Design of linked-domain protein inhibitors of UBE2D as tools to study cellular ubiquitination.

Ubiquitin (Ub) is a post-translational modification that largely controls proteostasis through mechanisms spanning transcription, translation, and notably, protein degradation. Ub conjugation occurs through a hierarchical cascade of three enzyme classes (E1, E2, and E3s) involving >1000 proteins that regulate the ubiquitination of proteins. The E2 Ub-conjugating enzymes are the midpoint, yet their cellular roles remain under-characterized, partly due to a lack of inhibitors.

2,5-Pyridinedicarboxylic acid is a bioactive and highly selective inhibitor of D-dopachrome tautomerase.

Macrophage migration inhibitory factor (MIF) and D-dopachrome tautomerase (D-DT) are two pleotropic cytokines, which are coexpressed in various cell types to activate the cell surface receptor CD74. Via the MIF/CD74 and D-DT/CD74 axes, the two proteins exhibit either beneficial or deleterious effect on human diseases. In this study, we report the identification of 2,5-pyridinedicarboxylic acid (a.

Ligand-induced conformational changes enable intersubunit communications in D-dopachrome tautomerase.

D-Dopachrome tautomerase (D-DT; or MIF-2) is a multifunctional protein with immunomodulatory properties and a documented pathogenic role in inflammation and cancer that is associated with activation of the cell surface receptor CD74. Alongside D-DT, macrophage migration inhibitory factor (MIF) is also known to activate CD74, promoting pathogenesis. While the role of the MIF/CD74 axis has been extensively studied in various disease models, the late discovery of the D-DT/CD74 axis has led to a poor investigation into the D-DT-induced activation mechanism of CD74.

[From psychosomatic medicine to medical psychology: the theoretical and institutional trajectory of Julio de Mello Filho].

Studies on the causality of pathologies and the doctor/patient relationship based on psychoanalytic formulations received two denominations in Brazil: psychosomatic medicine and medical psychology. The physician and psychoanalyst Julio de Mello Filho took a leading role in this movement after the psychiatrist and psychoanalyst Danillo Perestrello was incapacitated by illness. This study investigates how the theoretical concepts of the psychosomatic movement were structured and the institutional strategies used to establish this discipline in Brazil.

5-Substituted 3, 3', 4', 7-tetramethoxyflavonoids - A novel class of potent DNA triplex specific binding ligands.

Herein, we present a class of potent triplex DNA binding ligands derived from the natural product quercetin, which is the first of its kind that has ever been reported in the literature. The binding of 5-substituted quercetin derivatives (3, 3', 4', 7-tetramethoxyflavonoids) to triplex and duplex DNA was investigated using several biophysical tools, including thermal denaturation monitored by UV, circular dichroism, differential scanning calorimetry, and isothermal titration calorimetry. Experimental data reveal that several 5-substituted 3, 3', 4', 7-tetramethoxyflavonoids have remarkable effects on binding to DNA triple helices, and they do not influence the double-helical DNA structures.

[Danilo Perestrello and the psychosomatic medicine movement in Brazil: from theory to institutional acceptance].

In the 1950s, the psychosomatic medicine movement emerged in Brazil, led by psychiatrist and psychoanalyst Danilo Perestrello. This article analyzes the strategies developed to configure this proposal and establish this field of study. From the beginning, this movement was characterized by a plan to reformulate medicine based on psychoanalytic theory and obtain favorable reception in institutions.

Thiazole orange - Spermine conjugate: A potent human telomerase inhibitor comparable to BRACO-19.

In this report, we synthesized a series of TO conjugates containing different amino side chains and investigated their binding to telomeric G-quadruplex DNA (G4) using several biophysical methods including fluorometric titration and thermal denaturation monitored by fluorescence and circular dichroism. The composition of side chains strongly affects the binding of these molecules to G-quadruplex DNA. Incorporation of amino side chains increases the binding affinity of TO toward G4 but has a minimal effect on its selectivity for G4 over duplex DNA.