5-Substituted Flavones-Another Class of Potent Triplex DNA-Specific Ligands as Antigene Enhancers.

In the field of drug development, the quest for novel compounds that bind to DNA with high affinity and specificity never ends. In the present work, we report the newest development in this field, namely, triplex DNA-specific binding ligands based on the 5-substituted flavone scaffold in our lab. Biophysical studies showed that the newly synthesized flavone derivatives (depending on the side chains) bind to triplex DNA with binding affinities better than or similar to 5-substituted 3,3',4',7-tetramethoxyflavonoids.

Bioprinting of Aptamer-Based Programmable Bioinks to Modulate Multiscale Microvascular Morphogenesis in 4D.

Dynamic growth factor presentation influences how individual endothelial cells assemble into complex vascular networks. Here, programmable bioinks are developed that facilitate dynamic vascular endothelial growth factor (VEGF) presentation to guide vascular morphogenesis within 3D-bioprinted constructs. Aptamer's high affinity is leveraged for rapid VEGF sequestration in spatially confined regions and utilized aptamer-complementary sequence (CS) hybridization to tune VEGF release kinetics temporally, days after bioprinting.

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.

Increased AID results in mutations at the CRLF2 locus implicated in Latin American ALL health disparities.

Activation-induced cytidine deaminase (AID) is a B cell-specific mutator required for antibody diversification. However, it is also implicated in the etiology of several B cell malignancies. Evaluating the AID-induced mutation load in patients at-risk for certain blood cancers is critical in assessing disease severity and treatment options.

Embedded Printing of Hydrogels and Watery Suspensions of Cells in Patterned Granular Baths.

Bioprinting within support media has emerged as the superior alternative to conventional extrusion printing. Not only because it allows for more freedom over the shapes that can be printed but also because it allows for the printing of inks that would not retain shape fidelity in freeform deposition such as watery liquids. Apart from functioning as mechanical support during embedded printing, hydrogel microparticle support media can provide the unique advantage of offering distinct chemotactic cues to cells printed in the baths by varying the composition of the hydrogel microparticles.

Increased AID Results in Mutations at the CRLF2 Locus Implicated in Latin American ALL Health Disparities.

Activation-induced cytidine deaminase (AID) is a B cell-specific base editor required during class switch recombination and somatic hypermutation for B cell maturation and antibody diversification. However, it has also been implicated as a factor in the etiology of several B cell malignancies. Evaluating the AID-induced mutation load in patients at-risk for certain types of blood cancers is critical in assessing disease severity and treatment options.

Elevated temperature triggers increase in global DNA methylation, 5-methylcytosine expression levels, apoptosis and NOx levels in the gonads of Atlantic sea urchin.

Global warming is one of the greatest threats to living organisms. Among them, marine invertebrates are severely impacted on reproductive fitness by rising seawater surface temperatures due to climate change (e.g.

Attitudes scale toward cancer-related cognitive changes - an initial Colombian validation.

Objective: The aim of this study was to develop an initial valid tool to measure attitudes toward cancer-related cognitive changes.

Subjects And Methods: After revising the literature, three main dimensions were hypothesized. Eight judges were contacted to obtain content validity evidence.

Is it feasible to enhance quality assurance of cervical cancer screening in Latin America? A regional expert consensus.

Objectives: Cervical cancer elimination requires high-performance screening tests and high treatment rates, and thus high screening program performance is essential; however, Latin America lacks organized screening and quality assurance (QA) guidelines. We aimed to develop a core set of QA indicators suitable to the region.

Methods: We reviewed QA guidelines from countries/regions with highly organized screening programs and selected 49 indicators for screening intensity, test performance, follow-up, screening outcomes and system capacity.

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.

Diversity upon diversity: linking DNA double-strand break repair to blood cancer health disparities.

Chromosomal translocations arising from aberrant repair of multiple DNA double-strand breaks (DSBs) are a defining characteristic of many cancers. DSBs are an essential part of physiological processes in antibody-producing B cells. The B cell environment is poised to generate genome instability leading to translocations relevant to the pathology of blood cancers.

Visibility & support for first generation college graduates in medicine.

Of Being a First Generation (First Gen) college graduate is an important intersectionality which impacts the lens through which First Gen students learn to become physicians. In this Perspective, we define the First Gen identity and review some of the salient First Gen literature as it applies to the medical school experience. We discuss the conception, design and execution of First Gen initiatives and program development at our medical school as a call to action and model for other institutions to create communities for their First Gen populations, focusing on inclusion and tailored support.

A Propagation Study of LoRa P2P Links for IoT Applications: The Case of Near-Surface Measurements over Semitropical Rivers.

Internet of Things (IoT) radio networks are becoming popular in several scenarios for short-range applications (e.g., wearables and home security) and medium-range applications (e.

Fragment Binding to the Nsp3 Macrodomain of SARS-CoV-2 Identified Through Crystallographic Screening and Computational Docking.

The SARS-CoV-2 macrodomain (Mac1) within the non-structural protein 3 (Nsp3) counteracts host-mediated antiviral ADP-ribosylation signalling. This enzyme is a promising antiviral target because catalytic mutations render viruses non-pathogenic. Here, we report a massive crystallographic screening and computational docking effort, identifying new chemical matter primarily targeting the active site of the macrodomain.

[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.

Flash Flood Early Warning System in Colima, Mexico.

This paper presents a system of sensors used in flash flood prediction that offers critical real-time information used to provide early warnings that can provide the minutes needed for persons to evacuate before imminent events. Flooding is one of the most serious natural disasters humans confront in terms of loss of life and results in long-term effects, which often have severely adverse social consequences. However, flash floods are potentially more dangerous to life because there is often little or no forewarning of the impending disaster.

Multimodal small-molecule screening for human prion protein binders.

Prion disease is a rapidly progressive neurodegenerative disorder caused by misfolding and aggregation of the prion protein (PrP), and there are currently no therapeutic options. PrP ligands could theoretically antagonize prion formation by protecting the native protein from misfolding or by targeting it for degradation, but no validated small-molecule binders have been discovered to date. We deployed a variety of screening methods in an effort to discover binders of PrP, including F-observed and saturation transfer difference (STD) NMR spectroscopy, differential scanning fluorimetry (DSF), DNA-encoded library selection, and screening.

Scientific publications in cancer: in Latin America, strong scientific networks increase productivity (the TENJIN study).

Objectives: The objectives of this study are to evaluate the relationship between authorship networking, socioeconomic factors, and scientific productivity across Latin America.

Methods: In a bibliometric analysis of cancer-related Latin-American publications, the relationship between authorship network indicators, sociodemographic factors, and number of peer-reviewed indexed publications per country was explored. A systematic review of the literature for cancer publications between 2000 and 2018 using the Scopus database limited to Latin-American authors was used for the construction of coauthorship and publication networks and their respective metrics.

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.