell signaling in American trypanosomes and studies the role of cyclic adenosine monophosphate (cAMP) microdomains in environmental sensing and differentiation. In this mSphere of Influence, Dr. Lander reflects on three research articles in different eukaryotic models that had impacted on the way she thinks about the regulation of cAMP signals in Trypanosoma cruzi, the etiologic agent of Chagas disease. The articles “FRET biosensor uncovers cAMP nano-domains at β-adrenergic targets that dictate precise tuning of cardiac contractility” (N. C. Surdo, M. Berrera, A. Koschinski, M. Brescia, et al., Nat Commun 8:15031, 2017, https://doi.org/10.1038/ncomms15031), “Cyclic AMP signaling and glucose metabolism mediate pH taxis by African trypanosomes” (S. Shaw, S. Knüsel, D. Abbühl, A. Naguleswaran, et al., Nat Commun 13:603, 2022, https://doi.org/10.1038/s41467-022-28293-w), and “Encystation stimuli sensing is mediated by adenylate cyclase AC2-dependent cAMP signaling in Giardia” (H. W. Shih, G. C. M. Alas, and A. R. Paredez, Nat Commun 14:7245, 2023, https://doi.org/10.1038/s41467-023-43028-1) influenced her current hypothesis that cAMP signals are generated in response to environmental cues leading to changes in membrane fluidity at the flagellar tip and the contractile vacuole complex of T. cruzi, structures where cAMP mediates key cellular processes for developmental progression
A toolkit for real-time detection of cAMP: insights into compartmentalized signaling
No full textThe study of cAMP signaling has received a renewed impulse since the recognition that a key aspect of this pathway is the tight spatial control of signal propagation. The study of the mechanism that regulates cAMP signaling in space and time has prompted the development of new methodological approaches to detect cAMP in intact cells. Over the last decades, techniques to assess cAMP concentration with high spatial and temporal resolution in living cells have been elaborated that are based on fluorescent molecules and the phenomenon of fluorescence resonance energy transfer (FRET). A FRET-based indicator of cAMP concentration is typically a protein, including two fluorophores that are linked to a cAMP-binding domain. Binding of cAMP causes a change in the protein conformation and, as a consequence, in the distance between the fluorophores, thus altering the energy transfer between them. Several FRET indicators have been developed, differing in their affinity for cAMP, kinetic features and intracellular targeting. Such indicators enable the measurement of cAMP fluctuations as they happen in the complex intracellular environment and are proving to be effective tools to dissect compartmentalized cAMP signaling
