Amino acid-linked platinum(II) compounds: non-canonical nucleoside preferences and influence on glycosidic bond stabilities.

Nucleobases serve as ideal targets where drugs bind and exert their anticancer activities. Cisplatin (cisPt) preferentially coordinates to 2'-deoxyguanosine (dGuo) residues within DNA. The dGuo adducts that are formed alter the DNA structure, contributing to inhibition of function and ultimately cancer cell death. Despite its success as an anticancer drug, cisPt has a number of drawbacks that reduce its efficacy, including repair of adducts and drug resistance. Some approaches to overcome this problem involve development of compounds that coordinate to other purine nucleobases, including those found in RNA. In this work, amino acid-linked platinum(II) (AAPt) compounds of alanine and ornithine (AlaPt and OrnPt, respectively) were studied. Their reactivity preferences for DNA and RNA purine nucleosides (i.e., 2'-deoxyadenosine (dAdo), adenosine (Ado), dGuo, and guanosine (Guo)) were determined. The chosen compounds form predominantly monofunctional adducts by reacting at the N1, N3, or N7 positions of purine nucleobases. In addition, features of AAPt compounds that impact the glycosidic bond stability of Ado residues were explored. The glycosidic bond cleavage is activated differentially for AlaPt-Ado and OrnPt-Ado isomers. Formation of unique adducts at non-canonical residues and subsequent destabilization of the glycosidic bonds are important features that could circumvent platinum-based drug resistance.

Students in a Course-Based Undergraduate Research Experience Course Discovered Dramatic Changes in the Bacterial Community Composition Between Summer and Winter Lake Samples.

Course-based undergraduate research experience (CURE) courses incorporate high-impact pedagogies that have been shown to increase undergraduate retention among underrepresented minorities and women. As part of the Building Infrastructure Leading to Diversity program at the University of Detroit Mercy, a CURE metagenomics course was established in the winter of 2019. Students investigated the bacterial community composition in a eutrophic cove in Lake Saint Clair (Harrison Township, MI, United States) from water samples taken in the summer and winter. The students created 16S rRNA libraries that were sequenced using next-generation sequencing technology. They used a public web-based supercomputing resource to process their raw sequencing data and web-based tools to perform advanced statistical analysis. The students discovered that the most common operational taxonomic unit, representing 31% of the prokaryotic sequences in both summer and winter samples, corresponded to an organism that belongs to a previously unidentified phylum. This result showed the students the power of metagenomics because the approach was able to detect unclassified organisms. Principal Coordinates Analysis of Bray-Curtis dissimilarity index data showed that the winter community was distinct from the summer community [Analysis of Similarities (ANOSIM) r = 0.59829, n = 18, and p < 0.001]. Dendrograms based on hierarchically clustered Pearson correlation coefficients of phyla were divided into a winter clade and a summer clade. The conclusion is that the winter bacterial population was fundamentally different from the summer population, even though the samples were taken from the same locations in a protected cove. Because of the small class sizes, qualitative as well as statistical methods were used to evaluate the course's impact on student attitudes. Results from the Laboratory Course Assessment Survey showed that most of the respondents felt they were contributing to scientific knowledge and the course fostered student collaboration. The majority of respondents agreed or strongly agreed that the course incorporated iteration aspects of scientific investigations, such as repeating procedures to fix problems. In summary, the metagenomics CURE course was able to add to scientific knowledge and allowed students to participate in authentic research.

Complete Genome Sequences of Cluster G Mycobacteriophage Darionha, Cluster A Mycobacteriophage Salz, and Cluster J Mycobacteriophage ThreeRngTarjay.

Mycobacteriophages Darionha, Salz, and ThreeRngTarjay are mycobacteriophages isolated using the host Mycobacterium smegmatis mc2155. Following isolation from soil samples, all three siphoviridae phages were characterized, and their genomes were sequenced and annotated.