Supramolecular Cylinders Target Bulge Structures in the 5' UTR of the RNA Genome of SARS-CoV-2 and Inhibit Viral Replication.

The untranslated regions (UTRs) of viral genomes contain a variety of conserved yet dynamic structures crucial for viral replication, providing drug targets for the development of broad spectrum anti-virals. We combine in vitro RNA analysis with molecular dynamics simulations to build the first 3D models of the structure and dynamics of key regions of the 5' UTR of the SARS-CoV-2 genome. Furthermore, we determine the binding of metallo-supramolecular helicates (cylinders) to this RNA structure.

Supramolecular Cylinders Target Bulge Structures in the 5' UTR of the RNA Genome of SARS-CoV-2 and Inhibit Viral Replication*.

The untranslated regions (UTRs) of viral genomes contain a variety of conserved yet dynamic structures crucial for viral replication, providing drug targets for the development of broad spectrum anti-virals. We combine in vitro RNA analysis with molecular dynamics simulations to build the first 3D models of the structure and dynamics of key regions of the 5' UTR of the SARS-CoV-2 genome. Furthermore, we determine the binding of metallo-supramolecular helicates (cylinders) to this RNA structure.

Identification of New Subpopulations in Native Americans and Mestizos From Peru.

Region-specific subpopulations have been identified. It is proposed that the hspAmerind subpopulation is being displaced from the Americans by an hpEurope population following the conquest. Our study aimed to describe the genomes and methylomes of isolates from distinct Peruvian communities: 23 strains collected from three groups of Native Americans (Asháninkas [ASHA, = 9], Shimaas [SHIM, = 5] from Amazonas, and Punos from the Andean highlands [PUNO, = 9]) and 9 modern mestizos from Lima (LIM).

Rotaxanating Metallo-supramolecular Nano-cylinder Helicates to Switch DNA Junction Binding.

A class of rotaxane is created, not by encapsulating a conventional linear thread, but rather by wrapping a large cucurbit[10]uril macrocycle about a three-dimensional, cylindrical, nanosized, self-assembled supramolecular helicate as the axle. The resulting pseudo-rotaxane is readily converted into a proper interlocked rotaxane by adding branch points to the helicate strands that form the surface of the cylinder (like branches and roots on a tree trunk). The supramolecular cylinder that forms the axle is itself a member of a unique and remarkable class of helicate metallo-drugs that bind Y-shaped DNA junction structures and induce cell death.

Oral Chemotherapy Education: Using Innovation to Ensure Broad Access.

The purpose of this article is to share one institution's intervention to improve oral chemotherapy patient education. The overall aim was to provide clinicians with a single source of educational materials that would meet a diverse group of patients' educational needs and be consistent with published guidelines.
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A Structured Nursing Intervention to Address Oral Chemotherapy Adherence in Patients With Non-Small Cell Lung Cancer.

Purpose/objectives: To evaluate a nurse-led intervention to enhance medication knowledge and adherence using the Multinational Association for Supportive Care in Cancer Oral Agent Teaching Tool (MOATT).

Design: Longitudinal, descriptive feasibility study.

Setting: An ambulatory thoracic oncology disease center located at the Dana-Farber Cancer Institute in Boston, MA.

Socioeconomic and nutritional factors account for the association of gastric cancer with Amerindian ancestry in a Latin American admixed population.

Gastric cancer is one of the most lethal types of cancer and its incidence varies worldwide, with the Andean region of South America showing high incidence rates. We evaluated the genetic structure of the population from Lima (Peru) and performed a case-control genetic association study to test the contribution of African, European, or Native American ancestry to risk for gastric cancer, controlling for the effect of non-genetic factors. A wide set of socioeconomic, dietary, and clinic information was collected for each participant in the study and ancestry was estimated based on 103 ancestry informative markers.

Attenuated CagA oncoprotein in Helicobacter pylori from Amerindians in Peruvian Amazon.

Population genetic analyses of bacterial genes whose products interact with host tissues can give new understanding of infection and disease processes. Here we show that strains of the genetically diverse gastric pathogen Helicobacter pylori from Amerindians from the remote Peruvian Amazon contain novel alleles of cagA, a major virulence gene, and reveal distinctive properties of their encoded CagA proteins. CagA is injected into the gastric epithelium where it hijacks pleiotropic signaling pathways, helps Hp exploit its special gastric mucosal niche, and affects the risk that infection will result in overt gastroduodenal diseases including gastric cancer.

Helicobacter pylori from Peruvian amerindians: traces of human migrations in strains from remote Amazon, and genome sequence of an Amerind strain.

Background: The gastric pathogen Helicobacter pylori is extraordinary in its genetic diversity, the differences between strains from well-separated human populations, and the range of diseases that infection promotes.

Principal Findings: Housekeeping gene sequences from H. pylori from residents of an Amerindian village in the Peruvian Amazon, Shimaa, were related to, but not intermingled with, those from Asia.

4,4'-Dihydroxybenzophenone-2,4-dinitrophenylhydrazone (A-007): a topical treatment for cutaneous metastases from malignant cancers.

Purpose: This study is to document the activity and acceptability for a new topical agent, A-007, in the treatment of cutaneous metastases from cancer.

Patients And Methods: This is a multicenter study involving 27 patients with inoperable skin lesions from histologically confirmed cancers of the breast and oral cavity, non-Hodgkin's lymphoma, Kaposi's sarcoma, and angiosarcoma that had failed radiotherapy or systemic treatment. A-007, as a 0.

Stereoselective photooxidation of enecarbamates: reactivity of ozone vs singlet oxygen.

[reaction: see text]. Oxazolidinone-functionalized enecarbamates show contrasting behavior upon oxidation by singlet oxygen and by ozone. The observed stereoselectivity difference indicates that the oxidation with ozone is subject to classic steric effects, whereas the very high selectivity in the photooxidation with singlet oxygen is derived from vibrational deactivation.

Design, synthesis, and anticancer properties of 4,4'-dihydroxybenzophenone-2,4-dinitrophenylhydrazone and analogues.

4,4'-dihydroxybenzophenone-2,4-dinitrophenylhydrazone (A-007) has recently completed a phase I clinical trial in advanced cancer with minimal toxicity, and impressive objective responses were noted. A-007 possesses three moieties that appear to have an influence on its anticancer activities: diphenylmethane, hydrazone, and dinitrophenyl. The goals of this study were to modify A-007's chemical moieties with the ultimate goal of maximizing its anticancer activity through increased planarity and introduction of functional groups.

Anticancer activity for 4,4'-dihydroxybenzophenone-2,4-dinitrophenylhydrazone (A-007) analogues and their abilities to interact with lymphoendothelial cell surface markers.

The structure of the anticancer agent 4,4'-dihydroxybenzophenone-2,4-dinitrophenylhydrazone (A-007) has been modified through SAR and by incorporating barbituric acid, pyridine, quinoline, and alkylcarboxylic acids into A-007's moieties. Analogue anticancer activity and interacting with CD surface markers on a T-cell leukemia cell line were evaluated and the correlation between SAR and biological properties are discussed.