67 research outputs found

    Pin1 and neurodegeneration: a new player for prion disorders?

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    Pin1 is a peptidyl-prolyl isomerase that catalyzes the cis/trans conversion of phosphorylated proteins at serine or threonine residues which precede a proline. The peptidyl-prolyl isomerization induces a conformational change of the proteins involved in cell signaling process. Pin1 dysregulation has been associated with some neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and Huntington's disease. Proline-directed phosphorylation is a common regulator of these pathologies and a recent work showed that it is also involved in prion disorders. In fact, prion protein phosphorylation at the Ser-43-Pro motif induces prion protein conversion into a disease-associated form. Furthermore, phosphorylation at Ser-43-Pro has been observed to increase in the cerebral spinal fluid of sporadic Creutzfeldt-Jakob Disease patients. These findings provide new insights into the pathogenesis of prion disorders, suggesting Pin1 as a potential new player in the disease. In this paper, we review the mechanisms underlying Pin1 involvement in the aforementioned neurodegenerative pathologies focusing on the potential role of Pin1 in prion disorders

    Manipulating the Conformation of Single Organometallic Chains on Au(111)

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    The conformations of organometallic polymers formed via the bottom-up assembly of monomer units on a metal surface are investigated, and the relationship between the adsorption geometry of the individual monomer units, the conformational structure of the chain, and the overall shape of the polymer is explored. Iodine-functionalized monomer units deposited on a Au(111) substrate are found to form linear chain structures in which each monomer is linked to its neighbors via a Au adatom. Lateral manipulation of the linear chains using a scanning tunneling microscope allows the structure of the chain to be converted from a linear to a curved geometry, and it is shown that a transformation of the overall shape of the chain is coupled to a conformational rearrangement of the chain structure as well as a change in the adsorption geometry of the monomer units within the chain. The observed conformational structure of the curved chain is well-ordered and distinct from that of the linear chains. The structures of both the linear and curved chains are investigated by a combination of scanning tunneling microscopy measurements and theoretical calculations

    Band Formation from Coupled Quantum Dots Formed by a Nanoporous Network on a Copper Surface

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    The properties of crystalline solids can to a large extent be derived from the scale and dimensionality of periodic arrays of coupled quantum systems such as atoms and molecules. Periodic quantum confinement in two dimensions has been elusive on surfaces, mainly because of the challenge to produce regular nanopatterned structures that can trap electronic states. We report that the two-dimensional free electron gas of the Cu(111) surface state can be trapped within the pores of an organic nanoporous network, which can be regarded as a regular array of quantum dots. Moreover, a shallow dispersive electronic band structure is formed, which is indicative of electronic coupling between neighboring pore states.

    Molecular tweezers target a protein–protein interface and thereby modulate complex formation

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    Molecular tweezers for lysine and arginine select a few residues on a protein surface and by their unique complexation mode disrupt a critical protein–protein interaction. Detailed structural information was gained by NMR experiments, strongly supported by QM/MM calculations and further substantiated by ITC, fluorescence anisotropy, ELISA and bio-layer-interference studies

    Biological evaluation of coagulation problems in COVID-19 patients hospitalized at the centre hospitalier mĂšre-enfant monkole, kinshasa, Democratic Republic of the Congo

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    Background: COVID-19 is a viral infection caused by SARS-CoV-2, which enters the body via the ACE2 receptor. This study aims to evaluate the coagulation disorders of COVID-19 patients admitted to Centre Hospitalier MÚre-Enfant Monkole, Kinshasa. Methods: This descriptive cross-sectional hospital-based study of patient files was conducted between July 2020 and June 2021 at CHME-Monkole in Kinshasa. The sample size was 130 patients using a random sampling technique after interviewing the respondents. For each respondent, biological and socio-demographic data were collected on a questionnaire. The primary analyses included the determination of PT, APTT, Plasma determination of D-dimers, and platelet count. A descriptive analysis was performed for socio-demographic characteristics, while Pearson correlation was used to determine the associations between socio-demographic characteristics and different biological parameters using SPSS 25.0. For ethical reasons, informed consent from patients was sought, and confidentiality was assured. The authorization was provided by the Ethical Committee of CHME-Monkole (Ethical code: KIN/CHME/04/2020). Results: The findings showed D-dimer levels higher than 500 ”g/L in 87.7% of respondents, prolonged APTT (>40 seconds) in 43.1% of respondents, PT (<70%) in 36.9% of respondents, and thrombocytopenia (platelets <150,000) in 26.2% of respondents. A positive correlation was observed between socio-demographic characteristics and D-dimer levels. Conclusion: SARS-CoV-2 infection has a significant impact on coagulation. Thus, determining these biomarkers could predict the risk of disease severity or death in patients with COVID-19
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