Biology subjects

Montgomery, T.

Publications and source records attributed to Montgomery, T..

7 recordsLinked to original sources

bioRxiv2026

From Problems to Solutions: How Self-Questions Drive Strong Scientific Reasoning

Metacognition, or awareness and control of thinking, is essential for problem solving because it helps solvers select strategies for learning and decide when to enact them (planning), check their understanding in the moment (monitoring), and assess effectiveness of solutions and learning strategies (evaluating). Most studies that examine metacognition do so retrospectively, leaving a critical gap in how metacognition is used in-the-moment for problem solving. In this study, we utilized a think-aloud interview approach to capture and characterize the metacognitive skills that senior undergraduate life science students at three institution types in the United States used spontaneously while solving challenging biology problems. We found that the students (n = 39) displayed a wide variety and quantity of monitoring, some evaluating, and nearly no planning skills while creating a solution backed with high-quality reasoning. Students frequently used self-questions to monitor and evaluate their thinking. We found that self-questioning is a critical skill for generating solutions, but it only moves problem solving forward if the student asks and correctly answers the self-question out loud. This study illustrates how self-questioning and other metacognitive regulation skills provide links to bridge the gap between a student's prior knowledge and specific features of a challenging problem. Based on our student data, we conceptualized a model of metacognitive phases during problem solving with high-quality reasoning. Finally, we present a self-question scaffold to facilitate the proposed phases (planning, monitoring, reasoning, and evaluating) so educators can equip students with metacognitive and scientific reasoning tools for effective problem solving.

scientific communication and education↗

bioRxiv2026

A TCER-1-siRNA Regulatory Axis Suppresses Antibacterial Innate Immunity in C. elegans

Small interfering RNA (siRNA) are important regulators of gene expression with well-established roles in pathogen defense. Yet, their specific roles in antibacterial immunity are not well understood. Here, we identify an siRNA pathway involved in repressing antibacterial innate immunity in Caenorhabditis elegans. We show that genes required for the biogenesis or function of WAGO Argonaute-associated siRNAs, called 22G-RNAs, function in a common genetic pathway with the immune-suppressive transcription elongation and splicing factor TCER-1 to inhibit immunity. Loss of tcer-1 reduced levels of 22G-RNAs from a subset of WAGO targets, while mutations in several WAGO 22G-RNA pathway genes phenocopied the enhanced immunoresistance of tcer-1 mutants, suggesting a shared regulatory module. Integrative 22G-RNA-mRNA analyses and molecular genetic studied show that this module does not induce widespread gene silencing, but instead targets a restricted set of immune-relevant effectors, including scrm-4, encoding a phospholipid translocase that promotes host resistance. Together, our findings establish endogenous WAGO 22G-RNAs as repressors of antibacterial immunity and identify TCER-1 as a physiological regulator that promotes 22G-RNA biogenesis to constrain host defense. The results uncover a previously unrecognized small RNA-dependent mechanism linking transcription, metabolism, and antibacterial innate immunity.

immunology↗

bioRxiv2025

Acute E2/P4 loss compromises the biology and function of neurogenic niches during a vulnerable female aging period

Effects of aging on neural stem progenitor cells (NSPCs) have been studied in males, but less is known in females. Here we comparatively assess female NSPC biology, both in the subventricular zone and hippocampal dentate gyrus niches, across different ages of F344 rats (2, 6, 9 and 14 months). The rats were ovariectomized (OVX) or remained Intact at each of the aging stages, to assess the role of the female sex hormones, estradiol (E2) and progesterone (P4). Results show that while age-dependent decays become prominent at 14 months, ovariectomy-induced E2/P4 loss markedly reduces neurogenesis and associated behavioral function, earlier, at 9 months of age. Coinciding with this pattern of neurogenic decline, we also detect adaptive changes in estrogen and progesterone receptor expression, antioxidant expression, and brain E2/P4 levels. Fundamentally, these results reveal specific female time-periods, when the brain is sensitive to age and E2/P4 loss, potentially setting-up for disease susceptibility.

neuroscience↗

bioRxiv2025

Argonaute-siRNA loading via the RNA-binding protein RDE-4 in C. elegans

Small RNAs, such as microRNAs (miRNAs) and small interfering RNAs (siRNAs), associate with Argonaute proteins to control gene expression, impacting a wide range of cellular processes, such as antiviral defense, transposon silencing, and development1. Plants and animals typically have several classes of small RNAs, along with multiple Argonautes2. These Argonautes often confer distinct functionality to the various classes of small RNAs3. But how small RNAs are selectively loaded into the appropriate Argonaute is not well understood. miRNAs and siRNAs are typically generated from double-stranded RNA (dsRNA) precursors by the endoribonuclease Dicer4. siRNAs are often processed from fully base-paired precursors derived from various endogenous and exogenous sources, whereas miRNAs typically originate from genetically encoded partially base-paired hairpins1. In C. elegans, Dicer/DCR-1 processing of siRNAs and a related small RNA class, known as 26G- RNAs, is mediated by the dsRNA-binding protein RDE-45-7. Here, we show that RDE-4 also facilitates loading of siRNAs (but not miRNAs) into the Argonaute RDE-1, but not into ALG-1, and loading of 26G-RNAs into the Argonaute ERGO-1. Although we do not find evidence that ALG-3/4 associated 26G-RNAs require RDE-4 for Argonaute loading, their levels are strongly reduced in rde-4 mutants indicating that RDE-4 is broadly required for their formation or stability. Our findings reveal a role for RDE-4 as a critical determinant of small RNA loading specificity and provide insight into the mechanisms by which small RNAs are selectively paired with their corresponding Argonautes.

biochemistry↗

bioRxiv2021

Imaging translational control by Argonaute with single-molecule resolution in live cells

A major challenge to our understanding of translational control has been deconvolving the individual impact specific regulatory factors have on the complex dynamics of mRNA translation. MicroRNAs (miRNAs), for example, guide Argonaute and associated proteins to target mRNAs, where they direct gene silencing in multiple ways that are not well understood. To better deconvolve these dynamics, we have developed technology to directly visualize and quantify the impact of human Argonaute2 (Ago2) on the translation and subcellular localization of individual reporter mRNAs in living cells. We show that our combined translation and Ago2 tethering system reflects endogenous miRNA-mediated gene silencing. Using the system, we find that Ago2 association leads to progressive silencing of translation at individual mRNA. The timescale of silencing was similar to that of translation, consistent with a role for Ago2 in blocking translation initiation, leading to ribosome runoff. At early time points, we observed occasional brief bursts of translational activity at Ago2-tethered mRNAs undergoing silencing, suggesting that translational repression may initially be reversible. At later time points, Ago2-tethered mRNAs cluster and coalesce with endogenous P-bodies, where a translationally silent state is maintained. These results provide a framework for exploring miRNA-mediated gene regulation in live cells at the single-molecule level. Furthermore, our tethering-based, single-molecule reporter system will likely have wide-ranging application in studying general RNA-protein interactions.

molecular biology↗

bioRxiv2020

Associations of early social experience with offspring DNA methylation and later life stress phenotype

In a wild population of spotted hyenas, we tested the hypothesis that maternal care during the first year of life and social connectedness during two periods of early development lead to differences in DNA methylation and fecal glucocorticoid metabolites (fGCMs) later in life. We found that although maternal care and social connectedness during the communal den dependent period were not associated with fGCMs, greater social connectedness after hyenas leave their communal den is associated with lower adult fGCMs. Additionally, more maternal care and social connectedness after leaving the communal den corresponded with higher global (%CCGG) DNA methylation. Finally, we identified multiple DNA methylation biomarkers near genes involved in inflammation that may link maternal care and stress phenotype. Our findings suggest that both maternal care during the first year of life and social connections after leaving the den influence DNA methylation and contribute to a developmentally plastic stress response.

animal behavior and cognition↗

bioRxiv2017

USA300 MRSA lineages persist on multiple body sites following infection

Abstract\n\nBACKGROUNDUSA300 methicillin-resistant Staphylococcus aureus (MRSA) is a community- and hospital- acquired pathogen that frequently causes infections but also can survive on the human body asymptomatically as a part of the normal flora. We devised a comparative genomic strategy to track colonizing USA300 at different body sites after S. aureus infection.\n\nMETHODSWe sampled ST8 S. aureus from subjects at the site of a first known MRSA infection. Within 60 days of this infection and again 12 months later, each subject was tested for asymptomatic colonization in the nose, throat and perirectal region. 93 S. aureus strains underwent whole genome shotgun sequencing.\n\nRESULTSGenome sequencing revealed that 23 patients carried USA300 intra-subject lineages (ISLs), defined as having an index infection isolate (III) and closely related strains. Pairwise distance between strains in different ISLs was 48 to 162 single nucleotide polymorphisms (SNPs), whereas within the same ISL it was 0 to 26 SNPs. At the initial sampling time among 23 subjects, we isolated S. aureus from the nose, throat and perirectal sites from 15, 11 and 15 of them, respectively. Twelve months later we isolated S. aureus within the same ISL from 9 subjects, with 6, 3 and 3 strains from the nose, throat and perirectal area, respectively. The median time from initial acquisition of the S. aureus USA300 strains to culture of the index infection was estimated at 18 weeks. Strains in ISLs from the same subject differed in plasmid and prophage content, and contained deletions that removed the mecA-containing SCCmec and ACME regions. Five strains contained frameshift mutations in agr toxin-regulating genes. Persistence of an ISL was not associated with clinical or demographic subject characteristics.\n\nCONCLUSIONClonal lineages of USA300 may continue to colonize people at one or more anatomic sites up to a year after an initial infection and experience loss of the SCCmec, loss and gain of other mobile genetic elements, and mutations in the agr operon.

microbiology↗