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1. Interplay Between Polymorphic Short Tandem Repeats and Gene Expression Variation in Caenorhabditis elegans

   https://doi.org/10.1093/molbev/msad067  

   Zhang, Gaotian; Andersen, Erik C (April 2023, Molecular Biology and Evolution)

   Larracuente, Amanda (Ed.)

   Abstract Short tandem repeats (STRs) have orders of magnitude higher mutation rates than single nucleotide variants (SNVs) and have been proposed to accelerate evolution in many organisms. However, only few studies have addressed the impact of STR variation on phenotypic variation at both the organismal and molecular levels. Potential driving forces underlying the high mutation rates of STRs also remain largely unknown. Here, we leverage the recently generated expression and STR variation data among wild Caenorhabditis elegans strains to conduct a genome-wide analysis of how STRs affect gene expression variation. We identify thousands of expression STRs (eSTRs) showing regulatory effects and demonstrate that they explain missing heritability beyond SNV-based expression quantitative trait loci. We illustrate specific regulatory mechanisms such as how eSTRs affect splicing sites and alternative splicing efficiency. We also show that differential expression of antioxidant genes and oxidative stresses might affect STR mutations systematically using both wild strains and mutation accumulation lines. Overall, we reveal the interplay between STRs and gene expression variation by providing novel insights into regulatory mechanisms of STRs and highlighting that oxidative stress could lead to higher STR mutation rates. 

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2. Using an Observation Protocol To Evaluate Student Argumentation Skills in Introductory Biology Laboratories

   https://doi.org/10.1128/jmbe.00209-22  

   Clevenger, Lindsey; Teshera-Levye, Jennifer; Walker, Joi P.; Vance-Chalcraft, Heather D. (August 2023, Journal of Microbiology & Biology Education)

   Shaffer, Justin (Ed.)

   ABSTRACT Argumentation is vital in the development of scientific knowledge, and students who can argue from evidence and support their claims develop a deeper understanding of science. In this study, the Argument-Driven Inquiry instruction model was implemented in a two-semester sequence of introductory biology laboratories. Student’s scientific argumentation sessions were video recorded and analyzed using the Assessment of Scientific Argumentation in the Classroom observation protocol. This protocol separates argumentation into three subcategories: cognitive (how the group develops understanding), epistemic (how consistent the group’s process is with the culture of science), and social (how the group members interact with each other). We asked whether students are equally skilled in all subcategories of argumentation and how students’ argumentation skills differ based on lab exercise and course. Students scored significantly higher on the social than the cognitive and epistemic subcategories of argumentation. Total argumentation scores were significantly different between the two focal investigations in Biology Laboratory I but not between the two focal investigations in Biology Laboratory II. Therefore, student argumentation skills were not consistent across content; the design of the lab exercises and their implementation impacted the level of argumentation that occurred. These results will ultimately aid in the development and expansion of Argument-Driven Inquiry instructional models, with the goal of further enhancing students’ scientific argumentation skills and understanding of science. 

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3. Delta Variant with P681R Critical Mutation Revealed by Ultra-Large Atomic-Scale Ab Initio Simulation: Implications for the Fundamentals of Biomolecular Interactions

   https://doi.org/10.3390/v14030465  

   Adhikari, Puja; Jawad, Bahaa; Rao, Praveen; Podgornik, Rudolf; Ching, Wai-Yim (March 2022, Viruses)

   The SARS-CoV-2 Delta variant is emerging as a globally dominant strain. Its rapid spread and high infection rate are attributed to a mutation in the spike protein of SARS-CoV-2 allowing for the virus to invade human cells much faster and with an increased efficiency. In particular, an especially dangerous mutation P681R close to the furin cleavage site has been identified as responsible for increasing the infection rate. Together with the earlier reported mutation D614G in the same domain, it offers an excellent instance to investigate the nature of mutations and how they affect the interatomic interactions in the spike protein. Here, using ultra large-scale ab initio computational modeling, we study the P681R and D614G mutations in the SD2-FP domain, including the effect of double mutation, and compare the results with the wild type. We have recently developed a method of calculating the amino-acid–amino-acid bond pairs (AABP) to quantitatively characterize the details of the interatomic interactions, enabling us to explain the nature of mutation at the atomic resolution. Our most significant finding is that the mutations reduce the AABP value, implying a reduced bonding cohesion between interacting residues and increasing the flexibility of these amino acids to cause the damage. The possibility of using this unique mutation quantifiers in a machine learning protocol could lead to the prediction of emerging mutations. 

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4. A combinatorial system to examine the enzymatic repair of multiply damaged DNA substrates

   https://doi.org/10.1093/nar/gkac530  

   Hsu, Chia Wei; Conrad, James W; Sowers, Mark L; Baljinnyam, Tuvshintugs; Herring, Jason L; Hackfeld, Linda C; Hatch, Sandra S; Sowers, Lawrence C (July 2022, Nucleic Acids Research)

   Abstract DNA damage drives genetic mutations that underlie the development of cancer in humans. Multiple pathways have been described in mammalian cells which can repair this damage. However, most work to date has focused upon single lesions in DNA. We present here a combinatorial system which allows assembly of duplexes containing single or multiple types of damage by ligating together six oligonucleotides containing damaged or modified bases. The combinatorial system has dual fluorescent labels allowing examination of both strands simultaneously, in order to study interactions or competition between different DNA repair pathways. Using this system, we demonstrate how repair of oxidative damage in one DNA strand can convert a mispaired T:G deamination intermediate into a T:A mutation. We also demonstrate that slow repair of a T:G mispair, relative to a U:G mispair, by the human methyl-binding domain 4 DNA glycosylase provides a competitive advantage to competing repair pathways, and could explain why CpG dinucleotides are hotspots for C to T mutations in human tumors. Data is also presented that suggests repair of closely spaced lesions in opposing strands can be repaired by a combination of short and long-patch base excision repair and simultaneous repair of multiply damage sites can potentially lead to lethal double strand breaks. 

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5. Mediating Students’ Scientific Argumentation to Support Model Revision

   Zhou, J. Hmelo-Silver; C. E.; Danish, J.; Ryan, Z.; Cruz Gonzalez, C.; Duncan, R. G.; Chinn, C. A.; Murphy D. (July 2022, Computersupported collaborative learning)

   A. Weinberger; W. Chen; D.Hernández-Leo; D., B. Chen (Ed.)

   Scientific argumentation and modeling are both core practices in learning and doing science. However, they are challenging for students. Although there is considerable literature about scientific argumentation or modeling practice in K-12 science, there are limited studies on how engaging students in modeling and scientific argumentation might be mutually supportive. This study aims to explore how 5th graders can be supported by our designed mediators as they engage in argumentation and modeling, in particular, model revision. We implemented a virtual afterschool science club to examine how our modeling tool – MEME (Model and Evidence Mapping Environment), provided evidence, peer comments, and other mediators influenced students in learning about aquatic ecosystems through developing a model. While both groups that we examined constructed strong arguments and developed good models, we show how the mediators played different roles in helping them be successful. 

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